Endoscopic Ultrasound-Guided Radiofrequency Ablation as an Future Alternative to Pancreatectomy for Pancreatic Metastases from Renal Cell Carcinoma: A Prospective Study.

BACKGROUND: Pancreatic metastases (PM) from renal cell carcinoma (RCC) are rare, are associated with favorable outcomes and are usually handled by surgery or VEGFR inhibitors, which both have side effects. Endoscopic Ultrasound (EUS)-guided radiofrequency ablation (RFA) is an innovative approach to treat focally deep metastases and could be a relevant technique to control PM from RCC. METHODS: This monocentric, prospective study aimed to evaluate the safety and efficacy of EUS-RFA to treat PM. We included patients with confirmed and progressive PM from RCC. PM was ablated under general anesthesia with a linear EUS scope and a EUS-RFA 19-gauge needle electrode placed into the tumor. RESULTS: Twelve patients from Paoli-Calmettes Institute were recruited between May 2017 and December 2019. Median age was 70.5 years (range 61-75), 50% were female, 100% were ECOG 0-1. At inclusion, mean PM size was 17 mm (range 3-35 mm); and all were progressive before EUS-RFA. Seven patients had EUS-RFA as the only treatment for RCC. We performed 26 EUS-RFA procedures and 21 PM was ablated. Median follow up was 27.7 months (range 6.4-57.1). For evaluable PM, the 6- and 12-month focal control rates were 84% and 73% respectively. One patient treated with TKI developed a paraduodenal abscess 2 months after EUS-RFA and another patient with biliary stent developed hepatic abscesses few days after EUS-RFA. No other severe side effects were experienced. CONCLUSIONS: in this series, which is the largest ever reported, we showed that EUS-RFA is feasible and yields an excellent local control rate for PM from mRCC. With manageable complications, it could be a valuable alternative to pancreatic surgery in well-selected patients.

Development of a mucinous adenocarcinoma on a sigmoid colpoplasty for vaginal agenesis: About a case report and review of the literature.

We report a case of mucinous adenocarcinoma developed on sigmoid colpoplasty, performed for a congenital agenesis vaginal. The cancer development of neovagina remains exceptional. Its management consists, in the majority of cases, in surgery for a complete excision. Adjuvant treatments are associated according to the pathological results and the neovagina reconstruction technique performed.

PD-L1 expression and pattern of immune cells in pre-treatment specimens are associated with disease-free survival for HR-NMIBC undergoing BCG treatment.

PURPOSE: To assess the association between PD-L1 expression and disease-free survival (DFS) in High-Risk Non-Muscle Invasive Bladder Cancer (HR-NMIBC) patients treated with intravesical Bacillus Calmette-Guerin (BCG) instillations (IBI). METHODS: Retrospective study in five French centres between 2001 and 2015. Participants were 140 patients with histologically confirmed HR-NMIBC. All patients received induction and maintenance IBI. Pathological stage/grade, concomitant carcinoma in situ, lesion number and tumour size were recorded. CD3, CD8 and PD-L1 expression in tumour cells and in T cells in the tumour microenvironment (TME) was determined immunohistochemically. Median follow-up was 54.2 months. The primary outcome measure was DFS. Univariable and multivariable analyses were performed using the log rank test and Cox proportional hazards model. RESULTS: Of the 140 NMIBC, 52 (37.1%) were Ta, 88 (62.9%) were T1 and 100% were high grade. Median number of maintenance IBI was six (range 1-30). Twenty-five (17.9%) patients had recurrence/progression. In multivariable analysis, age (HR 1.07 [95% CI 1.02-1.13], p = 0.009), PD-L1 expression in tumour cells (HR per 10 units = 1.96 [95% CI 1.28-3.00], p = 0.02) and CD3/CD8 ratio (HR per 10 units = 3.38 [95% CI 1.61-7.11], p = 0.01) were significantly associated with DFS. However, using the cut-off corresponding for each PD-L1 antibodies, PD-L1 + status was not associated with DFS. CONCLUSION: Despite an association between PD-L1 expression and BCG failure in HR-NMIBC, the PD-L1 + status was not a prognostic factor in the response of BCG. Moreover, we confirmed the key role played by the IC within the microenvironment in BCG treatment. These findings highlighted the rationale to combine BCG and PD-L1/PD-1 antibodies in early bladder cancer.

Vitiligo Adverse Event Observed in a Patient With Durable Complete Response After Nivolumab for Metastatic Renal Cell Carcinoma.

Background: Renal cell carcinoma is the third most prevalent urological cancer worldwide and about 30% of patients present with metastatic disease at the time of diagnosis. Systemic treatments for metastatic renal cell carcinoma have improved recently. Vascular endothelial growth factor targeting therapies were the previous standard of care. However, immune checkpoint inhibitors used in second line therapy have now been shown to improve patient survival. We report a case of metastatic renal cell carcinoma with nivolumab as a second-line therapy after progression with tyrosine kinase inhibitor therapy. Unusual adverse events in metastatic renal cell carcinoma, such as vitiligo, were observed in this patient who developed a remarkable documented pathological complete response to his renal tumor. Case presentation: A 60-year-old caucasian male was diagnosed with a pulmonary metastatic clear cell renal cell carcinoma. Sunitinib was used as first line treatment without success. He received nivolumab in second-line treatment. He developed several immune-related adverse events, most notably vitiligo. The patient had a radiological complete response on metastatic sites, with a significant decrease of renal tumor volume and underwent cytoreductive nephrectomy after 2 years of treatment, confirming the pathological complete response. The patient remains disease-free for 10 months without further systemic therapy after nivolumab discontinuation. Conclusions: Pathological complete response with nivolumab in metastatic renal cell carcinoma is rare. This case further highlights the potentially predictive role of immune-related adverse events during nivolumab therapy for metastatic renal cell carcinoma and raises questions concerning the role of nephrectomy after immune checkpoint inhibitor therapy. Further studies are needed to better identify predictive factors for treatment response to immunotherapy in metastatic renal cell carcinoma, and to better understand the role of nephrectomy after nivolumab treatment.

Effect of glandular metastases on overall survival of patients with metastatic clear cell renal cell carcinoma in the antiangiogenic therapy era.

BACKGROUND: Glandular metastases (GMs) (pancreas, breast, parotid, thyroid, or contralateral adrenal) are rare in metastatic clear cell renal cell carcinoma (mccRCC). In a multicenter study we have assessed outcome from mccRCC with or without GMs. PATIENTS AND METHODS: Patients with mccRCC and GM or non-GM (NGM) at first presentation of mccRCC, treated at 9 European centers (5 French, 3 UK, and 1 Belgian centers) between January 2004 and October 2013, were retrospectively analyzed. Association between overall survival (OS) and site of metastases was assessed using the log-rank test for univariate analysis and the chi-square test for multivariable Cox regression. RESULTS: In all, 138 patients with GM mccRCC and 420 with NGM mccRCC were included; 37.2% patients with GM had Memorial Sloan-Kettering Cancer Center (MSKCC)-favorable risk vs. 18% NGM patients; 10.7% patients with GM had MSKCC-poor risk vs. 27% NGM patients (P<0.0001). Median interval from metastases to treatment was 4.2 months (range: 0-221.3mo). Median OS was 61.5 months (51.4-81.6mo) for GM and 37.4 months (31.3-42mo) for NGM (hazard ratio [HR] = 1.7; 95% CI = 1.3-2.2, P<0.001). In univariate OS analysis, age, delay between initial diagnosis and metastases, MSKCC, bone/lung metastases, and GM or NGM group were significant parameters (P<0.001). In multivariate analysis, adjusted according to MSKCC risk group, NGM vs. GM was a strong prognostic factor (HR = 1.4; 95% CI = 1.0-1.8, P=0.026); bone or liver metastases were also significant (HR = 1.3; 95% CI = 1.1-1.7, P<0.02; HR = 1.4; 95% CI = 1.1-1.7, P<0.02, respectively). Even in patients without bone or liver metastases, GM status was significant (HR = 1.8; 95% CI = 1.2-2.7, P<0.004). CONCLUSIONS: This large retrospective study shows that the presence of at least 1 GM site in development of mccRCC was associated with a significantly longer OS. The presence of GMs vs. NGM disease was an independent prognostic factor for survival irrespective of the presence or absence of bone or liver metastases. This finding could affect daily practice in which patients with mccRCC and GMs should receive more aggressive treatment with a potential for long-term survival. The causal mechanisms for this improved prognosis in GM mccRCC would be evaluated in translational studies.

Radiation therapy following targeted therapy in oligometastatic renal cell carcinoma.

Up to 40% of patients with renal cell carcinoma (RCC) with initially localized disease eventually develop metastasis following nephrectomy. The current standard of care for metastatic RCC (mRCC) is targeted therapy. However, complete response remains rare. A state of oligometastatic disease may exist, in which metastases are present in a limited number of locations; such cases may benefit from metastasis-directed local therapy, based on the evidence supporting resection of limited-volume metastases, allowing for improved disease control. We retrospectively analyzed 7 cases of response of RCC metastases, in patients treated with targeted therapies followed by radiation therapy (RT) of residual metastatic lesions in Paoli-Calmettes Institute (Marseille, France). We analyzed disease response rates, response to sequential strategy, relapse at the irradiated locations and disease evolution. The median follow-up was 34.1 months (range, 19.2-54.5 months). No progression at the irradiated sites was observed. A total of 5 patients had stable disease at the irradiated locations at the last follow-up; 3 remained in complete remission at the assessment, and 2 were stable. Excellent local response and clinical benefit may be achieved without added toxicity. In conclusion, sequential therapeutic strategies with RT following systemic treatment using sunitinib appear to be highly effective in patients with progressive mRCC and prompt the conduction of further confirmatory trials.

Cytokeratin 7 as a predictive factor for response to concommitant radiochemotherapy for locally advanced cervical cancer: a preliminary study.

BACKGROUND: The role of completion surgery after concurrent radiochemotherapy (CCRC) for advanced cervical cancer remains controversial. Individual predictive factors of CCRC response and survival are mandatory for treatment adaptation and to determine a population who would take interest in completion surgery after CCRC. The aim of this study was to evaluate the ability of biomarkers to predict the response to CCRC. PATIENTS AND METHODS: Between 1996 and 2008, in 58 patients with advanced cervical cancer for whom pre-therapeutic cone biopsy was available, we tested several biomarkers (ALDH1, CD44, CD24, IDO, Ki67, P63, CK7, p-Stat3, Foxp3 and IDO). RESULTS: Residual disease was found in 49.1% of cases (n=26). We found a significant association between progression-free survival and residual disease on completion hysterectomy (p=0.044). Univariate analysis of the different factors showed that negativity for cytokeratin 7 expression was a strong predictor for the presence of residual tumor (p=0.001). CONCLUSION: These results are encouraging and CK7 could be used as a predictive factor of response to CCRC.

The Junctional Adhesion Molecule-B regulates JAM-C-dependent melanoma cell metastasis.

Metastasis is a major clinical issue and results in poor prognosis for most cancers. The Junctional Adhesion Molecule-C (JAM-C) expressed by B16 melanoma and endothelial cells has been involved in metastasis of tumor cells through homophilic JAM-C/JAM-C trans-interactions. Here, we show that JAM-B expressed by endothelial cells contributes to murine B16 melanoma cells metastasis through its interaction with JAM-C on tumor cells. We further show that this adhesion molecular pair mediates melanoma cell adhesion to primary Lung Microvascular Endothelial Cells and that it is functional in vivo as demonstrated by the reduced metastasis of B16 cells in Jam-b deficient mice.

Epithelial ovarian tumors: value of dynamic contrast-enhanced MR imaging and correlation with tumor angiogenesis.

PURPOSE: To retrospectively evaluate the diagnostic performance of dynamic contrast material-enhanced magnetic resonance (MR) imaging for the characterization of ovarian epithelial tumors, by using histologic findings as the reference standard, and to correlate dynamic contrast-enhanced MR imaging findings with angiogenesis biomarkers. MATERIALS AND METHODS: Ethics committee approval was obtained, with waiver of informed consent. Patients consented to having their data used for future retrospective research. Forty-one women (age range, 22-73 years) with 48 epithelial ovarian tumors underwent dynamic contrast-enhanced MR imaging before surgical excision. In case of bilateral tumors (n = 7), only the most complex tumor was analyzed. Thus, 41 tumors (12 benign, 13 borderline, and 16 invasive) were examined with dynamic contrast-enhanced MR imaging and immunohistochemical methods. Dynamic contrast-enhanced MR imaging parameters (enhancement amplitude [EA], time of half rising [T(max)], and maximal slope [MS]) were analyzed according to histopathologic findings, microvessel density, pericyte coverage index (PCI), and vascular endothelial growth factor receptor 2 (VEGFR-2) expression. Statistical analyses were performed by using Kruskal-Wallis, Fisher exact, and Spearman tests and receiver operating curve analysis. RESULTS: EA was higher for invasive tumors than for benign (P < .001) and borderline (P < .05) tumors. T(max) was longer for benign tumors than for borderline (P < .05) and invasive (P < .01) tumors. MS was steeper for invasive tumors than for benign (P < .001) and borderline (P < .001) tumors. PCI was lower in invasive tumors than in borderline (P < .05) and benign (P < .05) tumors. Microvessels showed stronger immunohistochemical VEGFR-2 expression in invasive tumors than in benign or borderline tumors (P < .05). MS correlated with a lower PCI (r = -0.34, P = .04) and stronger VEGFR-2 expression by using both epithelial (r = 0.41, P < .01) and endothelial (r = 0.66, P < .001) cells. CONCLUSION: The early enhancement patterns of ovarian epithelial tumors on dynamic contrast-enhanced MR images can help distinguish among benign, borderline, and invasive tumors and were found to correlate with tumoral angiogenic status.