Perioperative, Oncological, and Functional Outcomes Between Robot-Assisted Laparoscopic Prostatectomy and Open Radical Retropubic Prostatectomy: A Randomized Clinical Trial.

PURPOSE: Limited high-quality studies have compared robot-assisted laparoscopic prostatectomy (RALP) vs open retropubic radical prostatectomy. We sought to compare their postoperative outcomes in a randomized setting. MATERIALS AND METHODS: In a single center, 354 men with newly diagnosed prostate cancer were assessed for eligibility; 342 were randomized (1:1). The primary outcome was 90-day complication rates. Functional outcomes and quality of life were assessed over 18 months, and oncological outcomes, biochemical recurrence-free survival, and additional treatment over 36 months. RESULTS: From 2014 to 18, 327 patients underwent surgery (retropubic radical prostatectomy = 156, RALP = 171). Complications occurred in 27 (17.3%) vs 19 (11.1%; P = .107). Patients undergoing RALP experienced lower median bleeding (250.0 vs 719.5 mL; P < .001) and shorter hospitalization time. Urinary EPIC (Expanded Prostate Cancer Index Composite) median scores were better for RALP over 18 months, with higher continence rate at 3 months (80.5% vs 64.7%; P = .002), 6 months (90.1% vs 81.6%; P = .036) and 18 months (95.4% vs 78.8%; P < .001). Sexual EPIC and Sexual Health Inventory for Men median scores were higher with RALP up to 12 months, while the potency rate was superior at 3 months (23.9% vs 5.3%; P = .001) and 6 months (30.6% vs 6.9%; P < .001). Quality of life over the 18 months and oncological outcomes over 36 months were not significantly different between arms. CONCLUSIONS: Complications at 90 days were similar. RALP showed superior sexual outcomes at 1 year, improved urinary outcomes at 18 months, and comparable oncological outcomes at 36 months. TRIAL REGISTRATION: Prospective Analysis of Robot-Assisted Surgery; NCT02292914. https://clinicaltrials.gov/ct2/show/NCT02292914?cond=NCT02292914&draw=2&rank=1.

Predicting individual outcomes after radical cystectomy in urothelial variants with Cancer of the Bladder Risk Assessment (COBRA) score.

OBJECTIVE: To validate the Cancer of the Bladder Risk Assessment (COBRA) score in patients with urothelial variants. METHODS: Epidemiological, clinical, radiological, and anatomopathological data were collected from patients with urothelial carcinoma who underwent radical cystectomy at the Institute of Cancer of São Paulo between May 2008 and December 2022. Patients with the presence of at least 10% of any urothelial variants in the radical cystectomy specimens' anatomopathological exam were included in the study. The COBRA score and derivatives were applied and correlated with oncological outcomes. RESULTS: A total of 680 patients [482 men (70.9%) and 198 women (29.1%)]; 66 years (IQR 59-73) underwent radical cystectomy for bladder tumor, and of these patients, a total of 167 patients presented any type of urothelial variant. The median follow-up time was 28.77 months (IQR 12-85). The three most prevalent UV were squamous differentiation (50.8%), glandular differentiation (31.3%), and micropapillary differentiation (11.3%). The subtypes with the worst prognosis were sarcomatoid with a median survival of 8 months (HR 1.161; 95% CI 0.555-2.432) and plasmacytoid with 14 months (HR 1.466; 95% CI 0.528-4.070). The COBRA score for patients with micropapillary variants demonstrated good predictive accuracy for OS (log-rank P = 0.009; 95% IC 6.78-29.21) and CSS (log-rank P = 0.002; 95% IC 13.06-26.93). CONCLUSIONS: In our study, the COBRA score proved an effective risk stratification tool for urothelial histological variants, especially for the micropapillary urothelial variant. It may be helpful in the prognosis evaluation of UV patients after radical cystectomy.

Evaluation of the endoscopic cure criteria in patients undergoing surgery for early gastric cancer.

BACKGROUND AND OBJECTIVES: Gastric cancer (GC) prognosis is influenced by the extent of the tumor, lymph node involvement (LNM), and metastasis. Endoscopic resection (ER) or gastrectomy with lymphadenectomy are standard treatments for early GC (EGC). This study evaluated LNM frequency according to eCura categories, clinicopathological characteristics, disease-free (DFS), and overall (OS) survival rates. METHODS: We included EGC patients who underwent curative gastrectomy between 2009 and 2020 from our single-center database. Anatomopathological and clinical reports were reviewed to analyze eCura categories. RESULTS: We included 160 EGC patients who underwent gastrectomy with eCura categories A, B, and C, comprising 26.3%, 13.8%, and 60%, respectively. Baseline clinical characteristics showed no intergroup disparities. LNM incidence for A, B, and C was 4.8%, 18.2%, and 19.8%. When evaluating the criteria for ER and its association with eCura categories, we found that 95.2% of eCura A and 100% of eCura B patients had classic or expanded criteria for ER. On the other hand, 97.9% of eCura C patients were referred to surgical resection. Multivariate analysis demonstrated that lymphatic (OR = 5.57, CI95% = 1.45-21.29, p = 0.012) and perineural (OR = 15.8, CI95% = 1.39-179.88, p = 0.026) invasions were associated with a higher risk of LNM. No significant differences in DFS or OS were found among eCura categories. CONCLUSION: The eCura categories were associated with the occurrence of LNM. In most patients, those with classic and expanded indication criteria for ER were classified as eCura A and B.

Rare Association Between Osteogenesis Imperfecta and Chondrosarcoma: Could a Pathogenic Variant in the Gene SERPINF1 Explain It?

Osteogenesis imperfecta (OI) type VI is a rare inherited disorder of the connective tissue caused by pathogenic variants in SERPINF1 gene, which encodes the pigment epithelium-derived factor (PEDF). PEDF is implicated in many biologic processes, including an anti-cancer role. This information is supported by in vitro and in vivo studies that evidenced its anti-angiogenic, anti-tumorigenic, and anti-metastatic properties. Although OI is related to skeletal changes such as bone fragility and deformities, as well as to other connective tissue defects, it does not represent a greater predisposition to the development of skeletal tumors. Here, we report on an adult with OI in which a deletion in exon 8 of the SERPINF1 gene (c.1152_1170del; p.384_390del) was identified. The patient presented popcorn calcification in both femoral epiphyses, but one of them presented radiological characteristics and evolution suspected of malignancy. Later, it was diagnosed as chondrosarcoma. This paper discusses that OI type VI patients may be at risk of developing some types of cancer.

A Prospective, Randomized Trial Comparing the Outcomes of Open vs Laparoscopic Partial Nephrectomy.

PURPOSE: Partial nephrectomy is the standard treatment for renal tumors <7 cm, and the trend toward minimally invasive surgery has increased. However, data that could support its use and benefits are still lacking. MATERIALS AND METHODS: We conducted a prospective, randomized controlled trial comparing surgical, functional and oncologic outcomes in patients undergoing open partial nephrectomy (OPN) or laparoscopic partial nephrectomy (LPN). Randomization was 1:1 to OPN or LPN for the treatment of renal tumors <7 cm. The primary endpoint was surgical complications up to 90 days after surgery. Secondary outcomes were comparison of surgical, oncologic and functional results. RESULTS: We randomized 208 patients between 2012 and 2020 (110 with OPN vs 98 with LPN). Operative data showed no differences in operative time, warm ischemia time, estimated blood loss, transfusions or length of hospital stay. Zero ischemia was more frequent in the OPN (35.4% vs 15.5%, p=0.02). OPN was associated with more abdominal wall complications (31.2% vs 13.1%, p=0.004). Regarding oncologic outcomes, no differences were noted. The LPN group had less kidney function reduction at 3 (-5.2% vs -10%, p=0.04; CI 0.09 to 9.46) and 12 months after surgery (-0.8% vs -6.3%, p=0.02; CI 1.18 to 12.95), and a lower rate of downstaging on the chronic kidney disease classification at 12 months (14.1% vs 32.6%, p=0.006). CONCLUSIONS: Surgical and oncologic outcomes of LPN were similar to OPN. Minimally invasive surgery may provide better preservation of kidney function. More studies, especially those involving robotic surgery, are necessary to confirm our findings.

Gastric cancer with microsatellite instability displays increased thymidylate synthase expression.

BACKGROUND: Gastric cancer (GC) with microsatellite instability (MSI) is a less aggressive disease and associated with resistance to 5-fluorouracil (5-FU)-based chemotherapy (CMT). Thymidylate synthase (TS) is inhibited by 5-FU, and another potential mediator of therapeutic resistance to 5-FU. Therefore, we aimed to analyze the association between MSI and TS expression in GC, and its impact on disease outcomes. METHODS: We retrospectively evaluated GC who underwent D2-gastrectomy. MSI and TS were analyzed by immunohistochemistry. We also investigated p53 expression, PD-L1 status, and tumor-infiltrating lymphocytes (CD4 and CD8). RESULTS: Out of 284 GC, 60 (21.1%) were MSI. Median TS-score for all cases was 16.5. TS expression was significantly higher in MSI compared to microsatellite-stable (MSS; p < 0.001). Considering both status, GC were classified in four groups: 167 (58.8%) MSS + TS-low; 57 (20.1%) MSS + TS-High; 24 (8.5%) MSI + TS-low; and 36 (12.7%) MSI + TS-high. MSI + TS-high group had less advanced pTNM stage, higher CD8+T cells levels (p < 0.001) and PD-L1 positivity (p < 0.001). Normal p53 expression was related to MSI GC (p < 0.001). Improved survival was observed in MSI + TS-high, but no survival benefit was seen with CMT. CONCLUSION: MSI GC was associated with high TS levels, which may explain therapeutic resistance to 5-FU. Additionally, MSI + TS-high showed better survival, but without improvement with CMT.

Prognostic implications of tumor-infiltrating lymphocytes in association with programmed cell death ligand 1 expression in remnant gastric cancer.

Objective: Remnant gastric cancer (RGC) is usually associated with a worse prognosis. As they are less common and very heterogeneous tumors, new prognostic and reliable determinants are required to predict patients' clinical course for RGC. This study aimed to investigate the tumor-infiltrating lymphocytes (TILs) and programmed cell death ligand 1 (PD-L1) status as prognostic biomarkers in a cohort of patients with RGC to develop an immune-related score. Methods: Patients with gastric cancer (GC) who underwent curative intent gastrectomy were retrospectively investigated. RGC resections with histological diagnosis of gastric adenocarcinoma were enrolled in the study. The risk score based on immune parameters was developed using binary logistic regression analysis. RGCs were divided into high-risk (HR), intermediate-risk (IR), and low-risk (LR) groups based on their immune score. The markers (CD3+, CD4+/CD8+ T cells and PD-L1) were selected for their potential prognostic, therapeutic value, and evaluated by immunohistochemistry (IHC). Results: A total of 42 patients with RGC were enrolled in the study. The score based on immune parameters exhibited an accuracy of 79% [the area under the receiver operating characteristic curve (AUC)=0.79, 95% confidence interval (95% CI), 0.63-0.94, P=0.002], and the population was divided into 3 prognostic groups: 10 (23.8%) patients were classified as LR, 15 (35.7%) as IR, and 17 (40.5%) as HR groups. There were no differences in clinicopathological and surgical characteristics between the three groups. In survival analysis, HR and IR groups had worse disease-free survival and overall survival rates compared to the LR group. In the multivariate analysis, lymph node metastasis and the immune score risk groups were independent factors related to worse survival. Conclusions: A scoring system with immune-related markers was able to distinguish prognostic groups of RGC associated with survival. Accordingly, tumor-infiltrating immune lymphocytes and PD-L1 status may serve as a potential prognostic biomarker for patients with RGC.

Epstein-Barr Virus Positive Gastric Cancer: A Distinct Subtype Candidate for Immunotherapy.

BACKGROUND: Epstein-Barr virus (EBV) positive gastric cancer (GC) has been described as a distinct molecular subtype of the disease, especially associated with gastric carcinoma with lymphoid stroma (GCLS). The possibility that EBV associated GC (EBVaGC) had better prognosis and may be susceptible to immunotherapy has increased the interest in this subtype. However, immune checkpoint and survival of EBVaGC are still controversial, especially with regard to GCLS and conventional gastric adenocarcinoma (CGA). This study aimed to evaluate the clinicopathological characteristics, immunohistochemical profiles and prognosis of EBVaGC according to the histological type GCLS and CGA. METHODS: we retrospectively evaluated a series of EBVaGC who underwent gastrectomy with D2-lymphadenectomy. Biomarkers and tumor-infiltrating cells were evaluated by immunohistochemistry. PD-L1 was evaluated using a combined positive score (CPS). RESULTS: From a total of 30 EBVaGC, 14 (46.7%) were identified as GCLS and 16 (53.3%) as CGA (9 Intestinal, 6 diffuse, 1 undetermined). There were no significant differences in age, sex, and pTNM between GCLS and CGA. CPS-positivity and high-CD8+ was significantly higher in GCLS compared with CGA (P = 0.007 and P = 0.005, respectively). Diffuse EBVaGC had worse survival than intestinal type (P = 0.020). There was no difference in survival between GCLS and intestinal CGA (P = 0.260). In multivariate analysis, CPS and pN status were related with survival in EBVaGC. CONCLUSIONS: CGLS was associated with a predominance of CD8+ cell infiltration and PD-L1 expression. CPS and lymph node metastasis were independent factors associated with prognosis in EBVaGC. These results suggest that specifically EBV-positive GCLS may be prime candidates for PD-1 directed therapy.

Cytotoxic T-lymphocyte-associated protein 4 in gastric cancer: Prognosis and association with PD-L1 expression.

BACKGROUND: Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is one of the most studied immune checkpoint in gastric cancer (GC). However, the prognostic role of CTLA-4 expression in GC is poorly described. This study aimed to evaluate CTLA-4 expression in GC and its impact on survival, including patients treated with standard platinum-based chemotherapy (CMT), and association with PD-L1 expression. METHODS: All GC patients who underwent D2-gastrectomy were investigated retrospectively. Tumor samples were examined for CTLA-4 and PD-L1 by immunohistochemistry. Tumor-infiltrating inflammatory cells, including CD4 + and CD8 + , were also examined. RESULTS: Among the 284 GC patients included, 159 (56%) were CTLA-4 positive and the remaining 125 (44%) were classified as negative. CTLA-4 positive GC was associated with increased inflammatory cell infiltration (p < 0.001), high CD8 + T cells (p = 0.016) and PD-L1 expression (p = 0.026). Considering GC referred for treatment, CTLA-4 negative patients who received CMT had a significant improvement in disease-free survival compared to untreated CLTA-4 negative (p = 0.028). In multivariate analysis, GC positive for both CTLA-4 and PD-L1 had a prognostic impact on survival. CONCLUSION: CTLA-4 positive was associated with PD-L1 expression and a high tumor-infiltrating CD8 + T cells. Accordingly, positivity for both CTLA-4 and PD-L1 was an independent factor associated to better survival in GC patients.

Sclerosing TSC1 mutated renal cell carcinoma: An unusual pattern mimicking MITF family translocation renal cell carcinoma.

The tuberous sclerosis genes and MTOR are increasingly being found to have important roles in novel subtypes of renal cancer, particularly emerging entities eosinophilic solid and cystic renal cell carcinoma (RCC) and high-grade oncocytic renal tumor (HOT)/RCC with eosinophilic and vacuolated cytoplasm. We report a unique renal neoplasm in a 66-year-old woman that initially mimicked MITF family translocation RCC due to mixed clear and eosinophilic cells, extensive stromal hyalinization, and psammoma bodies, yet which was negative for TFE3 and TFEB fluorescence in situ hybridization and a next generation sequencing (NGS) gene fusion assay. Cytoplasmic stippling triggered consideration of TSC-associated neoplasms, and a targeted NGS assay revealed a variant in exon 21 of TSC1 resulting in c.2626G>T p.(Glu876*) truncating mutation. This report adds to the morphologic spectrum of TSC-related renal neoplasms, including prominent stromal hyalinization as a potentially deceptive pattern. Due to the overlap in cytoplasmic stippling between eosinophilic solid and cystic RCC and HOT/RCC with eosinophilic and vacuolated cytoplasm, it is debatable which category this example would best fit. Further understanding of these entities and other renal neoplasms with alterations in the TSC genes will elucidate whether they should be considered a family of tumors.