Renal Cell Carcinoma With Tumor Thrombus: A Case Series in Puerto Rico.

INTRODUCTION:  Renal cell carcinoma (RCC) is one of the most common types of kidney cancer. While RCC tends to present as a localized tumor, a notable proportion may present with distant metastasis. In some instances, RCC may also present with intravascular tumor extension, often called tumor thrombus (TT). Its presence confers a worse prognosis and has important implications for the tumor's staging and treatment. Despite extensive documentation of RCC TT in the US, limited data exists regarding its presentation, management, and outcomes in Puerto Rico (PR). This study aims to broaden the available information on RCC TT, emphasizing surgical management and outcomes. We also provide descriptive data on patient demographics and clinical presentation to improve decision-making among clinicians caring for Puerto Rican men and women. METHODS:  In this single-center, retrospective study, we evaluated patients who underwent partial or total nephrectomy at Saint Luke's Episcopal Medical Center between 2018 and 2022. Data was abstracted from electronic health records (EHR). Patients without documented evidence of TT during the peri-operative period were excluded from the study. A total of 220 patient records were evaluated, of which 12 met the inclusion criteria for the study. Cases were categorized using the latest RCC TT guidelines. Central tendency measurements were used to describe the sample distribution. The mean was considered to make assumptions regarding the prevalent observations, and the median was considered to rule out possible outliers. Categorical data were evaluated using proportion analyses, including TT extension level and BMI variables. Fisher's exact test evaluated the association between the World Health Organization/International Society of Urological Pathology (WHO/ISUP) grade and TT extension level. RESULTS:  Most patients lacked TT-related symptoms. The most severe presenting symptom was a pulmonary embolism (8.3%). Hypertension (83.3%), BMI greater than 25 at the time of diagnosis (75%), and type 2 diabetes mellitus (66.7%) were the most common comorbid conditions within our cohort. Nearly 75% of patients underwent laparoscopic radical nephrectomy with TT resection. One left-sided level III case was managed by laparoscopic-assisted open radical nephrectomy with a right subcostal incision. There were zero intraoperative complications and two postoperative complications. The histopathological reports of all cases were consistent with clear cell carcinoma, and half of the cases (n=6) were WHO/ISUP G4. All patients are alive and free of disease. CONCLUSION:  RCC is a common renal neoplasm in PR that can present with intravascular tumor extension. Our findings do not establish a definitive association between BMI, tumor size, WHO/ISUP grading, and TT extension level. Our study shows that laparoscopic removal of RCC TT is a safe and effective approach. However, the generalizability of our findings is limited by the study's design and sample size. Future research should focus on identifying predictive markers, establishing effective screening protocols, and determining if our hybrid approach has comparable outcomes to the standard open approach.

Differential Expression of miRNAs Contributes to Tumor Aggressiveness and Racial Disparity in African American Men with Prostate Cancer.

Prostate cancer is the leading cancer in incidence and second leading cause of cancer mortality in US men. African American men have significantly higher incidence and mortality rates from prostate cancer than European American men. Previous studies reported that the disparity in prostate cancer survival or mortality can be explained by different biological backgrounds. microRNAs (miRNAs) regulate gene expression of their cognate mRNAs in many cancers. Therefore, miRNAs may be a potentially promising diagnostic tool. The role of miRNAs in prostate cancer aggressiveness and racial disparity has not been fully established. The goal of this study is to identify miRNAs associated with aggressiveness and racial disparity in prostate cancer. Here we report miRNAs that are associated with tumor status and aggressiveness in prostate cancer using a profiling approach. Further, downregulated miRNAs in African American tissues were confirmed by qRT-PCR. These miRNAs have also been shown to negatively regulate the expression of the androgen receptor in prostate cancer cells. This report provides a novel insight into understanding tumor aggressiveness and racial disparities of prostate cancer.

A role for laparoscopy in the age of robotics: a retrospective cohort study of perioperative outcomes between 2D laparoscopic radical prostatectomy vs 3DHD laparoscopic radical prostatectomy.

PURPOSE: Our study compares perioperative outcomes between two-dimensional (2D) laparoscopic radical prostatectomy (LRP) and the 4th generation three-dimensional/high definition (3DHD) LRP. METHODS: Retrospectively acquired data from patients that underwent 2D LRP (n = 75) and 3DHD LRP (n = 75) from March 2013 to October 2015 were evaluated. Procedures were performed by a single surgeon. The extra-peritoneal approach with 5 trocars was utilized. Perioperative outcomes, potency, and continence were compared between groups. RESULTS: Patient characteristics were similar between the two groups in terms of age (p = 0.44), prostate-specific antigen (PSA) levels (p = 0.34), and Gleason scores (p = 0.14). Body mass index (BMI) was significantly higher in the 3DHD group (p = 0.0036). Postoperatively, no significant differences were observed in Hgb loss (p = 0.50), positive surgical margins (p = 1.00), and post-op Gleason scores (p = 0.30). Significant differences were observed for length of hospital stay (p < 0.001) and Jackson-Pratt (JP) drainage (p < 0.001). Regarding potency, 73.7% and 51.6% of the patients in the 3DHD and 2D groups regained potency at 6 months, respectively (p = 0.0025). Almost 43% of the patients in the 3DHD group regained continence at 1 month while for the 2D groups it was only 17.3% (p = 0.0008). CONCLUSION: 3DHD and 2D LRP have resulted in good outcomes in the perioperative periods. Our results show decreased JP drainage, shorter length of hospital stay, earlier return of urinary control, and earlier return of sexual function in the 3DHD LRP group. In lower volume centers where robotics equipment is not feasible due to economic barriers 3DHD can be safely performed as a minimally invasive alternative.

Reduced DNA Repair Capacity in Prostate Cancer Patients: A Phenotypic Approach Using the CometChip.

Prostate cancer (PCa) accounts for 22% of the new cases diagnosed in Hispanic men in the US. Among Hispanics, Puerto Rican (PR) men show the highest PCa-specific mortality. Epidemiological studies using functional assays in lymphocytes have demonstrated that having low DRC is a significant risk factor for cancer development. The aim of this study was to evaluate variations in DRC in PR men with PCa. Lymphocytes were isolated from blood samples from PCa cases (n = 41) and controls (n = 14) recruited at a hospital setting. DRC levels through the nucleotide excision repair (NER) pathway were measured with the CometChip using UVC as a NER inductor. The mean DRC for controls and PCa cases were 20.66% (±7.96) and 8.41 (±4.88), respectively (p < 0.001). The relationship between DRC and tumor aggressiveness was also evaluated. Additional comparisons were performed to evaluate the contributions of age, anthropometric measurements, and prostate-specific antigen levels to the DRC. This is the first study to apply the CometChip in a clinical cancer study. Our results represent an innovative step in the development of a blood-based screening test for PCa based on DRC levels. Our data also suggest that DRC levels may have the potential to discriminate between aggressive and indolent cases.

Differential DNA Methylation in Prostate Tumors from Puerto Rican Men.

In 2020, approximately 191,930 new prostate cancer (PCa) cases are estimated in the United States (US). Hispanic/Latinos (H/L) are the second largest racial/ethnic group in the US. This study aims to assess methylation patterns between aggressive and indolent PCa including DNA repair genes along with ancestry proportions. Prostate tumors classified as aggressive (n = 11) and indolent (n = 13) on the basis of the Gleason score were collected. Tumor and adjacent normal tissue were annotated on H&E (Haemotoxylin and Eosin) slides and extracted by macro-dissection. Methylation patterns were assessed using the Illumina 850K DNA methylation platform. Raw data were processed using the Bioconductor package. Global ancestry proportions were estimated using ADMIXTURE (k = 3). One hundred eight genes including AOX1 were differentially methylated in tumor samples. Regarding the PCa aggressiveness, six hypermethylated genes (RREB1, FAM71F2, JMJD1C, COL5A3, RAE1, and GABRQ) and 11 hypomethylated genes (COL9A2, FAM179A, SLC17A2, PDE10A, PLEKHS1, TNNI2, OR51A4, RNF169, SPNS2, ADAMTSL5, and CYP4F12) were identified. Two significant differentially methylated DNA repair genes, JMJD1C and RNF169, were found. Ancestry proportion results for African, European, and Indigenous American were 24.1%, 64.2%, and 11.7%, respectively. The identification of DNA methylation patterns related to PCa in H/L men along with specific patterns related to aggressiveness and DNA repair constitutes a pivotal effort for the understanding of PCa in this population.

Dysregulation of DNA Methylation and Epigenetic Clocks in Prostate Cancer among Puerto Rican Men.

In 2021, approximately 248,530 new prostate cancer (PCa) cases are estimated in the United States. Hispanic/Latinos (H/L) are the second largest racial/ethnic group in the US. The objective of this study was to assess DNA methylation patterns between aggressive and indolent PCa along with ancestry proportions in 49 H/L men from Puerto Rico (PR). Prostate tumors were classified as aggressive (n = 17) and indolent (n = 32) based on the Gleason score. Genomic DNA samples were extracted by macro-dissection. DNA methylation patterns were assessed using the Illumina EPIC DNA methylation platform. We used ADMIXTURE to estimate global ancestry proportions. We identified 892 differentially methylated genes in prostate tumor tissues as compared with normal tissues. Based on an epigenetic clock model, we observed that the total number of stem cell divisions (TNSC) and stem cell division rate (SCDR) were significantly higher in tumor than adjacent normal tissues. Regarding PCa aggressiveness, 141 differentially methylated genes were identified. Ancestry proportions of PR men were estimated as African, European, and Indigenous American; these were 24.1%, 64.2%, and 11.7%, respectively. The identification of DNA methylation profiles associated with risk and aggressiveness of PCa in PR H/L men will shed light on potential mechanisms contributing to PCa disparities in PR population.

Long-term durability of laparoscopic decortication of symptomatic renal cysts.

OBJECTIVES: To assess the long-term results of patient symptoms and radiologic outcomes of laparoscopic renal cyst decortication in the treatment of symptomatic simple renal cysts. Renal cysts are common in the adult population. Symptomatic renal cysts have traditionally been treated by percutaneous aspiration with or without injection of sclerosant agents; however, this has a high rate of recurrence. METHODS: From April 1994 through July 2005, 45 patients underwent laparoscopic decortication of symptomatic simple renal cysts with renal cyst wall excision and fulguration of the epithelial lining. Complex renal cysts were excluded. Of the 45 patients, 24 (53.3%) had undergone previous cyst aspiration with injection of sclerosant material for intended ablation. The Wong-Baker pain scale was used to assess the preoperative and postoperative pain scores. Radiologic success was indicated as no recurrence on the most recent computed tomography scan. RESULTS: Of the 45 procedures, 44 were completed laparoscopically. One patient (1.8%) underwent open conversion because of excessive bleeding. The mean operative time was 89 minutes (range 48 to 170). Symptomatic success was achieved in 91.1% of patients, with a median follow-up of 52 months (range 3 to 132), and radiographic success was achieved in 95.5% of patients, with a median follow-up of 39 months (range 3 to 96). CONCLUSIONS: Long-term follow-up has confirmed that laparoscopic cyst decortication is an effective and durable treatment option for symptomatic simple renal cysts during long-term follow-up. The greater and durable success rates of this minimally invasive technique may favor this treatment option over other treatment modalities.

Does prolonged pneumoperitoneum affect oxidative stress compared with open surgical procedures?

BACKGROUND AND PURPOSE: As laparoscopic surgery has evolved, it has become part of the urologic surgical armamentarium and is now used to perform more complex procedures. Carbon dioxide, used to create pneumoperitoneum, produces physiologic changes in various organs, including the kidneys. Such changes are associated with altered redox status because of the release of free radicals and changes in oxidative stress signals. It is unknown whether prolonged pneumoperitoneum is associated with an increase in oxidative stress compared with open surgery. The objective of this study was to compare oxidative stress in patients undergoing urologic laparoscopic and open operations. PATIENTS AND METHODS: Urine samples were obtained immediately preoperatively, immediately postoperatively, and at 6 and 18 hours after surgery from 10 patients who underwent urologic laparoscopic surgery and 10 patients who underwent open surgery. Concentrations of the oxidative stress marker isoprostane (8- iso-prostaglandin F2a) were measured, and the results were analyzed with respect to clinical factors associated with the type of surgery. RESULTS: Urinary isoprostane concentrations (mean +/- SEM) in the laparoscopic and open groups showed an increase immediately after surgery to 189.0 +/- 64.2% and 141.1 +/- 45.8% of the preoperative values, respectively. A decrease in isoprostane was subsequently observed in both groups at 6 hours postoperatively, with preoperative values restored at 18 hours postoperatively (126.3 +/- 19.7% and 89.5 +/- 55.9% at 6 and 18 hours, respectively, in the laparoscopic group and 130.7 +/- 41.6% and 88.7 +/- 20.4% at 6 and 18 hours, respectively, in the open-surgery group). Although in both groups the peak PGF 2a concentration was observed immediately (0 hours) postoperatively, no significant differences were observed between the groups at 0, 6, and 18 hours. In the laparoscopic-surgery group, the mean increase tended to be higher and the decrease to be less prolonged than in the open-surgery group. CONCLUSION: Oxidative stress, as measured by urinary 8-iso-prostaglandin F2a, is produced by both laparoscopic and open urologic surgery. The findings of our nonrandomized study suggest a pattern of increased oxidative stress postoperatively with either type of surgery, with subsequent return almost to preoperative levels. Prolonged laparoscopic operative time did not affect oxidative stress levels.

In vivo proteomic analysis of cytokine expression in laser capture-microdissected urothelial cells of obstructed ureteropelvic junction procured by laparoscopic dismembered pyeloplasty.

BACKGROUND AND PURPOSE: Ureteropelvic junction obstruction (UPJO) is defined as an impediment to urinary flow from the renal pelvis into the ureter. The exact cause remains an enigma despite investigations along embryologic, anatomic, and histologic lines. Our goal was to investigate in vivo the expression profile of cytokines in hyperplastic urothelial cells as a means of determining the source of UPJO. MATERIALS AND METHODS: Cellular proteomes of matched normal and hyperplastic urothelial cells were analyzed by laser capture microdissection (LCM) and tissue microdissection and human cytokine proteomic chips. All specimens (N = 9) were surgically obtained from patients undergoing laparoscopic dismembered pyeloplasty and were immediately embedded in O.C.T. solution and flash-frozen in liquid nitrogen. Tissue sections (6 microm) were mounted on uncoated glass slides using a cryostat, fixed in 70% ethanol, stained with hematoxylin and eosin, and sequentially dehydrated in ethanol and xylene. Typically, paired samples of normal and hyperplastic urothelial cells were procured on separate caps from serial sections of each specimen by the Arcturus PixCell II LCM system using 3000 laser pulses and a spot diameter of 30 microm. Total proteins were harvested and quantitated. Differential expression profile analysis of 43 cytokines in normal and hyperplastic cells were performed using human protein chips. Briefly, the membranes were initially probed with protein (150 ng) from normal or hyperplastic cells and sequentially reacted with a cocktail of biotinylated cytokine antibodies and horseradish peroxidase-conjugated streptavidin. The membranes were developed using enhanced chemiluminescence and analyzed by densitometry. RESULTS: Comparative densitometric analysis revealed twofold to fourfold upregulation of growth-related oncogene alpha (GRO-alpha), interleukin (IL)-1alpha, interferon (INF)-gamma, IL-8, tumor necrosis factor (TNF)-alpha, RANTES, and macrophage inflammatory protein-1beta (MIP-1beta) and twofold to fourfold downregulation of transforming growth factor (TGF)-beta and IL-10 in hyperplastic urothelial cells compared with paired control cells. CONCLUSIONS: We here report the efficient application of LCM and proteomic array chips for expression profile analysis of cytokines in vivo. Because the etiology and pathogenesis of UPJO are still fragmentary, the marked heterogeneity of the observed cytokine alterations reported here may be of significance. Further studies are required to elucidate the functional significance of the differentially expressed cytokines in the pathogenesis of the disease.

Potential role for the nuclear transcription factor NF-kappa B in the pathogenesis of ureteropelvic junction obstruction.

BACKGROUND AND PURPOSE: In an effort to better understand the pathophysiology of ureteropelvic junction (UPJ) obstruction and to determine possible predisposing factors for endopyelotomy failures, we compared the activation of the nuclear factor NF-kappa B and proinflammatory cytokines in patients who failed endopyelotomy and post-primary pyeloplasty patients. We hypothesized that an imbalance toward proinflammatory cytokines may promote fibrosis prior to and after endopyelotomy in patients with severe hydronephrosis. PATIENTS AND METHODS: The charts of patients who underwent open pyeloplasty at our institution were reviewed. Group I was the control group, consisting of 10 patients who had undergone radical nephrectomy for renal-cell carcinoma without involvement of the renal pelvis. Group II was the endopyelotomy failure group and included 11 patients over the age of 15 years treated for symptomatic UPJ obstruction. Group III included six patients who underwent primary pyeloplasty. Paraffin-embedded blocks of UPJ segments from each of these patients were obtained, and immunohistochemical detection of NF-kappa B activation, interleukin (IL)-6, and hypoxia-inducing factor (HIF) was performed. As an in-vitro model, activation of NF-kappa B and cytokine gene expression were also monitored in human bladder T24 urothelial cells 24 hours after exposure to hypoxia (1% O(2)) in the presence and absence of NF-kappa B inhibitor. The activation of NF-kappa B was determined by immunocytochemical analysis, whereas cytokine gene expression was measured using reverse transcriptase-polymerase chain reaction. RESULTS: Immunoreactivity to NF-kappa B was observed in the nuclei of the urothelium and muscle layer in all patients in group II. Such immunostaining suggests increased nuclear translocation and activation of this transcription factor. Those patients with increased expression of NF-kappa B demonstrated increases in IL-6 expression as well. Hypoxia-inducing factor was identified in all the tissue samples tested in group II. Stimulation of the human urothelial cells by hypoxia, known to activate NF-kappa B, resulted in an increase in the levels of IL-1 and IL-6 transcripts compared with hypoxia-exposed cells in the presence of NF-kappa B inhibitors. CONCLUSIONS: The NF-kappa B factor was upregulated and proinflammatory cytokines were activated in patients with UPJ obstruction who failed endopyelotomy. Proinflammatory cytokines upregulated by this nuclear factor can result in fibrosis and affect healing after endopyelotomy. Hypoxia appears to activate this nuclear factor. Further studies correlating the degree of hydronephrosis with the activation of HIF are necessary to clarify the role of severe hydronephrosis and its management in UPJ obstruction.

Single-center analysis of living donor nephrectomy: hand-assisted laparoscopic, pure laparoscopic, and traditional open.

CONTEXT: Laparoscopic living donor nephrectomy has been shown to be a safe method for removing kidneys for transplantation, but concerns have been raised regarding safety and long-term kidney function. OBJECTIVE: To compare safety and long-term kidney function in hand-assisted laparoscopic, pure laparoscopic, and traditional open living donor nephrectomy. METHOD: The charts of 48 patients with more than 1 year follow-up were reviewed. Thirty-four consecutive patients underwent laparoscopic live donor nephrectomy, and 14 had open donor nephrectomy. All kidneys functioned immediately at transplantation. In the laparoscopic group, 11 had the pure laparoscopic technique, and 23 patients had hand-assisted laparoscopic nephrectomy. RESULTS: Total operative and warm ischemic times were reduced with the hand-assisted technique when compared with pure laparoscopy. Operative and warm ischemic times were similar in open nephrectomy and hand-assisted laparoscopy. Long-term follow-up of serum creatinine levels revealed no significant differences between the 3 groups. Complication rates in the 3 groups were similar. CONCLUSION: Laparoscopic donor nephrectomy appears to be comparable to open donor nephrectomy in terms of safety and long-term graft function.

Computerized tomography tailored for the assessment of microscopic hematuria.

PURPOSE: We report the results of a multicenter study of arterial, corticomedullary, nephrographic and excretory phase helical computerized tomography (CT) for detecting and characterizing abnormalities causing asymptomatic microscopic hematuria. MATERIALS AND METHODS: We evaluated 350 consecutive patients, including 216 men and 134 women 23 to 88 years old, with asymptomatic microscopic hematuria of undetermined cause at 4 medical centers. Patients with known urological pathology were excluded from study. We performed 4 helical CT sequences, including pre-enhancement phase imaging from kidney to symphysis pubis, arterial phase imaging of the kidney and lower pelvis, corticomedullary nephrographic phase imaging of the kidney and lower pelvis, and excretory phase imaging from kidney to symphysis pubis with 2 to 5 mm. collimation and 1 to 1.5 pitch. RESULTS: Of 171 proved lesions 158 were correctly diagnosed. There were 10 false-positive and 13 false-negative diagnoses, indicating 0.9239 sensitivity, 0.9441 specificity, 0.9404 positive and 0.9285 negative predictive values, (p <0.001). All cases of congenital renal lesions, calculous disease, ureteral lesion and neoplastic lesion of the bladder were correctly diagnosed, as were 40 of 41 inflammatory renal, 21 of 23 renal masses and 13 of 16 inflammatory bladder lesions. In 27 patients with renal calculi the study was limited to pre-enhancement spiral CT. CONCLUSIONS: A positive diagnosis rate of 45.1% (158 of 350 cases) for the causes of heretofore refractory cases of hematuria with high sensitivity and specificity attest to the effectiveness of our hematuria CT protocol and support its use.