Sarcopenic Obesity and its Prognostic Impact on Urological Cancers: A Systematic Review.

PURPOSE: Sarcopenia, an age-related loss of muscle mass and function, may predict adverse outcomes for patients with urological cancers. However, the clinical implications and significance of sarcopenic obesity are not well understood. We systematically reviewed data on the prevalence and prognostic impact of sarcopenic obesity for patients with renal cell carcinoma, urothelial carcinoma and prostate cancer undergoing treatment. MATERIALS AND METHODS: We searched EMBASE®, PubMed®/MEDLINE® and Scopus® for relevant original articles and abstracts published between January 2010 and February 2021. Primary outcomes were overall survival (OS), cancer-specific survival (CSS) and progression-free survival. The secondary outcome was the prevalence of sarcopenic obesity. RESULTS: A total of 15 studies comprising 3,866 patients were included. Of the 10 studies that evaluated survival outcomes, the association between sarcopenic obesity and survival was mixed. One of 10 studies showed a significant association of sarcopenic obesity with OS (HR 0.7, 95% CI 0.51-0.98; p=0.04). One additional study showed reported a trend for shorter OS (p=0.05) associated with sarcopenic obesity. Others reported that it is an adverse prognostic factor for CSS (HR 5.0, 95% CI 1.4-16.7; p=0.01). All other studies did not demonstrate that sarcopenic obesity was of prognostic relevance with regard to OS, CSS and progression-free survival. Overall, its mean prevalence was 27% (range 11-63). CONCLUSIONS: There is considerable heterogeneity in methods used to define sarcopenic obesity in the literature, and current data are limited. Future studies are needed to further understand the relationship of obesity and sarcopenia on the clinical trajectory of patients with urological cancer.

Frequent PD-L1 expression in primary and metastatic penile squamous cell carcinoma: potential opportunities for immunotherapeutic approaches.

BACKGROUND: Despite aggressive multimodal therapy, locally advanced and/or metastatic penile squamous cell carcinoma (SqCC) is associated with significant morbidity and mortality, indicating a need for new therapeutic options. Given the emerging clinical utility of immunotherapeutics, we sought to assess the incidence and potential clinical significance of PD-L1 expression in penile SqCC. PATIENTS AND METHODS: Using an anti-PD-L1 primary antibody (clone 5H1), immunohistochemistry was carried out on whole tumor sections from 37 patients with penile SqCC treated at our institution between 2005 and 2013. PD-L1-positive tumors were defined as those with membranous staining in ≥5% of tumor cells. Association between PD-L1 expression and clinicopathologic parameters was examined using Fisher's exact test. Correlation between PD-L1 expression in primary tumors and matched metastases was assessed using the Spearman rank correlation coefficient (ρ). The difference in cancer-specific mortality between PD-L1-positive and -negative groups was examined using the log-rank test. RESULTS: Twenty-three (62.2%) of 37 primary tumors were positive for PD-L1 expression, and there was strong positive correlation of PD-L1 expression in primary and metastatic samples (ρ = 0.72; 0.032 < P < 0.036). Primary tumor PD-L1 expression was significantly associated with usual type histology (P = 0.040) and regional lymph node metastasis (P = 0.024), as well as decreased cancer-specific survival (P = 0.011). CONCLUSIONS: The majority of primary penile SqCC tumors express PD-L1, which is associated with high-risk clinicopathologic features and poor clinical outcome. These data provide a rational basis for further investigation of anti-PD-1 and anti-PD-L1 immunotherapeutics in patients with advanced penile SqCC.

Mass-like peripheral zone enhancement on CT is predictive of higher-grade (Gleason 4 + 3 and higher) prostate cancer.

PURPOSE: To determine whether focal peripheral zone enhancement on routine venous-phase CT is predictive of higher-grade (Gleason 4 + 3 and higher) prostate cancer. MATERIALS AND METHODS: IRB approval was obtained and informed consent waived for this HIPAA-compliant retrospective study. Forty-three patients with higher-grade prostate cancer (≥Gleason 4 + 3) and 96 with histology-confirmed lower-grade (≤Gleason 3 + 4 [n = 47]) or absent (n = 49) prostate cancer imaged with venous-phase CT comprised the study population. CT images were reviewed by ten blinded radiologists (5 attendings, 5 residents) who scored peripheral zone enhancement on a scale of 1 (benign) to 5 (malignant). Mass-like peripheral zone enhancement was considered malignant. Likelihood ratios (LR) and specificities were calculated. Multivariate conditional logistic regression analyses were conducted. RESULTS: Scores of "5" were strongly predictive of higher-grade prostate cancer (pooled LR+ 9.6 [95% CI 5.8-15.8]) with rare false positives (pooled specificity: 0.98 [942/960, 95% CI 0.98-0.99]; all 10 readers had specificity ≥95%). Attending scores of "5" were more predictive than resident scores of "5" (LR+: 14.7 [95% CI 5.8-37.2] vs. 7.6 [95% CI 4.2-13.7]) with similar specificity (0.99 [475/480, 95% CI 0.98-1.00] vs. 0.97 [467/480, 95% CI 0.96-0.99]). Significant predictors of an assigned score of "5" included presence of a peripheral zone mass (p < 0.0001), larger size (p < 0.0001), and less reader experience (p = 0.0008). Significant predictors of higher-grade prostate cancer included presence of a peripheral zone mass (p = 0.0002) and larger size (p < 0.0001). CONCLUSION: Focal mass-like peripheral zone enhancement on routine venous-phase CT is specific and predictive of higher-grade (Gleason 4 + 3 and higher) prostate cancer.

Acute bilateral renal cortical necrosis as a cause of postoperative renal failure.

Acute renal failure after a major intra-abdominal operation is, unfortunately, not an infrequent occurrence. Acute tubular necrosis, the most common cause of postoperative renal failure, usually follows a predictable clinical course, with most patients recovering full renal function. We describe a patient who developed acute renal failure after orthotopic liver transplantation. Subsequent workup revealed the patient to have acute bilateral renal cortical necrosis. Bilateral renal cortical necrosis is an extremely rare cause of renal failure and an even rarer cause of postoperative renal failure. We discuss the diagnosis and management of this uncommon disorder and review the salient literature. Of the approximately 15 known reported cases involving native kidneys after a major nonobstetric abdominal operation in the world literature, we believe this is the first to be related to an orthotopic organ transplant.

Prostate stem cell antigen is overexpressed in human transitional cell carcinoma.

Prostate stem cell antigen (PSCA), a homologue of the Ly-6/Thy-1 family of cell surface antigens, is expressed by a majority of human prostate cancers and is a promising target for prostate cancer immunotherapy. In addition to its expression in normal and malignant prostate, we recently reported that PSCA is expressed at low levels in the transitional epithelium of normal bladder. In the present study, we compared the expression of PSCA in normal and malignant urothelial tissues to assess its potential as an immunotherapeutic target in transitional cell carcinoma (TCC). Immunohistochemical analysis of PSCA protein expression was performed on tissue sections from 32 normal bladder specimens, as well as 11 cases of low-grade transitional cell dysplasia, 21 cases of carcinoma in situ (CIS), 38 superficial transitional cell tumors (STCC, stages T(a)-T(1)), 65 muscle-invasive TCCs (ITCCs, stages T(2)-T(4)), and 7 bladder cancer metastases. The level of PSCA protein expression was scored semiquantitatively by assessing both the intensity and frequency (i.e., percentage of positive tumor cells) of staining. We also examined PSCA mRNA expression in a representative sample of normal and malignant human transitional cell tissues. In normal bladder, PSCA immunostaining was weak and confined almost exclusively to the superficial umbrella cell layer. Staining in CIS and STCC was more intense and uniform than that seen in normal bladder epithelium (P < 0.001), with staining detected in 21 (100%) of 21 cases of CIS and 37 (97%) of 38 superficial tumors. PSCA protein was also detected in 42 (65%) of 65 of muscle-invasive and 4 (57%) of 7 metastatic cancers, with the highest levels of PSCA expression (i.e., moderate-strong staining in >50% of tumor cells) seen in 32% of invasive and 43% of metastatic samples. Higher levels of PSCA expression correlated with increasing tumor grade for both STCCs and ITCCs (P < 0.001). Northern blot analysis confirmed the immunohistochemical data, showing a dramatic increase in PSCA mRNA expression in two of five muscle-invasive transitional cell tumors when compared with normal samples. Confocal microscopy demonstrated that PSCA expression in TCC is confined to the cell surface. These data demonstrate that PSCA is overexpressed in a majority of human TCCs, particularly CIS and superficial tumors, and may be a useful target for bladder cancer diagnosis and therapy.

Conservative management of a grade 4 renal laceration in a child.

Renal trauma associated with blunt abdominal trauma is common. Children presenting with grade 4 or 5 renal lacerations who are hemodynamically stable can be followed safely nonoperatively. No long-term complications from conservative management have been noted.

Gene therapy for prostate cancer. New perspectives on an old problem.

Recent advances in molecular biology have made the prospect of gene therapy for prostate cancer a reality. A wide variety of genetic strategies, vector designs, and delivery modalities are currently in use. This article examines the state of the art prostate cancer gene therapy and details the various options available to clinicians.

The association of selected pathological features with prostate cancer in a single-needle biopsy accession.

Isolated high-grade prostatic intraepithelial neoplasia (PIN) has been shown to be a positive predictor of prostate cancer (PCa) on follow-up biopsy. However, the incidence of isolated high-grade PIN in needle biopsy specimens has been reported with a highly variable frequency of 1% to 15%. The current study examined the relationship of various pathological features with PCa on a single biopsy accession. A study population of 388 community-based consecutive needle biopsy accessions was prospectively recorded by a single pathologist (T.M.W.). All of the individual biopsy specimens were coded for the presence of PCa, high-grade PIN, low-grade PIN, chronic inflammation (CI), intraluminal prostatic crystalloids (IPC) in benign glands, and mucinous metaplasia (MM). One hundred twenty-nine (33%) of the patients were diagnosed with PCa. The 8% incidence of isolated high-grade PIN was consistent with previous studies. The incidence of other pathological features were as follows: high-grade PIN, 14%; low-grade PIN, 13%; CI, 30%; IPC, 4%; and MM, 8%. Of the patients with high-grade PIN, 47% had PCa on a separate core biopsy, whereas 31% of patients without high-grade PIN were observed to have PCa (P=.021). Of the patients with CI, 21% were found to have PCa on a separate core, whereas 38% of patients without CI were found to have PCa (P=.0009). None of the other pathological features surveyed showed any significant association with PCa. High-grade PIN was a relatively common finding (14%) in this study and was positively associated with PCa on a separate core from the same accession biopsy. The negative association of CP with PCa within the same accession has not been reported previously and may be an artifact related to the clinical indications for a prostatic biopsy.

Transgenic mouse models for tumor suppressor genes.

The identification and cloning of tumor suppressor genes has mostly relied on familial human cancer predisposition syndromes and reverse genetics. Recent advances in manipulating the mouse genome by gene targeting techniques in embryonic stem (ES) cells has led to the generation of mutant mouse models mimicking many human syndromes. Mice lacking one or both alleles of known tumor suppressor genes have been generated to evaluate the normal function of these genes in vivo. These mice have proven to be highly susceptible to tumor development, indicating that the mouse is a potent in vivo assay system for tumor suppressor genes. The initiation of gonadal tumor development in mice lacking both copies of the alpha-inhibin gene demonstrates that this assay is also useful for identifying new tumor suppressor genes. In the future, murine ES cell/gene targeting strategies will continue to be used to identify novel tumor suppressors and analyze their in vivo roles in growth control.