Remarkable effect of presurgical nivolumab on originally inoperable papillary renal cell carcinoma with tumor thrombus in inferior vena cava.

For the long-term survival of a patient with renal cell carcinoma and a vena cava tumor thrombus, total resection is desired: inoperable patients are sometimes treated with drugs. The effect of the presurgical use of nivolumab, an anti-programmed cell death 1 (PD-1) antibody drug, has been described. Our patient had inoperable renal cancer with an inferior vena cava tumor thrombus. We were able to downsize the tumor to operable size by administrating nivolumab. The patient underwent a nephrectomy and thrombectomy safely. Pathological findings revealed papillary renal cell carcinoma type 2. No viable cells were identified in the removed thrombus. Anti-programmed cell death ligand 1 was expressed on the cell membrane in approximately 20% of the tumor cells, and PD-1 positive tumor-ifiltrating immune cells had infiltrated particularly at the edge of the tumor. This case indicates the positive effect of the presurgical use of nivolumab for advanced papillary renal cell carcinoma.

Serum C-reactive protein level is not associated with prostatic inflammation but with overactive detrusor in patients with benign prostatic hyperplasia.

AIM: Chronic prostatic inflammation is a critical factor that exacerbates lower urinary tract symptoms (LUTS). The serum C-reactive protein (CRP) level is one of the most common markers with which to assess the degree of inflammation, and it has been reported to be related to the severity of LUTS. However, it is not clear whether the CRP level is linked to the magnitude of prostatic inflammation. We evaluated the relationship between the serum CRP level and the magnitude of prostatic inflammation and assessed the influence of CRP on the severity of LUTS. METHODS: We evaluated the tissue specimens of 121 benign prostatic hyperplasia (BPH) patients who underwent surgery for BPH and preoperative measurement of the serum CRP level. We quantified the magnitude of prostatic inflammation histologically by determining the number of high endothelial venule (HEV)-like vessels and assessed the relationship between the serum CRP level and the HEV-like vessels. We divided the patients into two groups based on the median serum CRP level and compared the clinical parameters of the two groups. RESULTS: The serum CRP level was correlated with the overactive bladder symptom score, whereas it was not correlated with the number of HEV-like vessels. In filling cystometry and pressure-flow study, the proportion of patients with detrusor overactivity in the higher-CRP group was higher than that in the lower-CRP group. CONCLUSIONS: Our present study showed that the serum CRP level was significantly associated with storage dysfunction; in contrast, it was not a surrogate marker of prostatic inflammation.

Prostatic stromal inflammation is associated with bladder outlet obstruction in patients with benign prostatic hyperplasia.

BACKGROUND: Benign prostatic hyperplasia (BPH) is a common urologic disease in older men. Prostatic inflammation research has focused on the magnitude of inflammation; its location has received little attention. We investigated whether the anatomic location of prostatic inflammation is related to the severity of lower urinary tract symptoms (LUTS), measured subjectively and objectively. METHODS: We retrospectively analyzed hematoxylin+eosin-stained tissue specimens from 179 BPH patients who underwent transurethral resection of the prostate (TURP) or holmium laser enucleation of the prostate (HoLEP). Chronic prostatic inflammation was assessed by the grade (lymphocyte density), extent (lymphocyte distribution), and location of inflammation. Each inflammation-finding type was evaluated in relation to these clinical parameters: age, prostate volume, prostate-specific antigen (PSA) value, body mass index (BMI), the frequency of acute urinary retention (AUR) episodes, the international prostatic symptom score (IPSS), and urodynamic study results. RESULTS: The magnitude and extent of inflammation were not associated with any clinical parameters. We classified the BPH patients into stromal (n = 72) versus non-stromal (n = 105) groups based on their inflammation's dominant location. The stromal group's prostatic volume was significantly larger than the non-stromal group's (63.8 vs 53.8 mL; P = 0.032). AUR episodes were more significantly frequent in the stromal group (36.1% vs 11.4%; P = 0.006). Between-group differences in storage parameters (ie, maximum cystometric capacity) in the urodynamic study were not significantly different. Voiding parameters differed significantly between the stromal and non-stromal groups: maximum detrusor pressure (maxPdet) (116.8 vs 94.5 cmH2 O, P = 0.014), Pdet at the maximum flow rate (Qmax) (95.8 vs 75.4 cmH2 O, P = 0.014), and the bladder outlet obstruction index (BOOI) (78.5 vs 56.3, P = 0.014). The stromal group's Qmax was significantly lower than the non-stromal group's (7.3 vs 9.8 mL/s, P = 0.004). CONCLUSIONS: The location of inflammation in the prostate might be an important factor affecting the severity of LUTS, especially voiding dysfunction.

Clinicopathological implications to micropapillary bladder urothelial carcinoma of the presence of sialyl Lewis X-decorated mucin 1 in stroma-facing membranes.

OBJECTIVES: Bladder urothelial carcinoma (UC) comprises more than 90% of all bladder cancers. Among several UC variants, micropapillary UC (MPUC) is a rare one with high potential for lymphovascular invasion and subsequent lymph node metastasis. Histologically, MPUC is characterized by the presence of small papillary carcinoma cell clusters surrounded by lacunar spaces. Immunohistochemically, the outer circumference of these clusters, that is, the stroma-facing membrane of carcinoma cells, is reportedly almost invariably positive for mucin 1 (MUC1) protein and to a lesser extent for sialyl Lewis X (sLeX) carbohydrates; however, the clinicopathological implications of these expression patterns have not been fully investigated. MATERIALS AND METHODS: We performed immunohistochemical analysis of MPUC (n = 11) and conventional UC (n = 57) for MUC1 and sLeX to determine whether these factors immunolocalized. Dual immunofluorescence staining was also carried out to assess MUC1 and sLeX colocalization. We also performed Western blot analysis of Chinese hamster ovary cells misexpressing both recombinant epitope-tagged MUC1 and glycosyltransferases enabling sLeX biosynthesis. RESULTS: MPUC samples preferentially exhibited both MUC1 protein and sLeX carbohydrate expression on the stroma-facing membrane of carcinoma cells. Based on univariate analysis, MUC1 expression in that pattern was positively correlated with tumor extension, lymphovascular invasion, lymph node metastasis, disease stage, and relatively poor patient prognosis. A comparable sLeX expression pattern also correlated positively with tumor extension and nodal metastasis. Based on multivariate analysis, localization of MUC1 and sLeX on the stroma-facing side of the membrane was positively correlated with lymph node metastasis. CONCLUSIONS: Overall, our immunofluorescence findings as well as immunoprecipitation analyses of Chinese hamster ovary cell transfectants strongly suggest that MUC1 is a potential scaffold protein for sLeX carbohydrates in MPUC. Both MUC1 and sLeX may cooperatively contribute to MPUC histogenesis and clinicopathological characteristics.

Appearance of High Endothelial Venule-Like Vessels in Benign Prostatic Hyperplasia is Associated With Lower Urinary tract Symptoms.

BACKGROUND: Chronic prostatic inflammation is implicated in the pathogenesis of benign prostatic hyperplasia (BPH)-associated lower urinary tract symptoms (LUTS). Previous studies evaluated the degree of chronic prostatic inflammation based on histological scores, which may contain subjective factors. We previously demonstrated that the number of high endothelial venule (HEV)-like vessels correlates positively with the magnitude of inflammation in chronic inflammatory gastrointestinal diseases. Here, we evaluated the degree of BPH-associated chronic prostate inflammation based on appearance of HEV-like vessels and determined whether the extent of inflammation correlated with LUTS severity, as evaluated by a urodynamic study. METHODS: Eighty-six BPH tissue specimens derived from patients who had undergone urodynamic analysis were immunostained for CD34 and MECA-79 to determine HEV-like vessel number. Triple immunohistochemistry for either CD3 and CD20 or CD4 and CD8, together with MECA-79, was conducted to identify lymphocyte subsets associated with HEV-like vessels. We also determined whether the magnitude of chronic prostatic inflammation, as assessed by HEV-like vessel number, correlated with the degree of LUTS. RESULTS: HEV-like vessels were induced in lymphoid aggregates seen frequently in BPH. The number of HEV-like vessels positively correlated not only with the magnitude of chronic prostatic inflammation but also with the degree of LUTS, particularly with symptoms associated with voiding function, which was measured objectively in a pressure flow study. CONCLUSIONS: Chronic prostate inflammation may promote BPH and resulting voiding dysfunction. Assessment of the number of HEV-like vessels could be a surrogate for identifying the degree of chronic prostatic inflammation. Prostate 77:794-802, 2017. © 2017 Wiley Periodicals, Inc.