Epilogue

During the trailblazing years of endourology in that will not allow every patient to fall in or follow the early 1980s, any unusual or challenging case one of the arms of the algorithm. Instead in this provided an opportunity to envision, develop, portion of the textbook, I have outlined fifteen and try new approaches within this field. actual clinical cases from an approximate period Between 1983 and 1984, one such clinical of three decades. These sample cases of different scenario was an elderly female patient with poor aspects and stages of upper tract urothelial carci- renal function and transitional cell carcinoma of noma will illustrate a timeline with changes the renal pelvis who had refused nephrectomy to reflecting better, newer technology as well as a avoid hemodialysis, which she resented more retrospective review of these not run-of-the-mill than the thought of living fighting potential cases. The study of these actual clinical scenarios recurrence of cancer. This was the circumstance will allow for a brief recapitulation of all the for the first planned percutaneous renal pelvic modalities that have been described in the previ- tumor resection, which was followed by intra- ous chapters in a variety of forms. We are prac- cavitary instillation of thio-TEPA, a commonly tically seeing the applications of all the modalities used topical agent then, to decrease the recur- that have been described in the pages of this rence of the bladder tumors. The protocol used textbook. In some cases, multiple modalities have was similar to the one used in treatment of been used, as is the case usually in the manage- bladder cancers. We reported this case in video ment of these patients as they transition through format with my colleagues, Dr. Arthur Smith and different phases from diagnosis to the endpoint of Dr. Gopal Badlani in AUA meeting in 1985 [1]. treatment. These case reviews demonstrate suc- To my knowledge, this was the first reported cess as well as failure and as was mentioned elective systemic endoscopic resection combined earlier, not all of these cases can be compared to with intracavitary treatment in management of the radical nephroureterectomy or segmental resec- upper tract urothelial tumors. The conservative tion as alternative options. Two such examples: management of UTUC has evolved significantly case 1 of 58-year-old male patient with a small since then with a lot more to be accomplished as renal pelvic tumor managed endoscopically when outlined in the pages of this book. standard treatment of the time was nephroureter- It is often difficult or unrealistic to format the ctomy and the second case 8 of an 80-year-old treatment of all patients into preconceived or female with solitary kidney presented with anuria algorithmic models especially in cases of UTUC. secondary to large lesion causing complete This group of patients has often multiple factors obstruction and was resected percutaneously

© Springer International Publishing AG, part of Springer Nature 2018 337 M. Eshghi (ed.), Urothelial Malignancies of the Upper Urinary Tract, https://doi.org/10.1007/978-3-319-51263-1 338 Epilogue without recurrence while she went on to undergo Majid Eshghi, MD, FACS, MBA additional unrelated cancer surgeries. They Valhalla, New York should also serve as a constant reminder of the January 2018 need for diligent and unrelenting continuous follow-up surveillance of patients with upper tract Reference urothelial carcinoma … a disease with high potentials for recurrence and progression and 1. Smith A, Eshghi M, Badlani G: Percutaneous nephroureterectomy considered only if and when renal surgery, parts 1–2, AUA 2015, Abstract necessary. Book. Case Studies: A Spectrum of Upper Tract Urothelial Carcinoma

Neel Patel, Cristina Fox and Majid Eshghi

Corresponding author: Comment Majid Eshghi, MD, FACS, MBA Chief Section of Endourology and Minimally Today this patient will be managed completely in Invasive Urology, Westchester Medical Health a retrograde fashion: biopsy, urinary cytology, Network/New York Medical College, Depart- cell block and laser ablation. This would be ment of Urology, Valhalla, NY, United States similar to the procedure shown in Video 14.1. It also highlights that low-grade urothelial carci- noma of the upper tract can be managed suc- Case Study 1 cessfully with complete resection and proper surveillance. A 58-year-old male with one episode of hema- turia underwent a complete urological workup that was negative except for the intravenous Case Study 2 pyelogram showing a small filling defect in the right renal pelvis. A flexible ureteroscopy Patient is a 73-year-old non-smoker female with a revealed a small papillary lesion and the rest of history of renal stones who was found to have the collecting system was free of any pathology. significant left hydronephrosis on her follow-up Considering that 25 years ago, we did not have ultrasound. Her previous imaging studies 2 years proper ureteroscopic equipment to adequately earlier were negative. The patient was completely biopsy and ablate this lesion, patient underwent a asymptomatic and denied flank pain fever, percutaneous approach and the lesion was com- urinary tract infection, or hematuria. CT scan pletely removed using a cold cup and the base imaging revealed a filling defect in the left distal was fulgurated. A similar case is demonstrated in ureter associated with left hydroureteronephrosis. Chap. 14, Video 14.1 and Video 14.2. He was No stone was identified in the distal ureter. Office followed closely for 15 years before he retired cystoscopy was negative and urine cytology and moved to another state and reported negative showed some atypical cells. follow up studies. He was given recommendation A left ureteroscopy was performed showing a of close urological follow-up (Fig. C.1). papillary lesion that was resected using a rigid ureteroesectoscope. Evaluation of the rest of the

© Springer International Publishing AG, part of Springer Nature 2018 339 M. Eshghi (ed.), Urothelial Malignancies of the Upper Urinary Tract, https://doi.org/10.1007/978-3-319-51263-1 340 Case Studies: A Spectrum of Upper Tract Urothelial Carcinoma

Fig. C.2 CT showing L hydroureter from distal ureteral lesion

has been placed on a surveillance protocol with periodic imaging and endoscopy. At 9 months, surveillance endoscopy showed completely nor- mal bladder and ureter with multiple negative cytologies. Office ureteroscopy and cystoscopy repeated 18 months later is negative. Figures C.2, C.3, C.4 and C.5; Video C.1 and Video C.2.

Comment

Fig. C.1 Intravenous pyelogram prior to percutaneous This case illustrates aggressive endoscopic nephrostomy, which shows a small filling defect in the resection of low-grade bulky tumor of distal renal pelvis ureter using rigid ureteroresectoscope followed with topical chemotherapy via intentionally cre- collecting system was negative. The left orifice ated vesicoureteral reflux. Complete, deep and intramural ureter were resected to allow for resection of tumor and wide resection of the free reflux into the distal segment. Double pigtail orifice and intramural ureter are essential for a stent was placed and mitomycin was instilled successful outcome. Resection of ureteral orifice into the renal pelvis with an open-ended catheter allows for office ureteroscopy without anesthesia. placed next to the stent. A Foley was placed and clamped while the open-ended catheter was removed. The Foley was unclamped after one Case Study 3 hour. Pathology was consistent with papillary urothelial carcinoma with no muscle invasion. Patient is a 78-year-old male who was referred Patient underwent a 6 week course of intrav- from nephrologist after a routine evaluation for esical mitomycin and was instructed to lie on her chronic kidney disease. In 2014, renal and left side for at least one hour. Follow-up uretero- bladder ultrasound revealed severe left scopy revealed no residual tumor. She underwent hydronephrosis. Due to elevated creatinine, dia- another instillation of mitomycin at the end of the betes, and an aortic aneurysm, a contrast study procedure, it was felt although the lesion was had not been done. The patient had several low-grade mitomycin C would provide additional additional comorbidities. He underwent a cys- benefit. Urine cytology has remained negative. She toscopy and retrograde pyelogram revealing a Case Studies: A Spectrum of Upper Tract Urothelial Carcinoma 341

biopsy of the distal ureter demonstrating mucosa negative for tumor, only characteristic of fibrous soft tissue. Three months subsequent to the initial resection, the patient developed recurrent hydronephrosis and flank pain secondary to a distal ureteral stricture, requiring ureteral balloon dilation and stenting. Surveillance pyelography, ureteroscopy with biopsy, and stent exchange were subsequently performed at 6-month inter- vals in addition to serial urine cytology, all of which were negative for malignant cells. The patient underwent CT, albeit without contrast secondary to his chronic kidney disease Fig. C.3 Left retrograde pyelogram showing distal with a creatinine of approximately 2.4. In late ureteral filling defect 2015, CT demonstrated hydronephrosis and thickening the distal ureter, and in early 2016 three-centimeter-long filling defect suggesting surveillance cystoscopy revealed a few superfi- urothelial carcinoma in the left distal ureter cial bladder tumors that were fulgurated. nearing the ureterovesical junction. The patient Additionally, ureteroscopy revealed some underwent incision of a narrow distal ureter and narrowing of the left distal ureter. Post dilation, ureteroscopic resection of this lesion using the retrograde pyelography revealed a filling defect 11.5 French rigid ureteroresectoscope. Patho- of the mid ureter. Ureteroscopy revealed 3 small logic analysis of the specimen revealed nonin- mid ureteral tumors which were ablated with a vasive, low-grade papillary urothelial carcinoma. combination of Holmium and Nd–Yag lasers. One month subsequent to this original resec- The lesions were pathologically classified as low tion, the patient underwent repeat cystoscopy, grade, noninvasive papillary urothelial carcinoma retrograde pyelography, and ureteroscopic with no invasion to lamina propria. The patient will continue with endoscopic surveillance. CT

Fig. C.4 Left distal ureter biopsy showing low-grade urothelial carcinoma with no lamina propria or muscle invasion 342 Case Studies: A Spectrum of Upper Tract Urothelial Carcinoma

Fig. C.5 Distal ureteral biopsy showing urothelium shows ureteroresectoscopic resection of the tumor; V-2; lined with acute inflammation and necrosis/infarction, follow-up endoscopy showing no residual tumor negative for dysplasia or malignancy; V-1; this segment

Fig. C.6 a, b 2014 retrograde pyelogram during a ureteroscopic resection of distal ureteral tumor demonstrating 2– 3cmfilling defect in distal ureter as well as torturous ureter and hydronephrosis scan of the abdomen did not show any evidence of metastatic disease (Figs. C.6, C.7 and C.8). Case Study 4

Comment Patient is a 68-year-old male with a strong history of smoking and uric acid stones presented with an This case illustrates: use of rigid ureteroscope for episode of gross hematuria 30 years ago. Intra- resection of bulky low-grade distal ureteral venous pyelogram showed a slight filling defect of tumor in a patient with multiple medical the left upper pole calyx. One of the first generation comorbidities. flexible ureteroscope with active deflection was Case Studies: A Spectrum of Upper Tract Urothelial Carcinoma 343

Fig. C.7 Pathologic slide from 2014 ureteroscopic resection of distal left ureteral tumor consistent with low grade, papillary urothelial carcinoma. Muscle bundles are free of tumor

Fig. C.8 Pathologic slide from 2014 repeat surveillance biopsy of distal ureter performed 6 months post resection demonstrating fibrocollagenous tissue and areas of hemorrhage with no evidence of malignant cells used to perform a biopsy of the upper calyx, which the patient had one episode of superficial bladder showed high-grade urothelial carcinoma. The cancer which was resected without recurrence. patient underwent a left nephroureterectomy. Several years post nephrouterectomy, the Serial surveillance of the patient has been done by patient developed one episode of obstructive in office cystoscopy, annual urine cytology, as well uropathy, necessitating ureteroscopy. However, as CT urogram and renal/bladder ultrasound. The currently, the stones have been successfully patient has documented presence of multiple sim- managed medically without recurrence. The ple right renal cysts measuring approximately long-term sequela of the remote neoplasm 6 Â 6 cm in the upper pole, approximately experienced by this patient has been the gradual 1.3 Â 1.4 cm in the midpole cortex, and development of chronic kidney disease. The 1.0 Â 0.7 cm in the midpole parenchyma. These patient’s creatinine has slightly increased to 1.1, lesions have been stable in size over the many years he is post one MI and on multiple medications of surveillance. In the first few years of follow–up, for hypertension. He has had no recurrence to this date (Figs. C.9, C.10 and C.11). 344 Case Studies: A Spectrum of Upper Tract Urothelial Carcinoma

Comment

This case illustrates: early diagnostic and sam- pling using flexible ureteroscopes providing adequate tissue diagnosis of high-grade disease justifying nephroureterectomy, in the face of a suboptimal contralateral kidney, partially com- promised with stone disease. Prior to this era, most nephroureterectomies were based on imaging studies and clinical findings.

Case Study 5

This is a 71-year-old female with findings of microscopic hematuria. Her initial workup demonstrated a cystoscopy and CT Urogram at Fig. C.9 Retrograde pyelogram prior to ureteroscopic the time were within normal limits; however the biopsy of upper calyceal area 30 years ago urine cytology was equivocal. The patient’s repeat urine cytology was positive for malignant again obtained in the office which revealed cells. She then underwent random bladder biopsy high-grade urothelial cell carcinoma. and intra-operative ureteral washes were sent for The patient underwent a second round of cytology. The biopsies consisting of five samples random bladder biopsies as well as bilateral ret- were all negative, while the cytology from the rograde pyelogram and cytology. No abnormal- left ureter was negative A urine cytology was ities or filling defects were seen with the

Fig. C.10 Ureteroscopic biopsy from 1988 showed high-grade urothelial carcinoma Case Studies: A Spectrum of Upper Tract Urothelial Carcinoma 345

Fig. C.11 CT scan of abdomen and pelvis demonstrating simple renal cysts in right kidney several years post left nephroureterectomy retrograde pyelogram, while the bladder biopsies Comment were again negative with muscularis propria present in each specimen. The intra-operative This case illustrates high-grade lesion with CIS cytology showed high-grade urothelial cell car- and positive cytology responding to neoadjuvant cinoma from the bladder and positive malignant chemotherapy. Obtaining a definitive biopsy can cells from the left ureteral washing. Left ure- teroscopy with biopsy and cytology were per- formed which showed left renal pelvis lesion with urothelial atypia and left ureteral wash with positive malignant cells. The patient underwent a repeat left ureteroscopy and biopsy of a left upper pole lesion, which revealed atypical urothelial cells and fibrous connective tissue. A thorough discussion was held with the patient regarding her history of multiple urine cytologies with various findings ranging from benign to atypical to malignant, as well as multiple bladder biopsies showing no malignancy, and a finding of a left renal pelvic lesion that revealed atypical urothelial cells. Patient was given all treatment options: surveillance, endoscopic man- agement, and neoadjuvant chemotherapy fol- lowed by left nephroureterectomy. The patient opted for a course of neoadjuvant chemotherapy followed by left nephroureterectomy. Final pathology showed no detectable residual disease Fig. C.12 Retrograde pyelogram showing no filling (Figs. C.12, C.13 and C.14). defects 346 Case Studies: A Spectrum of Upper Tract Urothelial Carcinoma

Fig. C.13 Left renal pelvis biopsy showing focal marked urothelial atypia—fibrous connective tissue with chronic inflammation

Fig. C.14 Nephroureterectomy specimen showing benign unremarkable renal parenchyma and renal pelvis with no residual tumor seen Case Studies: A Spectrum of Upper Tract Urothelial Carcinoma 347 be challenging in some of these cases. It is hard A similar pattern of infiltrative disease is some- to assess long-term complete response without times seen in renal pelvis and upper ureter as nephroureterectomy. well without obvious papillary or sessile tumor. Ureteral wall thickening, ureteral obstruction, and abnormal cytology are telltale signs. Case Study 6

A77–year-old man with a strong history of Case Study 7 smoking was evaluated for gross painless hema- turia. Initial CT and Cystoscopy were found to be A 58-year-old female was evaluated with a fi negative. Despite initial negative ndings, the 10-month history of intermittent gross hematuria patient continued to have intermittent gross and right flank pain. Computed tomography hematuria. Due to high index of suspicion revealed mild hydronephrosis and thickening of because of strong history of smoking a follow-up, upper ureter. Previous ureteroscopy and biopsies CT Urogram that was performed later that at another institution were not diagnostic. She showed mild to moderate right hydronephrosis underwent repeat ureteroscopy which only with tapering of the right distal ureter. revealed firm ureteral wall with slightly abnormal The patient underwent right ureteroscopy and looking mucosa. Deep biopsies of renal pelvis was found to have a right distal ureteral stricture and very proximal ureter revealed high-grade and dilated ureter proximal to this area. Multiple urothelial carcinoma. cold cup biopsies were taken after the initial She was recommended to undergo radical dilation of the intramural ureter. Endoscopy of nephroureterectomy due to changes of ureteral the rest of the ureter and collecting system did wall, UPJ area and high-grade carcinoma. Final not show additional pathology. Pathology was pathology revealed infiltrative high-grade positive for a diagnosis of high-grade urothelial urothelial carcinoma (Fig. C.19). carcinoma involving the lamina propria, but the muscularis propria free of tumor. The patient underwent a robotic assisted Comment laparoscopic partial cystectomy with right distal ureterectomy and ureteral reimplantation. His The significance of this case is infiltrative sub- fi nal pathology showed high-grade urothelial mucosal disease without any papillary or ele- carcinoma within the right distal ureteral segment vated mucosal lesions. These lesions are like fire  measuring 0.6 0.3 cm with involvement into under the ash requiring aggressive treatment the muscle, negative proximal and distal margins before they completely penetrate through the as well as lack of lymphovascular invasion. This wall and as was described in case study number 6 fi was classi ed as pT2pNxMx. The patient was with the difference that in distal ureter the patient placed on a surveillance protocol involving could have the option of distal ureterectomy and imaging, cystoscopy, and urine cytology. The reimplantation. importance of surveillance protocol was empha- sized to the patient and he agreed to be compliant (Figs. C.15, C.16, C.17 and C.18). Case Study 8

Comment An 80-year-old female with a left solitary kidney was evaluated for anuria and serum creatinine of This case illustrates a non-papillary infiltrating 3.9. Her past cancer history included a Rt tumor causing obstruction. Endoscopic manage- nephrectomy for renal cell carcinoma, hysterec- ment is not a good option for such cases. tomy, colectomy, breast lumpectomy, resections 348 Case Studies: A Spectrum of Upper Tract Urothelial Carcinoma

Fig. C.15 CT showing right hydroureter with distal tapering of ureter

of melanoma and basal cell carcinoma. She also had history of open heart and aortic surgery. Imaging studies revealed a large filling defect in the renal pelvis and associated hydronephro- sis. Considering her strong history of malignan- cies and multiple comorbidities she decided to undergo organ preserving endoscopic treatment. She underwent percutaneous resection of a large broad based papillary renal pelvic tumor that had caused UPJ obstruction. Pathological diagnosis was low-grade papillary urothelial carcinoma (Video C.3). She underwent a 6-week course of intracavi- tary mitomycin C. Follow-up nephroscopy and biopsies were negative. She received a second Fig. C.16 Right retrograde pyelogram showing distal booster intracavitary treatment before the filling defect with proximal dilated ureter removal of the nephrostomy tube. Case Studies: A Spectrum of Upper Tract Urothelial Carcinoma 349

Fig. C.17 Right ureter biopsy showing high-grade urothelial carcinoma involving lamina propria, muscle is free of invasion

Fig. C.18 Right ureter s/p ureterectomy showing high-grade urothelial carcinoma with muscle invasion 350 Case Studies: A Spectrum of Upper Tract Urothelial Carcinoma

Fig. C.19 a Cross-sectional CT image of the UPJ area indwelling double pigtail stent in place; d ureteroscopic shows thickening of the wall; b additional section lower DEEP biopsy renal pelvis; e ureteroscopic renal pelvis down shows thickening of the upper ureteral wall without biopsy showing high-grade urothelial carcinoma; any intraluminal filling defect; c CT urogram recon- f low-power section of nephroureterectomy specimen struction of the collecting system showing irregularity showing high-grade disease; g high-power view shows and thickening of RT upper ureter and renal pelvis high-grade urothelial carcinoma without any intraluminal filling defect. There is an

A retrograde pyelogram and ureteroscopy renal function without evidence of any recur- after 6 months showed no evidence of recurrence rence (Fig. C.20). with negative urine cytology. She developed another colon cancer a year later requiring resection and was in coma in ICU Comment setting for a month before complete recovery. Three years after her original renal tumor This is a perfect example of an absolute imper- resection she slowly developed deterioration of ative case, due to multiple comorbidities and Case Studies: A Spectrum of Upper Tract Urothelial Carcinoma 351

Fig. C.19 (continued) strong history of several malignancies, with an concerned about renal function in case he would excellent outcome. Patient and family’s compli- need further chemotherapy. Approximately a ance with follow-up protocol played an impor- year later, during follow-up imaging he was tant role towards this outcome. found to have recurrence of the filling defect and he underwent left ureteroscopy and biopsy which was not quite adequate but suggesting low-grade Case Study 9 urothelial carcinoma. We evaluated patient at this time and he This patient is a 69-year-old male with history of underwent ureteroscopy of the left kidney for colorectal cancer one and half years ago who was repeat biopsy. Tumor was present and located in found to have a filling defect in the upper pole of a highly superior calyx which was bulky making the left kidney on subsequent imaging. The ureteroscopic management inadequate. Pathol- patient underwent chemotherapy for colon can- ogy at that time was consistent with low-grade cer and on interval imaging the filling defect was urothelial carcinoma. Patient then underwent a not seen on CT images. The patient was quite percutaneous nephroscopic complete resection of frail with multiple comorbidities and slight ele- the upper calyceal tumor. Percutaneous access vation of creatinine. Due to possibility of cancer was obtained by urology into the upper pole recurrence, patient and his oncologist were calyx allowing us to perform complete resection 352 Case Studies: A Spectrum of Upper Tract Urothelial Carcinoma

Fig. C.20 a A retrograde pyelogram at the time percu- biopsy of renal pelvis after resection and mitamycin C taneous resection. Note the large filling defect in the renal intracavitary treatment shows no obvious recurrence; pelvis; b endoscopic view of renal pelvis tumor showing e retrograde pyelogram 6 months later; f radiographic and a large papillary tumor; c low-power view of tumor endoscopic images of ureteroscopy after six months described as low-grade papillary carcinoma; d follow-up showed no residual or recurrence and ablation of all tumor burden within the calyx tissue. Multiple biopsies were taken of these using a urethroresectoscope. Pathology from this areas which showed urothelial denudation, sub- procedure with complete resection revealed mucosal fibrosis, fat necrosis and no evidence of high-grade urothelial carcinoma. malignancy. A nephrostomy was placed and As a result of the upstaging of the disease, patient underwent maintenance instillation of treatment options were discussed including Left mitomycin C before the removal of nephros- nephroureterectomy, which the patient refused tomy. Patient undergoes imaging, cytology, and due to fear of impaired renal function. Additional endoscopic surveillance (Figs. C.21, C.22, C.23, treatment options were discussed at this time and C.24 and C.25). patient agreed to intracavitary instillation of mitomycin C through a nephrostomy tube. Surveillance nephroscopy revealed no new Comment areas of tumor recurrence in the left calyx, renal pelvis, and proximal ureter. With thorough This case illustrates bulky lesion in the calyceal area, inspection of the left upper pole calyx, sites of which cannot be adequately managed in a retrograde prior resection showed fibrosis and sloughing of fashion. Additionally, the percutaneous resection Case Studies: A Spectrum of Upper Tract Urothelial Carcinoma 353

Fig. C.20 (continued) showed upstaging to high-grade disease indicating carcinoma in situ in 2001. At that time, the inadequacy of retrograde tumor management in patient was treated with a transurethral resection some cases. We recommend percutaneous resection of the tumor burden followed by intravesical for all bulky renal pelvis and large deep calyceal BCG and interferon for 6 weeks. After comple- tumor to avoid understaging. A 19–22 Fr slender tion of the induction course, the patient was urethroresectoscope is ideal for such resections. maintained on maintenance BCG, with comple- tion in 2003. The patient was then monitored with surveillance cystoscopy and imaging. In Case Study 10 2006, the patient demonstrated a distal right ureteral tumor and underwent a distal ureterec- This patient is an 81-year-old diabetic male tomy with pathologic diagnosis of high-grade T1 patient with an initial diagnosis of transitional transitional cell carcinoma. He remained disease cell carcinoma of the bladder with concomitant free until 2009 when he developed recurrence of 354 Case Studies: A Spectrum of Upper Tract Urothelial Carcinoma

except for a questionable lesion within the left upper pole calyx, from which biopsy was taken, and selective cytology was also obtained. Cytol- ogy and pathologic analysis confirmed urothelial cells consistent with transitional cell carcinoma. Given the location and volume of the lesion, the patient underwent percutaneous resection of the calyceal lesion using a 24 FR urethroresctoscope as per his choice. The lesion was resected deeply and into the neck of the calyceal infundibulum and a nephrostomy tube was placed for installation of mitomycin. The patient refused a nephroureterec- tomy. He underwent a 6-week course of intra- cavitary treatment using mitomycin. Follow-up surveillance endoscopy using a 12 French mini nephroscope revealed no additional lesions and several deep biopsies of the previous tumor bed were performed, which showed fibrotic tissue without evidence of disease. The patient under- went 3 additional installations of mitomycin Fig. C.21 Left retrograde pyelogram showing upper before the nephrostomy was removed. calyx filling defect Given the extensive comorbidity index of this patient including hypertension, diabetes, morbid bladder CIS and underwent an additional 6-week obesity, coronary artery disease necessitating course of BCG. Subsequent to this, the patient coronary stenting, as well as a 2011 diagnosis of experienced continued hematuria and persis- Gleason 6 adenocarcinoma of the prostate, treated tently positive urine FISH. with radiation therapy; when a surveillance MRI In 2010, an interval surveillance CT urogram revealed a suspicious left upper pole lesion, a revealed a subtle left upper pole lesion, which was percutaneous renal biopsy was performed not present in an MR urogram earlier that same revealing high-grade infiltrating transitional cell year. Consequently, the patient underwent a cys- carcinoma in a milieu of chronic inflammation toscopy, bilateral retrograde pyelogram, left ure- and fibrosis. Consequently, the patient underwent teroscopy, and biopsy of the left upper pole lesion. laparascopic nephroureterectomy. Pathologically, Intraoperatively, the patient was found to have a the specimen was high-grade transitional cell normal bladder mucosa, normal retrograde pyel- carcinoma with infiltration to the renal medulla ography of the collecting systems bilaterally, and cortex, involving the upper part of the right

Fig. C.22 a, b percutaneous nephrostomy performed to gain access to left upper pole calyx for tumor resection Case Studies: A Spectrum of Upper Tract Urothelial Carcinoma 355

Fig. C.23 Left kidney upper calyx biopsy showing low-grade papillary urothelial carcinoma

Fig. C.24 Left percutaneous renal calyx biopsy showing high-grade urothelial carcinoma 356 Case Studies: A Spectrum of Upper Tract Urothelial Carcinoma

Fig. C.25 Left kidney previous tumor site biopsy showing urothelial denudation with submucosal fibrosis and fat necrosis, no evidence of malignancy kidney, but sparing the renal capsule, pelvis, and co morbidities with recurrence necessitating sinus fat. Additionally, a small focus of nephrouretrectomy followed by adjuvant high-grade CIS was found at the ureterovesical chemotherapy. This case again emphasizes the junction. need for continuous monitoring of patients with At the time of diagnosis in 2012, MRI con- UTUC and transitioning to other modalities firmed 1.5 cm para-aortic lymphadenopathy; when one fails. hence, the patient underwent adjuvant chemotherapy and maintains close follow-up with oncology. The patient undergoes regular surveillance MR urogram, in light of a diagnosis of chronic kidney disease, as well as regular surveillance cystoscopy and urine cytology. At the present time, he has a low PSA, MR urogram and PET CT are normal, with no suspicious lesions or filling defects and absence of any lymphadenopathy, and a negative cystoscopy (Figs. C.26, C.27, C.28, C.29, C.30, C.31 and C.32).

Comment Fig. C.26 2010 antegrade nephrostogram intraopera- tively demonstrating left upper pole filling defect con- This cases illustrates: initial conservative treat- sistent with calyceal mass. This finding was treated ment as per patient’s resistance due to multiple endoscopically Case Studies: A Spectrum of Upper Tract Urothelial Carcinoma 357

Fig. C.27 2012 MRI of the abdomen and pelvis demonstrating left upper pole heterogeneous, enhancing mass measuring 4.6 Â 5.1 Â 4.6 cm. This mass was treated with nephroureterectomy and neoadjuvant chemotherapy due to hilhar lymphadenopathy

Fig. C.28 Pathology slide from 2011 ureteroscopic biopsy of left upper pole calyx consistent with fibro-connective and granulation tissue with focal areas of necrosis 358 Case Studies: A Spectrum of Upper Tract Urothelial Carcinoma

Fig. C.29 Pathology slide from 2011 ureteroscopic biopsy of left upper poly calyx demonstrated scattered atypical cells, suspicious for urothelial neoplasm but not fully characterized

Fig. C.30 a, b Pathologic slide from repeat 2011 ureteroscopic biopsy of left upper pole calyceal mass demonstrating urothelium with dysplasia in a milieu of chronic inflammation

history of renal stone 5 years earlier. In between Case Study 11 these two events she had developed gross hema- turia and left flank pain. After ureteroscopy and A 50-year-old female with strong history of biopsy revealed high-grade left ureteral tumor she smoking developed gross hematuria and several underwent Lt radical nephroureterectomy. bladder tumors were resected endoscopically. Her During her followup after the bladder tumor past medical history included a Rt pyeloplasty, resection her urine cytology was intermittently that had failed and was successfully managed positive or showed atypical cells in spite of with ureteroscopic cold knife endopyelotomy, negative imaging studies and thorough RT Case Studies: A Spectrum of Upper Tract Urothelial Carcinoma 359

Fig. C.31 a, b 2012 CT scan guided renal biopsy of left upper pole mass consistent with infiltrative high-grade urothelial carcinomas

Fig. C.32 a, b Pathology slides from 2012 renal biopsy preparation demonstrating positivity for CD20 (a, left) and Cytokeratin AE1 (b, right) ureterorpyeloscopy. She underwent random She succumbed to cardiopulmonary compli- biopsies of ureter and renal pelvis that were also cations secondary to her strong history of negative. Approximately two years later, she smoking. Two years later, there was no evidence developed visible mucosal lesions in the upper of active urothelial carcinoma at the time of her calyces that were managed endoscopically. death (Figs. C.33, C.34, C.35, C.36 and C.37). Because of positive cytology. She underwent placement of a nephrostomy resection of recur- rent tumor and intracavitary treatment with mit- Comment omycin C and BCG. After approximately one year she had a small lesion in the collecting This case depicts a continuum of urothelial car- system with suspicious cytology. She refused the cinoma metachronously affecting all different recommendation of nephroureterectomy. segments of the urinary tract and the need for After placement of a small pigtail nephros- vigilant follow-up of these patients. In 2010 she tomy tube, she underwent a course of intracavi- had intracavitary salvage treatment with gemc- tary treatment using gemcitabine with remission. itabine. It was also the first case to our 360 Case Studies: A Spectrum of Upper Tract Urothelial Carcinoma

low-grade urothelial lesion of the proximal right ureter. The rest of the collecting system was clear of tumor. She has multiple comorbidities: heavy smoker, multiple sclerosis, achalasia, and fibromyalgia. On subsequent follow-up in 2010 repeat cys- toscopy showed papillary frond like lesions in the bladder (consistent with papillary urothelial neoplasm of low malignant potential) and ure- teroscopy and barbotage were performed for the right ureter, which demonstrated no lesions and negative cytology. During this time patient continued to have Fig. C.33 Ureteroscopic biopsy of renal lesion showing urothelial carcinoma stable findings in the bladder with no recurrence of disease seen in the right collecting system. In 2012, when right-sided ureteroscopy was per- knowledge where salvage intracavitary gemc- formed it revealed tumor in the upper and lower itabine treatment was successfully used. pole calyx, after biopsies were taken laser abla- tion was performed. Pathology revealed low-grade papillary urothelial carcinoma. Ran- Case Study 12 dom bladder biopsies performed at that time were negative for malignancy. After placement Patient is a 65-year-old female with history of gross of a percutaneous nephrostomy Mitomycin C hematuria presenting originally in 2009. Workup was instilled in an antegrade fashion into the at that time including a CT showed fullness of the right collecting system draining down into the right collecting system with trace enhancement and bladder treating both upper and lower urinary filling defect of the proximal ureter. Patient tract. underwent rigid ureteroresctoscopic resection of

Fig. C.34 Whole mount of the biopsy sample showing urothelial carcinoma Case Studies: A Spectrum of Upper Tract Urothelial Carcinoma 361

Fig. C.35 High-power view of biopsy which shows superficial papillary carcinoma

Fig. C.36 Percutaneous resection of tumor

Since 2013–2017, patient has been managed with surveillance protocol consisting of urine Fig. C.37 Nephrostogram after tumor resection cytology and imaging every 6 months. Patient has undergone multiple repeat cystoscopies in the office with plan for biopsy and investigation her disease with no progression. The patient was of the upper tracts when tumor has been seen. offered nephroureterectomy several times which Multiple ureteroscopies and bladder biopsies at she refused. various times each year have periodically On recent evaluation there was evidence of revealed bladder tumors that have been consis- recurrence in the right collecting system which tent with papillary urothelial neoplasm of low was biopsied and ablated using a combination of malignant potential. She has had good control of holmium and neodymium YAG laser. Pathology 362 Case Studies: A Spectrum of Upper Tract Urothelial Carcinoma

Fig. C.38 CT showing fullness of right proximal ureter with wall enhancement revealed papillary urothelial carcinoma. She evaluated the patient for upper tract workup and completed a course of antegrade intracavitary treatment. Random biopsies were negative. After BCG treatment and is clear of active disease or percutaneous nephrostomy for deep biopsy of CIS on surveillance protocol (Figs. C.38, C.39, pelvis which was negative, urine showed positive C.40 and C.41). cytologies. He underwent antegrade intracavitary BCG immunotherapy with the presumptive diagnosis of upper tract CIS. Post treatment, Comment several urine cytology samples from nephros- tomy and bladder were negative. This patient is This case illustrates a frail patient with multiple being monitored closely with endoscopy, imag- comorbidities with recurrence of tumor in blad- ing and urinary cytologies (Figs. C.42 and C.43). der and progression from PUNLMP to low grade and areas of CIS. Obviously she has a high risk of recurrence, but over a period of 9 years she Comment has been managed successfully with endoscopic and topical treatment. This case illustrates the fact that in absence of bladder pathology a positive urine cytology with no visible tumor most probably reflects upper Case Study 13 tract CIS. Before initiating intracavitary chemo- or immunotherapy of upper tract, one must per- A 72-year-old male patient with history of neu- form a thorough investigation of the bladder and rogenic bladder on clean intermittent catheteri- the contralateral kidney to exclude them as the zation and poorly functioning left kidney was source for positive cytology. Conversion of managed with TURBT and BCG immunotherapy nephrostomy urine cytology from positive to after he developed bladder cancer. During negative is considered a positive response to follow-up, bladder evaluations were negative and intracavitary immunotherapy with BCG. right upper tract cytology was positive. We Case Studies: A Spectrum of Upper Tract Urothelial Carcinoma 363

ago his urinary cytology became positive. Cys- toscopy bladder biopsies, retrograde pyelogram and ureteroscopy were all negative. Selective cytology of right collecting system was suspi- cious. We evaluated this patient for assessment of possible urothelial carcinoma or CIS of his right solitary kidney. Biopsies of ureter and collecting system did not reveal any obvious pathology. With the assumption of positive cytology in absence of bladder pathology sug- gesting CIS of upper tract he underwent percu- taneous intracavitary topical treatment following which nephrostomy and voided urine cytologies were negative or atypical over a period of two months and nephrostomy tube was removed. Follow-up urine cytology was strongly positive with grossly negative CT scan. At the time of cystoscopy a slight mucosal irregularity was noted at the site of left ureteral orifice, a retro- grade pyelogram and ureteroscopy showed bulky intraluminal urothelial carcinoma. Distal ureterectomy with excision of bladder cuff was carried out with evidence high grade invasive urothelial carcinoma with periureteral disease. He underwent adjuvant chemotherapy. The patient’s brother was under the care of a nephrologist who was informed to have the patient go through diagnostic workup or a nephrectomy since the transplanted kidney had failed by then and he was on hemodialysis (Figs. C.44, C.45, C.46 and C.47). Figs. C.48 and C.49 are examples of transplant kidney.

Fig. C.39 Right retrograde pyelogram showing lower pole filling defect Comment

This case illustrates the significance of complete Case Study 14 nephroureterectomy in patients with upper tract urothelial carcinoma. Obviously donor nephrec- A 69-year-old male who had donated his left tomy screening rules out pre-existing malignan- kidney to his brother 14 years earlier was diag- cies and the nephrectomy is a considered a nosed with NMI bladder cancer 7 years ago. benign procedure and the distal ureter is never After transurethral resection of the tumor he removed. The critical point in this type of case is underwent intravesical BCG immunotherapy. periodic assessment of the ureteral stump when Over a period of 3 years he had two courses of urothelial malignancies have developed later BCG treatment with maintenance. Four years either in the donor or recipient. 364 Case Studies: A Spectrum of Upper Tract Urothelial Carcinoma

Fig. C.40 Bladder biopsy showing papillary urothelial neoplasm of low malignant potential

Fig. C.41 a Right calyx biopsy showing low-grade papillary urothelial neoplasm; b bladder biopsy showing low-grade papillary urothelial carcinoma

thirty-pound unexplained weight loss. This was Case Study 15 the very first time that she was diagnosed with renal stones and had no prior history of any The patient is a 42-year-old female with a history intervention or medical treatment. The patient of smoking, diagnosed with multiple bilateral was also found to have an exophytic, contrast large cystine stones secondary to congenital enhancing right upper pole mass on CT. Renal cystinuria at the time of diagnosis in 2013. She biopsy confirmed pathologic diagnosis of had been experiencing several months of con- high-grade urothelial carcinoma. Preoperative stitutional symptoms, flank pain, and a renal scan revealed equal differential function Case Studies: A Spectrum of Upper Tract Urothelial Carcinoma 365

Fig. C.42 Urine cytology from the right kidney showing Fig. C.44 Urine cytology showing malignant cells malignant cell

Fig. C.43 Urine cytology prepped slide from the right Fig. C.45 Low-power view of distal ureteral stump kidney after antegrade intracavitary BCG treatment showing high-grade invasive urothelial carcinoma showing no malignant cells 366 Case Studies: A Spectrum of Upper Tract Urothelial Carcinoma

Fig. C.46 High-power view shows high-grade invasive Fig. C.47 Para ureteral tissue shows clusters of urothelial carcinoma high-grade urothelial carcinoma

Fig. C.48 Section of a transplant ureter shows high-grade urothelial in situ carcinoma Case Studies: A Spectrum of Upper Tract Urothelial Carcinoma 367

Fig. C.49 Section through the transplant renal pelvis in the same patient shows similar findings and serum creatinine was 1.1 at baseline. Given extensive necrosis of the liver parenchyma. The the aggressive nature of the disease, the patient patient underwent adjuvant chemotherapy and underwent a right nephroureterectomy and right radiation to the marked area. She tolerated both retroperitoneal lymph node dissection. The interventions well, undergoes regular surveil- specimen was 7 cm, with negative margins lance CT and /MRI and PET scans and urine pathologically consistent with biopsy and five of cytology. the six nodes were negative for metastasis with The stone burden continues to be significant; the remaining node positive for urothelial carci- therefore, she periodically requires ureteroscopy, noma; staging the patient as T2N2. stone removal or laser lithotripsy, and stent Post nephrectomy, given the abundant stone exchange. Recent surveillance CT shows mild burden, the patient underwent multiple left per- hydronephrosis with stable nephrocalcinosis, and cutaneous nephrolithotomies and ureteroscopic no evidence of soft tissue mass or lym- procedures. She was also managed medically to phadenopathy. The patient impressively main- defray additional stone formation. On routine tains completely normal functional status and her surveillance MRI, the patient was found to have current creatinine is 1.60 (Figs. C.50, C.51, a mass in the nephrectomy bed, measuring C.52, C.53, C.54, C.55, C.56, C.57, C.58, C.59, 3.4 Â 3.6 Â 3.5 cm and adjacent lesion in the C.60 and C.61). liver. The patient underwent extensive laparo- scopic lysis of adhesions, resection of the retroperitoneal mass, partial hepatectomy, and Comment partial omentectomy. The boundaries of disease were marked by metallic clips. Pathologic anal- This case illustrates a multidisciplinary approach ysis revealed recurrence of high-grade urothelial of nephroureterectomy, lymph node dissection, carcinoma with metastasis of the omentum and resection of recurrent mass at the tumor bed, 368 Case Studies: A Spectrum of Upper Tract Urothelial Carcinoma liver, and omentum. This was followed by reflecting transitioning through several phases of adjuvant chemotherapy and radiation to the site treatment. This young patient elected to undergo of the recurrence identified by metal clips. Most an aggressive approach and has been free of of the modalities described in this book have obvious recurrence for 5 years. been used in management of this patient

Fig. C.50 2013 renal ultrasound of left kidney demonstrating large staghorn calculi obscuring the renal pelvis

Fig. C.51 2013 CT scan of abdomen and pelvis, renal mass protocol demonstrating a 5.6 Â 7 cm exophytic, enhancing, heterogeneous, right renal mass Case Studies: A Spectrum of Upper Tract Urothelial Carcinoma 369

Fig. C.52 2013 CT scan of abdomen and pelvis demonstrating bilateral renal stone burden prior to nephroureterectomy

Fig. C.53 2015 CT scan of abdomen and pelvis demonstrating persistent residual renal stone burden in left kidney after nephroureterectomy of right kidney for urothelial carcinoma 370 Case Studies: A Spectrum of Upper Tract Urothelial Carcinoma

Fig. C.54 2014 MRI of the abdomen demonstrating the *3.5 cm mass representing recurrence of urothelial carci- noma of the right retroperitoneal renal fossa

Fig. C.55 a, b Pathology slide from 2013 CT guided renal biopsy of right renal mass consistent with high-grade invasive urothelial carcinoma with elements of necrosis Case Studies: A Spectrum of Upper Tract Urothelial Carcinoma 371

Fig. C.56 Pathology slide from 2013 renal biopsy demonstrating positive P63 staining which is consistent with urothelial carcinoma

Fig. C.57 a, b Pathology slides of right kidney specimen from 2013 nephroureterectomy demonstrating high-grade papillary urothelial carcinoma. Analysis of kidney demonstrated negative resection margin with no lymphovascular invasion 372 Case Studies: A Spectrum of Upper Tract Urothelial Carcinoma

Fig. C.58 Pathology slide of right ureter from 2013 nephroureterectomy demonstrating high-grade papillary urothelial carcinoma

Fig. C.59 Pathology slide of precaval right lymph node at time of 2013 nephroureterectomy demonstrating presence of metastatic urothelial carcinoma Case Studies: A Spectrum of Upper Tract Urothelial Carcinoma 373

Fig. C.60 a, b Pathology slide of retroperitoneal mass from 2014 resection consistent with urothelial carcinoma involving fibroadipose tissue and liver parenchyma with extensive necrosis

Fig. C.61 Additional pathology slide preparation from 2014 retroperitoneal resection stained positive diffusely for P63 In My Mind’s Eye1

Majid Eshghi

Hamlet, who had the most vivid imagination of all Shakespeare’s characters, spoke those words over 400 years ago (1599–1602). Chares H. Duell, the commissioner of the United States Post Office in 1899, uttered: “Everything that can be invented has been invented.” The reality is that regardless of myriad inventions and novelties it is impossible to prevent the inquisitive human mind from bursting with new ideas and envisioning newer methods and more efficient tools. It is amazing what the human mind can foresee! Such has been the case in medicine and especially so in the field of urology: to improve treatments we sometimes need to go beyond standard boundaries to look for novel ideas at the edge. Thirty years ago, I envisioned the art on these two pages as a reminder that, with the rapid development of upper tract endoscopy, the sky would be the limit for what we would be able to achieve in the ensuing years. I usually used them as closing slides during lectures to remind the audi- ence to never stop imagining and keep searching to reach the unreachable for better and easier ways to serve our patients and in the words of Cervantes: “Para llegar a las estrellas inalcanzables (ref 2).”

© Springer International Publishing AG, part of Springer Nature 2018 375 M. Eshghi (ed.), Urothelial Malignancies of the Upper Urinary Tract, https://doi.org/10.1007/978-3-319-51263-1 376 In My Mind’s Eye

TELEMEDICINE

By the time this publication is completed, References there will already be numerous new methods, treatment protocols and innovations being intro- 1. Hamlet, The Prince of Denmark; 1599–1602, duced into clinical urology that have not been William Shakespeare addressed or adequately discussed in this book, 2. Don Quixote, published 1615, Miguel de for now this subject is exhausted (ref 3). The Cervantes purpose of this section is to provide a brief 3. Bernard Shaw; dramatic opinions and essays, description or snapshot of only some of what we volume 2; this subject is exhausted, so am I. know that is on the horizon. Review of Future Developments

Ali Fathollahi and Majid Eshghi

However, a few studies have shown that different Laboratory hydration protocols might help bypass this limi- tation and detect UTUC. PET scan has also been Serum Tumor Marker shown to be superior in detecting metastatic disease that might be otherwise missed by CT. In a research published in March 2016, researchers Researchers in Tokyo Medical and Dental in China investigated potential association of University investigated the diagnostic accuracy increased plasma fibrinogen level and UTUC. The of FDG PET/CT for detecting metastasis and its results of the study showed increased plasma fib- impact on patient management with UTUC. rinogen was an independent prognostic risk factor They performed 18F-FDG PET/CT after CT for for poor outcomes in UTUC. This may serve as an initial staging (n = 47) and for restaging at effective biomarker in the future. recurrence (n = 9) on patients with UTUC. In the lesion-based analysis, 142 lesions were diag- UGT1A nosed as metastases. The sensitivity of PET/CT UGT1A is a major phase II drug metabolism was significantly better than that of CT (85 vs. enzyme. It is known to play an important role in 50%, p = 0.0001). In the patient-based analysis, preventing bladder cancer initiation by detoxi- 22 patients were diagnosed as having metastases. fying carcinogenic compounds. A significant The sensitivity/specificity/accuracy of PET/CT decrease in the expression of UGT1A in UUTUC tended to be superior to those of CT, but these was seen suggesting its preventive role. Loss of values were not significantly different (95, 91, UGT1A expression was also found to correlate and 93% vs. 82, 85, and 84%; p = 0.25, 0.50, with tumor progression and a predictor of poor and 0.063, respectively). The clinicians changed prognosis. their assessments of disease extent and manage- ment plans in 18 (32%) and 11 (20%) patients, respectively, based on the PET/CT results. Imaging

PET Scan MRI

There is an emerging role for wider use of PET High-power MRI imaging and diffusion studies scan with a variety of agents for early diagnosis are showing promising results in predicting grade and assessment of the tumor stage. PET had and invasiveness of renal pelvic tumors. Hydra- traditionally been thought not to be much appli- tion of patient prior to MRI along with diuresis cable in detecting tumors of the urinary tract will allow filling of collecting system without the system, because of its excretion throughout the use of contrast agents. Yoshida et al. demon- urinary tract and resulting in obscured images. strated applicability of diffusion-weighted MRI

© Springer International Publishing AG, part of Springer Nature 2018 377 M. Eshghi (ed.), Urothelial Malignancies of the Upper Urinary Tract, https://doi.org/10.1007/978-3-319-51263-1 378 Review of Future Developments

(DW MRI) for a series of UTUC. DW MRI may allow for office ureteroscopy in uncompli- imaging was carried out in 10 consecutive cated cases. patients with suspected UTUC. While conven- tional imaging, detected seven renal pelvic tumors definitely, on DW MRI, all nine tumors NBI-Blue Light-Spectra showed hyperintensity with negligible urinary intensity. A case of benign stenosis had negative The endoscopic imaging has significantly evolved DW MRI. In another study in France, Roy et al. in the last decade with new digital video endo- assessed the value of DW MRI in detecting scopes with camera chips at the tip of the scopes malignant UTUC, and showed that adding providingsuperbhighdefinition intraluminal ima- another parameter, called apparent diffusion ges with true colors and impressive surface details. coefficient (ADC) is useful in differentiating Narrow Band Imaging and Blue Light are malignant lesions (78.3 and 95.5% sensitivity alreadyinclinicaluseinthe United States and the and specificity, respectively). Of note, they did Spectra (Karl Storz Endoscoy America, Secondo, not find ADC different in differentiating CA) system is in its early stages of use in Europe. low-grade versus high-grade tumors. Yoshida NBI and Blue Light have been discussed earlier. et al., however, found that ADC value can serve SpectrasystemandClaraarebasedonprinciples as an indicator of tumor grade in UTUC. They similar to NBI and utilization of red green and blue showed that high-grade tumors had lower ADC (RGB) bands (Figs. B.1, B.2 and B.3). value and that ADC can be used as an indepen- Prototype versions of miniature fiberscopes dent preoperative indicator of shorter cancer measuring about 3 Fr have been tested which specific survival.Virtual Ureteroscopy may eventually allow for office ureteroscopy for Image processing becomes more efficient, intu- surveillance. Once this technology is perfected it itive and computerized to make it less laborious. could potentially decrease the need for operating As these imaging techniques show more sensi- room procedures. tivity there will be less need for more invasive endoscopic surveillance.Elastography-Contrast Enhanced Ultrasound Optical Coherence Tomography Have shown encouraging results in some areas of urology imaging. They have not yet shown a Optical Coherence Tomography (OCT) is a specific role in collecting system imaging. high-resolution imaging technology that can be applied during URS and is analogous to ultra- sound. It uses backscattered light instead of back Endoscopy

The utilization of O-Arm in combination with ureteroscopy may allow instant CT imaging assessment of depth of treated areas with laser and possibly in the future with microwave fibers placed through the working channels of ureteroscopes it may be possible to treat small parenchymal endophytic lesions. Addition- ally HIFU can potentially be delivered via an ultrasound probe similar to the principles used in intraluminal ultrasound. Prototypes of small fiber scopes (3Fr) are being tested for clinical which

Fig. B.1 Spectra system and Clara Review of Future Developments 379

Interpretation of OCT findings should be cau- tious with large lesions filling ureteral lumen and inflammation, which may also lead to a false-positive result.

Magnetic Tracking It is conceivable that in near future, as was demonstrated in laboratory research, computer models of radiologic images showing certain pathologies can be accessed with a more precise accuracy using magnetic tracking devices.

Fig. B.2 Spectra system and Clara Confocal Laser Endomicroscopy (CLE) Recent advances in fiber-optics technology have enabled packaging of a confocal microscope into a small probe format compatible with standard endoscopes. A 488 nm low-power laser scans a targeted tissue below the surface. The tissue is nonspecifically stained with intravenous fluores- cein. Under excitation, the fluorescein emits light that is filtered through a pinhole so that only in-focus light is measured by a photodetector while the out-of-focus light is rejected, resulting in optical sectioning of the regions of interest with micron-scale resolution comparable to his- tology. Nuclear features are not routinely visu- alized, since fluorescein highlights the extracellular matrix and does not cross intact cell membranes. CLE images are acquired as video Fig. B.3 Spectra system and Clara sequences at a rate of 12 frames per second via direct contact of the probe with tissues of inter- est. This technique has more value when com- reflected sound waves to produce cross-sectional bined with other technologies. images and has the potential to provide real-time Bui et al. implemented this technique in information on grade and stage in UTUC [1]. imaging of UTUC. It showed characteristic fea- Bus et al. did a study on 26 patients who tures of tumors, including papillary structure, underwent diagnostic URS including biopsies pleomorphic cells, and fibro vascular stalks. and OCT imaging, followed by nephroureterec- Diagnostic accuracy of bladder cancer using tomy or segmental ureteral resection. They found white light source together with CLE, as clini- that in 83% of the specimen staging of lesions cally relevant, has been reported as having 89% were in accordance with final histopathology. sensitivity and 88% specificity (Fig. B.4). 380 Review of Future Developments

Fig. B.4 Cellvizio_DS27996 Source Permission is Dr. Eshghi’s chapter, Future Technology, in Urothelial Malig- nancies of the Upper Tract to be published by Springer in 2017

Chemo- and Immunotherapy: factor (TGIF) in specimens is associated with Novel Treatment worse prognosis in patients with UTUC. Their in Gemcitabine-Resistant results showed that increased TGIF is signifi- Disease cantly associated with chemo-resistance, poor progression-free survival, and higher Yeh et al. in Taiwan studied patients with cancer-related deaths from UTUC. In addition, gemcitabine-resistant advanced urothelial cancer. histone deacetylases inhibitor trichostatin A They demonstrated that increased TG-interacting (TSA) inhibited TGIF, p-AKTSer473 expression Review of Future Developments 381 and migration ability. Synergistic effects of bladder lesions and provides updated optical gemcitabine and TSA on NGR cells were also diagnostic criteria. demonstrated. Goh AC, Tresser NJ, Shen SS, The Nanoparticles appear to be very promis- Lerner SP. Optical coherence tomography as an ing in delivery of immuno therapy as the next adjunct to white light cystoscopy for intravesical line of treatment of the upper tract urothelial real-time imaging and staging of bladder cancer. carcinoma. Urology 2008;72:133–137. Mitogel (UroGen): Early laboratory and Koji Izumi, Satoshi Inoue, Hiroki Ide, et al. clinical trials with gels containing chemothera- MP27-01. UDP-glucuronosyltransferase 1A peutic agent mitomycin C shows promising (UGT1A) immunohistochemistry in urothelial results with the goal of increasing contact time of carcinoma of the upper urinary tract as a strong urothelium with the treating agent. In general prognosticator, Abstract, AUA Meeting 2016. nanoparticle delivery may become the treatment Lerner, Seth, Non Surgical Management of of choice for urothelial carcinoma. low grade upper tract urothelial cancer: An An interim report on clinical use of Mitogel interim analysis of the international multicenter showed in 34 patients for low grade disease Olympus trial, Plenary, AUA Meeting 2018 showed 58.8% initial response, 22 patients has (LBA-25). compassionate use with 44% response. Neumann H, Kiesslich R, Wallace MB, Suggested Readings Neurath MF. Confocal laser endomicroscopy: Asai S, Fukumoto T, Tanji N, et al. Fluo- technical advances and clinical applications. rodeoxyglucose positron emission Gastroenterology. 2010;139:388–392. 392. e1– tomography/computed tomography for diagnosis 392.e2. of upper urinary tract urothelial carcinoma. Int J Pan, Chong-Xian. State of the Art Lecture Clin Oncol. 2015; 20(5):1042–7. predicting chemo sensitivity in urothelial malig- Bui D, Mach KE, Lopez A, Liu JJ, Chang T, nancy: Nanotech and precision medicine. Ple- Lavelle J, Leppert JT, Liao JC. Optical biopsy of nary, AUA 2018. upper tract urothelial carcinoma with confocal Roy C, Labani A, Alemann G, et al. DWI in laser endomicroscopy. Eur. Urol. 2014; 13:e630. the etiologic diagnosis of excretory upper urinary Bus MT, de Bruin DM, Faber DJ, et al. tract lesions: can it help in differentiating benign Optical coherence tomography as a tool for from malignant tumors? A retrospective study of in vivo staging and grading of upper urinary tract 98 patients. AJR Am J Roentgenol. 2016;207 urothelial carcinoma: a study for diagnostic (1):106–13. doi:10.2214/AJR.15.15652.Epub accuracy. J Urol. 2016;27 S0022–5347(16) 2016 Apr 11. 30924s7 Sonn GA, et al. Optical biopsy of human Bus MT, Muller BG, de Bruin DM et al. bladder neoplasia with in vivo confocal laser Volumetric in vivo visualization of upper urinary endomicroscopy. J. Urol. 2009;182:1299–1305. tract tumors using optical coherence tomogra- [PubMed: 19683270] This paper was the initial phy: a pilot study. J Urol. 2013;190:2236–2242. feasibility study of in vivo confocal laser Ceriani L, Suriano S, Ruberto T et al. Could endomicroscopy in the urinary tract different hydration protocols affect the quality of Stephanie P, Chen and Joseph C. Liao. Con- 18F-FDG PET/CT images? J Nucl Med Technol. focal laser endomicroscopy of bladder and upper 2011;39:77–82 tract urothelial carcinoma: a new era of optical Chang TC, et al. Interobserver agreement of diagnosis? Curr Urol Rep. 2014;15(9): 437. confocal laser endomicroscopy for bladder can- Tanaka H, Yoshida S, Komai Y, et al. Clinical cer. J. Endourol. Endourol. Soc. 2013; 27:598– value of 18f-fluorodeoxyglucose positron emis- 603. This paper describes the interobserver sion tomography/computed tomography in upper agreement of confocal laser endomicroscopy of tract urothelial carcinoma: impact on detection of 382 Review of Future Developments metastases and patient management. Urol Int. of renal urothelial cell carcinoma. Clin Nucl Med 2016;96(1):65–6. 2009;34:829–830 Wu K, et al. Dynamic real-time microscopy of Yoshida S, Masuda H, Ishii C, Saito K, et al. the urinary tract using confocal laser endomi- Initial experience of functional imaging of upper croscopy. Urology. 2011;78:225–231. [PubMed: urinary tract neoplasm by diffusion-weighted mag- 21601243] This paper describes the suggested netic resonance imaging. Int J Urol. 2008;15 optical diagnostic criteria for normal urothelium, (2):140–3. doi:10.1111/j.1442–2042.2007.01950.x. benign inflammatory urothelium, low-grade Yoshida S, Uchida Y, Kobayashi S, et al. urothelial carcinoma, and high-grade urothelial MP27-07: Apparent diffusion coefficient as a carcinoma. prognostic biomarker of upper urinary tract Yeh BW, Li WM, Li CC, et al. Histone cancer. AUA abstract, May 7, 2016 deacetylase inhibitor trichostatin A resensitizes Zhang B, Song Y, Jin J, et al. Preoperative gemcitabine-resistant urothelial carcinoma cells plasma fibrinogen level represents an indepen- via suppression of TG-interacting factor. Toxicol dent prognostic factor in a Chinese cohort of Appl Pharmacol. 2016;290:98–106. patients with upper tract urothelial carcinoma. Yeh CL, Chen SW, Chen YK. Delayed PLoS One. 2016;11(3):e0150193. doi:10.1371/ diuretic FDG PET/CT scan facilitates detection journal.pone.0150193. eCollection 2016. Appendix A: Glossary and Abbreviations

Ali Fathollahi

The wide use of Internet has opened the medical B literature to the public and thus created a new Bacille also known as BCG, a weakened genre of readers and researchers reviewing such Calmette (attenuated) version of bacteria literature. This is not a single group and the Guerin called Mycobacterium bovis which reasons are multifaceted; a simple high school is closely related to Mycobac- report, college reports, medical students terium tuberculosis, the agent researching under a mentor, journalists, phar- responsible for tuberculosis. maceutical marketing and patients searching Intravesical (instillation inside the medical entities to understand their medical bladder) BCG therapy is highly problems better are just some examples. Not all effective for managing high-risk of these varied pools of readers have an adequate non-muscle-invasive (not pene- knowledge of all medical terms forcing them to trating the bladder muscle) urothe- frequently refer to dictionaries or similar lial carcinoma of the bladder resources which at times do not provide the Balkan a chronic kidney disease associ- specific information as presented in the texts. nephropathy ated with a high frequency of The purpose of this section is to provide accurate urothelial atypia, occasionally information on some of the entities for such culminating in tumors of the individuals and make the text more user friendly. renal pelvis and urethra BCG see Bacille Calmette Guerin Biomarker a measurable substance in an A organism whose presence is Ablation the surgical removal or destruc- indicative of some phenomenon tion of body tissue such as disease, cancer, infec- Adriamycin an antineoplastic (anti-tumoral) tion, or environmental exposure agent Bladder cuff the area around ureteral orifices Adjuvant an addition designed to help in the bladder which is usually therapy reach the ultimate goal. Adju- resected as part of surgery to treat vant therapy for cancer usually upper tract urothelial cancers refers to surgery followed by Bugbee a monopolar, flexible electrode chemo- or radiotherapy to help whichisusedincystoscopes, cure or decrease the risk of the resectoscopes and ureteroscopes. cancer recurring (coming back) The Bugbee electrode is used for Analgesia the inability to feel pain the ablation coagulation (desrtroy- Anaphylactic relating to or caused by a severe, ing by burning)of soft tissue potentially life-threatening aller- gic reaction

© Springer International Publishing AG, part of Springer Nature 2018 383 M. Eshghi (ed.), Urothelial Malignancies of the Upper Urinary Tract, https://doi.org/10.1007/978-3-319-51263-1 384 Appendix A: Glossary and Abbreviations

C from the kidneys to the Calyx the first unit in the system of bladder ducts in the kidney carrying Cubital of the forearm or the elbow urine from kidney to the Cyclosporine a drug used to prevent the renal pelvis and through rejection of grafts and the ureters transplants Carcinoma a cancer arising in the Cystectomy a surgical operation to epithelial tissue of the skin remove the urinary bladder or of the lining of the inter- Cystoscope a telescopic instrument nal organs inserted into the urethra Carcinoma also known as in situ neo- (urinary channel) for exam- in situ plasm (tumor) is a group of ining the inside of the uri- abnormal cells. While they nary bladder are a form of neoplasm there Cystogram an imaging visually used to is disagreement over visualize the urinary blad- whether CIS should be clas- der. Using a urinary cathe- sified as cancer. These ter, radiocontrast is instilled abnormal cells grow in their in the bladder, and X-ray normal place, thus “in situ” imaging is performed (from Latin for “in its place”) D Cardiopulmonary of or relating to the heart DaVinci a robotic surgical system made and the lungs by the American company Intu- Chemotherapy the treatment of disease by itive Surgical. Approved by the the use of chemical sub- Food and Drug Administration stances, especially the treat- (FDA) in 2000, it is designed to ment of cancer by cytotoxic facilitate complex surgery using and other drugs a minimally invasive approach, Circumaortic around the aorta (main and is controlled by a surgeon abdominal artery) from a console CIS see Carcinoma in situ Debulking surgical removal of as much of a Cold a type of forceps used to malignant tumor as possible Cup Forceps obtain biopsy material from Deflection in endoscopic instrumentation, the urinary tract angling or a turning aside or Comorbidity the simultaneous presence deviation from a straight line to of two or more chronic allow better visualization diseases or conditions in a Desmoplasia growth of fibrous or connective patient tissue, usually as a result of an Continent is an internal urinary reser- insult urinary diversion voir that a surgeon creates Dorsal a supine position in which the from a section of the bowel lithotomy hips and knees are fully flexed Corticomedullary relating to, or joining, the position with the legs spread apart and renal medulla (center) and raised and the feet resting in cortex (outer shell) straps CT urogram also CTU, an imaging exam Double J a type of ureteral stent (narrow used to evaluate urinary stent tube) tract, including the kidneys, Doxorubicin see Adrianycin the bladder and the tubes Doppler a diagnostic mode of ultrasonic (ureters) that carry urine beam; the ultrasound reflected Appendix A: Glossary and Abbreviations 385

from moving structures changes G its frequency and thus allowing Gadolinium a chemical substance used as a for measurement of flow and contrast in MRI speed Gemcitabine an antineoplastic agent used in chemotherapy E Genome the complete set of genes or genetic material present in a cell E coli. a bacterium or organism Endo-GIA a device for fastening together Gibson an oblique incision made in stapler tissues, e.g., bowel inside body incision lower lateral part of abdomen to Endourology a minimally invasive technique access lower part of ureter and using small scopes to treat a bladder variety of urinary tract Gonadal Veins and arteries going conditions Vessels to/coming from gonads (testis or fl Extravasation leakage of a uid out of urinary ovary) tract Guidewire A wire or spring used as a guide for placement of a larger device, F such as a catheter or scope Fiberoptic the use of thin flexible fibers of glass or other transparent solids H fl to transmit light signals, chie y Heparin Lock a type of intermittent intra- for telecommunications or for venous device for the internal examination of the administration of heparin, body fluids and variety of medi- FISH a way to visualize and map the cations. It does not require a genetic material in an individ- continuous flow of fluids; fi ual's cells, including speci c the intravenous fluid flow genes or portions of genes can be disconnected and the Fluconazole an antifungal medicine. It is heparin lock filled with a used to treat infections caused heparin solution that main- by fungus, which can invade tains patency of the needle any part of the body Hematuria the presence of blood in Fluorescence see FISH urine in situ Holmium:YAG a laser whose beam is in the hybridization near infrared spectrum at Fr French size is three times the 2100 nm; used for photoco- diameter in millimeters. A round agulation and photoablation catheter of 3 French has an Horseshoe kidney a congenital disorder in external diameter of 1 mm which the patient's kidneys Fulguration destruction of living tissue by fuse together at the bottom electric sparks generated by a to form a horseshoe-shape high-frequency current during development in the Fungal of or caused by a fungus or womb fungi Hounsfield unit a quantity commonly used Furosemide a diuretic medication used to in computed tomography fl treat uid build-up due to heart (CT) scanning to express failure, liver scarring, or kidney tissue density numbers in a disease 386 Appendix A: Glossary and Abbreviations

standardized and conve- Interferon a group of signaling proteins nient form made and released by host Hydronephrosis literally “water inside the cells in response to the pres- kidney”—refers to disten- ence of several pathogens, sion and dilation of the such as viruses, bacteria, par- renal pelvis and calyces, asites, and also tumor cells. usually caused by obstruc- They are important for fight- tion of the free flow of urine ing viral infections and for the from the kidney regulation of the immune Hyperchromatism the development of excess system chromatin (genetic material) Intramural situated or done within the or of excessive nuclear walls of a structure staining especially as a part Intravesical inside bladder of a pathological process Hyperechoic In ultrasound, denoting a J region in which the echoes are stronger (brighter in Jejunum second part of the small intestine in images) than normal or than humans surrounding structures Hypertrophy excessive development of K an organ or part; specifi- cally increase in bulk with- KTP a type of laser, in the blue-green to out multiplication of parts laser green (532-nm) spectrum, used for Hypoechoic In ultrasound, denoting a hemostasis and tissue ablation region in which the echoes are weaker (darker in L images) than normal or than surrounding structures Leukoplakia a whitish patch or plaque that cannot be character- ized clinically or patholog- I ically as any other disease, Ileal ureter restoration of continuity of and is not associated with urinary tract by replacing a any physical or chemical part or all ureter with a seg- causative agent, except the ment of small bowel use of tobacco IFN see Interferon Lumbotomy a type of incision to make Iliac artery main artery in pelvis branch- access to kidney from ing from aorta back Immunotherapy the prevention or treatment of Lumen the cavity of a tubular disease with substances that organ or part stimulate the immune Lymphadenectomy surgical removal of one or response more groups of lymph Indwelling tube left within a bodily organ or nodes passage to maintain drainage, prevent obstruction, or pro- M vide a route for administration of food or drugs Magnetic a technique that uses a fi Infundibulum a funnel-shaped part connect- Resonance magnetic eld and radio ing calyx to renal pelvis Imaging (MRI) waves to create detailed Appendix A: Glossary and Abbreviations 387

images of the organs and N tissues within your body Nd:YAG a laser whose beam is in Meatotomy refers to an incision or the near infrared spec- tearing done to enlarge the trum at approximately urethra or ureter 1060 nm; used for pho- Mesh a synthetic material that is tocoagulation and used to provide additional photoablation support to weakened or Neodymium: see Nd:YAG damaged tissue yttrium–aluminum– Miniperc performing percutaneous garnet nephrostomy access with a Nephroscopy inspecting and passing smaller caliber tract instruments into the inte- Mitomycin C any of a group of antibi- rior of the kidney otics produced by the soil Nephrostogram a radiograph of the kid- actinomycete Streptomyces ney after opacification of caespitosus that inhibit the renal pelvis by inject- DNA synthesis and are ing a contrast agent used against bacteria and through a nephrostomy cancerous tumor cells tube Mitosis a type of cell division that Nephrostomy tract an artificial opening cre- results in two daughter cells ated between the kidney each having the same num- and the skin which ber and kind of chromo- allows for the urinary somes as the parent diversion directly from nucleus, typical of ordinary the upper part of the tissue growth urinary system (renal MMC see Mitomycin C pelvis) MRI see Magnetic Resonance Nitrofurantoin a synthetic compound Imaging with antibacterial proper- Multivariate the statistical process of ties, used to treat infec- analysis simultaneously analyzing tions of the urinary tract multiple independent (or predictor) variables with multiple dependent (out- O come or criterion) variables Opacify on radiology studies, to make Mutagen an agent, such as radiation visible or a chemical substance, Orthotopic a bladder fashioned from intes- that causes genetic neobladder tine, placed at the site of the mutation excised natural bladder, and Myelosuppression decrease in production of draining through the intact cells responsible for pro- urethra viding immunity (leuko- cytes), carrying oxygen (erythrocytes), and/or those P responsible for normal Packed Red red blood cells (RBC, also blood clotting Blood Cells called erythrocytes) that (thrombocytes) have been collected, pro- cessed, and stored in bags as 388 Appendix A: Glossary and Abbreviations

blood product units available Pyelolymphatic pertaining to the renal pelvis for blood transfusion and renal lymphatics Palliative relieving pain or alleviating a Pyeloureteritis inflammation of a ureter and problem without dealing with the renal pelvis the underlying cause Pyelovenous pertaining to the renal pelvis Paraaortic near aorta (main abdominal and renal veins artery) Paracaval near inferior vena cava (main R abdominal vein) Parathormone also parathyroid hormone, a Radical The standard treatment hormone that regulates cal- nephroureterectomy strategy to remove a cium levels in a person's body (RNU) patient's kidney, ureter, PCN the placement of a small, and bladder cuff for flexible rubber catheter (tube) bulky, high-grade, or through the skin into the invasive upper tract kidney to drain the urine urothelial carcinoma Pelvicalyceal pertaining to the renal pelvis (UTUC) and calices Rads unit of absorbed radia- Percutaneous made, done, or effected tion dose through the skin Reflux see Vesicoureteral Percutaneous see PCN Reflux Nephrostomy Reimplantation a surgery to reattach Tube tubes (ureters) that con- PET scan an imaging test that uses a nect the bladder to the radioactive drug (tracer) to kidneys help reveal abnormal biologic Renal parenchyma functional parts of the activity in cancer patients human kidney, including Pfannenstiel also known as Bikini inci- the elements of the organ incision sion, a type of transverse low that create urine abdominal surgical incision Renal pelvis The area at the center of for cosmetic purposes that the kidney. Urine col- allows access to the abdo- lects in the renal pelvis men. It is most common and is funneled into the method for performing Cae- ureter sarian sections today Renal sinus a cavity within the kid- Pigtail stent a type of ureteral stent ney which is occupied by Pleomorphic variability in the size, similar the renal pelvis, renal to double J stent shape and calyces, blood vessels, staining of cells and/or their and fat nuclei Retina a layer at the back of the Positron see PET scan eyeball containing cells Emission that are sensitive to light Tomography and that trigger nerve scan impulses that pass via PRBC see Packed Red Blood Cells the optic nerve to the Appendix A: Glossary and Abbreviations 389

brain, where a visual of applications in different image is formed interventions Retrograde a urologic procedure Sulfamethoxazole/ an antibiotic used to treat a pyelogram where the physician trimethoprim variety of bacterial infec- injects contrast into the tions usually called sulfa ureter in order to visual- drug ize the ureter and urinary Suprapubic from the Latin “supra”, ducts inside the kidney. meaning above, and “pu- The flow of contrast (up bis”, meaning the front from the bladder to the bone of the pelvis kidney) is opposite the usual flow of urine, T hence the retrograde name T1 in staging of urinary Rhabdomyolysis the destruction of striated tract transitional cell muscle cells cancer, tumor has spread Segmental excision of a segment of to the subepithelial con- ureterectomy the ureter nective tissue but does Sensor a guiding wire with a not involve the bladder Guide Wire floppy smooth surface wall muscle (lamina pro- pria, the tissue below the inside lining of the S bladder) Sepsis the presence in tissues of T2 in staging of urinary harmful bacteria and their tract transitional cell toxins, typically through cancer, tumor has spread infection of a wound to the muscle of the Septicemia blood poisoning, especially bladder wall that caused by bacteria or T2a in staging of urinary their toxins tract transitional cell Sequential used in patients who are on cancer, tumor has spread compression bed rest or immobile to the inner half of the device because of an illness, muscle of the bladder injury, or surgery to pre- wall, which may be vent developing deep vein called the superficial thrombosis (DVT) muscle Somatic of or relating to the body. T2b in staging of urinary Also, of or relating to the tract transitional (urothe- body wall lial) cell cancer, tumor Spatulate make the edge of ureter has spread to the deep wider at the tip by incising muscle of the bladder it (the outer half of the Spinal needle a needle, provided with a muscle) stylet, for entering the T3 in staging of urinary inside of an obstructed or tract transitional cell normal space with a bore of cancer, tumor has grown at least 1 mm and 40 mm into the perivesical tissue or more in length. This (the fatty tissue that sur- type of needle has a variety rounds the bladder) 390 Appendix A: Glossary and Abbreviations

T3a in staging of urinary as leukemia, lymphoma, tract transitional cell and carcinoma cancer, tumor has grown Thoracoabdominal of, relating to, involving, into the perivesical tis- or affecting the chest and sue, as seen through a the abdomen microscope Thromboprophylaxis a measure taken to pre- T3b In staging of urinary vent the development of tract transitional cell blood clot cancer, tumor has grown Trabeculated thick walled and hyper- into the perivesical tissue trophied muscle bundles macroscopically, mean- in bladder, typically seen ing that the tumor(s) is in instances of chronic large enough to be seen obstruction during imaging tests or Transitional also urothelial cell carci- to be seen or felt by the Cell Carcinoma noma or UCC is a type surgeon (TCC) of cancer that typically T4 in staging of urinary occurs in the urinary tract transitional cell system: the kidney, uri- cancer, tumor has spread nary bladder, and acces- to any of the following: sory organs. It is the the abdominal wall, the most common type of pelvic wall, a man’s bladder cancer and can- prostate or seminal vesi- cer of the ureter, urethra, cle (the tube(s) that carry and urachus semen), or a woman’s Transurethral a surgical procedure that uterus or vagina resection of is used both to diagnose Ta In staging of urinary bladder bladder cancer and to tract transitional cell tumor (TURBT) remove cancerous tissue cancer, refers to nonin- from the bladder vasive papillary Transvesical passing through or per- carcinoma formed by way of the TCC see Transitional Cell urinary bladder Carcinoma Trocar a surgical instrument Tegaderm a transparent medical with a three-sided cut- dressing manufactured ting point enclosed in a by 3 M. Tegaderm trans- tube, used for withdraw- parent dressings can be ing fluid from or entry to used to cover and protect a body cavity for surgi- wounds and catheter cal reasons sites Tumoricidal destroying tumor cells Tetraploid (of a cell or nucleus) containing four homolo- U gous sets of chromo- somes i.e. two times UCC see Transitional Cell more than normal cells Carcinoma Thio- Tepa A sulfur-containing ana- UPJ junction between renal log of tepa, used in the pelvis and the proximal treatment of certain ureter malignant diseases such Appendix A: Glossary and Abbreviations 391

Upper urinary Tumors of the renal ureteroscope perform- tract urothelial calyces, renal pelvis ing variety of diagnos- carcinoma and ureters start in the tic or curative (UTUC) layer of tissue that lines procedures the bladder and the Urethra the duct by which urine upper urinary tract, is transported out of the called the urothelium. body from the bladder, Cancer that starts in the and which in male also urothelium is called transports semen urothelial (or transi- Urinary diversion any one of several sur- tional cell) cancer. This gical procedures to is the most common reroute urine flow from type of cancer found its normal pathway. It in the bladder as well may be necessary for Ureter the duct by which urine diseased or defective passes from the kidney ureters, bladder or ure- to the bladder thra, either temporarily Ureteral Catheter a long, small gauge or permanently. Some catheter designed for diversions result in a insertion directly into stoma a ureter, either through Urine Cytology a test to look for abnor- the urethra and bladder mal cancerous cells in or posteriorly via the urine kidney Urinoma collection of urine out- Ureteral orifice the opening of the side the urinary tract ureter in the bladder Urothelial see Transitional Cell situated one at each Cell Carcinoma Carcinoma lateral angle of the Urothelium an example of “transi- trigone; wide ostium tional epithelium”.Itis usually indicates vesi- the type of epithelium coureteral reflux that lines much of the Ureteritis cystica benign inflammatory urinary tract including reaction of the urothe- the renal pelvis, the lium to infection or ureters, the bladder, mechanical irritation and parts of the urethra Ureteral stricture a narrowing in ureteral URS see ureteroscopy lumen UTUC see Upper urinary tract Ureteroneocystostomy reimplantation of the urothelial carcinoma ureter into the bladder Ureteroscope a tube-like instrument V with: a light and lens or camera chip at its tip Vesicoureteral the backward flow of urine for examining the Reflux from the bladder into the inside of the ureter kidneys and renal pelvis Virtual an imaging technique in which Ureteroscopy an examination or pro- Endoscopy cross-sectional images cedure using a acquired by computed 392 Appendix A: Glossary and Abbreviations

tomography or magnetic reso- X nance imaging are processed Xyphoid a small cartilaginous process (ex- by computer to reconstruct a process tension) of the lower part of the three-dimensional display sim- sternum, which is usually ossified ilar to that seen through an in the adult human endoscope Voiding urination Voxel a value on a regular grid in Y three-dimensional space Yag yag laser a form of laser for tissue VUR see Vesicoureteral Reflux ablation

W Z Weck a multifunctional tissue sealing Zygote the cell resulting from the union of an ligaSure system, featuring an integrated cut- ovum (female egg) and a spermatozom ting mechanism for use in open and (male sperm) endoscopic Appendix B: Product and Manufacturer Information

Ali Fathollahi

Throughout this book, the authors mention or • KARL STORZ Endoscopy-America, Inc. refer to several medical products and manufac- 2151 E. Grand Avenue, turers. This is by no means an endorsement or EL Segundo, CA 90245-5017 considered promoting these products, rather mere • COBRA ENGINEERING reflection of authors’ preference, availability of 23801 E. La Palma Avenue products at their institute and their routines. The Yorba Linda, CA 92887 editor did not require disclosures from the authors • Olympus America Inc. in regards to their relations with the manufactur- 3500 Corporate Parkway ers and industry. P.O. Box 610 The following list, though not comprehensive, Center Valley, PA was created to help the practicing physicians, to • Greenwald Surgical Co., Inc. have access to some of the products mentioned in 2688 DeKalb Street this textbook through their manufacturers. Lake Station, IN 46405-1519 • DELTA MEDIX PC LOCATIONS • Richard Wolf Medical Instruments 503 Sunset Drive Corporation Dickson City, PA 18519 353 Corporate Woods Parkway • Lumenis Ltd. Vernon Hills, Illinois 60061 Yokneam Industrial Park • UROVISION GmbH Hakidma 6 Medi-Globe-Str. 1–5 P.O.B. # 240 83101 Achenmühle—Germany Yokneam 2069204 • COOK MEDICAL INC. Israel P.O. Box 4195 • Intuitive Surgical, Inc. Bloomington, IN 47402-4195 1020 Kifer Road U.S.A. Sunnyvale, CA 94086-5304 • BOSTON SCIENTIFIC • COVIDIEN, Medtronic 300 Boston Scientific Way. 710 Medtronic Parkway Marlborough, MA 01752-1234 Minneapolis, MN 55432-5604 • Coloplast US Headquarters • Teleflex 1601 West River Road North 3015 Carrington Mill Boulevard Minneapolis, MN 55411 Morrisville, NC 27560

© Springer International Publishing AG, part of Springer Nature 2018 393 M. Eshghi (ed.), Urothelial Malignancies of the Upper Urinary Tract, https://doi.org/10.1007/978-3-319-51263-1 394 Appendix B: Product and Manufacturer Information

• Ethicon US, LLC. • PHOTOCURE INC Route 22 West 104 Carnegie Center Somerville, NJ 08876 Suite 303 4545 Creek Road Princeton, NJ 08540 Cincinnati, OH 45242 USA Index

Note: Page numbers followed by f and t indicate figures and tables respectively

CHN/AAN, 6 A – – occupational exposure, 5 6 Adjuvant therapy, renal cell carcinoma, 328 330 smoking, 5 Adrenalectomy, 189 Taiwan, herbal medicine use in, 6–7 Adriamycin, 294, 307 narrow band imaging, 124 Advanced age, 24 BCG, 134 African-American patients, 27 role of, 132 5-Aminolevulinic acid (5-ALA), 149 therapeutic impact of, 134 Analgesic abuse, 7 TURBT, 135 Ancillary techniques, 57 renal transplant recipients, 250 Ancillary tests, urine cytology – urothelial cancer FISH/UroVysion, 99 100 risk factors, 8 immunostain, cytology combined with, 100 SEER database, 7, 8 somatic mutations, 101–102 – vs. UTCIS urine protein markers, 100 101 clinical course, 88–89 Anemia, 6, 24, 27 molecular alterations, 89–90 Aneuploidy, 73 Bladder carcinoma in situ (BCIS), 88 Anterior cystotomy, 181 Bladder cuff, 189, 190f, 191 Anuria, 215–216 fi excision, 200 Apparent diffusion coef cient (ADC), 376 Bladder tumor antigen (BTA), 77, 101 Aristolochic acid (AA), 6, 249, 268 Blood clot, 45, 47f Aristolochic acid nephropathy (AAN), 6 Blue light endoscopy (BLC) Aseptic nephro-ureterectomies, 184 photodynamic therapy Autotransplantation, 248 mechanism of, 146 f Axial CT images, 45 modern, history of, 146 f pyelogram image, 46 photochemical internalization, 151 urinary tract, 147 use of, 149 B é upper tract tumors, endoscopic management of, Bacille Calmette-Gu rin (BCG), 89, 92, 134, 304 147–149 endoscopic resection, adjuvant, 305 Bowel injury, 212–213 – t upper tract, CIS of, 304 305, 306 Bugbee electrode, 233 Balkan endemic nephropathy (BEN), 6, 72, 268 Balloon dissection, 187 Biomarkers C advanced-stage/non-organ-confined disease, 16–17 fi Calyceal area, 240 cancer-speci c and overall survival, 27 Calyx, 234 intravesical, loco-regional and distant metastatic fi – Cancer-speci c survival (CSS), 204 recurrence, 23 24 Carcinoembryonic antigen (CEA), 100 Biopsy, 65 Carcinogen exposure Bladder cancer, 74 AA, 6 carcinogen exposure BEN, 6 AA, 6 CHN/AAN, 6 analgesic abuse, 7 analgesic abuse, 7 BEN, 6

© Springer International Publishing AG, part of Springer Nature 2018 395 M. Eshghi (ed.), Urothelial Malignancies of the Upper Urinary Tract, https://doi.org/10.1007/978-3-319-51263-1 396 Index

occupational exposure, 5–6 transvesical laparoscopic techniques, 203–204 smoking, 5 urologists, 199 Taiwan, herbal medicine use in, 6–7 Distal ureter and bladder cuff Carcinoma in situ (CIS), 73 comparing methods, 192 UTCIS (see Upper urinary tract carcinoma in situ extravesical resection, 191–192 (UTCIS)) hydrovesicum, 192 Celiac artery, 211 intussusceptions, 191 Cell block, 99 lasso techniques, 192 Charge-coupled device (CCD), 123 open, 189 Chinese herb nephropathy (CHN), 6 pneumovesicum, 192 Chromosomal enumeration, 73–75 TUR-UO, 189–190 Chronic kidney disease (CKD), 6, 23, 270, 341, 354 Distal ureterectomy (DU) creatinine, 339 complications and management recommendations, and ESRD 173 effect of, 36 indications and contraindications, 169 financial costs of, 35 operative technical details renal preservation, value of, 34–35 patient positioning, 170–171 Clinical staging of UTUC, 63 procedure details, 171 Colon cancer, 5 patient pre-operative evaluation and preparation Complementary metal-oxide semiconductor (CMOS), endoscopic evaluation and biopsy, 170 123 lab work-up, 169 Computed tomography (CT), 55, 255 radiologic evaluation, 169–170 urography post-operative management and follow-up ancillary techniques, 57 brief literature review/oncologic efficacy, 174–175 contraindications, 57 oncologic follow-up, 174 imaging interpretation, 58 standard post-operative management, 174 single bolus technique, 56 DNA-based markers split-bolus technique, 56 chromosomal enumeration, 73–75 3D imaging, benefits of, 59 DNA-based mutation assays, 76 3D reconstruction, 57 microsatellite mutation analysis, 75–76 triple-bolus technique, 56 Driver mutations, 72 Computed tomography urogram (CTU), 56 goal of, 56 Confocal laser endomicroscopy (CLE), 377 E Congenital pelvic kidney, 247–248 E-cadherin, 78 Cytology, 73 Elastography-contrast enhanced ultrasound, 339 Electrocautery ablation, 244–245 End stage renal disease (ESRD), 249 D Endoluminal ultrasound (ELUS) De novo malignancies, 248 challenges and limitations, 68–69 Deep venous thrombosis (DVT), 215 equipment and preparation, 64 Denuded urothelium, 88 normal ureteral appearance, 65–66 Diffuse large B-cell lymphoma (DLBCL), 114 technique, 64–65 Digital flexible ureteroscopes (DFU), 124, 126 upper tract urothelial carcinoma Disease-specific survival (DSS), 220 abnormal findings, 66 Distal sensor digital ureteroscope, 123 clinical staging of, 63 Distal ureter high-risk, 63 bladder cuff, 200 validation studies of, 66, 68 categories, 200, 201f urologic application of, 64 endoscopic techniques, 201–203 vascular and nonvascular applications, 64 extravesical approach, 200–201 Endoscopy extravesical laparoscopic stapling technique, 203 confocal laser endomicroscopy, 340–341 historical, 200 magnetic tracking, 340 intravesical chemotherapy post-operatively, use of, NBI-blue light-spectra, 339–340 205 optical coherence tomography, 340 intravesical/transvesical approach, 200 Enhancing lesions, 41 laparoscopic vs. open nephroureterctomy, 204–205 External beam radiation therapy (EBRT), 323 RALNU, 205 RNU, 199, 200 Index 397

F Hypoxia-inducible factor, 78–79 Familial support, 282 FGFR3-positive tumors, 268 Fiberoptic ureteroscopes (FFU), 124 I Fibroepithelial polyp, 53 Imaging Fibronectin, 101 CT urography, 269 Field defect, 265 GU imaging, 269 Filling defects, 58, 59 MDCTU, 269 Financial costs, of kidney sparing surgery, 35 MRI, 270, 271 Flexible ureteroscopes NCCN guidelines, 269 cost of, 126 static fluid MRI, 270 DFU/FFU, 124 Inferior mesenteric artery (IMA), 258 durability of, 125–126 Inflammatory myofibroblastic tumor (IMT), 113, 114 optical fiber and distal sensor digital ureteroscope, 123 Interferon (IFN), 293, 307 pyelocalyceal system, navigation in, 124 Interferon-a2B, 92 scope tip, deflection of, 122 Intracavitary therapy tip design, 122–123 adriamycin, 307 Flexible ureterorenoscopy (FUS), 167 antegrade, 301 indications, 165 BCG, 304 Floppy diaphragm, 214 endoscopic resection, adjuvant, 305 Fluorescent in situ hybridization (FISH), 73, 272 upper tract, CIS of, 304–305, 306t UroVysion, 99–100 complications of, 308 Fluoroscopy, 65 delivery, 300 Food and Drug Administration (FDA), 99 differential effectiveness of, 299–300 Fractionated heparin (FH), 215 expert commentary, 310 18 Fr sheath, 236 gemcitabine, 308 Fungal infections, 46 IFN, 307–308 FXYD3, 76 MMC, 301, 307 nephrostomy, 302 new advances, 309 G office treatment, 302–303 Gemcitabine, 294, 308 retrograde, 301 Gemcitabine-resistant disease, 341 thiotepa, 308 Genetics, of UUT urothelial carcinomas treatment, end point of, 310 BEN patients, 72 Intraoperative radiation therapy (IORT), 326 driver mutations, 72 Invasive urothelial carcinoma germline mutations, 72 glandular differentiation, 112 MIBC, 72 high-grade, 112 MMR genes, 73 lamina propria/deeper tissue, 109 MSI mutations, 73 renal cell carcinoma, 112 p53 and FGFR3 positive tumors, 72 squamous differentiation, 112 somatic mutations, 71 Genitourinary cancers, 249 Genitourinary imaging, 269 J Gerota’s fascia, 188 Japanese and Caucasian patients, comparison, 27 Gibson-flank approach, 180 Glomerular filtration rate (GFR), 34, 57, 63 Gonadal vessels, 186 K Kidney cancers, 72 Kidney-sparing surgery H CKD and ESRD Hematuria, 4, 55, 97 effect of, 36 Hereditary non-polyposis colon cancer (HNPCC), 4, 73, financial costs of, 35 268 renal preservation, value of, 34–35 Hexaminolevulinate (HAL), 146, 147 nephron-sparing surgery High-grade muscle-invasive tumors, 101 financial costs of, 35 Hydronephrosis, 42 management of, effect of, 35–36 Hydronephrotic ureter, 223 Hydrovesicum, 192 398 Index

L renal hilum, 188 Lamina propria/deeper tissue, 109 transperitoneal laparoscopic, 186 Laparoscopic vs. open nephroureterctomy, 204–205 ureter courses, 186 Laser ablation, 244–245 Mismatch repair (MMR), 5, 72, 268 Laser resection, 65 Mitomycin C (MMC), 181, 225, 227f, 283, 293, 301, 307 Lasso techniques, 192 MMR genes, 73 Leukoplakia, 46 Molecular alterations, 89–90 Ligasure technology, 192 Molecular markers Looposcopy, 273, 276 cytology, 73 Low-density lipoproteins (LDL), 146 DNA-based markers Low-grade papillary non-muscle-invasive tumors, 101 chromosomal enumeration, 73–75 Lower urinary tract, examination of, 155–156 DNA-based mutation assays, 76 L-type amino acid transporter 1 (LAT 1), 79 microsatellite mutation analysis, 75–76 Lymph node (LN) protein-based markers (see also Protein-based mark- incidence, 254 ers), 76–79 regional, 254 Molecular profiling, 72, 269 Lymph node density, 257 Multidetector computed tomography (MDCT), 56 Lymph node dissection (LND), 173 4 and 8 detector, 59 benefit of, 260 Multidetector computed tomography urography complications, 259–260 (MDCTU), 269, 270, 271 guidelines, 260 Muscle-invasive bladder cancer (MIBC), 72 lymph node incidence, 254 regional, 254 N lymphadenectomy, role of (see Lymphadenectomy) Narrow band imaging (NBI), 69, 86 open vs. laparoscopic/robotic, 259 application of, 131 Lymphadenectomy, 181 bladder cancer staging role, 255–257 BCG, 134 therapeutic role, 256–257 role of, 132 Lymphoma, 114 therapeutic impact of, 134 Lynch syndrome, 5, 75 TURBT, 135 -blue light-spectra, 339–340 flexible endoscopic equipment, 132 M preliminary testing, 131 Magnetic resonance imaging (MRI), 61, 339 RGB, optical filters for, 131 of upper urinary tract, 270, 272 use of, 131 Magnetic tracking, 377 UTUC, 136 Malacoplakia, 46 WLI and, 132 Maximum intensity projection (MIP), 57 National Comprehensive Cancer Network (NCCN) Metal dilator, 232 guidelines, 178, 269 Methylation, 76 Neoadjuvant chemotherapy, 195–196 Microsatellite instability (MSI), 73, 75–76 Neo-ureteral orifices (NUOs), 273 mutations, 73 Nephron-sparing surgery (NSS), 179–180 Microsatellite mutation analysis financial costs of, 33–34 Lynch syndrome, 75 management of, effect of, 35–36 MSI, 75–76 Nephrostogram, 243 Minimally invasive surgery (MIS), 200 Nephrostomy, 302 purpose of, 184–185 Nephroureterectomy (NU), 63, 266 Minimally invasive techniques basis of, 196 adrenalectomy, 189 complications, incidence of, 209–210 balloon dissection, 187 distal ureter and bladder cuff colon, 186 comparing methods, 192 Gerota’s fascia, 188 extravesical resection, 191–192 gonadal vessels, 186 hydrovesicum, 192 lymphadenectomy, 189 intussusceptions, 191 nephroureterectomy lasso techniques, 192 retroperitoneal, 187 open, 189 robotic-assisted, 187–188 pneumovesicum, 192 PSC, 188 TUR-UO, 189–190 Index 399

history of, 183–184 P intraoperative complications Pancreatic injury, 213–214 access related, 210–211 Papillary necrosis, 46 bowel injury, 212–213 Partial nephrectomy, 34 pancreatic injury, 213–214 Patient doctor therapeutic relationship, 285 splenic injury, 213 Patient fatigue, 281 vascular injury, 211–212 Patient post-operative management and follow-up minimally invasive surgery, purpose of, 184–185 brief literature review/oncologic efficacy, 174–175 minimally invasive techniques oncologic follow-up, 174 adrenalectomy, 189 standard post-operative management, 174 balloon dissection, 187 Patient pre-operative evaluation and preparation colon, 186 endoscopic evaluation and biopsy, 170 Gerota’s fascia, 188 lab work-up, 169 gonadal vessels, 186 radiologic evaluation, 169–170 lymphadenectomy, 189 Patient side cart (PSC), 188, 275 PSC, 188 Patient-related factors renal hilum, 188 advanced-stage/non-organ-confined disease, 16–17 retroperitoneal nephroureterectomy, 187 cancer-specific and overall survival, 24–27 robotic-assisted nephroureterectomy, 187–188 intravesical, loco-regional and distant metastatic transperitoneal laparoscopic, 186 recurrence, 20–23 ureter courses, 186 Pelvic kidneys, 247 neoadjuvant chemotherapy, 195–196 Pelvicalyceal system, 159, 161–162 postoperative complications Pelvicalyceal tumors, 161 anuria, 215–216 Percutaneous (PCN) resection incidence of, 215 calyceal area, 240 intra-abdominal abscess, 215 complication rate, 231, 231t pneumonia, risk of, 215 dilation, 235–236 tumor seeding, 216 electrocautery and laser ablation, 244–245 urinary leakage, 216 exit strategy, 241–243 VTE, 215 initial inspection, 240 preoperative considerations, 210 instrumentation, 232 segmental ureterectomy, 193–194, 275–276 nephrostogram, 243 survival and recurrence, 185–186 operating room set up, 233–234 Nomogram, 20 postop intracavitary treatment, 243 Nonabsorbable polymer ligating (NPL), 212 postop management, 243–244 Noninvasive urothelial carcinoma, 108 preoperative assessment, 231–232 Non-muscle-invasive bladder cancers, 266 puncture technique, 234–235 Non-neoplastic lesions, 45 recurrence rates, 230 Non-organ-confined (NOC), 16 renal function, preservation of, 230 Nuclear Matrix Protein (NMP), 272 renal pelvic tumors, 230 NMP-22, 78 ureteropelvic junction, 240 ureteral lesions, 229 Peri-orificeal incision, 180 O Pfannenstiel incision, 177, 178f, 184 Occupational exposure, 5–6 p53 family, 76 Open nephroureterectomy (ONU) p53 positive tumors, 72 distal ureter and bladder cuff, management of, 180 Phenacetin (p-ethoxyacetanilide), 7 lymphadenectomy, 181 Photochemical internalization, 151 lymphatic vessels, 179 Photodynamic diagnosis (PDD), 86 thoracoabdominal approach, 178 Photodynamic therapy (PDT) UTUC, open nephron-sparing surgery for, 179–180 mechanism of, 146 wound closure and drainage, 181 modern, history of, 146 Open radical nephroureterectomy (ONU), 177 photochemical internalization, 151 Operating room set up, 233–234 urinary tract, 147 Operative technical details, of distal ureterectomy use of, 149 patient positioning, 170–171 Photon–electron interaction, 322 procedure details, 171 Photosensitizers (PS), 146 Optical coherence tomography (OCT), 376 Pluck technique (see Transurethral resection of ureteral Optical fiber and distal sensor digital ureteroscope, 123 orifice (TUR-UO)) 400 Index

Pneumonia, risk of, 215 Radical nephrectomy (RN), 34, 260 Pneumovesicum, 192 Radical nephroureterctomy (RNU), 199 Polyethylene glycol (PEG), 150 distal ureter, 199 Positive predictive values (PPV), 74, 272 UTUC, 90 Positron emitted tomography (PET) scan, 375 Recurrence-free survival (RFS), 204, 256 Postoperative complications, of nephroureterectomy Renal artery, 211 anuria, 215–216 Renal cell carcinoma incidence of, 215 adjuvant therapy, 328–330 intra-abdominal abscess, 215 neoadjuvant therapy, 330 pneumonia, risk of, 215 Renal pelvicalyceal region, 58 tumor seeding, 216 Renal pelvis cancers, 55 urinary leakage, 216 Renal-sparing surgery, 33, 36 VTE, 215 Renal units (RU), 300 Predictive tools Renal vein, 211 advanced-stage/non-organ-confined disease, 20 Retrograde approach cancer-specific and overall survival, 27–28 antegrade, 162 intravesical, loco-regional and distant metastatic lower urinary tract, examination of, 155–156 recurrence, 24 pelvicalyceal system, assessment of, 159, 161–162 Protein-based markers percutaneous approach, 162 clinical ureteral access BTA, 77 difficult ureteral access, 157–158 ImmunoCyt, 76–77 proximal floppy tip, 156 NMP-22, 78 pyelography, 156, 157f investigative protein-based markers ureteroscopic biopsy, 158–159 E-cadherin, 78 Retrograde ureteropyelogram (RGP), 64, 165 hypoxia-inducible factor, 78–79 Retroperitoneal lymph node dissection (RPLND), 260 investigative biomarkers, 79 Reverse thermosensitive polymer (RTP), 150 LAT 1, 79 Rigid uretero-resectoscope survivin, 78 bladder recurrence, 220 telomerase, 79 DSS, 220 Proximal floppy tip, 156 equipment, 221 Pulmonary embolism (PE), 215 Wolf uretero-resectoscope, 222, 222f Puncture technique, 234–235 Storz uretero-resectoscope, 222, 223f Pyelocalyceal system, 124 expert management, 221 Pyelography, 156, 157f recurrence, risk factor for, 219 Pyeloureteritis cystic tumors, 46 renal preservation, 220 resection technique hydronephrotic ureter, 223 Q mitomycin C, 225 Quality-adjusted life years (QALYs), 36 superficial biopsy technique, 225 Robotic assisted laparoscopic nephroureterctomy (RALNU), 205 R Robotic surgery, 184 Radiation therapy Robotic-assisted nephroureterectomy, 184 aspects of, 321 EBRT, 323 IORT, 326 S modern approaches, 324 Segmental ureterectomy (SU) outcome data, 328 complications and management recommendations, patient considerations and technical aspects, 327–328 174 photon–electron interaction, 322 indications and contraindications, 169 renal pelvis and ureter, 331–332 operative technical details renal cell carcinoma patient positioning, 170–171 adjuvant therapy, 328–330 procedure details, 171–173 neoadjuvant therapy, 330 patient pre-operative evaluation and preparation stereotactic radiation therapy, 325–326 endoscopic evaluation and biopsy, 170 three-dimensional and intensity modulated radiation lab work-up, 169 therapy, 324–325 radiologic evaluation, 169–170 Radical cystectomy, 9, 36 post-operative management and follow-up Index 401

brief literature review/oncologic efficacy, 174–175 upper tract tumors, radiologic appearance of oncologic follow-up, 174 delayed nephrogram, 46 standard post-operative management, 174 filling defects, 42, 45 Semirigid ureteroscope (SRU), 122t fungal infections, 46 basic elements of, 121 leukoplakia, 46 indications, 165 malacoplakia, 46 instruments for, 166t non-neoplastic lesions, 45 RPG, 165 papillary necrosis, 46 ureteroscopes (see Ureteroscopes (URS)) pyeloureteritis cystic, 46 Sequential compression devices (SCD), 215 ultrasound, 48 Serum creatinine, 34 ureteral and pyelocalyceal tumors, 52–53 Serum tumor marker, 375 Upper tract urothelial carcinoma (UTUC) Single bolus technique, 56 adjuvant chemotherapy, 315–316 Smoking, 5 agents, 294 Somatic mutations analysis, 288–289 high-grade muscle-invasive tumors, 101 autotransplantation, 248 low-grade papillary non-muscle-invasive tumors, 101 BCG for TCGA, 101, 102 CIS, 290–291, 292t TERT gene, 102 endoscopic resection, adjuvant, 291–293 Splenic injury, 213 MMC, 293 Split contrast bolus technique, 41 case studies, 337 Squamous cell carcinoma (SCC), 112 CKD and ESRD Study of Heart and Renal Protection (SHARP), 35 effect of, 36 Surveillance upper tract financial costs of, 35 family and patient, 282 renal preservation, value of, 34–35 outline, 282–283 clinical evaluation, 155 patient doctor therapeutic relationship, 285 conservative treatment, 294 physician, 283 endourological treatment, 294 protocol, 283–285, 284t evidence acquisition, 16 Surveillance, Epidemiology and End Result (SEER), 7 neoadjuvant chemotherapy, 314–315 nephron-sparing surgery financial costs of, 33–34 T management of, effect of, 35–36 Taiwan herbal medicine, 6–7 pelvic kidneys, 247 Telomerase, 79 percutaneous resection, 290 The Cancer Genome Atlas (TCGA), 101 prognostic factors and predictive tools Thiotepa, 293, 306 advanced-stage/non-organ-confined disease, 16–20 Transurethral resection cancer-specific and overall survival, 24–28 of bladder tumors (TURBT), 135, 232 intravesical, loco-regional and distant metastatic of ureteral orifice (TUR-UO), 184, 201 recurrence, 20–42 Tumor/surgery-related factors rates, 85 advanced-stage/non-organ-confined disease, 17–19 retrograde approach cancer-specific and overall survival, 27 lower urinary tract, examination of, 155–156 intravesical, loco-regional and distant metastatic pelvicalyceal system, assessment of, 159, 161–162 recurrence, 23 percutaneous approach, 162 ureteral access, 156 ureteroscopic biopsy, 158–159 U risk stratification, 313–314 Unfractionated heparin (UFH), 215 systemic chemotherapy for, 314 Upper tract collecting system neoplasms, radiology of topical therapy, 290–291 staging upper tract urothelial carcinoma, 51 transplant kidney tumor identification and screening aristolochic acid, 249 CT urogram, 41 de novo malignancies, 248 PET scanning, 42 historical, 248 pyelography, 41–42 renal transplant, 248, 249 renal parenchyma, 41 ureteroscopic resection, 288 retrograde ureteropyeloscopy, 42 Upper urinary tract urothelial carcinomas (UUT UC) split contrast bolus technique, 41 BEN, 268 ultrasound, 42 biologic behavior of, 129 402 Index

bladder recurrence, 130 age, 3 Chinese herbal nephropathy, 268 incidence, 3 conservative endoscopic management for, 138 sex, 3–4 diagnosis and management of, 265 presentation DNA-based markers Lynch syndrome, 4, 5 chromosomal enumeration, 73–75 risk factors, 4 DNA-based mutation assays, 76 signs and symptoms of, 4, 5t microsatellite mutation analysis, 75–76 transitional cell bladder cancer, RC, 9–10 endoscopy, 272–274 Upper urinary tract carcinoma in situ (UTCIS) FGFR3-positive tumors, 268 bladder vs. field defect, 265 clinical course, 88–89 genetics of (see Genetics, of UUT urothelial molecular alterations, 89–90 carcinomas) concomitant UTCIS and papillary tumors, 90 groups, 266 diagnosis of imaging (see Imaging) definitions, 85–86, 86t immunoglobulin G4-related kidney disease, 115 modalities, 86–87 IMT, 113, 114 primary lesion, 87–88 intratubular spread, 109, 110t treatment of, 90–92, 91t invasive urothelial carcinoma (see Invasive urothelial Ureteral intussusception technique, 191 carcinoma) Ureteral wall thickening, 58 kidney, rhabdoid tumor of, 114–115 Ureteropelvic junction (UPJ), 64, 240 lymphoma, 114 Ureteroscopes (URS), 167 MMR, 268 channel size and irrigation adequacy of, 125 molecular profiling, 269 flexible ureteroscopes molecular studies of, 268 cost of, 126 MSI mutations, 268 DFU/FFU, 124 natural history of, 130 durability of, 125–126 NBI technology (see also Narrow band imaging optical fiber and distal sensor digital ureteroscope, (NBI)) 123 application of, 131 pyelocalyceal system, navigation in, 124 flexible endoscopic equipment, 132 scope tip, deflection of, 122 preliminary testing, 131 tip design, 122–123 RGB, optical filters for, 131 SRU (see also Semirigid ureteroscope (SRU)), 121, use of, 131 122t WLI and, 132 Urine cytology nephrouretectomy, 267 ancillary tests /segmental ureterectomy, 275–276 FISH/UroVysion, 99–100 noninvasive urothelial carcinoma, 108 immunostain, cytology combined with, 100 normal structure, overview of, 107–108 somatic mutations, 101–102 pathologic parameters, 268 urine protein markers, 100–101 protein-based markers (see also Protein-based mark- common indication for, 97 ers), 76–79 large specimen processing, 102–103 radical cystectomy, 274–275 specimen collection, 97 risk factor for, 266 catheterized urine, 98 ureteropelvic junction, 115 upper tract washings and brushings, 98 urinary biomarkers cytology, 272 voided urine, 97 Upper urinary tract (UUT) sample processing, 99 bladder, urothelial cancer of Urothelial carcinoma (UC), 71, 107 risk factors, 8 autotransplantation, 248 SEER database, 7, 8 congenital pelvic kidney, 247–248 carcinogen exposure, bladder cancer ESRD, 249–250 smoking, 5 higher risk, 247 AA, 6 invasive, 109, 112 BEN, 6 noninvasive, 108 CHN/AAN, 6 patients, surveillance of, 51–52 analgesic abuse, 7 renal transplant recipients, bladder cancer in, 250 occupational exposure, 5–6 transplant kidney Taiwan, herbal medicine use in, 6–7 aristolochic acid, 249 epidemiology de novo malignancies, 248 Index 403

historical, 248 single bolus technique, 56 renal transplant, 248, 249 split-bolus technique, 56 upper urinary tract, 71 3D imaging, benefits of, 59 UroVysion, 99 3D reconstruction, 57 triple-bolus technique, 56 hematuria, 55 V upper urinary tract system, 55 Vascular injury, 211–212 Volume formation (VF), 57 Venous thromboembolism (VTE), 215 Volume rendering (VR), 58 Virtual ureteroscopy, 376 CT urography ancillary techniques, 57 W contraindications, 57 White light cystoscopy (WLC), 147 imaging interpretation, 58 White light imaging (WLI), 132