Comparison of Tumor Seeding and Recurrence Rate After Laparoscopic vs. Open Nephroureterectomy for Upper Urinary Tract Transitional Cell Carcinoma

Introduction: Laparoscopic surgery for Upper Urinary Tract Urothelial Cell Carcinoma (UTUC) is still debated for its possible seeding risk and thus consequent oncological recurrences, especially for atypical ones. The aim of the study is to compare recurrence and survival after Laparoscopic vs. Open Radical Nephroureterectomy (RNU) for Upper Urinary Tract Urothelial Cancer (UTUC).Method: A retrospective evaluation of UTUC consecutive surgeries from 2008 to 2019 was conducted, including pT ≥ 2, High Grade UTUC who underwent RNU with bladder cuff excision without concomitant lymphadenectomy in three urological tertiary centers. Statistical analyses compared recurrence and cancer specific survival, based on surgical approach, while logistic multivariate analyses and Kaplan Meyer survival curve analyzed possible risk factors for recurrence and survival.Results: One hundred seven cases of RNU, 47 (43.9%) laparoscopic and 60 (56.1%) open, were included in this report. Preoperative characteristics were comparable between groups. However, tumor stage was higher in the Open arm [T3–T4 in 44 (73.3%) vs. 20 (43.4%) in Laparoscopic]. Mean follow-up was 91.6 months in laparoscopy RNU vs. 93.5 months in open RNU. Recurrence rate (RR) was comparable between groups (p = 0.594), and so was the site, although 3 (6.3%) peritoneal recurrences were found only in laparoscopic group (p = 0.057). At multivariate logistic regression, tumor stage and surgical approach were independent predictors of recurrence (p < 0.05), while only tumor stage was predictor of cancer specific death (p = 0.029).Conclusion: Surgical approach has no impact on recurrence site, overall survival, and RR. Still, according to our data peritoneal carcinomatosis was present only in laparoscopic arm, despite how it didn't reach statistical significance.

Oncologic Impact and Safety of Pre-Operative Radiotherapy in Localized Prostate and Bladder Cancer: A Comprehensive Review from the Cancerology Committee of the Association Française d’Urologie

Preoperative radiotherapy (RT) is commonly used for the treatment of various malignancies, including sarcomas, rectal, and gynaecological cancers, but it is preferentially used as a competitive treatment to radical surgery in uro-oncology or as a salvage procedure in cases of local recurrence. Nevertheless, preoperative RT represents an attractive strategy to prevent from intraoperative tumor seeding in the operative field, to sterilize microscopic extension outside the organ, and to enhance the pathological and/or imaging tumor response rate. Several clinical works support this research field in uro-oncology. In this review article, we summarized the oncologic impact and safety of preoperative RT in localized prostate and muscle-invasive bladder cancer. Preliminary studies suggest that both modalities can be complementary as initial primary tumor treatments and that a pre-operative radiotherapy strategy could be beneficial in a well-defined population of patients who are at a very high-risk of local relapse. Future prospective trials are warranted to evaluate the oncologic benefit of such a combination of local treatments in addition to new life-prolonging systemic therapies, such as immunotherapy, and new generation hormone therapies. Moreover, the safety and the feasibility of salvage surgical procedures due to non-response or local recurrence after pelvic RT remain poorly evaluated in that context.

Stromal remodeling regulates dendritic cell abundance and activity in the tumor microenvironment

Stimulatory dendritic cells (SDC), enriched within Batf3-DC (cDC1), engage in productive interactions with CD8+ effectors along tumor-stroma boundaries. The paradoxical accumulation of poised cross-presenting Batf3-DC within stromal sheets, distal to tumoral nests, is unlikely to simply reflect passive exclusion away from immunosuppressive tumor cores. Drawing parallels with embryonic morphogenesis, we hypothesized that invasive margin stromal remodeling may generate developmentally conserved cell-fate cues that regulate Batf3-DC behavior. We find that CD8+ T-cells massively infiltrate tumor matrices undergoing proteoglycan versican (VCAN) proteolysis, an essential organ-sculpting modification in development and adult tissue-plane forging. VCAN proteolysis releases a bioactive fragment (matrikine), versikine, that is necessary and sufficient for Batf3-DC accumulation. Versikine does not influence tumor-seeding pre-DC differentiation; rather, it orchestrates a distinctive activation program conferring exquisite sensitivity to DNA-sensing, coupled with survival support from atypical innate lymphoid cells. Thus, homeostatic signals from stroma invasion regulate SDC survival and activity to promote T-cell inflammation.

Clinical Efficacy of Liver Tumor Biopsy With Radiofrequency Ablation of the Puncture Route Using a Co-access Needle

Background/Aim: Tumor biopsy are needed frequency for accurate diagnosis. However, percutaneous liver tumor biopsy presents a risk of complications such as bleeding and tumor seeding. We investigated the feasibility of liver tumor biopsy, followed by cauterization with expandable radiofrequency ablation. Patients and Methods: Tumor biopsies using a co-access needle were performed in 102 patients. Expandable radiofrequency ablation was used to ensure cauterization and hemostasis of the puncture route. We evaluated the clinical background and complications. Results: The average (±standard deviation) tumor diameter was 56.87±39.45 mm. Pathological diagnosis was possible in all cases. In 20 patients, the postoperative pathological diagnosis differed from the preoperative diagnosis. No significant anemia progression was observed in any patients after biopsy, and no peritoneal seeding was observed during a mean follow-up observation period of 18.5 months. Conclusion: Liver tumor biopsy, followed by cauterization with expandable radiofrequency ablation via a co-access needle, is safe and useful for obtaining reliable diagnoses.

Hemangioma of the Rib Mimicking Chondrosarcoma: A Report of Two Cases and Literature Review

Cases. Case 1 was a 58-year-old man who presented with an incidentally detected, slowly growing mass in the right hypochondrium area. An imaging study showed the mass arising from the 11th rib, with ill-defined margins and cortical destruction. Differential diagnoses included chondrosarcoma and metastatic malignant tumor. Open biopsy was associated with moderate bleeding (300 mL) despite small incision. Microscopic findings showed numerous irregular, dilated, and thin-walled vessels, consistent with the diagnosis of hemangioma of bone, and en bloc excision was performed with no surgical complication. Case 2 was a 49-year-old man who presented with an incidentally detected 4th rib mass with calcification on computed tomography scan. Chondrosarcoma was suspected according to imaging features. An open biopsy was considered to have a risk of tumor seeding because the tumor was located behind the scapula. En bloc excision of the tumor without biopsy was performed. The pathological findings were consistent with hemangioma of bone. Conclusion. We reported two cases of rare hemangioma arising from the rib, which mimicked chondrosarcoma. The preoperative diagnosis was challenging, both clinically and radiologically. Because biopsy for hemangioma of the rib is associated with a bleeding risk, the en bloc excision without biopsy can be a practical treatment option.

Identification of TAZ-Dependent Breast Cancer Vulnerabilities Using a Chemical Genomics Screening Approach

Breast cancer stem cells (BCSCs) represent a subpopulation of tumor cells that can self-renew and generate tumor heterogeneity. Targeting BCSCs may ameliorate therapy resistance, tumor growth, and metastatic progression. However, the origin and molecular mechanisms underlying their cellular properties are poorly understood. The transcriptional coactivator with PDZ-binding motif (TAZ) promotes mammary stem/progenitor cell (MaSC) expansion and maintenance but also confers stem-like traits to differentiated tumor cells. Here, we describe the rapid generation of experimentally induced BCSCs by TAZ-mediated reprogramming of human mammary epithelial cells, hence allowing for the direct analysis of BCSC phenotypes. Specifically, we establish genetically well-defined TAZ-dependent (TAZDEP) and -independent (TAZIND) cell lines with cancer stem cell (CSC) traits, such as self-renewal, variable resistance to chemotherapeutic agents, and tumor seeding potential. TAZDEP cells were associated with the epithelial to mesenchymal transition, embryonic, and MaSC signature genes. In contrast, TAZIND cells were characterized by a neuroendocrine transdifferentiation transcriptional program associated with Polycomb repressive complex 2 (PRC2). Mechanistically, we identify Cyclin D1 (CCND1) as a critical downstream effector for TAZ-driven tumorigenesis. Overall, our results reveal a critical TAZ-CCND1-CDK4/CDK6 signaling axis, suggesting novel therapeutic approaches to eliminate both BCSCs and therapy-resistant cancer cells.

Needle tract seeding in renal tumor biopsies: experience from a single institution

Background Percutaneous needle biopsy of renal masses has been increasingly utilized to aid the diagnosis and guide management. It is generally considered as a safe procedure. However, tumor seeding along the needle tract, one of the complications, theoretically poses potential risk of tumor spread by seeded malignant cells. Prior studies on the frequency of needle tract seeding in renal tumor biopsies are limited and clinical significance of biopsy-associated tumor seeding remains largely controversial. Methods Here we investigated the frequencies of biopsy needle tract tumor seeding at our institution by reviewing the histology of renal cell carcinoma nephrectomy specimens with a prior biopsy within the last seventeen years. Biopsy site changes were recognized as a combination of foreign body reaction, hemosiderin deposition, fibrosis and fat necrosis. The histologic evidence of needle tract tumor seeding was identified as clusters of tumor cells embedded in perinephric tissue spatially associated with the biopsy site. In addition, association between parameters of biopsy techniques and tumor seeding were investigated. Results We observed needle tract tumor seeding to perinephric tissue in six out of ninety-eight (6 %) renal cell carcinoma cases including clear cell renal cell carcinoma, papillary renal cell carcinoma, chromophobe, and clear cell papillary renal cell carcinoma. The needle tract tumor seeding was exclusively observed in papillary renal cell carcinomas (6/28, 21 %) that were unifocal, small-sized (≤ 4 cm), confined to the kidney and had type 1 features. No recurrence or metastasis was observed in the papillary renal cell carcinoma cases with tumor seeding or the stage-matched cases without tumor seeding. Conclusions Our study demonstrated a higher than reported frequency of needle tract tumor seeding. Effective communication between pathologists and clinicians as well as documentation of tumor seeding is recommended. Further studies with a larger patient cohort and longer follow up to evaluate the impact of needle tract tumor seeding on long term prognosis are needed. This may also help reach a consensus on appropriate pathologic staging of renal cell carcinoma when the only site of perinephric fat invasion is within a biopsy needle tract.

Chronic intermittent hypoxia promoted lung cancer stem cell-like properties via enhancing Bach1 expression

Background An adverse role for obstructive sleep apnea (OSA) in cancer aggressiveness and mortality has recently emerged from clinical and animal studies, and the reasons have not been fully determined. Cancer stem cells (CSCs) are regarded as the main cause of carcinoma metastasis. So far, the relationship between OSA and lung CSCs has not been explored. Method In the present study, we established an orthotopic mouse model of primary lung cancer and utilized chronic intermittent hypoxia (CIH) exposure to mimic OSA status. Results We observed that CIH endows lung cancer with greater metastatic potential, evidenced by increased tumor growth, tumor seeding, and upregulated CSC-related gene expression in the lungs. Notably, the transcription factor BTB and CNC homology 1 (Bach1), a key factor in responding to conditions of oxidative stress, is increased in lung cancer after CIH exposure in vitro and in vivo. Meanwhile, exposing lung cancer cells to CIH promoted cell proliferation, clonal diversity, induced stem-like cell marker expression, and gave rise to CSCs at a relatively higher frequency. Furthermore, the increase of mitochondrial ROS (mtROS) and CSC-marker expression induced by CIH exposure was abolished in Bach1 shRNA-treated lung cancer cells. Conclusions Our results indicated that CIH promoted lung CSC-like properties by activating mtROS, which was partially mediated by Bach1.