Intratumoral injection of ilixadencel, consisting of proinflammatory allogeneic dendritic cells, before nephrectomy, followed by sunitinib treatment after nephrectomy showed a trend for improved ...tumor response rate and overall survival, compared with sunitinib monotherapy.
The prognosis of patients with synchronous metastatic renal cell carcinoma (mRCC) is poor. Whereas single-agent tyrosine kinase inhibition (TKI) is clearly insufficient, the effects can be enhanced by combinations with immune checkpoint inhibitors. Innovative treatment options combining TKI and other immune-stimulating agents could prove beneficial.
To evaluate the clinical effects on metastatic disease when two doses of allogeneic monocyte-derived dendritic cells (ilixadencel) are administrated intratumorally followed by nephrectomy and treatment with sunitinib compared with nephrectomy and sunitinib monotherapy, in patients with synchronous mRCC.
A randomized (2:1) phase 2 multicenter trial enrolled 88 patients with newly diagnosed mRCC to treatment with the combination ilixadencel/sunitinib (ILIXA/SUN; 58 patients) or sunitinib alone (SUN; 30 patients).
The primary endpoints were 18-mo survival rate and overall survival (OS). A secondary endpoint was objective response rate (ORR) assessed up to 18 mo after enrollment. Statistic evaluations included Kaplan-Meier estimates, log-rank tests, Cox regression, and stratified Cochran-Mantel-Haenszel tests.
The median OS was 35.6 mo in the ILIXA/SUN arm versus 25.3 mo in the SUN arm (hazard ratio 0.73, 95% confidence interval 0.42–1.27; p = 0.25), while the 18-mo OS rates were 63% and 66% in the ILIXA/SUN and SUN arms, respectively. The confirmed ORR in the ILIXA/SUN arm were 42.2% (19/45), including three patients with complete response, versus 24.0% (six/25) in the SUN arm (p = 0.13) without complete responses. The study was not adequately powered to detect modest differences in survival.
The study failed to meet its primary endpoints. However, ilixadencel in combination with sunitinib was associated with a numerically higher, nonsignificant, confirmed response rate, including complete responses, compared with sunitinib monotherapy.
We studied the effects of intratumoral vaccination with ilixadencel followed by sunitinib versus sunitinib only in a randomized phase 2 study. The combination treatment showed numerically higher numbers of confirmed responses, suggesting an immunologic effect.
Összefoglaló. Bevezetés: A kis méretű vesedaganatok között lényegesen gyakoribbak a benignus elváltozások, és a kis malignus tumorok biológiai tulajdonságai is kedvezőbbek, mint a nagyobb ...daganatokéi. Célkitűzés: Szerzők a kis méretű vesetumorok tulajdonságait vizsgáltuk különböző alcsoportokban. Módszer: 2000. január 1. és 2015. január 1. között 1272 beteg esetén végeztünk műtétet vesedaganat miatt. Közülük 496 betegnek volt kis méretű vesetumora. A betegek átlagéletkora 59 ± 12 év volt. A betegeket a tumorméret alapján három csoportba osztottuk. Az 1. csoportban a daganat mérete ≤4 cm, a 2. csoportban ≤3 cm és a 3. csoportban ≤2 cm volt. Eredmények: Az eltávolított daganat nagysága átlagosan 29 ± 8 mm volt. A szövettan 418 esetben (84%) malignus, míg 78 alkalommal (16%) benignus elváltozást mutatott. A 2 cm-nél kisebb daganatoknál malignitás csak az esetek 73,2%-ában fordult elő. A malignus és a benignus tumorok méretében szignifikáns eltérés volt (p = 0,008). Rosszul differenciált daganat - grade 3. és 4. - az esetek 10,8%-ában, 14,4%-ában, illetve 20,7%-ában volt jelen, amikor a tumorméret kisebb mint 2 cm, 2,1-3 cm, illetve 3,1-4,0 cm volt. A vesecarcinomáknál az átlagosan 10 éves utánkövetési idő alatt progresszió az esetek 5,5%-ában fordult elő. Következtetés: A kis méretű vesetumor az összes vesedaganat 39%-át tette ki. Ezek nagy része malignus volt, és benignus elváltozás az esetek 16%-ában fordult elő. A malignitás előfordulása a 2 cm-nél kisebb tumoroknál volt a legalacsonyabb. A tumorméret szoros összefüggést mutatott a malignitás gyakoriságával és a daganat differenciáltságával. A kedvező patológiai és biológiai eredmények alapján a 2 cm alatti daganatoknál felmerül annak lehetősége, hogy esetükben az aktív követés vagy minimálisan invazív kezelés alkalmazása kerüljön előtérbe. Orv Hetil. 2021; 162(42): 1693-1697.
The incidence of benign lesions is more common in small renal masses (SRMs) and biological behavior of small malignancies is better compared to larger ones.
The authors measured the characteristics of SRMs in different subgroups.
From January 1, 2000 to January 1, 2015, 1272 patients underwent surgery for renal tumors. In 496 of the 1272 cases, the patients had SRMs. The mean age of the patients was 59 ± 12 years. Based on the sizes, the SRMs were divided into three groups. The sizes of the renal tumors were ≤4 cm in Group 1, ≤3 cm in Group 2 and ≤2 cm in Group 3.
The mean diameter of the removed SRMs was 29 ± 8 mm. Histology confirmed renal cell carcinoma in 418 cases (84%), while benign tumor was present in 78 patients (16%). However, with the tumor size ≤2 cm, malignancy was detected in 73.2% of the cases. There was a significant difference in the sizes of the malignant and the benign masses (p = 0.008). Grade 3 or 4 tumors were present in 10.8%, 14.4% and 20.7% when the tumor size was ≤2 cm, 2.1 to 3 cm, and 3.1 to 4 cm in diameter, respectively. During the mean 10-year follow-up period, tumor progression was detected only in 5.5% of malignancies.
In 39% of all cases, the patients had SRMs. The majority of SRMs were malignant, and benign lesion occurred only in 16% of the cases. The incidence of malignant tumors was the lowest when the size of SRMs was ≤2 cm. The size of the tumor was highly associated with probability of malignancy and tumor grading. Based on the favorable pathological and biological results in tumors below 2 cm, active surveillance or minimally invasive treatment could be the preferred management. Orv Hetil. 2021; 162(42): 1693-1697.
Background: MicroRNAs (miRNAs) play a regulatory role in various human cancers. The roles of hsa-miR-15a-5p, hsa-miR-99b-5p, and hsa-miR-181a-5p have not been fully explored in the angiogenesis of ...renal cell carcinoma (RCC). Aims: The present study aimed to evaluate the expression of these miRNAs in tumorous and adjacent healthy tissues of RCC. Methods: Paired tumorous and adjacent normal kidney tissues from 20 patients were studied. The expression levels of hsa-miR-15b-5p, hsa-miR-99b-5p, and hsa-miR-181a-5p were quantified by TaqMan miRNA Assays. Putative targets were analyzed by qRT-PCR. Results: Significant downregulation of all three miRNAs investigated was observed in tumorous samples compared to adjacent normal kidney tissues. Spearman analysis showed a negative correlation between the expression levels of miRNAs and the pathological grades of the patients. Increased expression of vascular endothelial growth factor-A (VEGF-A) and hypoxia-inducible factor-1α (HIF-1α), a tissue inhibitor of metalloproteinases-1 (TIMP-1), was observed in tumorous samples compared to adjacent normal tissues. Depletion of tissue inhibitors of metalloproteinase-2 (TIMP-2) and metalloproteinase-2 (MMP-2) was detected compared to normal adjacent tissues. The examined miRNAs might function as contributing factors to renal carcinogenesis. However, more prospective studies are warranted to evaluate the potential role of miRNAs in RCC angiogenesis.
Purpose
To compare the androgen receptor (AR) status of the appendix testis (AT) in congenital undescended and retractile testes.
Materials and methods
Twenty-four appendix testes (AT) were removed ...from 21 boys to detect AR expression by immunohistochemistry and immunofluorescence staining. Group 1 (
n
= 3) includes ATs from three patients with unilateral and group 2 (
n
= 6) with bilateral congenital undescended testis. All patients with bilateral form had been previously treated with human chorionic gonadotropin (hCG) without an acceptable effect. Group 3 (
n
= 12) includes ATs collected from 12 boys with acquired undescended testis or retractile testicle. Group 4 (
n
= 3) includes ATs from three young adults who received hCG treatment for undescended testis in their childhood and underwent open testicular biopsy to investigate infertility. Further seven ATs were collected to detect AR mRNA using RT-PCR analysis.
Results
Both immunohistochemistry and immunofluorescence staining of ATs showed AR expression in 100 % of the cases in groups 3 and 4 (12/12 and 3/3), but there was no visible AR expression in groups 1 and 2 (0/3 and 0/6); however, RT-PCR analysis revealed mRNA expression of AR both in congenital undescended and in retractile testicles.
Conclusions
The presence of AR in the epithelial cells of AT in patients with retractile testicle and its absence in patients with congenital undescended testis can be a possible cause of the effectiveness of hormonal treatment in retractile testis and its inefficacy in patients with congenital undescended testis.
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