What the urologist needs to know before radical prostatectomy: MRI effective support to pre-surgery planning.

BACKGROUND: Radical prostatectomy (RP) is recommended in case of localized or locally advanced prostate cancer (PCa), but it can lead to side effects, including urinary incontinence (UI) and erectile dysfunction (ED). Magnetic resonance imaging (MRI) is recommended for PCa diagnosis and staging, but it can also improve preoperative risk-stratification. PURPOSE: This nonsystematic review aims to provide an overview on factors involved in RP side effects, highlighting anatomical and pathological aspects that could be included in a structured report. EVIDENCE SYNTHESIS: Considering UI evaluation, MR can investigate membranous urethra length (MUL), prostate volume, the urethral sphincter complex, and the presence of prostate median lobe. Longer MUL measurement based on MRI is linked to a higher likelihood of achieving continence restoration. For ED assessment, MRI and diffusion tensor imaging identify the neurovascular bundle and they can aid in surgery planning. Finally, MRI can precisely describe extra-prostatic extension, prostate apex characteristics and lymph-node involvement, providing valuable preoperative information for PCa treatment. CONCLUSIONS: Anatomical principals structures involved in RP side effects can be assessed with MR. A standardized MR report detailing these structures could assist urologists in planning optimal and tailored surgical techniques, reducing complications, and improving patients' care.

Low cancer yield in PI-RADS 3 upgraded to 4 by dynamic contrast-enhanced MRI: is it time to reconsider scoring categorization?

OBJECTIVES: To evaluate MRI diagnostic performance in detecting clinically significant prostate cancer (csPCa) in peripheral-zone PI-RADS 4 lesions, comparing those with clearly restricted diffusion (DWI-score 4), and those with equivocal diffusion pattern (DWI-score 3) and positive dynamic contrast-enhanced (DCE) MRI. METHODS: This observational prospective study enrolled 389 men referred to MRI and, if positive (PI-RADS 3 with PSA-density [PSAD] ≥ 0.15 ng/mL/mL, 4 and 5), to MRI-directed biopsy. Lesions with DWI-score 3 and positive DCE were classified as "PI-RADS 3up," instead of PI-RADS 4. Univariable and multivariable analyses were implemented to determine features correlated to csPCa detection. RESULTS: Prevalence of csPCa was 14.5% and 53.3% in PI-RADS categories 3up and 4, respectively (p < 0.001). MRI showed a sensitivity of 100.0%, specificity 40.9%, PPV 46.5%, NPV 100.0%, and accuracy 60.9% for csPCa detection. Modifying the threshold to consider MRI positive and to indicate biopsy (same as previously described, but PI-RADS 3up only when associated with elevated PSAD), the sensitivity changed to 93.9%, specificity 57.2%, PPV 53.0%, NPV 94.8%, and accuracy 69.7%. Age (p < 0.001), PSAD (p < 0.001), positive DWI (p < 0.001), and PI-RADS score (p = 0.04) resulted in independent predictors of csPCa. CONCLUSIONS: Most cases of PI-RADS 3up were false-positives, suggesting that upgrading peripheral lesions with DWI-score 3 to PI-RADS 4 because of positive DCE has a detrimental effect on MRI accuracy, decreasing the true prevalence of csPCa in the PI-RADS 4 category. PI-RADS 3up should not be upgraded and directed to biopsy only if associated with increased PSAD. KEY POINTS: • As per PI-RADS v2.1 recommendations, in case of a peripheral zone lesion with equivocal diffusion-weighted imaging (DWI score 3), but positive dynamic contrast-enhanced (DCE) MRI, the overall PI-RADS score should be upgraded to 4. • The current PI-RADS recommendation of upgrading PI-RADS 3 lesions of the peripheral zone to PI-RADS 4 because of positive DCE decreased clinically significant prostate cancer detection rate in our series. • According to our results, the most accurate threshold for setting indication to prostate biopsy is PI-RADS 3 or PI-RADS 3 with positive DCE both associated with increased PSA density.

Prognostic Role of Mismatch Repair Status, Histotype and High-Risk Pathologic Features in Stage II Small Bowel Adenocarcinomas.

BACKGROUND: Small bowel adenocarcinoma is a relatively rare cancer, often diagnosed in an advanced stage. In localized and resectable disease, surgery alone or in combination with adjuvant chemotherapy is the mainstay of treatment. In the recently published National Comprehensive Cancer Network Clinical Practice guidelines, criteria for selecting patients with stage II small bowel adenocarcinoma to receive adjuvant chemotherapy are provided, and they are mainly extrapolated from studies on colorectal cancer. PATIENTS AND METHODS: In the present study, we aimed to verify whether mismatch repair deficiency phenotype, high-risk pathologic features (including T4, positive resection margins and a low number of lymph nodes harvested), as well as tumor histologic subtype, were associated with cancer-specific survival in 66 stage II non-ampullary small bowel adenocarcinoma patients, collected through the Small Bowel Cancer Italian Consortium. A central histopathology review was performed. Mismatch repair deficiency was tested by immunohistochemistry for MLH1, MSH2, MSH6 and PMS2, and confirmed by polymerase chain reaction for microsatellite instability. RESULTS: We identified mismatch repair deficiency, glandular/medullary histologic subtype, and celiac disease as significant predictors of favorable cancer-specific survival using univariable analysis with retained significance in bivariable models adjusted for pT stage. Among the high-risk features, only T4 showed a significant association with an increased risk of death; however, its prognostic value was not independent of mismatch repair status. CONCLUSIONS: Mismatch repair protein expression, histologic subtype, association with celiac disease, and, in the mismatch repair proficient subset only, T stage, may help identify patients who may benefit from adjuvant chemotherapy.

Pancreatic ductal adenocarcinoma and distal cholangiocarcinoma: a proposal of preoperative diagnostic score for differential diagnosis.

PURPOSE: The differential diagnosis between primary adenocarcinoma of the pancreas head and distal cholangiocarcinoma remains a clinical challenge. Recent studies have shown important differences in terms of survival between these tumors. Therefore, different treatments should be considered, but the preoperative histological diagnosis is still difficult. Aim of this study is to create a preoperative diagnostic score for differential diagnosis between primary pancreatic adenocarcinoma and primary distal cholangiocarcinoma. METHODS: One hundred eighty consecutive patients who underwent pancreaticoduodenectomy at Sapienza University of Rome from January 2010 to December 2019 were retrospectively analyzed. Inclusion criteria were pancreatic or biliary histologic origin obtained by definitive postoperative histological examination. Exclusion criteria were diagnosis of ampullary carcinoma, non-ampullary duodenal adenocarcinoma, pancreatic metastasis, and benign disease. One hundred one patients were considered eligible for the retrospective study. Preoperative biological, clinical, and radiological parameters were considered. RESULTS: CRP > 10 mg/dL (p = 0.001), modified Glasgow Prognostic Score 2 (p = 0.002), albumin < 35 g/L (p = 0.05), CA 19-9 > 230 U/mL (p = 0.001), and Wirsung diameter > 3 mm (p < 0.001) were significant at univariate logistic analysis. Multivariate logistic analysis has shown that parameters independently associated with primary pancreatic adenocarcinoma were CRP > 10 mg/dL (p = 0.012), CA 19-9 > 230 U/mL (p = 0.043), and diameter of the Wirsung > 3 mm (p = 0.005). Through these parameters, a diagnostic score has been developed to predict a primary pancreatic adenocarcinoma when > 1 and a primary distal cholangiocarcinoma when < 1. CONCLUSION: This feasible and low-cost diagnostic score could have a potential impact to differentiate pancreatic cancer histologic origin and to improve target therapeutic strategy.

Zero-ischemia testis-sparing surgery for probably benign pediatric testicular tumors.

Permanent ischemia-induced testicular damage may occur as early as 30 min in prepupertal rats. With the goal of potentially enhancing testicular function and fertility preservation, we performed testis-sparing surgery (TSS) without ischemia for testicular lesions in select children with negative markers and high likelihood of benignity on ultrasonography. Preliminary experience suggests that off-clamp TSS should be more liberally encouraged, especially in infants and prepubertal children, given their particularly vulnerable spermatic cord elements.

Correction: PD-L1 in small bowel adenocarcinoma is associated with etiology and tumor-infiltrating lymphocytes, in addition to microsatellite instability.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

PD-L1 in small bowel adenocarcinoma is associated with etiology and tumor-infiltrating lymphocytes, in addition to microsatellite instability.

Small bowel adenocarcinomas (SBAs) are often associated with poor prognosis and have limited therapeutic options. Programmed cell death protein-1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway blockade is an effective treatment in many microsatellite instability-high (MSI-H) solid tumors. We aimed at investigating PD-L1 and PD-1 expression in non-hereditary, non-ampullary SBAs, associated with celiac disease (CeD), Crohn's disease (CrD), or sporadic, recruited through the Small Bowel Cancer Italian Consortium. We assessed PD-L1 and PD-1 by immunohistochemistry in a series of 121 surgically resected SBAs, including 34 CeD-SBAs, 49 CrD-SBAs, and 38 sporadic SBAs. PD-L1 and PD-1 expression was correlated with several clinico-pathological features, such as the etiology, microsatellite instability status, and tumor-infiltrating lymphocyte (TIL) density. The prevalence of PD-L1 positivity according to combined positive score (CPS) was 26% in the whole cohort of SBAs, with significantly (p = 0.001) higher percentage (35%) in both CeD-SBAs and CrD-SBAs in comparison with sporadic SBAs (5%). CPS ≥ 1 SBAs were significantly (p = 0.013) more frequent in MSI-H cases (41%) than in non-MSI-H ones (18%); however, 15 CPS ≥ 1 microsatellite stable SBAs were also identified. CPS ≥ 1 SBAs showed higher TIL and PD-1+ immune cell density, more frequently medullary histotype, as well as a better outcome in comparison with CPS < 1 cases. This study demonstrates an increased proportion of PD-L1+ cases in both CeD-SBAs and CrD-SBAs in comparison with sporadic SBAs. In addition, the identification of a subset of PD-L1+ microsatellite stable SBAs supports the need to ascertain additional biomarkers of response to immune checkpoint inhibitors along with MSI-H.

tsRNA signatures in cancer.

Small, noncoding RNAs are short untranslated RNA molecules, some of which have been associated with cancer development. Recently we showed that a class of small RNAs generated during the maturation process of tRNAs (tRNA-derived small RNAs, hereafter "tsRNAs") is dysregulated in cancer. Specifically, we uncovered tsRNA signatures in chronic lymphocytic leukemia and lung cancer and demonstrated that the ts-4521/3676 cluster (now called "ts-101" and "ts-53," respectively), ts-46, and ts-47 are down-regulated in these malignancies. Furthermore, we showed that tsRNAs are similar to Piwi-interacting RNAs (piRNAs) and demonstrated that ts-101 and ts-53 can associate with PiwiL2, a protein involved in the silencing of transposons. In this study, we extended our investigation on tsRNA signatures to samples collected from patients with colon, breast, or ovarian cancer and cell lines harboring specific oncogenic mutations and representing different stages of cancer progression. We detected tsRNA signatures in all patient samples and determined that tsRNA expression is altered upon oncogene activation and during cancer staging. In addition, we generated a knocked-out cell model for ts-101 and ts-46 in HEK-293 cells and found significant differences in gene-expression patterns, with activation of genes involved in cell survival and down-regulation of genes involved in apoptosis and chromatin structure. Finally, we overexpressed ts-46 and ts-47 in two lung cancer cell lines and performed a clonogenic assay to examine their role in cell proliferation. We observed a strong inhibition of colony formation in cells overexpressing these tsRNAs compared with untreated cells, confirming that tsRNAs affect cell growth and survival.

Upfront debulking surgery versus interval debulking surgery for advanced tubo-ovarian high-grade serous carcinoma and diffuse peritoneal metastases treated with peritonectomy procedures plus HIPEC.

BACKGROUND: Whether patients with advanced tubo-ovarian high-grade serous cancer (HGSC) fare better after upfront debulking surgery (UDS) or neoadjuvant chemotherapy with interval debulking surgery (NACT-IDS) remains controversial. METHODS: We studied patients with HGSC who underwent UDS or NACT-IDS between July 2000 and December 2015, with peritonectomy procedures combined with hyperthermic intraperitoneal chemotherapy (HIPEC). Clinical reports were included peritoneal cancer index (PCI), NACT responses, surgical complexity score (SCS), completeness of cytoreduction (CC), complete follow-up with timing, site, and treatment of recurrence. Outcome measures were morbidity, progression-free survival (PFS), PFS2, and overall survival during a mean 5-year follow-up. RESULTS: A total of 34 patients (23.6%) underwent UDS and 110 (76.4%) NACT-IDS both combined with HIPEC. At a median 66.3-month follow-up, patients who underwent UDS or NACT-IDS had similar outcomes. NACT subgroup responses correlated with PCI, SCS, morbidity, and CC. Patients who underwent UDS had lower recurrence rates than those who responded partly or poorly to NACT (PFS, P < .04; PFS2, P < .01). Despite HIPEC, the peritoneal disease recurred in 42.5% of the overall patients. CONCLUSION: In patients with primary HGSC who undergo UDS or NACT-IDS, despite similar outcomes, peritonectomy procedures combined with HIPEC seem unable to prevent peritoneal recurrence.

Intrapancreatic accessory spleen false positive to 68Ga-Dotatoc: case report and literature review.

BACKGROUND: Intrapancreatic accessory spleen (IPAS) is an uncommon finding of pancreatic mass. Differential diagnosis with pancreatic tumor, especially with non-functional neuroendocrine tumor (NF-NET), may be very hard and sometimes it entails unnecessary surgery. A combination of CT scan, MRI, and nuclear medicine can confirm the diagnosis of IPAS. 68-Ga-Dotatoc PET/CT is the gold standard in NET diagnosis and it can allow to distinguish between IPAS and NET. CASE PRESENTATION: A 69-year-old man was admitted to our hospital for an incidental nodule in the tail of the pancreas with focal uptake of 68-Ga-dotatate at PET/CT. NET was suspected and open distal splenopancreatectomy was performed. Pathologic examination revealed an IPAS. CONCLUSION: This is the second IPAS case in which a positive 68Ga-Dotatoc uptake led to a false diagnosis of pancreatic NET. Here is a proposal of a literature review.

Dynamic contrast-enhanced magnetic resonance imaging in locally advanced rectal cancer: role of perfusion parameters in the assessment of response to treatment.

PURPOSE: To correlate dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters to tumor grading and to assess their reliability in predicting pathological complete response (pCR) before neoadjuvant chemoradiotherapy (CRT) in patients with locally advanced rectal cancer (LARC). MATERIALS AND METHODS: Forty patients (24 male; mean age, 67.3 ± 8.1 years) with histologically proven LARC who had undergone 3-Tesla DCE-MRI before (MRI_1) and after CRT (MRI_2) between August 2015 and February 2016 were included in this retrospective study. DCE-MRI parameters at MRI_1 and MRI_2 were extracted by two board certified radiologists in consensus reading with Olea Sphere 2.3 software using the extended Tofts model. Based on DCE-MRI results, patients were divided in complete responders (CR) and non-complete responders (nCR) and the perfusion parameters were correlated to tumor grading and pCR. RESULTS: Wash-out and Kep at MRI_1 showed significant correlation with LARC grading (P = 0.004 and 0.01, respectively). Ve showed a significant increase between MRI_1 (0.47 ± 0.27) and MRI_2 (0.63 ± 0.23; P = 0.007). Ktrans measured at MRI_1 was significantly higher in CR (0.66 ± 0.48) compared to nCR (0.53 ± 0.34, P = 0.02). CONCLUSION: Wash-out and Kep measured before CRT correlate with LARC grading. Ve changes during CRT, while Ktrans measured before CRT may predict the response to therapy. Therefore, DCE-MRI parameters can predict tumor aggressiveness and CRT efficacy, playing a role as imaging biomarkers in patients with LARC.

Cytoreductive Surgery Plus Hyperthermic Intraperitoneal Chemotherapy for Patients with Peritoneal Metastases from Endometrial Cancer.

BACKGROUND: More information is needed for selection of patients with peritoneal metastases from endometrial cancer (EC) to undergo cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: This study analyzed clinical, pathologic, and treatment data for patients with peritoneal metastases from EC who underwent CRS plus HIPEC at two tertiary centers. The outcome measures were morbidity, overall survival (OS), and progression-free survival (PFS) during a median 5 year follow-up period. Uni- and multivariate analyses were performed to identify significant factors related to outcome. RESULTS: A total of 33 patients met the inclusion criteria and completed the follow-up period. At laparotomy, the median peritoneal cancer index (PCI) was 15 (range 3-35). The CRS procedure required a mean 8.3 surgical procedures per patient, and for 22 patients (66.6%), a complete cytoreduction was achieved. The mean hospital stay was 18 days, and major morbidity developed in 21% of the patients. The operative mortality was 3%. When surgery ended, HIPEC was administered with cisplatin 75 mg/m2 for 60 min at 43 °C. During a median follow-up period of 73 months, Kaplan-Meier analysis indicated a 5 year OS of 30% (median 33.1 months) and a PFS of 15.5% (median 18 months). Multivariate analysis identified the completeness of cytoreduction (CC) score as the only significant factor independently influencing OS. Logistic regression for the clinicopathologic variables associated with complete cytoreduction (CC0) for patients with metachronous peritoneal spread from EC who underwent secondary CRS plus HIPEC identified the PCI as the only outcome predictor. CONCLUSIONS: For selected patients with peritoneal metastases from EC, when CRS leaves no residual disease, CRS plus HIPEC achieves outcomes approaching those for other indications such as colon and ovarian carcinoma.

Depth of colorectal-wall invasion and lymph-node involvement as major outcome factors influencing surgical strategy in patients with advanced and recurrent ovarian cancer with diffuse peritoneal metastases.

BACKGROUND: More information is needed on the anatomopathological outcome variables indicating the appropriate surgical strategy for the colorectal resections often needed during cytoreduction for ovarian cancer. METHODS: From a phase-II study cohort including 70 patients with primary advanced or recurrent ovarian cancer with diffuse peritoneal metastases treated from November 2000 to April 2009, we selected for this study the 52 consecutive patients who needed colorectal resection. Data collected included type of colorectal resection, peritoneal cancer index (PCI), histopathology (depth of bowel-wall invasion and lymph-node spread), cytoreduction rate and outcome. Correlations were tested between possible prognostic factors and Kaplan-Meier five-year overall and disease-free survival. A Cox multivariate regression model was used to identify independent variables associated with outcome. RESULTS: In the 52 patients, the optimal cytoreduction rate was 86.5% (CC0/1). In all patients, implants infiltrated deeply into the bowel wall, in 75% of the cases up to the muscular and mucosal layer. Lymph-node metastases were detected in 50% of the cases; mesenteric nodes were involved in 42.3%. Most patients (52%) had an uneventful postoperative course. Operative mortality was 3.8%. The five-year survival rate was 49.9% and five-year disease-free survival was 36.7%. Cox regression analysis identified as the main prognostic factors completeness of cytoreduction and depth of bowel wall invasion. CONCLUSIONS: Our findings suggest that the major independent prognostic factors in patients with advanced ovarian cancer needing colorectal resections are completeness of cytoreduction and depth of bowel wall invasion. Surgical management and pathological assessment should be aware of and deal with dual locoregional and mesenteric lymphatic spread.

Buschke-Löwenstein tumor with squamous cell carcinoma treated with chemo-radiation therapy and local surgical excision: report of three cases.

Treatment of anorectal Buschke-Löwenstein tumor (BLT) with squamous cell carcinoma (SCC) transformation is not univocal given the rarity of the disease. BLT is characterized by its large size and tendency to infiltrate into underlying tissues. Malignant transformation can occur and it is important to identify the presence of neoplastic foci to decide the proper treatment. Our aim was to assess the effectiveness of neo-adjuvant chemo-radiation therapy (CRT) and local excision in order to avoid abdomino-perineal resection (APR). Three cases of anorectal BLT with SCC transformation are presented. All patients were HIV positive and treated with antiretroviral drugs. They underwent preoperative endoanal ultrasound, biopsies, total body tomography and anal brushing. Treatment consisted of neo-adjuvant chemo-radiation therapy (45 Gy to the pelvis plus a boost with 14.40 Gy to the primary tumor for a total of 59.40 Gy, and mitomycin-C in bolus on the first day, plus 5-fluorouracil by continuous infusion in the first and in the sixth week) and subsequent local surgical excision. During the follow-up, patients were subjected to the same preoperative diagnostic investigations and high resolution anoscopy. All patients showed a complete regression of the lesion after CRT and were treated by local surgical excision, thus avoiding permanent colostomy. In conclusion neo-adjuvant chemo-radiation therapy with local surgical excision could be considered an effective therapy in the treatment of anorectal BLT with SCC transformation to avoid APR.

Clinical and pathological features of primary renal synovial sarcoma: analysis of 64 cases from 11 years of medical literature.

OBJECTIVE: To describe, for the first time, the clinical characteristics of primary renal synovial sarcoma (SS) and to examine the association of histological features with the expression of immunohistochemical markers. PATIENTS AND METHODS: We collated published data on all cases of primary renal SS, from its first description in 2000 to September 2011. Data on clinical and pathological characteristics were extracted and used to create a database. Disease-free survival (DFS) and overall survival (OS) rates were estimated using the Kaplan-Meier method with Rothman's 95% confidence intervals (CIs) and compared across the groups using the log-rank test. The associations between tumour extension and histological features were evaluated using the non-parametric Spearman rank test. A chi-squared test was used to assess the differences between groups. RESULTS: In the overall cohort, the median OS was 48 months (95% CI, 14.1-81.9). Cox analysis showed that the risk of death at diagnosis was greatly increased in patients with metastatic disease compared with those with non-metastatic disease (hazard ratio [HR]: 343.9, 95% CI, 2.8-42,000; P= 0.017). The median DFS was 33.0 months (95% CI, 16.8-49.2), and patients who develop metastatic disease have a very poor prognosis with a median survival of 6 months (95% CI, 5.1-6.9). Microscopic features were monophasic, biphasic and poorly differentiated synovial sarcoma in 76, 16 and 8% of patients, respectively. Significant differences in expression of immunohistochemical markers or genetic mutation were found between different subtypes. CONCLUSIONS: Despite its retrospective nature, this study shows that renal SS comprises different histological subtypes, which are characterized by specific immunohistochemical stains and by specific translocations. When diagnosed at metastatic stage, the prognosis was very poor compared with that for non-metastatic disease, even though one out of three patients with non-metastatic disease had disease relapse. Cooperative efforts and publication of cases with adequate follow-up are necessary to better define prognosis and therapeutic strategies for this rare disease.

MRI-directed biopsy for primary detection of prostate cancer in a population of 223 men: MRI In-Bore vs MRI-transrectal ultrasound fusion-targeted techniques.

OBJECTIVES: To compare the detection rates of overall prostate cancer (PCa) and clinically significant PCa (csPCa) and the median percentage of cancer per biopsy core between MRI-guided In-bore and MRI-TRUS fusion-targeted biopsy (TBx). METHODS: In this retrospective study, 223 patients who underwent prostate multiparametric MRI (mpMRI) and subsequent MR-directed biopsy were included. For PCa and csPCa detection rate (DR), contingency tables were tested via the Pearson's chi-squared to explore the variance of the outcome distribution. The percentage of cancer per biopsy core was tested with a two-tailed Mann-Withney test. RESULTS: One hundred and seventeen and 106 patients underwent MRI-TRUS fusion or MRI In-bore TBx, respectively. 402 MRI biopsy targets were identified, of which 206 (51.2%) were biopsied with the MRI-TRUS TBx and 196 (48.8%) with the MRI In-bore TBx technique. Per-patient PCa and csPCa detection rates were 140/223 (62.8%) and 97/223 (43.5%), respectively. PCa-DR was 73/117 (62.4%) and 67/106 (63.2%) for MRI-TRUS and MRI In-Bore TBx (p = 0.9), while csPCa detection rate reached 50/117 (42.7%) and 47/106 (44.3%), respectively (p = 0.81). The median per-patient percentage of malignant tissue within biopsy cores was 50% (IQR: 27-65%) for PCa and 60% (IQR: 35-68%) for csPCa, with a statistically significant difference between the techniques. CONCLUSION: No statistically significant difference in the detection rate of MRI In-bore and MRI-TRUS fusion TBx was found. MRI In-bore TBx showed higher per-core percentage of malignant cells. ADVANCES IN KNOWLEDGE: MRI In-bore biopsy might impact risk stratification and patient management considering the higher per-core percentage of malignant cells, especially for patients eligible for active surveillance or focal therapy.

An organoid model of colorectal circulating tumor cells with stem cell features, hybrid EMT state and distinctive therapy response profile.

BACKGROUND: Circulating tumor cells (CTCs) are responsible for the metastatic dissemination of colorectal cancer (CRC) to the liver, lungs and lymph nodes. CTCs rarity and heterogeneity strongly limit the elucidation of their biological features, as well as preclinical drug sensitivity studies aimed at metastasis prevention. METHODS: We generated organoids from CTCs isolated from an orthotopic CRC xenograft model. CTCs-derived organoids (CTCDOs) were characterized through proteome profiling, immunohistochemistry, immunofluorescence, flow cytometry, tumor-forming capacity and drug screening assays. The expression of intra- and extracellular markers found in CTCDOs was validated on CTCs isolated from the peripheral blood of CRC patients. RESULTS: CTCDOs exhibited a hybrid epithelial-mesenchymal transition (EMT) state and an increased expression of stemness-associated markers including the two homeobox transcription factors Goosecoid and Pancreatic Duodenal Homeobox Gene-1 (PDX1), which were also detected in CTCs from CRC patients. Functionally, CTCDOs showed a higher migratory/invasive ability and a different response to pathway-targeted drugs as compared to xenograft-derived organoids (XDOs). Specifically, CTCDOs were more sensitive than XDOs to drugs affecting the Survivin pathway, which decreased the levels of Survivin and X-Linked Inhibitor of Apoptosis Protein (XIAP) inducing CTCDOs death. CONCLUSIONS: These results indicate that CTCDOs recapitulate several features of colorectal CTCs and may be used to investigate the features of metastatic CRC cells, to identify new prognostic biomarkers and to devise new potential strategies for metastasis prevention.

Clinical Effects of Oral Bacteriotherapy on Anal HPV Infection and Related Dysplasia in HIV-Positive MSM: Results from the "HPVinHIV" Trial.

BACKGROUND: Anal HPV infection, anal dysplasia and, ultimately, anal cancer are particularly common in HIV-infected men who have sex with men. Treatment of anal dysplasia, aiming to prevent evolution to squamous cell carcinoma of the anus, is currently limited to direct ablation and/or application of topical therapy. The aim of the present study is to investigate the effect of oral bacteriotherapy (Vivomixx® in EU, Visbiome® in USA) on anal HPV infection and HPV-related dysplasia of the anal canal in HIV-infected men who have sex with men. METHODS: In this randomized, placebo-controlled, quadruple-blinded trial (NCT04099433), HIV-positive men who have sex with men with anal HPV infection and HPV-related dysplasia were randomized to receive oral bacteriotherapy or placebo for 6 months. Anal HPV test, anal cytology and high resolution anoscopy with biopsies of anal lesions were performed at baseline and at the end of the study. Safety and tolerability of oral bacteriotherapy were also evaluated. Interim analysis results were presented. RESULTS: 20 participants concluded the study procedures to date. No serious adverse events were reported. In respect to participants randomized to placebo, individuals in the experimental arm showed higher rate of anal dysplasia regression (p = 0.002), lower rate of onset of new anal dysplasia (p = 0.023) and lower rates of worsening of persistent lesions (p = 0.004). Clearance of anal HPV infection was more frequently observed in the bacteriotherapy group (p = 0.067). CONCLUSION: Being an interim analysis, we limit ourselves to report the preliminary results of the current study. We refer the conclusions relating to the possible effectiveness of the intervention to the analysis of the definitive data.

Prospective comparative trial on nerve-sparing radical prostatectomy using a robot-assisted versus laparoscopic technique: expectation versus satisfaction and impact on surgical margins.

INTRODUCTION: The aim of this study was to analyze whether differences exist in a population selected for a nerve-sparing (NS) procedure between robot-assisted (RARP) and laparoscopic radical prostatectomy (LRP), and whether they can have an impact on surgical margins (SM) status. MATERIAL AND METHODS: This is a single center prospective comparative trial on prostate cancer patients submitted to a RARP-NS or LRP-NS. A self-administered questionnaire on expectations before surgery, and level of satisfaction after surgery was used. RESULTS: A total of 134 cases were included in our analysis. A higher percentage of capsular bulging was found in the RARP group, compared to the LRP group (p = 0.077). At biopsy, the percentage of positive cores and multifocality were higher in the RARP group (p = 0.005). Positive SM (SM+) rate was higher in the RARP, than in LRP group (p = 0.046). On univariable analysis, the risk of SM+ increased 1.95 times using RARP when compared with LRP. On multivariable analysis, the surgical approach did not maintain a significant predictive role in terms of risk for SM+. Expectations before surgery were mainly focused on oncological radicality, however in the RARP group a higher percentage of cases focused on sexual function recovery. Satisfaction after surgery was lower in the RARP than in the LRP group. CONCLUSIONS: Comparing LRP-NS with RARP-NS in a high-volume single center, the expectation/satisfaction ratio is in favor of LRP. Worse oncologic preoperative characteristics in the RARP group may influence the higher incidence of SM+. However, the surgical approach does not result as a significant and independent factor able to influence SM positivity.

A Prognostic Score for Predicting Survival in Patients With Pancreatic Head Adenocarcinoma and Distal Cholangiocarcinoma.

BACKGROUND/AIM: Survival of patients with pancreatic cancer remains poor despite improvements in therapeutic strategies. This study aims to create a novel preoperative score to predict prognosis in patients with tumors of the pancreaticobiliary head. PATIENTS AND METHODS: Data on 190 patients who underwent to pancreaticoduodenectomy at Sapienza University of Rome from January 2010 to December 2018 were retrospectively analyzed. After exclusion criteria, 101 patients were considered eligible for retrospective study. Preoperative biological, clinical and radiological parameters were considered. RESULTS: Pancreatic ductal adenocarcinoma [hazard ratio (HR)=1.995, 95% confidence intervaI (CI)=1.1-3.3; p=0.01], carbohydrate antigen 19.9 (CA 19.9) >230 U/ml (HR=2.414, 95% CI=2.4-1.5, p<0.0001) and Wirsung duct diameter >3 mm (HR=1.592, 95% CI=1.5-0.9; p=0.08) were the only parameters associated with poor prognosis. Through these parameters, a prognostic score (PHT score) was developed which predicted worst survival when exceeding 2 and better survival when ≤2. CONCLUSION: The PHT score may have a potential impact on predicting overall survival and consequently modulate the timing and type of treatment (up-front surgery vs. neoadjuvant therapy) patients are offered.