Patterns of failure and prognostic factors for locoregional recurrence after radical surgery in upper urinary tract transitional cell carcinoma: implications for adjuvant radiotherapy.

AIMS: We investigated the patterns of failure and prognostic factors for locoregional control (LRC) in patients with upper urinary tract (UUT) transitional cell carcinoma (TCC) treated with radical surgery to evaluate the role of adjuvant radiotherapy. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 76 patients with TCC of the renal pelvis and ureter without distant metastasis who underwent curative-intent surgery. No locoregional or distant failure occurred in 19 patients with pTa-1 tumor, and we evaluated patterns of failure and prognostic factors in 57 patients with pT2 or more tumors. Adjuvant chemotherapy was applied in 25 patients. RESULTS: Recurrences occurred in a total of 23 patients, and 20 of these experienced some kind of locoregional failure during follow-up. The overall crude and initial isolated locoregional recurrence rates were 35 and 28%, respectively. In pT2 patients, all 4 recurrences were isolated locoregional recurrences, and 3 of them were successfully salvaged with chemoradiotherapy. Patients with pT3-4 or who were positive for nodal disease (N+) had a lower rate of LRC and worse prognosis after recurrences. On multivariate analysis, incomplete surgery, venous invasion and squamous metaplasia were identified as independent prognostic factors for LRC. CONCLUSIONS: Initial loco-regional recurrence was commonly detected by routine computed tomography in locally advanced UUT-TCC. Incomplete surgery, venous invasion and squamous metaplasia were independently associated with poor LRC. Active postoperative adjuvant treatment such as concurrent chemoradiotherapy could be considered in pT3-4 or N+ patients with adverse risk factors.

Postoperative adjuvant radiotherapy for patients with upper tract urothelial carcinoma (UTUC) who underwent kidney-sparing surgery (KSS): a single-center study.

OBJECTIVE: The purpose of this study was to evaluate the efficacy of postoperative adjuvant radiotherapy for patients with upper tract urothelial carcinoma (UTUC) who underwent kidney-sparing surgery (KSS). METHODS: We retrospectively reviewed the clinical records of 31 patients with primary UTUC who underwent kidney-sparing surgery (KSS) and who were treated with adjuvant radiotherapy at our center between October 1998 and May 2017. Statistical analyses were performed with SPSS 23.0. The primary endpoints of this study included overall survival (OS) and local recurrence-free survival (LRFS); the secondary endpoints were disease-free survival (DFS) and treatment-related toxicity. RESULTS: The median follow-up was 58.4 months (range, 12.7-185.3 months), and the median local recurrence time was 59.0 months (range, 7.0-185 months). All of the patients completed radiotherapy on schedule, and no grade 3-4 late-stage reaction was observed. The estimated 5-year and 10-year OS, DFS and LRFS rates of the patients were 64.0%, 61.1%, 69.6% and 48.0%, 40.9%, 64.6%, respectively. Univariate analysis showed that age (χ2 = 4.224, P = 0.040), R0 resection (χ2 = 3.949, P = 0.047), and early stage (I + II) (χ2 = 6.515, P = 0.011) were associated with good OS; DFS benefit in early stage patients (χ2 = 6.151, P = 0.013) and age<70 years old (χ2 = 5.091, P = 0.024). Patients with distal ureteral segments had better LRFS than patients with proximal ureteral cancer (χ2 = 5.248, P = 0.022). However, multivariate analysis showed that age was the only factor of OS (χ2 = 4.099, P = 0.043). CONCLUSION: Adjuvant radiotherapy is safe and tolerated, and LRFS was superior in middle and distal ureteral cancer than in proximal ureteral cancer.

Adjuvant Treatments for Advanced Stage, Non-metastatic Upper Tract Urothelial Carcinoma: A Multicenter Study.

PURPOSE: We assessed the efficacy of adjuvant treatments in patients with peripelvic/periureteral fat-infiltrating (pT3b), nonmetastatic upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy. METHODS AND MATERIALS: The multicenter data of 222 patients with pT3bN0-x disease treated with radical nephroureterectomy were analyzed. The effects of adjuvant radiation therapy and chemotherapy on local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and cancer-specific survival (CSS) were evaluated. RESULTS: Adjuvant radiation therapy and chemotherapy were given to 39 (17.6%) and 74 patients (33.3%), respectively. Seventeen patients (7.7%) received concomitant adjuvant radiation therapy and chemotherapy. The median follow-up duration was 34.4 months. After adjusting for age, sex, tumor location, multifocality, tumor grade, presence of lymphovascular invasion, surgical margin, execution of node dissection, and other types of concomitant adjuvant treatment (radiation therapy or chemotherapy) through propensity-scored matching, adjuvant radiation therapy significantly reduced the local recurrence (5-year LRFS, 83.9 vs 54.2%; P = .001), distant metastasis (5-year DMFS, 72.1 vs 48.1%; P = .032), and cancer-specific death (5-year CSS, 76.4% vs 55.5%; P = .038) in pT3b UTUC. However, in the same condition, adjuvant chemotherapy did not reduce the local recurrence (5-year LRFS, 69.0% vs 66.2%; P = .786), distant metastasis (5-year DMFS, 65.3% vs 61.1%; P = .436), and cancer-specific death (5-year CSS, 67.9% vs. 67.9%; P = .458) in pT3b UTUC. CONCLUSIONS: Our study suggests that adjuvant radiation therapy may be beneficial in patients with T3bN0-x UTUC; however, prospective clinical trials are needed to clarify this issue.

[Transitional carcinoma of the ureter with osseous metaplasia of the stroma: a case report]. / Carcinome urothélial de l'uretère avec métaplasie osseuse du stroma.

Transitional cell carcinoma with osseous metaplasia of the stroma is a rare variant of urothelial carcinoma which must be distinguished from sarcomatoid carcinoma. We report here a further observation of this tumor variant, in a very unusual location, the ureter, in order to underline the radiological and pathological characteristics useful for the correct diagnosis, and to point out the problems of differential diagnosis. The diagnosis was made in an 85-year-old patient, presenting with chronic right lombalgias. Imaging studies showed a calcified thickening of the right ureter, associated with a major dilatation of the right excretory cavities and a parenchymal atrophy of the right kidney. A right nephro-ureterectomy was performed. Macroscopical examination showed an ossified, ill-limited tumor, measuring 4 cm in diameter, infiltrating the right ureteral wall. At histological examination, the lesion was identified as a high grade transitional cell carcinoma with extensive osseous metaplasia of the stroma. There was no evidence for a sarcomatous component (absence of mesenchymal cell proliferation, absence of mitosis in stromal cells). An early locoregional recurrence was observed three months after surgery. Our case report underlines the radiological and histological features of a rare variant of transitional cell carcinoma, which may be diagnosed by pre-operative imaging studies and which must be distinguished from a highly aggressive sarcomatoid carcinoma.

[Prospective study of the treatment of localised ureteric strictures by wire mesh stent]. / Etude prospective de traitement des sténoses urétérales localisées par endoprothèse grillagée métallique.

AIMS: To assess efficacy of Mémotherm BARD ureteral metallic stent in the treatment of non-operable ureteral stenoses. MATERIAL AND METHOD: Prospective evaluation of ureteral stenoses consecutively treated using Mémotherm BARD ureteral metallic stent. Assessment criteria (recurrence frequency, permeability, tolerance, complications) were measured by clinical examination, Intra Veinous Pyelography, renal sonography, urine culture at 1, and every 3 months. RESULTS: Thirteen stents were inserted in 12 patients (mean age: 68 yrs) presenting with subsequent ureteral stenosis (9 neoplastic, 3 following radiotherapy) over a 3 year period. No technical difficulty was observed. Mean follow-up was 19 months. Stenosis recurrence was observed in 5 patients, due to tumoural progression, but with no tumour in-growth. There was non incrustation or migration, pain, hematuria, infection due to the stent. All stent remained permeable and functional in surviving patients. CONCLUSIONS: In our experience, Mémotherm BARD ureteral metallic stent could be considered a useful cost-effective alternative to double J stent or traditional surgery in non-operable or end-of-life patients. The high ureteral stenosis recurrence rate was linked to the patient initial pathology. Considering these encouraging results, this study could represent the first stage of a multicenter tracker-study, which would permit to take into account further technological development of this type of material.

Impact of Tumor Location on Local Recurrence After Nephroureterectomy for Upper Tract Urothelial Carcinoma: Implications for Adjuvant Radiotherapy.

PURPOSE: To evaluate the impact of tumor location on local recurrence in upper tract urothelial carcinoma (UTUC). PATIENTS AND METHODS: Among UTUC patients who underwent radical nephroureterectomy, 192 with renal pelvic tumors and 161 with ureteral tumors were included. Local recurrence was divided into regional lymph node recurrence (rLNR) and surgical bed recurrence (SBR). RESULTS: During a mean follow-up of 73 months, local recurrence occurred in 33 patients (9.3%). The postoperative 5-year local recurrence-free survival (80.5% vs. 94.2%; P = .002), rLNR-free survival (89.8% vs. 96.5%; P = .046), and SBR-free survival (88.3% vs. 97.6%; P = .005) were poorer in ureteral tumor than renal pelvic tumor. Ureteral tumor (hazard ratio [HR], 2.552; P = .017), high-grade tumor (HR, 3.064; P = .016), and advanced tumor stage (T3 or greater) (HR, 3.236; P = .002) were associated with local recurrence. Ureteral tumor (HR, 3.516; P = .033) and advanced tumor stage (HR, 2.907; P = .039) were risk factors for SBR. Although tumor location was not associated with rLNR, lymphovascular invasion (HR, 5.451; P < .001) and high-grade tumor (HR, 4.191; P = .012) were related to rLNR. CONCLUSION: Ureteral tumors are associated with local recurrence in the form of SBR. Adjuvant radiotherapy or surgical techniques aimed at reducing the risk of SBR should be considered in patients with ureteral tumors.

Renal failure from metastatic breast carcinoma reversed by radiotherapy and chemotherapy.

We treated a patient who had acute renal failure secondary to obstructive uropathy from metastatic breast carcinoma. Attempts at ureteral catheterization and nephrostomy failed. Bilateral ureteral irradiation was given, followed immediately by chemotherapy, with relief of obstruction and normalization of renal function. Nineteen months later, the patient died; at that time, her serum urea nitrogen and serum creatinine levels were normal.

A cemented acetabular component with a reinforcement cross provides excellent medium-term fixation in total hip arthroplasty after pelvic irradiation.

Conventional cemented acetabular components are reported to have a high rate of failure when implanted into previously irradiated bone. We recommend the use of a cemented reconstruction with the addition of an acetabular reinforcement cross to improve fixation. We reviewed a cohort of 45 patients (49 hips) who had undergone irradiation of the pelvis and a cemented total hip arthroplasty (THA) with an acetabular reinforcement cross. All hips had received a minimum dose of 30 Gray (Gy) to treat a primary nearby tumour or metastasis. The median dose of radiation was 50 Gy (Q1 to Q3: 45 to 60; mean: 49.57, 32 to 72). The mean follow-up after THA was 51 months (17 to 137). The cumulative probability of revision of the acetabular component for a mechanical reason was 0% (0 to 0%) at 24 months, 2.9% (0.2 to 13.3%) at 60 months and 2.9% (0.2% to 13.3%) at 120 months, respectively. One hip was revised for mechanical failure and three for infection. Cemented acetabular components with a reinforcement cross provide good medium-term fixation after pelvic irradiation. These patients are at a higher risk of developing infection of their THA.

Prognostic factors in urothelial renal pelvis and ureter tumours: a multicentre Rare Cancer Network study.

To assess the prognostic factors in patients with transitional-cell carcinoma of the renal pelvis and/or ureter, a series of 138 patients with transitional-cell carcinoma of the renal pelvis and/or ureter was collected in a retrospective multicentre study. 12 patients with distant metastases were excluded from the statistical evaluation. All but 3 patients underwent radical surgery: nephroureterectomy (n = 71), nephroureterectomy and lymphadenectomy (n = 20), nephroureterectomy and partial bladder resection or transurethral resection (n = 20), nephrectomy (n = 10), and ureterectomy (n = 5). Sixty-one per cent (n = 77) of the tumours were located in the renal pelvis, and 21% (n = 27) in the ureter (both in 22 [17%]). Following surgery, residual tumour was still present in 33 patients (16 microscopic and 17 macroscopic). Postoperative radiotherapy was given to 45 (36%) patients. The median follow-up period was 39 months. In a median period of 9 months, 66% of the patients relapsed (34 local, 7 locoregional, 16 regional, and 24 distant). The 5- and 10-year survival were 29% and 19%, respectively, in all patients. In univariate analyses, statistically significant factors influencing the outcome were Karnofsky index, pT-classification, pN-classification, tumour localisation, grade, and residual tumour after surgery. Multivariate analysis revealed that independent prognostic factors influencing outcome were pT-classification, the existence of residual tumour, and tumour localisation. In patients with urothelial renal pelvis and/or ureter tumours, a radical surgical attitude is mandatory; and the presence of tumour in the ureter is associated with a poorer prognosis.

Adjuvant radiotherapy in high stage transitional cell carcinoma of the renal pelvis and ureter.

This review was undertaken to assess the influence of adjuvant radiation therapy on failure patterns and survival in high stage transitional cell carcinoma of the renal pelvis or ureter. Ninety-four patients with transitional cell carcinoma of the renal pelvis or ureter were retrospectively reviewed. Twenty-six had American Joint Commission stage T3 or T4 N0/+, M0 disease and underwent curative resections (median follow-up 13.5 months, range 3-311). Local failure was defined as recurrence in the tumor bed, regional nodes, or ureteral stump. Time to recurrence and survival were calculated from the time of pathologic diagnosis. Variables associated with local failure, distant metastasis, and survival were analyzed using univariate and multivariate analysis. Seventeen received surgery only, nine received adjuvant radiation therapy (median dose 50 Gy). Local failure occurred in 9 of 17 without and 1 of 9 with adjuvant radiation therapy (p = 0.07). Actuarial 5-year local control was 34% without and 88% with adjuvant radiation therapy. Cox step-wise regression confirmed adjuvant radiation therapy (p = 0.006) and grade (p = 0.006) as significantly associated with local failure. No patients with low grade lesions suffered local failure either with or without adjuvant radiation therapy. High grade lesions had an local failure rate of 15% with and 71% without adjuvant radiation therapy. Metastatic disease occurred in 4 of 9 and 8 of 17 with and without radiation therapy. No significant factors influencing distant failure were identified. Five-year actuarial survival was 44% with and 24% without adjuvant radiation therapy. The survival differences were not statistically significant on univariate or multivariate analysis. High staged transitional cell carcinoma of the renal pelvis or ureter has a substantial local failure risk after surgery alone. Adjuvant radiation therapy markedly reduces this risk but has no impact on distant disease which occurs in approximately 50%. Effective adjuvant therapy will require effective systemic therapy in addition to adjuvant radiation therapy.

Micronuclei expression in tumors as a test for radiation sensitivity.

Dose-effect curves were determined for the frequency of micronuclei and impairment of cell clonogenicity from two types of tumours of different sensitivity irradiated in situ. Micronucleated cells were measured 24, 48 and 72 h after treatment. The quantitative relationships between cell reproductive death and the induction of micronuclei are the same for both tumours.

Analysis of cell survival after multiple fractions per day and low-dose-rate irradiation of two in vitro cultured rat tumor cell lines.

Two rat tumor cell lines which differ significantly in radiosensitivity, a rhabdomyosarcoma (R-1) and a ureter carcinoma (RUC-2), were treated with multiple fractions per day and low-dose-rate gamma radiation. The purpose of these experiments was to investigate (i) the influence of fraction size and interfraction interval on repair of sublethal damage (SD) and (ii) whether low-dose-rate irradiation can be simulated by giving multiple fractions per day which might be applied in clinical treatments. In both cell lines, multiple doses were given at 1- to 4-hr intervals. SD repair was at a maximum in 2 hr but did not reach the theoretically expected level. For both cell lines, survival at higher total doses was different from that theoretically expected if repair of SD was assumed to be completed and at the maximum level. To account for the observation that less than complete repair of SD occurred, theoretical survival curves were calculated with the assumption of a constant but less than 100% level of SD repair. Experimental data correlated well with these calculated curves. There were only very small differences in survival after the different multiple fractions per day regimens. Survival after irradiation at a dose rate of 1.00 Gy/hr was found to be similar to that after multiple fractions per day.

Analysis of prognostic factors in patients with pyeloureteral carcinoma.

Clinicopathological parameters and therapeutic results of 100 patients with primary pyeloureteral cancers were examined, and prognostic factors were identified by monovariable and multivariable analyses. For the whole group, the 5- and 10-year survival rates were 57.0% and 44.8%, respectively. The site-specific 5-year survival rates were 61.0% for pelvic cancer, 51.9% for ureteral cancer, and 61.7% for pyeloureteral cancer, showing no significant differences among the sites. Monovariable analysis indicated age, tumor form, and histological stage and grade as important prognostic factors. Using multivariable analysis, concurrence of bladder cancer, age, histological stage, radiotherapy, surgery, chemotherapy, and histological grade were shown to be prognostic factors, given in order of decreasing importance. Age and histological stage, which were common to the results of both analyses, were considered to be most important as prognostic factors.

Monoarthritis secondary to joint metastasis. Two case reports and literature review.

Synovial metastases from neoplasms are uncommon. We report two cases of knee monoarthritis due to joint metastasis. Joint fluid cytology established the diagnosis. In one patient, an epidermoid carcinoma of the ureter metastasized to the left knee. The other patient had chronic monoarthritis of the left knee unresponsive to conventional treatment and was found to have distal femoral metastases from a lung adenocarcinoma. Only 28 cases of synovial metastases from solid tumors have been reported in the literature. The knee is the most common target, the lung the most common site of the primary (12 cases), and adenocarcinoma the most common histological type (12 cases). Joint metastasis carries a poor prognosis with a mean survival of less than 5 months.

[Value of postoperative radiotherapy in malignant tumors of the upper urinary tract. Apropos of a series of 26 patients]. / Intérêt de la radiothérapie postopératoire dans les tumeurs malignes de la voie excrétrice supérieure. A propos d'une série de 26 patients.

To evaluate the role of adjuvant radiation therapy in invasive transitional cell carcinoma of the upper urinary tract, we retrospectively reviewed a series of 26 patients who underwent radical surgery plus post-operative prophylactic irradiation for such a tumor. Between 1980 and October 1993, 18 men and eight women (mean age: 65 +/- 9 years) were treated for an invasive transitional cell carcinoma of the upper urinary tract. Tumor location was the renal pelvis in 15 patients (58%). The tumor was pathological stage B in 11 patients (42%) and stage C in 15 patients (58%). Tumor grade was 2 in ten patients, 3 in 15 and unknown in one. Nine patients had node involvement. All patients underwent surgery followed by radiation therapy to a total dose of 45 Gy to the tumor bed (23 patients) and/or regional nodes (18 patients). After a mean follow-up of 45 months, 13 patients (50%) were alive and 11 were disease-free. Local tumor relapse, nodal recurrence, metastasis and second urothelial location were noted in one, four (15%), 14 (54%) and eight patients (30%) respectively. Overall 5-year survival and 5-year disease-free survival were 49% and 30% respectively. Overall 5-year survival rates were 60% for stage B and 19% for stage C disease (P = 0.07), 43% for node-negative versus 15% for node-positive cancer (P = 0.04) and 90% for grade 2 and 0% for grade 3 tumors (P < 0.01). In this study using a radio-surgical approach, local control of disease and survival were similar to those reported previously in surgical series. Prophylactic post-operative radiation therapy is not recommended.

[Post-radiation duodenal ulceration treated with hyperbaric oxygen]. / Ulcération duodénale post-radique traitée par oxygène hyperbare.

Radiation enteric disorders are rare and difficult to treat. A case of radiation duodenitis treated by hyperbaric oxygen is reported. A sixty-year-old man underwent right nephroureterectomy, chemotherapy (platin and 5 fluorouracil) and radiation therapy (54 Gy) for excretory urinary carcinoma. Six months later, even though he was under omeprazole therapy for reflux oesophagitis, he experienced antroduodenitis, duodenal ulceration, and duodenal telangiectasia. Symptoms and duodenal ulcer disappeared 2 months later with hyperbaric oxygen (10 one hour sessions at 2 ATA). Most likely, hyperbaric oxygen can reduce the consequences of obliterative endarteritis due to irradiation, responsible for ischaemia and fibrosis later on.

[Radiotherapy of kidney pelvis and ureteral cancers]. / Strahlentherapie bei Nierenbecken- und Ureterkarzinomen.

The indications and possibilities of radiotherapy in carcinomas of the renal pelvis and the ureter are demonstrated. Based on the literature and our own experience in 22 cases, postoperative radiotherapy should be performed in cases of deep infiltrating carcinomas, after subtotal surgery, and in cases with lymph node metastases. The radiation dose applied should be 50-55 Gy to the tumor bed and 45 (-50) Gy to the regional lymph nodes. Local recurrences can be greatly diminished without severe complications. Therefore, postoperative radiotherapy in carcinomas of the renal pelvis and the ureter can be recommended.

[Reconstructive surgery of the efferent urinary tract in pelvic exenteration of gynecological tumors]. / Rekonstruktive Chirurgie der ableitenden Harnwege bei exenterativer Resektion gynäkologischer Tumoren.

In locally advanced or recurrent tumors of the female genital tract anterior or total exenteration may be mandatory in case of tumor invasion into the lower urinary tract or if a second course of radiation therapy is not feasible. The management of resection and reconstruction of the affected lower urinary tract has to be well integrated into the gynecological therapeutic concept. In 11/32 patients the reconstruction of the partially resected lower urinary tract was feasible with preservation of a functionally intact urinary bladder. Urinary diversion following pelvic exenteration was achieved in 13/17 patients with a continent urinary reservoir and in 4/17 patients with an ileal conduit. Operative reinterventions were needed only in patients with continent urinary diversion in 5 cases. All these patients had a past history of primary radiation therapy of their gynecological tumor. In the remaining other 11 patients with a history of primary radiation therapy no complications occurred. 9 of 32 patients survived the operative procedure 40.8 (25-57) month with no evidence of recurrent tumor. Continent urinary diversion represents an excellent therapeutic option for replacement of function lost due to exenterative pelvic surgery. Stringent selection of patients is mandatory to consider the presented therapeutic concept a reasonable tool in the management of the described clinical situations.

[Primary sarcomatoid carcinoma of the ureter]. / Primäres sarkomatoides Karzinom des Ureters.

INTRODUCTION: We present a case of unusually rapid tumor progression in a patient with primary sarcomatoid carcinoma of the ureter. CASE REPORT: An 82-year-old female patient underwent total nephroureterectomy for a ureteral tumor that turned out to be a primary sarcomatoid carcinoma of the ureter. After a normal postoperative course, the patient developed a metastatic symptomatic that seemed to have appeared "like an explosion" on the 33rd p. o. day. She died shortly thereafter. CONCLUSION: This is the second case of primary sarcomatoid carcinoma of the ureter published in the literature, a rare and aggressive variant of urothelial carcinoma with a highly malignant potential. As no effective adjuvant treatment has been reported as yet, we recommend mandatory radical excision of the sarcomatoid tumor and early postoperative radiation therapy to increase survival.