|Year : 2018 | Volume
| Issue : 4 | Page : 186-192
Indications for ureteropyeloscopy in the detection of upper urinary tract tumors
Jun Morita1, Michio Naoe1, Kohzo Fuji1, Aya Hiramatsu1, Tsutomu Unoki1, Yuki Matsui1, Hideaki Shimoyama1, Takehiko Nakasato1, Kazuhiko Oshinomi1, Katsuyuki Saito2, Yoshiko Maeda1, Yoshio Ogawa1
1 Department of Urology, School of Medicine, Showa University, Tokyo, Japan
2 Department of Urology, Tokyo Metropolitan Health and Medical Treatment Corporation, Ebara Hospital, Tokyo, Japan
|Date of Web Publication||23-Jul-2018|
Department of Urology, School of Medicine, Showa University, 1-5-8, Hatanodai, Shinagawa-Ku, Tokyo, 142-8666
Source of Support: None, Conflict of Interest: None
Objectives: Ureteropyeloscopy has recently become an essential technique in the diagnosis of upper urinary tract tumors. However, no consensus has been reached regarding its indications. In addition, it is accompanied by several limitations and potential adverse events such as dissemination of malignant cells, adhesion of the ureter to the surrounding tissue, ureteral stricture, and ureteral perforation. In order to determine when and what circumstances dictate the need for ureteropyeloscopy to detect upper urinary tract tumors, we investigated the indications for ureteropyeloscopy based on voided urine cytology and preoperative radiographic findings. Patients and Methods: In this retrospective study, we evaluated 92 patients (62 men and 30 women) with a mean age of 66.4 years (range, 15–87 years) who had undergone diagnostic ureteropyeloscopy at our institution for the past 10 years. All patients were divided into six subgroups based on voided urine cytology and preoperative radiographic findings: subgroups A1 (n = 18) and A2 (n = 2), positive cytology (positive catheter urine cytology/negative catheter urine cytology) and positive images; Subgroup B (n = 19), positive cytology and negative images; Subgroups C1 (n = 30) and C2 (n = 10), negative cytology and positive images (upper urinary tract carcinomas/other abnormal findings); Subgroup D (n = 13), negative cytology and negative images. Ureteropyeloscopic findings including histology were compared with urine cytology and radiographic findings. Results: Voided urine cytology exhibited 60.4% sensitivity and 77.3% specificity, while preoperative radiographic findings exhibited 70.8% sensitivity and 63.6% specificity. Carcinomas were detected in all patients in Subgroups A1 and A2. Carcinomas were also detected in 9 patients (47.4%) in Subgroup B, of whom 5 showed a history of bladder tumors. The remaining 10 patients all had a history of bladder cancer. In Subgroups C1, C2, and D, carcinomas were detected in 14 patients (46.7%), 1 patient (10%), and 4 patients (30.8%), respectively. These results suggested that ureteropyeloscopy should be recommended for patients with negative cytology. Three complications (pyelonephritis, renal failure, and urinary retention) were noted, but none of these was severe and all were cured within a few days. No malignant findings were obtained in any of the patients during follow-up after negative findings in ureteropyeloscopy. Conclusions: Ureteropyeloscopy is essential for detecting upper urinary tract carcinoma in patients with negative voided urine cytology and positive radiographic findings. In addition, ureteropyeloscopy seems to be used commonly among patients with positive urine cytology and negative radiographic findings, or those with bleeding from the ureteral orifice. However, unless conservative nephron-sparing treatment is considered, ureteropyeloscopy may be unnecessary for patients with positive urine cytology and positive radiographic findings.
Keywords: Indications, upper urinary tract tumors, ureteropyeloscopy
|How to cite this article:|
Morita J, Naoe M, Fuji K, Hiramatsu A, Unoki T, Matsui Y, Shimoyama H, Nakasato T, Oshinomi K, Saito K, Maeda Y, Ogawa Y. Indications for ureteropyeloscopy in the detection of upper urinary tract tumors. Urol Sci 2018;29:186-92
|How to cite this URL:|
Morita J, Naoe M, Fuji K, Hiramatsu A, Unoki T, Matsui Y, Shimoyama H, Nakasato T, Oshinomi K, Saito K, Maeda Y, Ogawa Y. Indications for ureteropyeloscopy in the detection of upper urinary tract tumors. Urol Sci [serial online] 2018 [cited 2018 Aug 15];29:186-92. Available from: http://www.e-urol-sci.com/text.asp?2018/29/4/186/237360
| Introduction|| |
Upper urinary tract tumors account for 5%–6% of all tumors originating in the urothelium, which is not a high occurrence relative to other cancers of the urinary system. Two-thirds of the predilection sites are located in the renal pelvis, and the remaining one-third is in the ureter, predominantly the lower urinary tract. Developmental characteristics include a strong tendency to develop in a multicentric fashion, regardless of whether carcinoma is synchronous or metachronous. Reportedly, 20%–50% of cases are associated with bladder cancer, whereas the frequency of upper urinary tract recurrence following total cystectomy for bladder cancer is suggested to be <5%. However, compared to bladder cancer, renal pelvic and ureteral cancers, especially ureteral cancer, are often found to be highly invasive. Given the poor prognoses, early diagnosis and treatment are essential.
Main symptoms of upper urinary tract tumors include macrohematuria. To obtain their diagnosis, past medical history, family history, and clinical signs are taken into consideration, and cystoscopy, voided urine cytology, and various diagnostic imaging tests such as ultrasounds, computed tomography (CT) and CT urography (CTU) may be performed, sometimes including retrograde pyelography (RP) and catheter urine cytology. A recent report showed that both sensitivity and specificity of ureteropyeloscopy approach 90% due to technical advances brought on by the diversification of rigid and flexible scopes and minimization of scope diameter, Consequently, recent years have seen an increased use such that ureteropyeloscopy is now considered an important test for upper urinary tract tumor screening.
With respect to indications, however, there is no clear set of criteria regarding the circumstances under which ureteropyeloscopy should be performed. Moreover, while the ureteroscope is diagnostically useful, it is not free of complications such as tumor dissemination, ureteral damage, ureteral stricture, and ureteral adhesion in consideration of future surgery., Furthermore, other concerns exist, such as the physical impact of hospitalization and anesthesia, risks, and time delay due to the procedure. In the present study, we examined actual cases in which diagnostic ureteropyeloscopy was performed to diagnose upper urinary tract tumors in order to determine indicative criteria for ureteropyeloscopy based mainly on urine cytology and radiographic findings.
| Patients and Methods|| |
We examined 92 patients (60 men and 32 women; mean age, 66.4 years) who underwent diagnostic ureteropyeloscopy at our institution for the past 10 years. The affected side was left in 40 patients, right in 51 patients, and bilateral in 1 patient. Urine examination at the first visit detected microhematuria in 77 of 92 patients (83.7%), and 28 of 92 patients (30.4%) had a history of bladder cancer. Over 40% (38 patients (41.3%) noted macrohematuria as the chief complaint, followed by back pain (15 patients (16.3%), microhematuria (10 patients (10.9%), and positive urine cytology (10 patients (10.9%) [Table 1].
All patients underwent the initial examination, which included urine cytology and diagnostic imaging with at least one of the following patterns: CT and intravenous urography, or CTU, or magnetic resonance urography. For the present study purposes, we selected only cases in which ureteropyeloscopy was performed for the purpose of upper urinary tract cancer diagnosis, which included those with a suspicion of carcinoma based on the radiographic findings, those with positive urine cytology, and those with bleeding from the upper urinary tract. Therefore, transurethral ureteral lithotripsy cases, ureteral dilatation (ureteral stenosis) cases, and transurethral ureteral tumor resection (laser) cases were excluded from the present study. Furthermore, cystoscopy confirmed that patients with even the slightest suspicion of a bladder tumor, including those with no significant radiographic findings and those with positive urine cytology only, showed no bladder tumor. RP may also be performed in advance, but this is commonly performed at the discretion of the attending physician, and no standard criteria currently exist. The present study included patients who had undergone RP. We indicated the examples for positive radiographic finding in [Figure 1]a and [Figure 1]b.
|Figure 1: (a) Computed tomography revealed the thickening of the left ureter wall and contrast effect. (b) Retrograde pyelography showed the defect of the left ureter|
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In urine cytology, Classes IV and V were considered positive cytology, while Class III and below was considered negative. In imaging, positive findings included ureteric filling defects, consecutive stricture, thickening of the ureter wall, and associated hydronephrosis.
In all cases, ureteropyeloscopy was performed under general anesthesia using either an 8.0-Fr rigid ureteroscope (Richard Wolf GmbH, Knittlingen, Germany) or 7.4-F flexible ureteroscope (Karl Storz, Tuttlingen, Germany). Use of a guidewire was avoided as much as possible; however, an auxiliary guidewire was occasionally used to advance the rigid ureteroscope from the lower urinary tract to the upper urinary tract during observation. For the renal pelvis and calyx, a flexible ureteroscope was mainly used to observe the mucous membrane. In addition, cold biopsy was performed for neoplastic lesions and irregular mucosal sections in the ureter and the mucous membrane of the renal pelvis to verify the presence of tumors, as needed. For perfusion of the ureteroscope, saline was used through a pump device (Uromat), while paying attention to maintain a flow rate of 200 ml/min and a flow pressure below 40 mmHg.
All patients were divided into subgroups based on the results of urine cytology and diagnostic imaging as shown in [Table 2], and ureteroscopic findings were compared in each subgroup. Subgroups A1 and A2 consisted of patients with positive urine cytology and radiographic findings suspicious for upper urinary tract tumors (A1, positive catheter urine cytology; A2, negative catheter urine cytology). Subgroup B consisted of patients with positive urine cytology but no specific radiographic findings. Subgroup C consisted of patients with entirely negative urine cytology and abnormal radiographic imaging. These patients were further divided into C1 if radiographic findings directly suggested the presence of upper urinary tract tumor, and C2 if radiographic findings were limited to the presence of hydronephrosis, ureteral filling defects, and wall thickening (i.e., findings that do not directly lead to a suspicion of a neoplastic lesion). For example, [Figure 1]a divides into C1 because contrast effect.
Finally, patients with no abnormal urine cytology or radiographic findings who presented with bleeding from the upper urinary tract, as revealed directly by cystoscopy (and were thus required to undergo ureteroscopic examination of the upper urinary tract) were classified as Subgroup D.
| Results|| |
Results of ureteroscopic findings in each group based on urine cytology and radiographic findings are shown in [Table 3]. Malignant findings were obtained in all 20 patients in Subgroups A1 (18 patients) and A2 (2 patients) (21.7%) who presented with positive urine cytology and radiographic findings suspicious of an upper urinary tract tumor. These findings included renal pelvic tumor (6 patients), ureteral tumor (13 patients), and malignant lymphoma (1 patient). Follow-up for the 20 patients revealed that 13 patients received radical nephroureterectomy, 1 patient received partial ureterectomy, 5 patients with advanced tumors and/or were under poor general conditions either underwent chemotherapy or were transitioned to palliative care, and 1 patient with malignant lymphoma underwent chemotherapy upon hematology consultation.
In Subgroup B, malignant findings were obtained in only 9 of 19 patients (47.4%), which was roughly half of the total. Four of the 9 patients had a renal pelvic tumor, 3 had a ureteral tumor, and the remaining 2 had metastases from other tumors (adenocarcinoma). All four cases of renal pelvic tumors had carcinoma in situ (CIS) and received treatment with instillation of bacillus Calmette-Guerin (BCG) into the renal pelvis. One of the patients with a ureteral tumor, which was identified as a ureteral CIS, also received BCG instillation therapy, whereas the other two patients underwent radical nephroureterectomy for tumors that were determined to be superficial urinary tract epithelial tumors. In the present study, no malignant findings were obtained in more than half of the patients in Subgroup B (10 patients); these 10 patients had a history of bladder cancer. Biopsy revealed that 6 of the 10 patients had synchronous bladder CIS; these patients received intravesical BCG therapy. In addition, two patients were found to have metachronous bladder tumors, and we followed-up stringently with the remaining two. Five patients in Subgroup B had no history of bladder cancer; malignancy in the upper urinary tract was detected in all cases.
In Subgroup C, the negative urine cytology group, roughly half of the patients (14/30) (46.7%) assigned to C1 exhibited malignancy in the upper urinary tract. Five of the 14 patients had a renal pelvic tumor, 8 had a ureteral tumor, and the remaining 1 had metastases from other tumors (adenocarcinoma). On follow-up, radical nephroureterectomy was performed in 7 of the 14 patients, whereas conservative treatment approaches such as radiation therapy and wait-and-see were taken for the remainder. Of the remaining 16 patients, 9 patients, or more than half of the total, showed inflammatory changes. Of the 10 patients classified as C2, 1 patient showed evidence of a ureteral tumor and was treated with radical nephroureterectomy; no malignancy was found in the remaining 9 patients, including the 3 who exhibited inflammatory changes.
In Subgroup D, malignant findings were obtained in 4 of 13 patients (30.8%), and endoscopic resection, BCG instillation into the renal pelvis, and radical nephroureterectomy were performed in 1, 1, and 2 patients, respectively. All four patients had a history of bladder cancer, and ureteropyeloscopy was performed because periodic cystoscopy detected bleeding from the ureteral orifice. Overall, patients in Subgroups C and D with no malignant findings each received treatment for benign disease as needed, and no malignant findings were obtained in any of the patients during the subsequent observation period.
Based on these results, the sensitivity, specificity, positive predictive, and negative predictive values of urine cytology were 60.4%, 77.3%, 74.4%, and 64.2%, respectively. The sensitivity, specificity, positive predictive, and negative predictive values of diagnostic imaging were 70.8%, 63.6%, 68.0%, and 66.7%, respectively. Although urine cytology tends to exhibit high specificity relative to other tests, the obtained specificity was just 77.3%, and given the high sensitivity of 60.4% obtained in the present study, the overall difference was not apparent.
To the best of our knowledge, adverse events due to use of the ureteroscope were noted in a total of three patients. One patient developed postprocedural acute pyelonephritis caused by urinary tract infection, the second patient developed postrenal failure due to ureteral stricture, and the third patient developed postprocedural acute urinary retention. However, each of these was resolved within a few days while conditions were still minor following symptomatic treatment, which included infusion of antibiotics, ureteral stent placement, and urinary balloon catheter placement. No serious complications such as urinary tract damage and rupture were noted in this study.
| Discussion|| |
In the diagnosis of upper urinary tract tumors, the diagnostic sensitivity of ureteropyeloscopy and following biopsy is very high, ranging from 82% to 100% according to some reports.,,, In fact, the present study found no false-negative results in subsequent surgery among those who were confirmed to have malignant lesions by ureteropyeloscopy. Patients with no confirmed malignancy each received treatment for benign lesions as needed, and no malignant findings were noted during the observation period. Consequently, ureteropyeloscopy has been considered an important test for upper urinary tract tumor screening.
While ureteroscopy is becoming an essential test, in actual clinical practice, not all patients with a suspicion of upper urinary tract tumor undergo this procedure, and questions constantly arise regarding whether diagnosis of renal pelvic tumor should always require ureteroscopy, or the circumstances under which ureteroscopy should be performed. That is, no clear indication criteria have been established. Moreover, while the ureteroscope is diagnostically useful, it is not free of complications such as tumor dissemination, ureteral damage, ureteral stricture, and ureteral adhesion in consideration of future surgery., Furthermore, other concerns exist, such as the physical impact of hospitalization and anesthesia, risks, and time delay due to the procedure. The present study showed that both urine cytology and radiographic findings exhibited overall sensitivity and specificity of 60%–80%, but their diagnostic capabilities should further increase by classifying different conditions. It will be important to recognize the conditions under which the need of ureteroscopy increases, or when it can be avoided. So far, only a few reports have described indications for ureteroscopy.,, The present study was conducted to address this issue based on actual cases for which diagnostic ureteroscopic examination was performed.
Patients in the present study were classified into subgroups. First, in Subgroups A1 and A2, malignant findings were obtained in all 20 patients without any exception, as expected. Under such circumstances, one option would be to proceed to the next course of treatment without performing ureteroscopy. In contrast, the significance of carrying out ureteroscopy may be limited to cases where endoscopic treatment is indicated, e.g., if patients have a bilateral or solitary renal lesion, which necessitates active consideration of nephron-sparing surgery, if radical surgery is difficult to perform due to complications or other issues such as age, and if the tumor is low grade/stage.
Next, with respect to Subgroup B patients, the presence of bladder cancer, especially CIS, is an important issue. Under normal circumstances, if bladder cancer is denied completely and catheter urine cytology reveals the location of cancer, then it is possible to omit ureteroscopy because the responsible lesion is apparent, given the specificity of urine cytology. However, if urine cytology is unclear in terms of cancer localization, then CIS in particular becomes the central issue in both the bladder and upper urinary tract. Ureteroscopy will thus be essential, with subsequent treatment in mind. How accurately a diagnosis of CIS can be made is indeed a debatable question; however, in the present study, nine patients with malignant findings in Subgroup B, including the five with CIS and the other four without, were accurately assessed. No CIS finding in the upper urinary tract was obtained in any of the 10 patients who lacked malignant findings, at least during the observation period. In patients with positive urinary cytology, if the lesion cannot be identified, careful examination is needed so as to not overlook a high-grade urothelial tumor and CIS. To this end, ureteroscopic examination of the upper urinary tract and mucosal biopsy can be very useful.
On the other hand, given the extremely small size of the ureteroscopic biopsy specimen, obtaining an accurate diagnosis can be difficult. One report has shown that even if imaging and macroscopic findings suggest a lesion, accurate pathological diagnosis cannot be obtained in one-quarter of the total cases due to insufficient tissue sampling. Another report suggested that in more than one-third of cases where abnormal findings are obtained in the initial ureteroscopy, under-grading or under-staging is subsequently noted. In actual clinical practice, however, quite a few patients who receive radical nephroureterectomy present with no malignant lesions, suggesting that ureteroscopy and biopsy can be very important in deciding the subsequent treatment course.
Some debates remain regarding RP and catheter urine collection from one of the kidneys and no common ground has been reached. In this study, we performed retrospective analysis, and thus these procedures were not carried out in a uniform manner. For example, in Subgroups A1 and A2, patients were divided and compared based on the results of catheter urine cytology, but even in patients with negative cytology, if their urine cytology results were positive, malignant findings were obtained. In actual clinical practice, RP and urine sampling from one of the kidneys would likely be considered if the patient only showed positive urine cytology, without bladder tumor or any abnormal radiographic findings. However, if RP is positive regardless of the result of catheter urine cytology, then the patient would be placed in Subgroup A, and ureteroscopy may be avoided. Of course, if catheter urine cytology is positive, then local diagnosis and definitive diagnosis can be further supported. On the other hand, in other cases (i.e. those for which RP is negative), the possibility of proceeding with subsequent ureteroscopy will be higher. Given recent developments within the field of CTU in imaging studies, RP and catheter urine cytology merely play an auxiliary role in examinations, and there may be no need to perform them on a constant basis, depending on the patient.
Next, regarding Subgroups C and D which included patients with negative urine cytology, the portion of patients in whom upper urinary tract tumors were actually confirmed did not even reach half of the total, even when those classified as C1 with a suspicion of upper urinary tract tumors were included. In the remaining half, benign lesions such as inflammatory changes, stricture, and calculus were detected. Given that the observation period spanned the past 10 years, improvements in the diagnostic capacity of current imaging modalities should be considered. As expected, these groups appeared to represent the population for which ureteropyeloscopy should be indicated. Similarly, as demonstrated by the 10% in Subgroup C2, and 30.8% in Subgroup D with bleeding from the ureteral orifice, ureteropyeloscopy should be aggressively performed when the localization and presence of lesions are unclear. In particular, in the case of Subgroup D, endoscopic operations in the renal pelvis and ureter involve not only searching for lesions, but also hemostasis, and many other therapeutic elements depending on the cause.
Finally, how much negative impact does a patient actually experience by undergoing ureteroscopy? In terms of adhesion of the ureter at the time of surgery, a direct comparison is difficult, and none have reported on this. In terms of tumor dissemination, however, Ishikawa et al. reported that in patients with upper urinary tract tumors who underwent radical nephroureterectomy, no significant impact was found on subsequent intravesical recurrence or survival in 55 patients who underwent ureteroscopy and the 153 patients who did not undergo ureteroscopy. In addition, Serrano Pascual et al. reported that ureteroscopy is also useful for percutaneous endoscopic resection of upper urinary tract tumors in limited cases where patients have low-stage and low-grade tumors, or if nephron-sparing surgery is a possible option. This group also reported that in light of tumor dissemination, no significant risk is involved. Furthermore, in terms of time consumed in a ureteroscopic examination, Boorjian et al. reported that no effect was found on postoperative recurrence or survival in 75 patients who underwent radical nephroureterectomy after ureteroscopic biopsy and 12 patients who underwent radical nephroureterectomy after ureteroscopic biopsy and laser tumor ablation, compared to 34 patients who underwent no ureteroscopy. In addition, Gurbuz et al. reported that in patients undergoing radical nephroureterectomy for upper urinary tract tumors, no effect on the recurrence rate or survival was observed in 175 patients with a history of ureteroscopic tumor ablation compared to 1093 patients with no history, and that in selected patients, endoscopic tumor ablation can be effective.
Complications due to the ureteroscopic procedure include intraoperative complications such as bleeding, mucosal damage, and ureteral perforation, as well as postoperative complications such as urinary tract infection, blood clots, and ureteral obstruction due to edema, and ureteral stricture, which occurs in the late stage. Compared to lithotripsy, the frequency of complications is low in diagnostic ureteroscopy. In particular, almost no intraoperative complications occur, as suggested by the present study and previous reports. Moreover, even with combining all ureteroscopic surgery cases from various reports, ureteral mucosal damage was noted in <3.5%, and ureteral perforation in <1.7%.
Furthermore, Brien et al. reported that analyses of patients with upper urinary tract tumors who were treated with radical nephroureterectomy revealed that the presence of preoperative hydronephrosis, ureteroscopic biopsy grade, and urinary cytology are the factors that help to distinguish between local invasion and advanced cancer, and are useful in selecting surgical treatment and preoperative chemotherapy regimens. Similarly, one report showed that biopsy grade closely matched the extended operation sample, that the nonrecurrence rate and survival rate were similar between the radical nephroureterectomy group and the nephron-sparing group, with the exception of G3 and pT2 tumors, and that in low-grade cases, biopsy is important in the sense that there is room to select nephron-sparing surgery. Low-grade cases tend to show no practical difference between radical nephroureterectomy and endoscopic treatment in terms of recurrence and survival. Of course, the fact that radical nephroureterectomy is a standard surgical procedure does not change, and endoscopic treatment should be considered an option in select patients, such as those considered for renal function preservation, while keeping in mind that there are possibilities for biopsy grading error (i.e., under-staging), recurrence, and progression. In summary, ureteroscopy is not only helpful from the perspective of diagnostics but also useful in various other aspects, such as to gain an advantage in proceeding with subsequent treatment. Moreover, since it is minimally invasive, it can be performed safely without substantial disadvantages.
| Conclusions|| |
While ureteroscopy is an important tool for diagnosing upper urinary tract tumors, it is not essential in all cases. Thus, in actual clinical practice, ureteroscopy is performed by considering indicated cases from various angles. The present study found that indications for ureteroscopy can be considered according to the flowchart shown in [Figure 2]. While each case embodies a unique set of necessary considerations, ureteroscopic examination tends to be chosen for patients with negative voided urine cytology and positive radiographic findings, and patients with poor radiographic findings and positive urine cytology with no clear signs of bladder cancer, and patients with poor radiographic findings and negative urine cytology, and bleeding from the ureter orifice, which warrants examination of the upper urinary tract. Given that fewer complications and disadvantages exist, ureteroscopy should be aggressively performed in patients for whom even a slight challenge in the diagnosis is evident. Notably, ureteroscopy is not always necessary in patients with both positive urine cytology and positive radiographic findings (with the exception of those considering endoscopic treatment); these patients should proceed to the next treatment stage.
|Figure 2: The present study found that indications for ureteroscopy can be considered|
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There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]