Neutrophils Driving Unconventional T Cells Mediate Resistance against Murine Sarcomas and Selected Human Tumors.

Neutrophils are a component of the tumor microenvironment and have been predominantly associated with cancer progression. Using a genetic approach complemented by adoptive transfer, we found that neutrophils are essential for resistance against primary 3-methylcholantrene-induced carcinogenesis. Neutrophils were essential for the activation of an interferon-γ-dependent pathway of immune resistance, associated with polarization of a subset of CD4- CD8- unconventional αß T cells (UTCαß). Bulk and single-cell RNA sequencing (scRNA-seq) analyses unveiled the innate-like features and diversity of UTCαß associated with neutrophil-dependent anti-sarcoma immunity. In selected human tumors, including undifferentiated pleomorphic sarcoma, CSF3R expression, a neutrophil signature and neutrophil infiltration were associated with a type 1 immune response and better clinical outcome. Thus, neutrophils driving UTCαß polarization and type 1 immunity are essential for resistance against murine sarcomas and selected human tumors.

PTX3 is an extrinsic oncosuppressor regulating complement-dependent inflammation in cancer.

PTX3 is an essential component of the humoral arm of innate immunity, playing a nonredundant role in resistance against selected microbes and in the regulation of inflammation. PTX3 activates and regulates the Complement cascade by interacting with C1q and with Factor H. PTX3 deficiency was associated with increased susceptibility to mesenchymal and epithelial carcinogenesis. Increased susceptibility of Ptx3(-/-) mice was associated with enhanced macrophage infiltration, cytokine production, angiogenesis, and Trp53 mutations. Correlative evidence, gene-targeted mice, and pharmacological blocking experiments indicated that PTX3 deficiency resulted in amplification of Complement activation, CCL2 production, and tumor-promoting macrophage recruitment. PTX3 expression was epigenetically regulated in selected human tumors (e.g., leiomyosarcomas and colorectal cancer) by methylation of the promoter region and of a putative enhancer. Thus, PTX3, an effector molecule belonging to the humoral arm of innate immunity, acts as an extrinsic oncosuppressor gene in mouse and man by regulating Complement-dependent, macrophage-sustained, tumor-promoting inflammation.

Diagnostic performance of microUltrasound at MRI-guided confirmatory biopsy in patients under active surveillance for low-risk prostate cancer.

BACKGROUND: Active surveillance (AS) represents a standard of care of low-risk prostate cancer (PCa). However, the identification and monitoring of AS candidates remains challenging. Microultrasound (microUS) is a novel high-resolution imaging modality for transrectal ultrasonography (TRUS). We explored the impact of microUS TRUS and targeted biopsies in mpMRI-guided confirmatory biopsies. METHODS: Between October 2017 and September 2021, we prospectively enrolled 100 patients scheduled for MRI-guided confirmatory biopsy at 1 year from diagnosis of ISUP 1 PCa. TRUS was performed using the ExactVu microUS system; PRI-MUS protocol was applied to identify suspicious lesions (i.e., PRIMUS score ≥ 3). All patients received targeted biopsies of any identified microUS and mpMRI lesions and complementary systematic biopsies. The proportion of patients upgraded to clinically significant PCa (defined as ISUP ≥ 2 cancer; csPCa) at confirmatory biopsies was determined, and the diagnostic performance of microUS and mpMRI were compared. RESULTS: Ninety-two patients had a suspicious MRI lesion classified PI-RADS 3, 4, and 5 in respectively 28, 16, and 18 patients. MicroUS identified 82 patients with suspicious lesions, classified as PRI-MUS 3, 4, and 5 in respectively 20, 50, and 12 patients, while 18 individuals had no lesions. Thirty-four patients were upgraded to ISUP ≥ 2 cancer and excluded from AS. MicroUS and mpMRI showed a sensitivity of 94.1% and 100%, and an NPV of 88.9% and 100%, respectively, in detecting ISUP ≥ 2 patients. A microUS-mandated protocol would have avoided confirmatory biopsies in 18 patients with no PRI-MUS ≥ 3 lesions at the cost of missing four upgraded patients. CONCLUSIONS: MicroUS and mpMRI represent valuable imaging modalities showing high sensitivity and NPV in detecting csPCa, thus allowing their use for event-triggered confirmatory biopsies in AS patients. MicroUS offers an alternative imaging modality to mpMRI for the identification and real-time targeting of suspicious lesions in AS patients.

Diagnostic Performance and Clinical Impact of PSMA PET/CT versus mpMRI in Patients with a High Suspicion of Prostate Cancer and Previously Negative Biopsy: A Prospective Trial (PROSPET-BX).

BACKGROUND: This prospective single-arm study is designed to compare in parallel 68Ga-PSMA PET/TRUS (transrectal or transperineal) fusion biopsy ("experimental test") with multiparametric MRI (mpMRI)/TRUS fusion prostate biopsy ("standard test") in men with a high suspicion of prostate cancer (PCa) after at least one negative biopsy. The primary objective was to evaluate the diagnostic performance of 68Ga-PSMA PET/TRUS fusion prostate biopsy in comparison to mpMRI/TRUS fusion prostate biopsy analyzed in parallel. Secondarily, we aimed to determine the relationship between the "experimental test" and the histopathological characteristics of the specimen, along with the clinical utility of the "experimental test" compared to the "standard test." SUMMARY: To test the superiority of 68Ga-PSMA PET/CT compared to mpMRI, we will enroll a minimum cohort of 128 patients. Inclusion criteria comprise: age >18 years; blood PSA level >4.0 ng/mL; free-to-total PSA ratio <20%; progressive rise of PSA levels in two consecutive blood samples despite antibiotics; serum blood tests suspicious for PCa; at least one previous negative biopsy; ASAP and/or high-grade PIN; negative digital rectal examination. All eligible patients will undergo 68Ga-PSMA PET/CT and mpMRI scans within 1 month's distance from each other, followed by biopsy session to be completed within 1 month's distance. Targeted TRUS fusion needle biopsy will be performed for all lesions detected with PET and mpMRI. The total duration of the study is 36 months. KEY MESSAGES: By comparing the "experimental test" and the "standard test" in parallel, we will be able to determine the superior diagnostic performance of 68Ga-PSMA PET/CT over mpMRI in detecting PCa, and in particular clinically significant PCa, in the specific cohort of patients with a high suspicion of PCa who are candidates to re-biopsy. The clinical impact of the "experimental test" will be subsequently analyzed in terms of the number of prostate biopsies that could be spared, time-consuming, patient friendliness, and cost-effectiveness.

Testicular Germ-Cell Tumors with Spermatic Cord Involvement: A Retrospective International Multi-Institutional Experience.

The 8th Edition of the American Joint Committee on Cancer (AJCC) Staging Manual designates discontinuous involvement of spermatic cord soft tissue by testicular germ cell tumors as a metastatic deposit. We conducted a retrospective international multi-institutional study to validate the current recommendations. Thirty-three (72%) nonseminomatous and 13 (28%) seminomatous testicular germ cell tumors were collected from 15 institutions in America, Europe, and Asia. Testicular tumor size ranged from 1.3 to 18.0 cm (mean: 6.1). Cases were classified as discontinuous involvement of spermatic cord soft tissue (n = 26), continuous cord involvement (n = 17), or cord lymphovascular invasion (n = 3). The mean follow-up was 39 months. Clinical stage for discontinuous involvement of spermatic cord soft-tissue patients was I (local disease) in 2/24 (8%), II (regional disease) in 6/24 (25%), and III (distant disease) in 16/24 (67%) cases; 16 (67%) patients presented with distant metastasis. Clinical stage for continuous cord involvement patients was I in 9/17 (53%), II in 4/17 (23%), and III in 4/17 (23%); 4 (23%) patients presented with distant metastasis. Disease progression was seen in 4 patients with discontinuous involvement of spermatic cord soft tissue and 5 with continuous cord-involvement (p = 0.699). When comparing discontinuous and continuous cord involvement, a significant difference was found in cord margin status (p = 0.044), spermatic cord tumor size (p = 0.016), lymph-node involvement (p = 0.037), distant metastasis (p = 0.010), individual clinical stage (p = 0.003), and nonadvanced vs. advanced disease (p = 0.003) at presentation. In multivariate analysis, after adjusting for age, histology, testicular tumor size, percent of embryonal carcinoma, lymphovascular invasion, and cord margin status, discontinuous involvement of spermatic cord soft tissue was significantly associated (p = 0.011) with advanced clinical stage at presentation. Our findings support the designation of metastatic disease for discontinuous involvement of spermatic cord soft tissue, as introduced by the 8th edition of the AJCC staging.

The Prognostic Role of ß-Catenin Mutations in Desmoid-type Fibromatosis Undergoing Resection Only: A Meta-analysis of Individual Patient Data.

OBJECTIVE: This meta-analysis (PROSPERO CRD42018100653) uses individual patient data (IPD) to assess the association between recurrence and CTNNB1 mutation status in surgically treated adult desmoid-type fibromatosis (DTF) patients. SUMMARY OF BACKGROUND DATA: The majority of sporadic DTF tumors harbor a CTNNB1 (ß-catenin) mutation: T41A, S45F, and S45P or are wild-type (WT). Results are conflicting regarding the recurrence risk after surgery for these mutation types. METHODS: A systematic literature search was performed on June 6th, 2018. IPD from eligible studies was used to analyze differences in recurrence according to CTNNB1 mutation status using Cox proportional hazards analysis. Predictive factors included: sex, age, mutation type, tumor site, tumor size, resection margin status, and cohort. The PRISMA-IPD guideline was used. RESULTS: Seven studies, describing retrospective cohorts were included and the IPD of 329 patients were used of whom 154 (46.8%) had a T41A mutation, 66 (20.1%) a S45F mutation, and 24 (7.3%) a S45P mutation, whereas 85 (25.8%) patients had a WT CTNNB1. Eighty-three patients (25.2%) experienced recurrence. Multivariable analysis, adjusting for sex, age, and tumor site yielded a P-value of 0.011 for CTNNB1 mutation. Additional adjustment for tumor size yielded a P-value of 0.082 with hazard ratio's of 0.83 [95% confidence interval (CI) 0.48-1.42), 0.37 (95% CI 0.12-1.14), and 0.44 (95% CI 0.21-0.92) for T41A, S45P and WT DTF tumors compared to S45F DTF tumors. The effect modification between tumor size and mutation type suggests that tumor size is an important mediator for recurrence. CONCLUSIONS: Primary sporadic DTFs harboring a CTNNB1 S45F mutation have a higher risk of recurrence after surgery compared to T41A, S45P, and WT DTF, but this association seems to be mediated by tumor size.

The Microbiome of Catheter Collected Urine in Males with Bladder Cancer According to Disease Stage.

PURPOSE: The dogma that urine is sterile has been overturned and dysbiosis of the urinary microbiome has been linked to many urological disorders. We tested the hypothesis that the urinary microbial composition may be different between men with or without bladder cancer in catheter collected urines, bladder washouts and midstream voided urines, and may be dependent on tumor staging. MATERIALS AND METHODS: Liquid samples were collected from male patients with bladder cancer, and sex and age matched nonneoplastic controls. Total DNA was extracted and processed for 16S rRNA gene sequencing. Bioinformatic analysis for microbial classification was performed to assess diversity and variations. RESULTS: The urinary microbiome associated with catheter collected urine samples of patients with bladder cancer was characterized by a significantly increased abundance of Veillonella (p=0.04) and Corynebacterium (p=0.03), and decreased Ruminococcus (p=0.03) compared to controls, with differences exacerbating with disease progression. Compared to catheterized urines, bladder cancer washouts showed the specific increase of some taxa, like Burkholderiaceae (p=0.014), whereas midstream urines were enriched in Streptococcus (p <0.0001), Enterococcus (p <0.0001), Corynebacterium (p=0.038) and Fusobacterium (p <0.0001). CONCLUSIONS: The bladder is colonized by endogenous bacteria and microbial modifications characterize the microbiome of patients with bladder cancer. Different microbial compositions can be characterized by changing sampling strategy. These results pave the way for exploring new diagnostic and therapeutic options based on the manipulation of the bacterial community.

Digital Pathology During the COVID-19 Outbreak in Italy: Survey Study.

BACKGROUND: Transition to digital pathology usually takes months or years to be completed. We were familiarizing ourselves with digital pathology solutions at the time when the COVID-19 outbreak forced us to embark on an abrupt transition to digital pathology. OBJECTIVE: The aim of this study was to quantitatively describe how the abrupt transition to digital pathology might affect the quality of diagnoses, model possible causes by probabilistic modeling, and qualitatively gauge the perception of this abrupt transition. METHODS: A total of 17 pathologists and residents participated in this study; these participants reviewed 25 additional test cases from the archives and completed a final psychologic survey. For each case, participants performed several different diagnostic tasks, and their results were recorded and compared with the original diagnoses performed using the gold standard method (ie, conventional microscopy). We performed Bayesian data analysis with probabilistic modeling. RESULTS: The overall analysis, comprising 1345 different items, resulted in a 9% (117/1345) error rate in using digital slides. The task of differentiating a neoplastic process from a nonneoplastic one accounted for an error rate of 10.7% (42/392), whereas the distinction of a malignant process from a benign one accounted for an error rate of 4.2% (11/258). Apart from residents, senior pathologists generated most discrepancies (7.9%, 13/164). Our model showed that these differences among career levels persisted even after adjusting for other factors. CONCLUSIONS: Our findings are in line with previous findings, emphasizing that the duration of transition (ie, lengthy or abrupt) might not influence the diagnostic performance. Moreover, our findings highlight that senior pathologists may be limited by a digital gap, which may negatively affect their performance with digital pathology. These results can guide the process of digital transition in the field of pathology.

En bloc re-resection of high-risk NMIBC after en bloc resection: results of a multicenter observational study.

PURPOSE: To investigate the role of en bloc re-resection (EBRS) in patients who had undergone previous en bloc resection for high-risk non-muscle-invasive bladder cancer (NMIBC). METHODS: An international, multicenter, observational retrospective analysis of prospectively collected data. Patients with a high-risk NMIBC who had previously undergone en bloc resection were scheduled for EBRS of the resected area after 40 days. The primary outcome was the presence of residual tumor or recurrence-free survival. RESULTS: Overall, 78 patients underwent EBRS. Only five (6.41%) residual cancers were found: one patient had a pTa G3 (1.28%) cancer and four (5.13%) had a pTis. The detrusor muscle was preserved in all samples. Only one patient had a positive margin on EBRS. No procedure called for a conversion to traditional re-TURBT. No patient experienced bladder perforation or other intra-operative complications. The recurrence rate at the first follow-up cystoscopy (RRFF-C at 3 months) was 3.85% (three patients). The median follow-up period was 30.8 months (range 6.9-76.0 months). In univariate analysis, the only predictor of recurrence was grade. Overall we observed 11 recurrences. Only one tumor progressed to T2 MIBC. CONCLUSIONS: The low rates of residual tumor, recurrence, and progression seem to raise doubts about the efficacy of EBRS in patients who have previously undergone en bloc resection. EBRS appears to be a feasible and safe procedure with a low rate of complications. However, further data will be needed before EBRS can be used in clinical trials or recommended as a treatment modality.

Clinical performance of Xpert Bladder Cancer (BC) Monitor, a mRNA-based urine test, in active surveillance (AS) patients with recurrent non-muscle-invasive bladder cancer (NMIBC): results from the Bladder Cancer Italian Active Surveillance (BIAS) project.

PURPOSE: To investigate the clinical performance of a new mRNA-based urine test, aiming to avoid unnecessary follow-up cystoscopy in patients under active surveillance (AS) for recurrent NMIBC. METHODS: This is a prospective cohort study enrolling patients with history of low-grade (LG) NMIBC, who developed a recurrence during the follow-up and underwent AS. Their urinary samples were analyzed by Xpert BC Monitor (Cepheid, Sunnyvale, CA, USA). The primary endpoint was to investigate if Xpert BC Monitor could avoid unnecessary cystoscopy during the follow-up period. Its sensitivity, specificity, PPVs and NPVs were calculated. A cutoff of 0.4 "linear discriminant analysis" (LDA) was optimized for the AS setting. RESULTS: The cohort consisted of 106 patients with a mean age of 72 ± 9.52 and a median follow-up from AS start of 8.8 (range 0-56.5) months. No statistically significant difference was found for the mean age, smoker status, lesion size, and number of lesions with a cutoff of 0.4. Of 106 patients, 22 (20.8%) were deemed to require treatment because of cystoscopic changes in size and/or number of lesions during the follow-up period. Using a cutoff value of < 0.4, 34 (33.7%) cystoscopies could be avoided due to low LDA value, missing 2/22 (9%) failures, none with high-grade (HG) NMIBC. Further research on larger population remains mandatory before its clinical use. CONCLUSION: Xpert BC Monitor seems to be a reliable assay, which might avoid unnecessary cystoscopies without missing HG NMIBC when its cutoff is optimized for the AS setting.

Extensive and systematic rewiring of histone post-translational modifications in cancer model systems.

Histone post-translational modifications (PTMs) generate a complex combinatorial code that regulates gene expression and nuclear functions, and whose deregulation has been documented in different types of cancers. Therefore, the availability of relevant culture models that can be manipulated and that retain the epigenetic features of the tissue of origin is absolutely crucial for studying the epigenetic mechanisms underlying cancer and testing epigenetic drugs. In this study, we took advantage of quantitative mass spectrometry to comprehensively profile histone PTMs in patient tumor tissues, primary cultures and cell lines from three representative tumor models, breast cancer, glioblastoma and ovarian cancer, revealing an extensive and systematic rewiring of histone marks in cell culture conditions, which includes a decrease of H3K27me2/me3, H3K79me1/me2 and H3K9ac/K14ac, and an increase of H3K36me1/me2. While some changes occur in short-term primary cultures, most of them are instead time-dependent and appear only in long-term cultures. Remarkably, such changes mostly revert in cell line- and primary cell-derived in vivo xenograft models. Taken together, these results support the use of xenografts as the most representative models of in vivo epigenetic processes, suggesting caution when using cultured cells, in particular cell lines and long-term primary cultures, for epigenetic investigations.

Lymphatic endothelium contributes to colorectal cancer growth via the soluble matrisome component GDF11.

Colorectal cancer (CRC) is one of the most malignant tumors worldwide. Stromal cells residing in the tumor microenvironment strongly contribute to cancer progression through their crosstalk with cancer cells and extracellular matrix. Here we provide the first evidence that CRC-associated lymphatic endothelium displays a distinct matrisome-associated transcriptomic signature, which distinguishes them from healthy intestinal lymphatics. We also demonstrate that CRC-associated human intestinal lymphatic endothelial cells regulate tumor cell growth via growth differentiation factor 11, a soluble matrisome component which in CRC patients was found to be associated with tumor progression. Our data provide new insights into lymphatic contribution to CRC growth, aside from their conventional role as conduits of metastasis.

Active Surveillance for Low Risk Nonmuscle Invasive Bladder Cancer: A Confirmatory and Resource Consumption Study from the BIAS Project.

PURPOSE: We investigated predictive factors of failure and performed a resource consumption analysis in patients who underwent active surveillance for nonmuscle invasive bladder cancer. MATERIALS AND METHODS: This prospective observational study monitored patients with a history of pathologically confirmed stage pTa (grade 1-2) or pT1a (grade 2) nonmuscle invasive bladder cancer, and recurrent small size and number of tumors without hematuria and positive urine cytology. The primary end point was the failure rate of active surveillance. Assessment of failure predictive variables and per year direct hospital resource consumption analysis were secondary outcomes. Descriptive statistical analysis and Cox regression with univariable and multivariable analysis were done. RESULTS: Of 625 patients with nonmuscle invasive bladder cancer 122 with a total of 146 active surveillance events were included in the protocol. Of the events 59 (40.4%) were deemed to require treatment after entering active surveillance. Median time on active surveillance was 11 months (IQR 5-26). Currently 76 patients (62.3%) remain under observation. On univariable analysis only time from the first transurethral resection to the start of active surveillance seemed to be inversely associated with recurrence-free survival (HR 0.99, 95% CI 0.98-1.00, p = 0.027). Multivariable analysis also revealed an association with age at active surveillance start (HR 0.97, 95% CI 0.94-1.00, p = 0.031) and the size of the lesion at the first transurethral resection (HR 1.55, 95% CI 1.06-2.27, p = 0.025). The average specific annual resource consumption savings for each avoided transurethral bladder tumor resection was €1,378 for each intervention avoided. CONCLUSIONS: Active surveillance might be a reasonable clinical and cost-effective strategy in patients who present with small, low grade pTa/pT1a recurrent papillary bladder tumors.

68Ga-PSMA Positron Emission Tomography/Computerized Tomography for Primary Diagnosis of Prostate Cancer in Men with Contraindications to or Negative Multiparametric Magnetic Resonance Imaging: A Prospective Observational Study.

PURPOSE: 68Ga labeled prostate specific membrane antigen positron emission tomography/computerized tomography may represent the most promising imaging modality to identify and risk stratify prostate cancer in patients with contraindications to or negative multiparametric magnetic resonance imaging. MATERIALS AND METHODS: In this prospective observational study we analyzed 68Ga labeled prostate specific membrane antigen positron emission tomography/computerized tomography in a select group of patients with persistently elevated prostate specific antigen and/or Prostate Health Index suspicious for prostate cancer, negative digital rectal examination and at least 1 negative biopsy. The cohort comprised men with equivocal multiparametric magnetic resonance imaging (Prostate Imaging-Reporting and Data System, version 2 score of 2 or less), or an absolute or relative contraindication to multiparametric magnetic resonance imaging. Sensitivity, specificity and CIs were calculated compared to histopathology findings. ROC analysis was applied to determine the optimal cutoff values of 68Ga labeled prostate specific membrane antigen uptake to identify clinically significant prostate cancer (Gleason score 7 or greater). RESULTS: A total of 45 patients with a median age of 64 years were referred for 68Ga labeled prostate specific membrane antigen positron emission tomography/computerized tomography between January and August 2017. The 25 patients (55.5%) considered to have positive positron emission tomography results underwent software assisted fusion biopsy. We determined the uptake values of regions of interest, including a median maximum standardized uptake value of 5.34 (range 2.25 to 30.41) and a maximum-to-background standardized uptake value ratio of 1.99 (range 1.06 to 14.42). Mean and median uptake values on 68Ga labeled prostate specific membrane antigen positron emission tomography/computerized tomography (ie the maximum standardized uptake value or the maximum-to-background standardized uptake value ratio) were significantly higher for Gleason score 7 lesions than for Gleason score 6 or benign lesions (p <0.001). On ROC analysis a maximum standardized uptake value of 5.4 and a maximum-to-background standardized uptake value ratio of 2 discriminated clinically relevant prostate cancer with 100% overall sensitivity in each case, and 76% and 88% specificity, respectively. CONCLUSIONS: Our findings support the use of 68Ga labeled prostate specific membrane antigen positron emission tomography/computerized tomography for primary detection of prostate cancer in a specific subset of men.

Rediscovering Secondary Tumors of the Prostate in the Molecular Era.

Metastatic involvement of the prostate from noncontiguous solid tumors is a rare event occurring by means of vascular dissemination. The reported cases of biopsy and surgical samples with metastatic involvement have increased; however, a comprehensive understanding of secondary tumors of the prostate is currently missing. Metastases to the prostate carry a dismal prognosis and may pose serious diagnostic challenges to both clinicians and pathologists, with crucial therapeutic implications. Secondary tumors of the prostate spread more frequently from the digestive tract, the lung, and the kidney. The integration of clinicoradiologic data with appropriate pathologic and immunohistochemical analyses is essential for the identification and the characterization of secondary tumors of the prostate, whereas molecular analyses could provide additional and complementary information, enabling precise diagnosis and appropriate clinical management. Patients with solitary metastases could benefit from prostatic resection and adjuvant therapy, whereas in cases of disseminated diseases, symptom control may be obtained with palliative procedures. The purpose of this review was to assess the current state of knowledge of secondary tumors involving the prostate gland and to discuss short-term future perspectives, while providing a practical approach to these uncommon conditions for pathologists and oncologists.

Active surveillance for low-risk non-muscle-invasive bladder cancer: mid-term results from the Bladder cancer Italian Active Surveillance (BIAS) project.

OBJECTIVE: To report the oncological safety and the risk of progression for patients with non-muscle-invasive bladder cancer (NMIBC) included in an active surveillance (AS) programme after the diagnosis of recurrence. PATIENTS AND METHODS: This is a prospective study enrolling patients with history of pathologically confirmed low grade pTa-pT1a NMIBC and diagnosed with a tumour recurrence. Inclusion criteria consisted of negative urine cytology, presence of ≤5 lesions with a diameter of ≤10 mm, absence of carcinoma in situ (CIS) or persistent gross haematuria. The primary outcome of interest was adherence to AS. Need to proceed with treatment was defined as progression in number/dimension/positive cytology/symptoms (gross haematuria persistent) or any further intervention (resection or electro-fulguration). Finally, we assessed the up-grading and up-staging when transurethral resection of bladder tumour was performed. RESULTS: The study population consisted of 55 patients with a previous diagnosis of NMIBC (70 AS events) prospectively recruited since 2008. The mean patient age was 69.8 years. The median follow-up was 53 months. The median time patients remained under AS was 12.5 months. There was disease progression in 28 patients (51%). No patient progressed to muscle-invasive disease. In all, 15 patients (27.3%) had an increase in the number and/or size of the tumour, nine (16.4%) had haematuria, and four (7.3%) had a positive cytology. Only five (9%) patients in the whole series progressed to a high-grade tumour (Grade 3) or presented with associated CIS. The overall adherence to the follow-up schedule was 95%. CONCLUSION: Our data show that an AS protocol for NMIBC could be a reasonable option in a select group of patients with small, recurrent cancers.

Role of surgery in the multimodal treatment of primary and recurrent leiomyosarcoma of the inferior vena cava.

BACKGROUND: The optimal treatment of leiomyosarcoma (LMS) of the inferior vena cava (IVC) is still unclear, especially in the metastatic and/or recurrent setting. We herein evaluated the long-term outcome after aggressive management. METHODS: Eleven patients underwent surgery for primary LMS of the IVC between 2000 and 2012. The clinical, pathological, and survival data were reviewed. RESULTS: The IVC was managed by graft replacement in four cases, primary repair in four, and ligation in three. The R0 resection rate was 64%. The median follow-up was 60 months. Nine patients developed distant relapse, two of them concomitant local recurrence; no exclusive local recurrence was observed. The 3- and 5-year distant recurrence free survival were 30% and 10%, respectively. The 3- and 5-year overall-survival (OS) were 77.8%. The presence of residual disease after surgery (P = 0.024) and the time to recurrence (P = 0.033) were associated with the OS in a univariate analysis. The time to recurrence was related to the post-metastases survival (P = 0.032). CONCLUSIONS: An adequate surgery minimizes the risk of local recurrence and remains the main treatment for primary LMS of the IVC. Nevertheless, the rate of distant metastases remains extremely high. An aggressive surgical policy may be of benefit to selected patients with metastatic disease. J. Surg. Oncol. 2016;114:44-49. © 2016 Wiley Periodicals, Inc.

Follicular dendritic cell sarcoma with atypical features surrounding undescended testis: description of a rare case.

Dendritic cell tumors are extremely rare neoplasms and occur both in nodal and extranodal sites. We report a case of an intra-abdominal follicular dendritic cell sarcoma (FDCS). The aim of this study is to describe histological, immunohistochemical, and ultrastructural features of FDCS in order to better define an abdominal mass with unusual immunophenotype and atypical clinical and radiological presentation.

Atypical lipomatous tumors: should they be treated like other sarcoma or not? Surgical consideration from a bi-institutional experience.

BACKGROUND: To identify the best surgical approach to atypical lipomatous tumors we reviewed 171 patients who underwent surgery at two sarcoma referral centers with different surgical policies. METHODS: Of the 151 patients (88 %) with primary tumors, 95 were treated at Institution A and 76 were treated at Institution B. At Institution A, a wide surgical resection, including a slight cuff of soft tissue around the mass, was adopted, which was defined as marginal resection (MR) according to the Enneking classification. At Institution B, a simple tumor resection (SR), according to the Enneking classification, was employed. En bloc surgical resection was the goal in both centers. The primary outcomes of the study were local recurrence-free survival (LRFS), incidence of secondary dedifferentiation at recurrence, and presence of residual tumor after re-excision. RESULTS: Sixteen patients (9 %) had local recurrence. The 10-year LRFS was 82 %. No cases of secondary dedifferentiation were observed. Residual tumor after re-excision was found in 46 % of cases. In univariate analysis, sclerosing subtype, tumor rupture, and SR were unfavorable prognostic factors for LRFS. Sclerosing subtype and tumor rupture were independent prognostic factors for LRFS in multivariate analysis. SR was significantly associated with tumor rupture. CONCLUSIONS: Sclerosing subtype and tumor rupture are unfavorable prognostic factors for local recurrence. MR is associated with a lower risk of tumor rupture than SR. Neurovascular and major muscle resections are not necessary in principle. Re-excision after unplanned surgery is not always mandatory. A preoperative core needle biopsy could be useful in identifying the sclerosing subtype.