Effects of the 2012 and 2018 US preventive services task force prostate cancer screening guidelines on pathologic outcomes after prostatectomy.

BACKGROUND: In May 2018, the US Preventive Services Task Force (USPSTF) recommended prostate cancer (PCa) screening for ages 55-69 be an individual decision. This changed from the USPSTF's May 2012 recommendation against screening for all ages. The effects of the 2012 and 2018 updates on pathologic outcomes after prostatectomy are unclear. METHODS: This study included 647 patients with PCa who underwent prostatectomy at our institution from 2005 to 2018. Patient groups were those diagnosed before the 2012 update (n = 179), between 2012 and 2018 updates (n = 417), and after the 2018 update (n = 51). We analyzed changes in the age of diagnosis, pathologic Gleason grade group (pGS), pathologic stage, lymphovascular invasion (LVI), and favorable/unfavorable pathology. Multivariable logistic regression adjusting for pre-biopsy covariables (age, prostate-specific antigen [PSA], African American race, family history) assessed impacts of 2012 and 2018 updates on pGS and pathologic stage. A p  < 0.05 was statistically significant. RESULTS: Median age increased from 60 to 63 (p = 0.001) between 2012 and 2018 updates and to 64 after the 2018 update. A significant decrease in pGS1, pGS2, pT2, and favorable pathology (p < 0.001), and a significant increase in pGS3, pGS4, pGS5, pT3a, and unfavorable pathology (p < 0.001) was detected between 2012 and 2018 updates. There was no significant change in pT3b or LVI between 2012 and 2018 updates. On multivariable regression, diagnosis between 2012 and 2018 updates was significantly associated with pGS4 or pGS5 and pT3a (p < 0.001). Diagnosis after the 2018 update was significantly associated with pT3a (p = 0.005). Odds of pGS4 or pGS5 were 3.2× higher (p < 0.001) if diagnosed between 2012 and 2018 updates, and 2.3× higher (p = 0.051) if after the 2018 update. Odds of pT3a were 2.4× higher (p < 0.001) if diagnosed between 2012 and 2018 updates and 2.9× higher (p = 0.005) if after the 2018 update. CONCLUSIONS: The 2012 USPSTF guidelines negatively impacted pathologic outcomes after prostatectomy. Patients diagnosed between 2012 and 2018 updates had increased frequency of higher-risk PCa and lower frequency of favorable disease. In addition, data after the 2018 update demonstrate a continued negative impact on postprostatectomy pathology. Thus, further investigation of the long-term effects of the 2018 USPSTF update is warranted.

Optimal PSA Threshold for Obtaining MRI-Fusion Biopsy in Biopsy-Naïve Patients.

OBJECTIVE: The study investigates the prostate-specific antigen threshold for adding targeted, software-based, magnetic resonance imaging-ultrasound fusion biopsy during a standard 12-core biopsy in biopsy-naïve patients. It secondarily explores whether the targeted biopsy is necessary in setting of abnormal digital rectal examination. METHODS: 260 patients with suspected localized prostate cancer with no prior biopsy underwent prostate magnetic resonance imaging and were found to have Prostate Imaging Reporting and Data System score ≥ 3 lesion(s). All 260 patients underwent standard 12-core biopsy and targeted biopsy during the same session. Clinically significant cancer was Gleason ≥3 + 4. RESULTS: Percentages of patients with prostate-specific antigen 0-1.99, 2-3.99, 4-4.99, 5-5.99, 6-9.99, and ≥10 were 3.0%, 4.7%, 20.8%, 16.9%, 37.7%, and 16.9%, respectively. Cumulative frequency of clinically significant prostate cancer increased with the addition of targeted biopsy compared with standard biopsy alone across all prostate-specific antigen ranges. The difference in clinically significant cancer detection between targeted plus standard biopsy compared to standard biopsy alone becomes statistically significant at prostate-specific antigen >4.3 (p=0.031). At this threshold, combination biopsy detected 20 clinically significant prostate cancers, while standard detected 14 with 88% sensitivity and 20% specificity. Excluding targeted biopsy in setting of a positive digital rectal exam would save 12.3% magnetic resonance imaging and miss 1.8% clinically significant cancers in our cohort. CONCLUSIONS: In biopsy-naïve patients, at prostate-specific antigen >4.3, there is a significant increase in clinically significant prostate cancer detection when targeted biopsy is added to standard biopsy. Obtaining standard biopsy alone in patients with abnormal digital rectal examinations would miss 1.8% clinically significant cancers in our cohort.

Primary prostatic squamous cell carcinoma.

Primary prostate squamous cell malignancies are rare and very aggressive. A 65-year-old man presented to our institution with clinical and radiographic findings concerning for advanced prostatic malignancy. Surgical pathology of the tumor revealed poorly differentiated carcinoma with squamous differentiation, and histopathological markers were positive for markers of squamous differentiation negative for all urothelial and prostatic markers.

Heterotopic Ossification Leading to Ureteral Obstruction Resulting in Nephrectomy.

Background: Heterotopic ossification (HO) is the presence of bone in soft tissue where bone normally does not exist. This can be acquired or inherited with the acquired form most often seen with either trauma, spinal cord injury, or central nervous system injury. HO most commonly affects the flexors and abductors of the hip, medial knees, and the shoulders and rarely affects the genitourinary (GU) system. Case Presentation: We discuss a 67-year-old Caucasian male patient who presented with left-sided ureteral obstruction. He was involved in an airplane accident in 2001 resulting in a spinal cord injury. This ultimately led to heterotopic bone growth within the retroperitoneal space involving the left psoas muscle and encasing the ureter. Owing to the ureteral obstruction, a nephrectomy was performed to treat the patient's urinary symptoms. Conclusion: Although HO is relatively common after spinal cord injuries and trauma, it rarely infiltrates the GU system. Management ultimately involves treating the symptoms that arise because of the complications from the abnormal bone formation. For this case, because of extensive ossification resulting in obstruction of the ureter and inability to separate the kidney from the psoas, the ultimate outcome was a nephrectomy.

A comparison of outcomes for standard and multiplex partial nephrectomy in a solitary kidney: The National Cancer Institute experience.

OBJECTIVES: To study the short and intermediate surgical, renal functional, and oncologic outcomes of multiplex partial nephrectomy (mPN) and standard partial nephrectomy (sPN) in the setting of a solitary kidney. PATIENTS AND METHODS: Review of a prospectively maintained database of patients undergoing solitary kidney partial nephrectomy at our institution was performed. Patients were stratified into 2 cohorts: mPN-where 3 or more renal tumors were resected and sPN-where 1 or 2 tumors were resected. Perioperative, renal functional, and oncological outcomes were compared. RESULTS: Ninety-three patients with a solitary kidney underwent a total of 121 surgical procedures; 43 (35.5%) were sPN and 78 (64.4%) were mPN. The total and major (Clavien Grade III and IV) complication rates between sPN and mPN were similar (57.1% vs. 70.1%, P = 0.2; 31.0% vs. 35.1%, P = 0.3). At 12 months post-op, the percentage of patients with eGFR > 45 was similar in each group (sPN 87.0%, mPN 73.7%; P = 0.2), and long-term hemodialysis rates were 4.7% and 6.4%, respectively. Completion nephrectomy was performed in 2.3% of sPN and 2.6% of mPN. At a median follow-up of 40.1 months, the metastasis rate was 8.6% in the sPN group and 4.1% in the mPN group (P = 0.4). CONCLUSIONS: Partial nephrectomy in the setting of a solitary kidney can effectively preserve renal function. The renal functional and oncologic outcomes were similar in sPN and mPN, with low hemodialysis rates and complication rates within the expected range of these operations. Three or more tumors in a solitary kidney should not be a contraindication for nephron sparing surgery.

Assessing Time of Full Renal Recovery Following Minimally Invasive Partial Nephrectomy.

OBJECTIVE: To assess renal function in the operated kidney at different time points post partial nephrectomy (PN) and establish the time in which optimal recovery occurs. Recovery of renal function post-PN has received significant attention. However, the optimal time to determine full recovery has not been clearly established. MATERIALS AND METHODS: Renal function following minimally invasive (laparoscopic and robotic) PNs performed between 2002 and 2015 was reviewed. Patients included in this study had renal function assessed preoperatively as well as 3 days, 6-12 weeks, and 1 year post-PN, using a combination of estimated glomerular filtration rate (eGFR) from serum creatinine and relative renal uptake (RRU) from Tc99m-MAG3 renal scintigraphy. Together, eGFR and RRU provide the ipsilateral renal function (IRF) of the operated organ. RESULTS: At 6-12 weeks postoperatively, percent preserved eGFR, RRU, and IRF (relative to preoperative baselines) were 92.1%, 83.3%, and 77.4% respectively. %IRF at 6-12 weeks was significantly improved from %IRF at 3 days postoperatively, but did not differ significantly from 1 year postoperatively. Furthermore, 89% of patients had RRU values at 6-12 weeks which differed by less than 5% from RRU values at 1 year. CONCLUSION: Our data suggest that renal function recovery at 6-12 weeks was equivalent to long-term recovery at 1 year in the majority of post-PN patients. This has important implications for post-PN follow-up, particularly in assessing the functional outcomes utilizing novel minimally invasive PN strategies, as well as in planning staged procedures for bilateral synchronous renal masses.

Genomic and metabolic characterization of a chromophobe renal cell carcinoma cell line model (UOK276).

Chromophobe renal cell carcinoma (ChRCC) represents 5% of all RCC cases and frequently demonstrates multiple chromosomal losses and an indolent pattern of local growth, but can demonstrate aggressive features and resistance to treatment in a metastatic setting. Cell line models are an important tool for the investigation of tumor biology and therapeutic drug efficacy. Currently, there are few ChRCC-derived cell lines and none is well characterized. This study characterizes a novel ChRCC-derived cell line model, UOK276. A large ChRCC tumor with regions of sarcomatoid differentiation was used to establish a spontaneously immortal cell line, UOK276. UOK276 was evaluated for chromosomal, mutational, and metabolic aberrations. The UOK276 cell line is hyperdiploid with a modal number of 49 chromosomes per cell, and evidence of copy-neutral loss of heterozygosity, as opposed to the classic pattern of ChRCC chromosomal losses. UOK276 demonstrated a TP53 missense mutation, expressed mutant TP53 protein, and responded to treatment with a small-molecule therapeutic agent, NSC319726, designed to reactivate mutated TP53. Xenograft tumors grew in nude mice and provide an in vivo animal model for the investigation of potential therapeutic regimes. The xenograft pathology and genetic analysis suggested that UOK276 was derived from the sarcomatoid region of the original tumor. In summary, UOK276 represents a novel in vitro and in vivo cell line model for aggressive, sarcomatoid-differentiated, TP53 mutant ChRCC. This preclinical model system could be used to investigate the novel biology of aggressive, sarcomatoid ChRCC and evaluate the new therapeutic regimes.

Managing Renal Cell Carcinoma Associated Paraneoplastic Syndrome with Nephron-sparing Surgery in a Patient with von Hippel-Lindau.

A patient with germline von Hippel-Lindau (VHL) gene alteration and history of multiple tumors present with classical paraneoplastic syndrome (PNS) associated with renal cell carcinoma (RCC). She underwent open nephron sparing surgery with resolution of symptoms. She remained without recurrence of RCC for the initial 2 years of her follow-up. To the best of our knowledge, this case represents the first in which PNS was specifically resolved using a partial nephrectomy in a patient with VHL. This case report provides initial evidence for the potential role of nephron sparing surgery in the management of paraneoplastic symptoms associated with hereditary RCC.

Multiple Recurrent Paraganglioma in a Pediatric Patient with Germline SDH-B Mutation.

Magnetic Resonance Imaging (MRI) and fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) are recognized approaches for locating paragangliomas. Recently, gallium-68 DOTA-octreotate (DOTATATE) scans have shown promise detecting neuroendocrine tumors missed by FDG-PET and MRI. 13-year-old male with SDH-B mutation presented with symptoms of paraganglioma and elevated catecholamines. MRI did not demonstrate the T2 hyper intense signal typical of paraganglioma and pheochromocytoma; FDG-PET scan did not reveal increased foci of uptake. DOTATATE scan revealed a signal consistent only with residual adrenal tissue. Resection of the right adrenal bed revealed paraganglioma. Following surgery, no further symptoms were reported and biochemical tests normalized.

Ipsilateral renal function preservation following minimally invasive partial nephrectomy: The effect of tumour characteristics and warm ischemic time.

INTRODUCTION: The relative impact of preoperative and perioperative variables on renal function following partial nephrectomy (PN) is controversial. To further investigate, we assess the effects of tumour complexity, warm ischemic time (WIT), and volume of resected renal parenchyma on ipsilateral renal function (IRF) outcomes following minimally invasive PN. METHODS: Of patients who underwent laparoscopic or robotic-assisted PN between 2002 and 2011 at our institution, 99 met our inclusion criteria. The effects of preoperative tumour complexity (using RENAL nephrometry score), perioperative WIT, and pathological tumour volumes on ipsilateral renal function preservation (%IRF) were analyzed. %IRF was defined as the proportion of postoperative to preoperative ipsilateral renal function calculated using MAG3 nuclear renography. RESULTS: Increasing RENAL nephrometry score (RNS) and WIT were independently predictive of inferior %IRF at 6-12-week postoperative followup in univariate and multivariate analyses. Of RNS properties, masses that were endophytic, near the collecting system, or central in location were associated with inferior %IRF, with nearness to collecting system as the strongest predictor; however, RNS was no longer predictive of %IRF in cases requiring more than 30 minutes of WIT. CONCLUSIONS: In renal masses amenable to resection by minimally invasive PN, longer WIT was the most important predictor of inferior %IRF. Although increasing RNS score influenced %IRF, the overall clinical significance of RNS is limited and should not influence operative decision-making in efforts to preserve renal function. Furthermore, small volumes of renal parenchyma can be safely resected without impairment of long-term IRF.

Development of a novel classification system for anatomical variants of the puboprostatic ligaments with expert validation.

INTRODUCTION: We propose a novel classification system with a validation study to help clinicians identify and typify commonly seen variants of the puboprostatic ligaments (PPL). METHODS: A preliminary dissection of 6 male cadavers and a prospective dataset of over 300 robotic-assisted laparoscopic radical prostatectomies (RARP) recorded on video were used to identify 4 distinct ligament types. Then the prospectively collected database of surgical videos was used to isolate images of the PPL from RARP. Over 300 surgical videos were reviewed and classified with 1 to 5 pictures saved for reference of the type of PPL. To validate the new classification system, we selected 5 independent, blinded expert robotic surgeons to classify 100 ligaments based on morphology into a 4-type system: parallel, V-shaped, inverted V-shape, and fused. One week later, a subset of 25 photographs was sent to the same experts and classified. Statistical analyses were performed to determine both the intra-rater and inter-rater reliability of the proposed system. RESULTS: Inverted V-shaped ligaments were noted most frequently (29.97%), parallel and V-shaped ligaments were found at 19.19% and 11.11%, respectively and fused ligaments were noted less frequently (6.06%). There was good intra-rater agreement (κ = 0.66) and inter-rater agreement (κ = 0.67) for the classification system. CONCLUSIONS: This classification system provided standardized descriptions of ligament variations that could be adopted universally to help clinicians categorize the variants. The system, validated by several blinded expert surgeons, demonstrated that surgeons were able to learn and correctly classify the variants. The system may be useful in helping to predict peri- and postoperative outcomes; however, this will require further study.

Primary mucinous cystadenocarcinoma of the pelvic retroperitoneum in a male.

Primary mucinous cystadenocarcinoma of the retroperitoneum is an extremely rare malignancy with only 2 male patients reported in the literature. We describe an unusual case presenting as a pelvic mass in a male with previous pan-proctocolectomy and end ileostomy for Crohn's disease and review the available literature.