Tumor cell-based glycolytic metabolism and single-cell sequencing of urinary exfoliated cells for the diagnosis and molecular profiling of urothelial carcinoma / 中华病理学杂志

Objective: To explore the diagnostic values of HK2 testing and single-cell sequencing in the urothelial carcinoma (UC). Methods: The qualified urine specimens of 265 suspected UC patients or postoperative patients from the Cancer Hospital of Chinese Academy of Medical Sciences, Beijing, China were collected. Both exfoliative cytology and HK2 testing were performed on clinically suspected UC or postoperative patients. The performance of diagnostic cytology and HK2, including consistency, sensitivity, specificity, positive predictive value and negative predictive value, was evaluated based on histopathological, clinical and imaging diagnosis. Isolated HK2 metabolically abnormal cells were subject to single-cell sequencing to verify the reliability of HK2 detection performance and to explore the molecular characteristics of UC. Results: The concordance rate of HK2 testing and cytology for detecting UC was 90.3% (102/113, Kappa=0.604). Compared with cytology, the sensitivity of HK2 was significantly higher (85.2% versus 75.6%, P=0.024). The detection sensitivity of combined HK2 testing and cytology was increased to 91.1%. HK2 testing was significantly more sensitive than cytology for diagnosing UC in the upper urinary tract (81.8% versus 65.5%, P=0.022). It was also more sensitive than cytology for diagnosing early-stage UC (82.6% versus 69.5%, P=0.375) and low-grade UC (69.6% versus 47.8%, P=0.125). Single-cell sequencing of the ten patients, whose samples were positive for HK2, demonstrated highly concordant copy number variations (CNVs) in tumor cells from the same UC patient, with heterogeneity in CNV profiles among different patients. Deletion of chromosome 8p was found in 3 of the 4 urine samples of renal pelvis UC. The 2 patients with benign lesions had no CNVs in all sequenced cells. Conclusions: The test for abnormal urinary glycolytic HK2 metabolism can assist urine cytology to improve the sensitivity of UC diagnosis, and it provides a novel and reliable approach for early detection of upper urinary tract UC and lower grade UC. Meanwhile, this study has preliminarily revealed the feasibility of single-cell sequencing in urinary samples, which is expected to improve the diagnostic specificity of HK2 testing.

Clinicopathological Features of Primary Small Cell Neuroendocrine Carcinoma of the Bladder / 中国医学科学院学报

Objective To investigate the clinicopathological features,immunohistochemical features,diagnosis,and relationship with sporadic prostate cancer in primary small cell neuroendocrine carcinoma of the bladder. Methods We retrospectively analyzed the clinical characteristics of 12 patients with primary small cell neuroendocrine carcinoma of the bladder diagnosed at Beijing Chao-Yang Hospital affiliated to Capital Medical University from January 2013 to September 2022.The histological features of primary small cell neuroendocrine carcinoma of the bladder were re-evaluated by two pathologists according to the 2022 revision of the World Health Organization Classification of Tumors of the Urinary System and Male Genital Organs.Electronic medical records were retrieved,and telephone follow-up was conducted from the time of histopathological diagnosis to the death or the end of the last follow-up until January 31,2023. Results The 12 patients include 7 patients in pT3 stage and 1 patient in pT4 stage.Eight patients were complicated with other types of tumors,such as high-grade urothelial carcinoma of the bladder and squamous cell carcinoma.Five patients had sporadic prostate cancer.Immunohistochemical staining showed that 12 (100.0%),10 (83.3%),and 8 (66.7%) patients were tested positive for CD56,Syn,and CgA,respectively.The Ki67 proliferation index ranged from 80% to 90%.Five patients with urothelial carcinoma were tested positive for CK20,GATA3,and CK7.P504S was positive in all the 5 patients with prostate cancer,while P63 and 34βE12 were negative.The follow-up of the 12 patients lasted for 3-60 months.Eight of these patients died during follow-up,with the median survival of 15.5 months.Four patients survived. Conclusions Primary small cell neuroendocrine carcinoma of the bladder is a rare urological tumor with high aggressiveness and poor prognosis.In male patients with bladder prostatectomy,all prostate tissue should be sampled.If prostate cancer is detected,the prostate-specific antigen level should be monitored.

A novel upper tract ureteroscopic biopsy technique: the "form tackle"

ABSTRACT Introduction and Objective: Upper tract urothelial carcinoma (UTUC) represents 5% of all urothelial malignancies (1-3). Accurate pathologic diagnosis is key and may direct treatment decisions. Current ureteroscopic biopsy techniques include cold-cup, backloaded cold-cup and stone basket (4-6). The study objective was to compare a standard cold-cup biopsy technique to a novel cold-cup biopsy technique and evaluate histopathologic results. Materials and Methods: We developed a novel UTUC biopsy technique termed the "form tackle" biopsy. Ureteroscope is passed into ureter/renal collecting system. Cold-cup forceps are opened and pressed into the lesion base (to engage the urothelial wall/submucosal tissue) then closed. Ureteroscope/forceps are advanced forward 3-10mm and then extracted from the patient. We compared standard versus novel upper tract biopsy techniques in a series of patients with lesions ≥1cm. In each procedure, two standard and two novel biopsies were obtained from the same lesion. The primary study aim was diagnosis of malignancy. IRB approved: 21-006907. Results: Fourteen procedures performed on 12 patients between June 2020 and March 2021. Twenty-eight specimens sent (14 standard, 14 novel) (Two biopsies per specimen). Ten procedures with concordant pathology. In 4 procedures the novel biopsy technique resulted in a diagnosis of UTUC (2 high-grade, 2 low-grade) in the setting of a benign standard biopsy. Significant difference in pathologic diagnoses was detected between standard and novel upper tract biopsy techniques (p=0.008). Conclusions: The "form tackle" upper tract ureteroscopic biopsy technique provides higher tissue yield which may increase diagnostic accuracy. Further study on additional patients required. Early results are encouraging.

Tabaquismo y tumores mayores de 2 centímetros son predictores de mortalidad en pacientes sometidos a nefro-ureterectomías por carcinoma de urotelio alto / Prognostic factors in patients with upper urinary tract urothelial carcinoma undergoing nephro-ureterectomy

BACKGROUND: Upper urinary tract urothelial carcinoma (UTUC) represents 5-10% of urothelial carcinomas. It is managed with nephroureterectomy (NUR); however, kidney-sparing techniques are growingly used. AIM: To report the results of a 20-year series of NUR conducted in an academic center. Patients and Methods: Review of clinical and pathological characteristics of patients undergoing NUR between 1999 and 2020. Patients were followed for 63 months. Global survival curves (OS) and mortality predictors were established through Cox regression. RESULTS: We included 90 patients with a median age of 68 years undergoing NUR, of whom 68 (75%) had a pelvic tumor and 22 (25%) had a proximal ureteral tumor. A laparoscopic NUR was performed in 60 patients (66%). Thirty-three patients (37%) had tumors confined to the urothelium (pTa), penetrating the lamina propria (pT1) or carcinoma in situ (CIS), 10 patients (11%) had a tumor spreading to the muscle layer (pT2) and 47 (52%) had a tumor spreading to nearby organs (pT3 / T4). Average tumor size was 3.69 cm, nodal disease (pN) was present 12 patients (13%). Twelve patients (13%) received adjuvant chemotherapy. A higher mortality was observed among smokers (Hazard ratio (HR) 8.79, 95% confidence intervals (CI) 1.5-49.0, p = 0.01), patients with tumors classfied as pT≥ 2 (HR 1.09, 95% CI 0.01-1.0, p = 0.04) and those with tumors larger than 2 cm (HR 14.79, CI 95% 1.5-272, p = 0.01). CONCLUSIONS: Smoking patients, those with invasive tumors (T2-T4) and greater than 2 cm have higher mortality. Therefore, they should not be candidates for conservative management.

Fibroblast growth factor receptor 3 gene (FGFR3) mutations in high-grade muscle-invasive urothelial bladder cancer in a Brazilian population: evaluation and prevalence

ABSTRACT Objective To understand the feasibility of FGFR3 tests in the Brazilian public health context, and to sample the mutational burden of this receptor in high-grade muscle invasive bladder cancer. Methods A total of 31 patients with high-grade muscle-invasive bladder cancer were included in the present study. Either transurethral resection of bladder tumor or radical cystectomy specimens were analyzed. Formalin-fixed paraffin-embedded tissue blocks were sectioned, hematoxylin and eosin stained, and histologic sections were reviewed. Total RNA was extracted using the RNeasy DSP formalin-fixed paraffin-embedded kit. Qualitative results were displayed in Rotor-Gene AssayManager software. Results Six patients were excluded. From the samples analyzed, four (16.7%) were considered inadequate and could not have their RNA extracted. Two patients presented FGFR3 mutations, accounting for 9.5% of material available for adequate analysis. The two mutations detected included a Y373C mutation in a male patient and a S249C mutation in a female patient. Conclusion FGFR3 mutations could be analyzed in 84% of our cohort and occurred in 9.5% of patients with high-grade muscle invasive bladder cancer in this Brazilian population. FGFR3 gene mutations are targets for therapeutic drugs in muscle-invasive bladder cancer. For this reason, know the frequency of these mutations can have a significant impact on public health policies and costs provisioning.

Synchronous presentation of muscle-invasive urothelial carcinoma of bladder and peritoneal malign mesothelioma

ABSTRACT Introduction Cancer is one of the most important leading cause of death in man and woman in the world. The occurrence of new cancer has become more frequent in recent years due to strict screening protocols and occupational and environmental exposure to carcinogens. The incidence of secondary malignancies has also increased due to close medical follow-up and advanced age. Herein, we report a case and its management diagnosed as synchronous peritoneal malignant mesothelioma and muscle-invasive urothelial carcinoma. Case Description A 71-year-old male presented with macroscopic hematuria and abdominal distension increasing gradually. A contrast enhanced computerized tomography demonstrated bladder mass and diffuse ascites with nodular peritoneal thickening and umbilical mass. He was treated with the multidisciplinary team working including urologist, medical oncologist and general surgeon. Conclusions To our knowledge, this is the first case of peritoneal malign mesothelioma with synchronous muscle-invasive urothelial carcinoma. Because of the rarity of this condition, there is still no consensus on the definitive treatment protocols, yet. Individualized treatment with multidisciplinary close follow-up might improve the survival outcomes.

Can Neutrophil-to-Lymphocyte ratio predict the response to BCG in high-risk non muscle invasive bladder cancer?

ABSTRACT Objectives: To evaluate the neutrophil-to-lymphocyte ratio (NLR) as a prognostic factor for response of high risk non muscle invasive bladder cancer (HRNMIBC) treated with BCG therapy. Materials and Methods: Between March 2010 and February 2014 in a tertiary center 100 consecutive patients with newly diagnosed HRNMIBC were retrospectively analyzed. Patients were divided according to NLR value: 46 patients with NLR value less than 3 (NLR < 3 group), and 54 patients with NLR value more than 3 (NLR ≥ 3 group). At the end of follow-up 52 patients were high grade disease free (BCG-responder group) and 48 patients underwent radical cystectomy for high grade recurrence or progression to muscle invasive disease (BCG non-responder group). The average follow-up was 60 months. Intervention: analysis and correlation of preoperative NLR value with response to BCG in terms of recurrence and progression. Results: The optimal cut-off for NLR was ≥ 3 according to the receiver operating characteristics analysis (AUC 0.760, 95% CI, 0.669-0.850). Mean NLR value was 3.65 ± 1.16 in BCG non-responder group and 2.61 ± 0.77 in BCG responder group (p = 0.01). NLR correlated with recurrence (r = 0.55, p = 0.01) and progression risk scores (r = 0.49, p = 0.01). In multivariate analysis, NLR (p = 0.02) and EORTC recurrence risk groups (p = 0.01) were associated to the primary endpoint. The log-rank test showed statistically significant difference between NLR < 3 and NLR ≥ 3 curves (p < 0.05). Conclusions: NLR value preoperatively evaluated could be a useful tool to predict BCG response of HRNMIBC. These results could lead to the development of prospective studies to assess the real prognostic value of NLR in HRNMIBC.

Overexpression of UHRF1 gene correlates with the major clinicopathological parameters in urinary bladder cancer

ABSTRACT Introduction Recently, expression of the UHRF1 gene was found to be up-regulated in numerous neoplasms, including the urinary bladder transitional cell carcinoma (TCC). Objective The aim of our study was to determine if the expression levels of UHRF1 gene correlates with the major pathological characteristics of the tumor and patients’ clinical outcome. Materials and Methods In our study, we have analyzed the tissue samples derived from group of 70 patients with histologically confirmed TCC of the urinary bladder, while normal urinary bladder mucosa obtained from 40 patients with nonmalignant diseases was used as a negative control group. Expression of UHRF1 gene in each patient sample was determined using reverse transcriptase-polymerase chain reaction. Results UHRF1 gene expression was found to be app. 2.5 times higher in samples from patients with TCC in comparison with normal epithelium derived from control group patients. Analysis show that gene expression correlates with the malignancy of the tumor. A highly significant differences were found between the expression values of samples from low and high grade TCC, as well as between the high grade and control group. UHRF1 expression was higher in patients with non-muscle invasive disease than in those with muscle invasive disease. Conclusions The result of this study indicates that UHRF1 gene expression levels correlates with the major pathological characteristics of TCC samples and with the clinical outcome of those patients. Determination of UHRF1 gene expression could have a potential to be used as a sensitive molecular marker in patients with urinary bladder cancer.

Radical cystectomy with pelvic lymphadenectomy: pathologic, operative and morbidity outcomes in a Brazilian cohort

ABSTRACT Introduction and Objective Radical cystectomy (RC) with pelvic lymph node dissection is the standard treatment for muscle invasive bladder cancer and the oncologic outcomes following it are directly related to disease pathology and surgical technique. Therefore, we sought to analyze these features in a cohort from a Brazilian tertiary oncologic center and try to identify those who could negatively impact on the disease control. Patients and Methods We identified 128 patients submitted to radical cystectomy, for bladder cancer treatment, from January 2009 to July 2012 in one oncology tertiary referral public center (Mario Penna Institute, Belo Horizonte, Brazil). We retrospectively analyzed the findings obtained from their pathologic report and assessed the complications within 30 days of surgery. Results We showed similar pathologic and surgical findings compared to other large series from the literature, however our patients presented with a slightly higher rate of pT4 disease. Positive surgical margins were found in 2/128 patients (1.5%). The medium number of lymph nodes dissected were 15. Major complications (Clavien 3 to 5) within 30 days of cystectomy occurred in 33/128 (25.7%) patients. Conclusions In the management of invasive bladder cancer, efforts should focus on proper disease diagnosis and staging, and, thereafter, correct treatment based on pathologic findings. Furthermore, extended LND should be performed in all patients with RC indication. A critical analysis of our complications in a future study will help us to identify and modify some of the factors associated with surgical morbidity.

Is [F-18]-fluorodeoxyglucose FDG-PET/CT better than ct alone for the preoperative lymph node staging of muscle invasive bladder cancer?

ABSTRACT Objective: To evaluate whether the use of [F-18]-FDG-PET/CT can accurately predict pelvic lymph node metastasis in patients with muscle invasive TCC of the bladder undergoing radical cystectomy. Materials and Methods: Fifteen patients with muscle invasive bladder cancer had undergone FDG-PET/CT scan from the skull base to the mid-thighs after IV injection of 6.5MBq (Mega-Becquerel)/Kg of FDG. After intravenous hydration IV furosemide was given to overcome the difficulties posed by urinary excretion of 18F-FDG. PET/CT data were analyzed as PET and CT images studied separately as well as fused PET/CT images. The imaging findings were correlated with the histopathology of the nodes (gold standard). Results: CT and FDG-PET had demonstrated positive lymph nodes in 9 & 8 patients respectively. Among the 15 patients 3 had documented metastasis on histopathology. Both CT and PET could detect the nodes in all these 3 patients (100% sensitivity). Nodes were histologically negative amongst 6&5 patients who had node involvement by CT and PET respectively. Therefore, specificity, positive predictive value (PPV) & negative predictive value (NPV) for CT and PET/CT were 50%, 33.3%, 100% and 58.3%, 37.5%, 100% respectively. Conclusion: The theoretical advantage of this cutting edge technology for whole body imaging has not been translated into clinical practice as we found minimal advantage of combined FDG-PET/CT over CT alone for nodal staging of muscle invasive bladder cancer. This may be due to substantial overlap between standardized uptake values (SUVs) from active inflammatory processes with those of malignant lesion.

Low grade urothelial carcinoma mimicking basal cell hyperplasia and transitional metaplasia in needle prostate biopsy

ABSTRACT Purpose The vast majority of urothelial carcinomas infiltrating the bladder are consistent with high-grade tumors that can be easily recognized as malignant in needle prostatic biopsies. In contrast, the histological changes of low-grade urothelial carcinomas in this kind of biopsy have not been studied. Materials and Methods We describe the clinicopathologic features of two patients with low-grade bladder carcinomas infiltrating the prostate. They reported dysuria and hematuria. Both had a slight elevation of the prostate specific antigen and induration of the prostatic lobes. Needle biopsies were performed. At endoscopy bladder tumors were found in both cases. Results Both biopsies showed nests of basophilic cells and cells with perinuclear clearing and slight atypia infiltrating acini and small prostatic ducts. The stroma exhibited extensive desmoplasia and chronic inflammation. The original diagnosis was basal cell hyperplasia and transitional metaplasia. The bladder tumors also showed low-grade urothelial carcinoma. In one case, the neoplasm infiltrated the lamina propria, and in another, the muscle layer. In both, a transurethral resection was performed for obstructive urinary symptoms. The neoplasms were positive for high molecular weight keratin (34BetaE12) and thrombomodulin. No metastases were found in either of the patients, and one of them has survived for five years. Conclusions The diagnosis of low-grade urothelial carcinoma in prostate needle biopsies is difficult and may simulate benign prostate lesions including basal cell hyperplasia and urothelial metaplasia. It is crucial to recognize low-grade urothelial carcinoma in needle biopsies because only an early diagnosis and aggressive treatment can improve the prognosis for these patients.

Cutaneous invasion from sarcomatoid urothelial carcinoma: clinical and dermatopathologic features

Abstract In Brazil, without considering the non-melanoma skin tumors, bladder cancer in men is the eighth most common, and the urothelial carcinoma or transitional cell carcinoma is the most common among these. Cutaneous metastases from urothelial neoplasms appear as single or multiple erythematous, infiltrated nodules or plaques, and like other cases of distant disease, it is indicative of poor prognosis. The invasive urothelial carcinoma is recognized for its ability to present divergent differentiation and morphological variants. The sarcomatoid urothelial carcinoma is a rare cancer that consists of two different components: one composed of epithelial tissue and the other with sarcomatoid features of mesenchymal origin. The authors describe a case of cutaneous metastasis of sarcomatoid urothelial carcinoma in a 63-year-old male patient.

Adjuvant chemotherapy for locally advanced upper tract urothelial carcinoma: updated results of the Seoul National university hospital experience

Objectives: The objective of this study was to update the long-term outcome in the treatment of locally advanced upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU) regarding the role of adjuvant chemotherapy. Materials and methods: Clinical data from 138 patients who underwent RNU for locally advanced UTUC (pT3/4 or pN+) were analyzed. Results: The adjuvant chemotherapy group comprised 66 patients, and other 72 patients did not receive adjuvant chemotherapy. Cisplatin-based chemotherapy was the most common regimen, depending on the patient's eligibility and renal function. The median follow-up period was 48.7 months (interquartile range: 29.2-96.9 months). The 3-and 5-year disease-specific survival (DSS) rates were 76.0% and 69.9% for the non-adjuvant chemotherapy group versus 74.6% and 54.5% for the adjuvant chemotherapy group (p=0.301, log-rank test). Overall survival (OS) rates for the same time period were 70.1% and 62.9% for the non-adjuvant chemotherapy group versus 73.8% and 53.2% for the adjuvant chemotherapy group (p=0.931, log-rank test). On multivariate analysis, adjuvant chemotherapy could not predict DSS and OS after surgery. When patients who received cisplatin-based adjuvant chemotherapy (n=59) were compared to those who did not receive adjuvant chemotherapy, similar results were found. Conclusions: There does not appear to be a significant DSS or OS benefit associated with adjuvant chemotherapy. Prospective randomized clinical trials are necessary to verify the effect of adjuvant chemotherapy on locally advanced UTUC.

Clinical significance of serum and urinary HER2/neu protein levels in primary non-muscle invasive bladder cancer

Objective: We aimed to compare serum and urinary HER2/neu levels between healthy control group and patients with non-muscle invasive bladder cancer. Additionally, we evaluated relationship of HER2/neu levels with tumor stage, grade, recurrence and progression. Materials and Methods: Fourty-four patients with primary non-muscle invasive bladder tumors (Group 2) and 40 healthy control group (Group 1) were included the study. Blood and urinary samples were collected from all patients and HER2/neu levels were measured by ELISA method. Blood and urinary HER2/neu levels and additionally, ratio of urinary HER2/neu levels to urinary creatinine levels were recorded. Demographic data and tumor characteristics were recorded. Results: Mean serum HER2/neu levels were similar between two groups and statistically significant difference wasn't observed. Urinary HER2/neu levels were significantly higher in group 2 than group 1. Ratio of urinary HER2/neu to urinary creatinine was significantly higher in group 2 than group 1, (p=0,021). Serum and urinary HER2/ neu levels were not associated with tumor stage, grade, recurrence and progression while ratio of urinary HER2/neu to urinary creatinin levels were significantly higher in high-grade tumors. HER2/neu, the sensitivity of the test was found to be 20.5%, and the specificity was 97.5%, also for the urinary HER2/neu/urinary creatinine ratio, the sensitivity and specificity of the test were found to be 31.8% and 87.5%, respectively. Conclusions: Urinary HER2/neu and ratio of urinary creatinine urine were significantly higher in patients with bladder cancer compared to healthy subjects. Large series and controlled studies are needed for use as a tumor marker.

Prognostic impact of preoperative statin use after radical nephroureterectomy for upper urinary tract urothelial carcinoma

PURPOSE: The objective was to investigate the impact of statin use on prognosis after radical nephroureterectomy for upper urinary tract urothelial carcinoma (UTUC). MATERIALS AND METHODS: A retrospective review of medical records identified 277 patients who underwent radical nephroureterectomy for primary UTUC at Asan Medical Center between January 2006 and December 2011. Information on preoperative statin use was obtained from patient charts in an electronic database. We assessed the impact of statin use on recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). RESULTS: Of these 277 patients, 62 (22.4%) were taking statin medications. Compared to the statin nonusers, the statin users were older, had a higher body mass index, and had higher rates of cardiovascular disease and diabetes. The 5-year RFS rates of statin users and nonusers were 78.5% and 72.5%, respectively (p=0.528); the 5-year CSS rates were 85.6% and 77.7%, respectively (p=0.516); and the 5-year OS rates were 74.5% and 71.4%, respectively (p=0.945). In the multivariate analysis, statin use was not an independent prognostic factor for RFS (hazard ratio, 0.47; p=0.056), CSS (hazard ratio, 0.46; p=0.093), or OS (hazard ratio, 0.59; p=0.144) in patients who underwent radical nephroureterectomy for UTUC. CONCLUSIONS: Statin use was not associated with improved RFS, CSS, or OS in the sample population of patients with UTUC.

Predictors of Intravesical Recurrence After Radical Nephroureterectomy for Upper Urinary Tract Urothelial Carcinoma: An Inflammation-Based Prognostic Score

PURPOSE: Systemic inflammatory responses, which are defined in terms of the Glasgow prognostic score (GPS), have been reported to be independent predictors of unfavorable outcomes in various human cancers. We assessed the utility of the GPS as a predictor of intravesical recurrence after radical nephroureterectomy (RNU) in upper urinary tract carcinoma (UTUC). MATERIALS AND METHODS: We collected data for 147 UTUC patients with no previous history of bladder cancer who underwent RNU from 2004 to 2012. Associations between perioperative clinicopathological variables and intravesical recurrence were analyzed by using univariate and multivariate Cox regression models. RESULTS: Overall, 71 of 147 patients (48%) developed intravesical recurrence, including 21 patients (30%) diagnosed with synchronous bladder tumor. In the univariate analysis, performance status, diabetes mellitus (DM), serum albumin, C-reactive protein, GPS, and synchronous bladder tumor were associated with intravesical recurrence. In the multivariate analysis, performance status (hazard ratio [HR], 2.33; 95% confidence interval [CI], 1.41-3.85; p=0.001), DM (HR, 2.04; 95% CI, 1.21-3.41; p=0.007), cortical thinning (HR, 2.01; 95% CI, 1.08-3.71; p=0.026), and GPS (score of 1: HR, 6.86; 95% CI, 3.69-12.7; p=0.001; score of 2: HR, 5.96; 95% CI, 3.10-11.4; p=0.001) were independent predictors of intravesical recurrence. CONCLUSIONS: Our results suggest that the GPS as well as performance status, DM, and cortical thinning are associated with intravesical recurrence after RNU. Thus, more careful follow-up, coupled with postoperative intravesical therapy to avoid bladder recurrence, should be considered in these patients.

Delayed Ureterectomy after Incomplete Nephroureterectomy for Upper Tract Urothelial Carcinoma: Pathologic Findings and Outcomes

Objectives To evaluate the pathologic findings and outcomes after distal ureterectomy for a retained ureteral segment following incomplete nephroureterectomy for urothelial carcinoma of the renal pelvis or ureter. Materials and Methods After IRB approval, an institutional database identified patients who underwent distal ureterectomy for a retained ureteral segment after assumed complete nephroureterectomy for urothelial carcinoma of the upper ureter or renal pelvis. Clinical and pathologic variables were analyzed. Results From January 1993 to July 2007, 12 patients were identified with median age at the time of ureterectomy of 60.5 years (41-85 years). Initial approach to surgery was open in 9 patients and laparoscopic in 3 patients. The median time from nephroureterectomy to distal ureterectomy was 23.5 months (range 2-66). At the time of initial surgery, pathologic stage was Ta, T1, T2, and T3 in 3,4,1, and 4 patients respectively. Initial pathology was urothelial carcinoma; grade 2 in 6 patients and grade 3 in six patients. Pathology from the subsequent surgery demonstrated urothelial carcinoma in the retained ureteral segment in 8 patients, dysplasia or atypia in 3 patients, and 1 patient with chronic inflammation. Local recurrence in 2 patients was present in a segment of ureter discontinuous with the bladder after laparoscopic nephroureterectomy. Three patients (25%), all with initial grade 3 renal pelvis lesions, developed metastatic disease. Conclusions Tumor recurrence in a retained ureteral segment after incomplete nephroureterectomy is a significant problem and may contribute to intravesical recurrence or metastatic disease. Complete, en bloc resection is imperative to minimize these risks. .

Is TURBT able to cure high risk recurrent superficial or muscle invasive bladder cancer: Factors resulting in pT0 radical cystectomy specimens

Purpose In 76% of radical cystectomy patients there is discrepancy between the initial stage at transurethral resection and the final pathological stage of the cystectomy specimen. More specifically in contemporary series the absence of tumor at radical cystectomy specimens (stage pT0) is estimated at 5-25%. Our aim was to determine which factors contributed to the absence of tumor in our series of radical cystectomy patients. Materials and Methods Fifty one patients were submitted to radical cystectomy in our department over the last 10 years (January 2002-January 2012). A thorough analysis of the patients' files with no residual tumor on the cystectomy specimen (pT0) was performed. Possible factors contributing to such a result were described and a systematic analysis of the relevant literature was performed. Results Five patients had a pT0 stage after radical cystectomy. Four of them had transitional cell carcinoma and one of them had squamous cell carcinoma of the bladder on the initial transurethral resection. None of the tumors presented lymphovascular invasion. Four patients are still alive and one died 45 months postoperatively from a cardiac cause. Conclusions Four factors were identified in our study to contribute towards a pT0 cystectomy result. Those included the absence of lymphovascular invasion, the completeness of transurethral resection, the experience of the surgeon and the use of a standardized technique for the transurethral resection. The time to cystectomy in our series did not have a negative effect on pT0 final pathology result. .

role of tri-modality treatment in bladder preservation of invasive bladder carcinoma: turt,concurrent irradiation and twice weekly gemcitabine

This study was conducted to evaluate the efficacy of transurethral resection plus chemo radiation in achieving bladder preservation, using conformal radiotherapy and twice weekly Gemcitabine. Thirty seven TCC patients with good performance status, and maximum possible transuretheral resection .They received. 46 GY/23 fractions with twice weekly Gemcitabine 30mg/m2. An evaluation was done after 2 weeks by cystoscopy and biopsy from the tumor bed. Patients who had a complete response continued in phase II, 20 GY/2 weeks, with twice weekly Gemcitabine 30 mg/m2. Patients who had invasive bladder cancer were subjected to radical cvsteclomy. Thirty two patients had complete response. Treatment schedule was tolerable. It was associated with moderate toxicity that was tolerable apart of patients who developed G3 wxicity [hat required treatment interruption till improvement .After 2 years of follow up, 29 patients achieved good local control and the 2 years LRFS was 79%. The 2 years over al survival and bladder intact survival was 70%, 69%, respectively. Trimodality bladder-sparing approach consists of inmsureihral resection, chemotherapy twice daily using gemcitabine and radiotherapy is well tolerated with high rate of bladder preservation. This approach can be considered a reasonable alternative to cystectomy in the proper selected group

Metástasis gástricas: un hallazgo no solo de autopsias / [Gastric metastases: not only identified at autopsies].

Metastases to the stomach from an extra-digestive neoplasm are an unusual event, identified in less than 2

of cancer patients at autopsy (between 1.7

). The stomach may be involved by hematogenous spread from a distant primary tumor (most commonly lung, breast and melanoma). Tumors of neighboring organs, such as esophagus, pancreas and gallbladder, may reach the stomach by continuity or by lymphatic-hematogenous spread. Endoscopic routine studies with biopsies have improved the diagnosis of this pathology. Nevertheless, in some cases the histologic study is a false negative because the neoplasia can be placed in the deepest layers of the stomach. We report the case of a 56-year-old man who presented a gastric metastasis of a high gradeuro thelial carcinoma of urinary bladder and we review the literature.