Immune checkpoint inhibitors for BCG-resistant NMIBC: the dawn of a new era.

INTRODUCTION: High risk non-muscle invasive bladder cancer (NMIBC) is a recurring and potentially lethal disease. To date, with the exception of radical surgery, there are no validated strategies for patients not responding to intravesical BCG therapy. Immune checkpoint inhibitors (ICI) are currently being tested for BCG-resistant NMIBC. We report current available data and ongoing trials exploring the efficacy and safety of ICI in this setting. EVIDENCE ACQUISITION: A narrative search was performed including the combination of the following words: ("immunotherapy") AND ("BCG" AND "resistant" OR "non-muscle AND invasive") AND ("bladder AND "cancer"). Three search engines: PubMed, Embase and Web of Science were queried up to November 1, 2020. Congress abstracts reporting results and not only trials' design were also referenced. The US National Library of Medicine was queried via clinicaltrials.gov to explore ongoing trials on the subject. EVIDENCE SYNTHESIS: Pembrolizumab demonstrated a promising 40.6% (95% CI: 30.7-51.1) complete response within the KEYNOTE-057, with a median duration of response of 16.2 months. Preliminary data in the phase II SWOG S1605 trial with atezolizumab showed a 41.1% complete response at 3 months. Avelumab is being tested in the PREVERT phase II study exploring ICI with radiotherapy (60-66 Gy) of the whole bladder. CheckMate 9UT analyzes nivolumab monotherapy versus nivolumab + BMS-986205 (IDO-1 inhibitor) with or without BCG in patients with BCG-unresponsive, carcinoma in situ with or without papillary component. Finally, durvalumab is being studied in the BCG resistant space with radiotherapy in the ADAPT-BLADDER study. After proving its safety profile in the phase 1, the trial will randomize patients to durvalumab + BCG, durvalumab + radiation therapy (6Gy 3×) or BCG rechallenge. CONCLUSIONS: Pembrolizumab has received FDA approval in the treatment of BCG-resistant NMIBC. All five other ICI molecules are currently being extensively tested within clinical trials. The results of the currently ongoing studies are awaited with impatience by the uro-oncologic community and will probably open a new era in the treatment of BCG-resistant NMIBC.

Testicular microlithiasis: Systematic review and Clinical guidelines.

INTRODUCTION: There are no clear recommendations on how patients with testicular microlithiasis should be followed up. The aim of our systematic review is to give clinical guidelines based on the evidence in the literature. METHODS: A web search was conducted during February 2018 based on Pubmed data, Embase and Cochrane database. The eligibility of articles was defined using the PICOS method, in concordance with the PRISMA recommendations. RESULTS: Fifty three articles were selected for our final synthesis. Our review highlighted an association between testicular microlithiasis and the already known risk factors of testicular germ cell tumor. The presence of testicular microlithiasis in patients with such risk factors increases more the risk of cancer. In the absence of risk factors, the risk to develop testicular cancer is similar to the risk in general population. CONCLUSION: In patients at risk to develop testicular cancer, observation versus testicular biopsy is debatable. We recommend an individualized approach based on the age of the patient, the presence of concurrent features of testicular dysgenesis syndrome, the fertility of the couple, the desire of paternity and the ultrasound pattern (bilateral and clustered vs. unilateral and limited).

Pitfalls of Diagnosing Left Lower Quadrant Pain Causes: Making the Uncommon Common Again.

BACKGROUND Left-sided acute appendicitis, although well described in the literature, is still an easily missed diagnosis. Midgut malrotation and situs inversus are 2 known leading conditions that contribute to misdiagnosis of appendicitis. CASE REPORT Here is the case of a 27-year-old male without any previous medical history, who presented with left lower quadrant tenderness and was misdiagnosed with gastroenteritis as an outpatient and sent home; the patient presented the next day to the emergency department where he was found to have acute appendicitis with situs inversus. He underwent laparoscopic appendectomy where a phlegmon was identified. Pathology came back as peri-appendiceal mucocele with no signs of malignancy. CONCLUSIONS This case report aimed to revisit the idea of left-sided acute appendicitis and discuss the management of a perforated appendiceal mucocele contained by a phlegmon.

Association between phosphodiesterase type 5 inhibitors and prostate cancer: A systematic review.

INTRODUCTION: We aim to assess the effect of phosphodiesterase type 5 inhibitors (PDE5I) on prostate cancer risk as well on biochemical recurrence after radical prostatectomy. METHOD: We performed a research using the following keywords "Phosphodiesterase type 5 inhibitors" and "Prostate cancer". Only trials examining the effect of PDE5I on prostate cancer risk and recurrence after radical prostatectomy were included. RESULTS: Seventeen preclinical trials and seven clinical trials were included. Preclinical studies demonstrate a pivotal role for PDE5I as a modulator of apoptosis preventing prostate carcinogenesis. The clinical benefit of PDE5I was not demonstrated. PDE5I use was not associated with decreased prostate cancer diagnosis in two retrospective cohort studies. Biochemical recurrence after radical prostatectomy was not lower (nor higher) in patients taking PDE5I in three retrospective case match studies. CONCLUSION: Based on this review, a change in our practice regarding pharmacological reeducation after radical prostatectomy is not justified.