Ultrasound-Guided Renal Mass Biopsy and Its Clinical Utility: A Single-Centre Experience.

INTRODUCTION: Renal mass biopsy (RMB) is still underutilized, partially because many urologists argue that it does not substantially influence the management of renal masses. We sought to evaluate the influence of RMB on the management of renal tumours in our institution. MATERIALS AND METHODS: A total of 387 RMBs performed at our institution from January 2016 to June 2020 were included. Patient demographics, mass size, biopsy result, and subsequent clinical management were retrospectively reviewed. RESULTS: The mean mass size was 47.8 mm. Fifty-six percentage of tumours ≤40 mm (247) and 8% of tumours >40 mm (64) were biopsied. Seventy-six RMBs of disseminated tumours were performed. 14.9% of RMBs were non-diagnostic, and 27.1% of RMBs of tumours ≤40 mm were benign. The majority of tumours with first non-diagnostic RMB followed by histopathological verification were found to be malignant. There was significantly more conservative management and no radical nephrectomies in the benign biopsy group. One case of Clavien-Dindo grade ≥2 complication occurred. CONCLUSIONS: RMB result affects treatment decisions. Ultrasound-guided RMB is a safe procedure, and performing biopsies of tumours ≤40 mm may reduce the number of unnecessary interventions. Non-diagnostic RMBs should be repeated or treated as malignant.

Changes in Immunogenicity during the Development of Urinary Bladder Cancer: A Preliminary Study.

In the present study, we evaluated tumor-infiltrating lymphocytes (TILs) and blood regulatory T lymphocyte (Tregs, CD4+/CD25+/FoxP3+) expression in bladder cancer patients. The number of CD4+, CD8+, CD25+, FoxP3+ and CD20+ TILs was analyzed in association with clinico-pathomorphological features. In more advanced metastasizing tumors, showing non-classic differentiation (ND) and a more aggressive tissue invasion type (TIT), the number of TILs decreased. A low number of CD4+ TILs was associated with poor prognosis. Similarly, Treg frequency before surgery and after surgical treatment was significantly lower in more advanced tumors. The changes in TILs, as well as of local and systemic Tregs, were accompanied by changes in the histological phenotype of urothelial carcinoma regarding pT stage, NDs, TIT, and clinical outcomes. The number of TILs and the frequency of blood Tregs (indicators of antitumor response) may be essential for choosing an immunotherapy that is adjusted to the immune status according to the phase of tumor growth. Moreover, a significant reduction in the number of CD4+ and CD8+ TILs with the development of NDs in more advanced tumors may be associated with lower tumor immunogenicity, resulting in immune tolerance towards tumor tissue. These observations and the tendency of urothelial bladder carcinoma to undergo NDs in a heterogeneous manner during tumor progression suggest complex interactions between bladder cancer immunogenicity and stages of tumor progression.

Expression of Vitamin D Receptor (VDR) Positively Correlates with Survival of Urothelial Bladder Cancer Patients.

Vitamin D3 shows tumoristatic and anticancer effects by acting through the vitamin D receptor (VDR), while hydroxylation of 25-hydroxyvitamin D3 at position 1α by CYP27B1 is an essential step in its activation. The expression of both the VDR and CYP27B1 has been found in many normal and cancer tissues, but there is a lack of information about its expression in human bladder cancers. The aim of the present research was to examine whether the expression of the VDR and CYP27B1 in bladder cancer was related to the prognostic markers and disease outcome. We analyzed VDR and CYP27B1 in samples of tumor and normal tissues obtained from 71 urinary bladder cancer patients. The highest VDR immunostaining was found in normal epithelium and was significantly lower in bladder cancer cells (p<0.001 with Mann-Whitney U test). VDR expression was lowest in more advanced (pT2b-pT4) (p=0.005 with Mann-Whitney U test) and metastasizing cancers (p<0.05 and p=0.004 with Mann-Whitney U test for nuclear and cytoplasmic VDR immunostaining, respectively). The lack of cytoplasmic and nuclear VDR was also related to shorter overall survival (for cytoplasmic VDR immunolocalization 13.3 vs. 55.3 months of survival, HR=1.92, p=0.04 and for nuclear VDR immunostaining 13.5 vs. 55.3 months of survival, HR=2.47, p=0.002 with Mantel-Cox test). In cases with the lack of high cytoplasmic VDR staining the non-classic differentiations (NDs) was observed in higher percentage of tumor area. CYP27B1 expression was lower in cancer cells than in normal epithelial cells (p=0.03 with Mann-Whitney U test), but its expression did not correlate with tumor stage (pT), metastasizing, grade, mitotic activity or overall survival. In conclusion, expression of the VDR and CYP27B1 are deregulated in urothelial bladder cancers. Although our results showing a relationship between the decreased VDR expression and prognostic markers and survival time indicate potential usefulness of VDR as a new indicator of a poorer prognosis, further studies are needed in different patient cohorts by independent groups to validate this hypothesis. We also suggest that vitamin D-based therapies may represent an adjuvant strategy in treatment for bladder cancers expressing VDR.

Expression of RCAS1 correlates with urothelial bladder cancer malignancy.

RCAS1 is a protein that participates in regulation of the tumor microenvironment and its immune responses, all in order to evade the immune system. The aim of this study was to analyze RCAS1 expression in urothelial bladder cancer cells (and in fibroblasts and macrophages of the tumor stroma) and its relationship with the histological pattern of malignancy. Eighty-three postcystectomy patients were enrolled. We analyzed the histological maturity (grade), progress (pT stage), tissue invasion type (TIT), nonclassic differentiation number (NDN), and the ability to metastasize (pN). The expression of RCAS1 protein was analyzed by immunohistochemistry. Indicators of histological malignancy were observed solely in association with the RCAS1 expression in cells in the border parts (BPs) of the tumor. Histological malignancy of the tumor, indicated by the pT and pN, and metastasis-free survival time, correlated significantly with RCAS1 expression in tumor neoplastic cells, whereas malignancy determined by grade, TIT, and NDN correlated with RCAS1 expression in fibroblasts and macrophages in the tumor microenvironment. These findings suggest that the increased RCAS1 expression depends on its cellular source and that RCAS1 expression itself is a component of various signaling pathways. The immune escape occurs within the tumor BPs, where the increase in the RCAS1 expression occurs within tumor cells and stromal cells in its microenvironment. We conclude that the histological pattern of tumor malignancy, indicated by grade, TIT, NDN, pT, and pN is a morphological indicator of immune escape.

Expression of OCT4A: the first step to the next stage of urothelial bladder cancer progression.

OCT4 (octamer-binding transcription factor) is a transcription factor responsible for maintaining the pluripotent properties of embryonic stem cells. In this paper, we present the results of studies to investigate the role of the OCT4 splicing variant in urothelial bladder cancer and the relationship between the OCT4 phenotype and the morphological parameters of tumor malignancy. Ninety patients who received a cystectomy for bladder cancer were enrolled. The expression of OCT4 protein was analyzed by immunohistochemistry. The ratio of OCT4-positive cells was the lowest in pT1 (pathological assessment (p)--tumor extent confined to mucosa (T1)) tumors and the highest in pTis (non-papillary tumor extent confined to urothelium) and pT2 (tumor extent including muscularis propria) tumors. Information about the percentage of OCT4A-positive tumor cells could facilitate choosing the treatment mode in borderline pTis-pT1 (crossing the border of the basement membrane; the first stage of progression) and pT1-pT2 (crossing the border of the muscularis propria; the second stage of progression) cases: a higher percentage of OCT4A-positive cells should support more radical therapy. A significantly higher percentage of cases with moderate OCT4 intensity was found in metastasizing (the third stage of progression) cases with >2 positive lymph nodes. The percentage of OCT4-positive cells was significantly higher for cancers with a high grade, higher non-classic differentiation number and greater aggressiveness of invasion. The differentiation, maturation and aggressiveness of tumor invasion appear to depend on the expression of the OCT4 phenotype in cancer cells, similar to the successive stages of malignancy progression in urothelial cancer.

Perioperative and Oncological Outcomes of Percutaneous Radiofrequency Ablation versus Partial Nephrectomy for cT1a Renal Cancers: A Retrospective Study on Groups with Similar Clinical Characteristics.

Over the recent years, progress in imaging techniques has led to an increased detection of kidney tumours, including small renal masses. While surgery is still the standard of care, there is a growing interest in minimally invasive methods. Ultrasound (US)-guided percutaneous ablation is particularly attractive because it is a safe and relatively simple procedure. In this study, we investigated the results of US-guided percutaneous radiofrequency ablation (RFA) and partial nephrectomy (PN) in the treatment of cT1a renal cancers. Between August 2016 and February 2022, 271 patients with renal tumours underwent percutaneous RFA as initial treatment in our institution. In the same period, 396 patients with renal tumours underwent surgical tumour excision. For the purpose of this study, only patients with confirmed renal cancer with matched age and tumour characteristics (size, location) were selected for both groups. Thus, a group of 44 PN patients and 41 RFA patients were formed with the same qualification criteria for both groups. Parameters such as procedure length, blood loss, hospital stay, analgesics used, and pre- and post-procedural serum creatinine were compared between these groups. Patients followed up with contrast-enhanced CT. There was no significant difference in age, tumour size, tumour location, and creatinine levels between these groups. All procedures were generally well tolerated. During a median follow-up of 28 months, two cases of recurrence/residual disease were found in each group. The overall survival was 100% in both groups, and all patients were disease-free at the end of observation. Percutaneous RFA was associated with a significantly shorter procedure length and hospital stay, lower blood loss, and lower analgesics used than PN. In the selected group of renal cancer patients, US-guided percutaneous RFA was associated with a shorter hospital stay, less analgesics used, and a shorter procedure length than PN, without differences in the oncological results or kidney function.

Ablative therapies for small renal tumors.

Ablative therapies of renal tumors are steadily gaining popularity in clinical practice due to the many benefits they offer to patients. Moreover, ablative procedures hold promise in the field of uro-oncology for the best compromise between low invasiveness, high efficacy and advantages in terms of procedural costs. Reported outcomes with ablative therapies for small renal tumors are excellent and without significant differences for surgical procedures based on nephron-sparing surgery. Nevertheless, these methods for treatment of small renal tumors should still be confined to carefully selected patients. This review discusses the currently used ablative techniques in urology.

Indications for postoperative radiotherapy in patients with prostate cancer after surgery with positive surgical margins.

AIM OF THE STUDY: Prostate cancer is the second most prevalent cancer among men in Poland. The main methods of radical treatment are radical prostatectomy and radiotherapy. In patients who have been correctly qualified for surgery, a positive surgical margin is always an unexpected and undesirable factor. The aim of this prospective study was to evaluate the incidence of positive margins in more than 100 consecutive patients with prostate cancer undergoing radical prostatectomy. MATERIAL AND METHODS: The study included 114 patients aged 44-78 years (mean 61.5 years) who underwent surgery for prostate cancer in stage cT1-3N0/M0 (according to the TNM staging system) in the years 2010-2011 in the Clinical Department of Oncological Urology in the Center of Oncology in Bydgoszcz. RESULTS: The presence of positive surgical margins was found in 45 (39.47%) patients, and in 20 (17.54%) margins were assessed as close (1-2 mm). Among the patients with positive surgical margins about 22% had biochemical recurrence. Among patients with negative surgical margins 13% of pT2c and 12.5% of pT3a had biochemical recurrence. Patients with positive surgical margins, along with patients diagnosed with tumor extending beyond the prostate (pT3a) or invading seminal vesicles (pT3b), are at an increased risk of recurrence and progression, reaching up to 30-50% over 10 years. The risk is 2-4 times higher than in patients without positive operating margins.

Ultrasound-Guided Percutaneous Thermal Ablation of Renal Cancers-In Search for the Ideal Tumour.

Over the recent years, the progress in imaging techniques has led to an increased detection of kidney tumours, including small renal masses. While surgery is still the standard of care, there is a growing interest in minimally invasive methods. Ultrasound (US)-guided percutaneous ablation is particularly attractive because it is a safe and relatively simple procedure. In this study, we investigated the success of percutaneous radiofrequency ablation (RFA) in relation to kidney tumour diameter and location. Between August 2016 and September 2021, 253 patients with 259 renal tumours underwent US-guided RFA as a primary treatment in our institution. A total of 67 patients were excluded from this study. Abdominal computed tomography (CT) and tumour biopsy were performed before the procedure. Patients were followed with contrast-enhanced CT, the average follow-up time was 28 months. The studied group was composed of 186 patients with 191 renal tumours-only biopsy-confirmed renal cancers were included. During the follow-up, 46 cases of residual disease and 4 cases of local progression were found. There was a significant correlation between tumour size and the ablation success rate. The success rate was 73.5% and 87.6% for lesions ≤25 mm, 94.6% for lesions ≤25 mm and exophytic, 79.1% for lesions 26-30 mm and 84.4% for lesions 26-30 mm and exophytic, respectively. Four Clavien-Dindo grade ≥2 complications were observed. US-guided percutaneous RFA of T1a renal cancers is safe and well-tolerated. Its effectiveness depends on tumour size, with best results for exophytic lesions smaller than 3 cm. Most of the recurrent or residual tumours can be successfully re-treated with US-guided percutaneous RFA.

Can we rely on PET in the follow-up of advanced seminoma patients?

The management of residuals after completion of chemotherapy in advanced seminoma is controversial. It has been proposed that fluorodeoxyglucose-positron emission tomography (FDG-PET) can be used as a follow-up. In this study we investigated FDG-PET as a follow-up tool in advanced seminoma patients treated previously with chemotherapy or radiotherapy. Thirty-seven patients assigned to an advanced seminoma group based on CT and/or FDG-PET/CT and then treated with chemotherapy were included in the study. All these patients underwent FDG-PET/CT examination as a part of the follow-up scheme. Patients underwent retroperitoneal lymph node dissection (RPLND), radiotherapy, or were followed clinically by CT and/or PET/CT every 6 months. In 8 cases FDG-PET was positive: 5 of them underwent RPLND and 3 radiotherapy. Two patients with negative FDG-PET but positive CT also underwent RPLND. The remaining patients with negative FDG-PET results were followed up. FDG-PET/CT was false positive in one case >3 cm and one <3 cm, in 6 cases >3 cm it was true negative. While FDG-PET can find a viable tumor, there also is an important question of false positive results. It was clinically proven that a negative FDG-PET was correlated with stable disease, but we were unable to examine specimens in these cases.

Comprehensive cancer-oriented biobanking resource of human samples for studies of post-zygotic genetic variation involved in cancer predisposition.

The progress in translational cancer research relies on access to well-characterized samples from a representative number of patients and controls. The rationale behind our biobanking are explorations of post-zygotic pathogenic gene variants, especially in non-tumoral tissue, which might predispose to cancers. The targeted diagnoses are carcinomas of the breast (via mastectomy or breast conserving surgery), colon and rectum, prostate, and urinary bladder (via cystectomy or transurethral resection), exocrine pancreatic carcinoma as well as metastases of colorectal cancer to the liver. The choice was based on the high incidence of these cancers and/or frequent fatal outcome. We also collect age-matched normal controls. Our still ongoing collection originates from five clinical centers and after nearly 2-year cooperation reached 1711 patients and controls, yielding a total of 23226 independent samples, with an average of 74 donors and 1010 samples collected per month. The predominant diagnosis is breast carcinoma, with 933 donors, followed by colorectal carcinoma (383 donors), prostate carcinoma (221 donors), bladder carcinoma (81 donors), exocrine pancreatic carcinoma (15 donors) and metachronous colorectal cancer metastases to liver (14 donors). Forty percent of the total sample count originates from macroscopically healthy cancer-neighboring tissue, while contribution from tumors is 12%, which adds to the uniqueness of our collection for cancer predisposition studies. Moreover, we developed two program packages, enabling registration of patients, clinical data and samples at the participating hospitals as well as the central system of sample/data management at coordinating center. The approach used by us may serve as a model for dispersed biobanking from multiple satellite hospitals. Our biobanking resource ought to stimulate research into genetic mechanisms underlying the development of common cancers. It will allow all available "-omics" approaches on DNA-, RNA-, protein- and tissue levels to be applied. The collected samples can be made available to other research groups.

Radiofrequency ablation of small renal masses in comorbid patients.

INTRODUCTION: Over the recent years, the progress in imaging techniques has led to increased detection of small renal masses (SRMs), including in elderly and high-risk patients. Partial nephrectomy (nephron-sparing surgery - NSS), the current standard of care in T1a kidney tumours, has some limitations in patients who are poor candidates for surgery, as it is associated with potential perioperative complications and possible renal function loss. Radiofrequency ablation (RFA), a minimally invasive method that can be performed percutaneously, is an option in such cases. AIM: To present our experience in treatment of SRMs using RFA in comorbid patients. MATERIAL AND METHODS: In the years 2006-2012, 103 percutaneous, ultrasound-guided RFA procedures were performed in the Oncology Centre in Bydgoszcz in patients with an ASA score ≥ 3. Abdominal computed tomography and tumour biopsy were performed before the procedure. The average follow-up time was 46 months. RESULTS: The 1, 3 and 5-year overall survival rates were respectively 97%, 90% and 75%, while cancer-specific survival was 100%. No Clavien-Dindo grade ≥ 3 complications were observed. CONCLUSIONS: Radiofrequency ablation performed percutaneously is a minimally invasive treatment and may be applied in patients who are, due to comorbidities, poor candidates for surgery. In comorbid patients, where other causes of death play an important role, the application of a minimally invasive treatment method with satisfactory oncological effectiveness is justified.

Frequency of CD4+CD25+Foxp3+ cells in peripheral blood in relation to urinary bladder cancer malignancy indicators before and after surgical removal.

Tumor cells communicate with stromal cells, including cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs), to form microenvironment inhibiting immune responses. Regulatory T cells (Tregs, CD4+CD25+FoxP3+) stimulate immune tolerance and facilitate tumor progression. We analyzed the changes in Treg frequencies assessed using flow cytometry in the peripheral blood of patients with urothelial bladder cancer before and after tumor-removal. Changes in Treg frequency were investigated in relation to clinicopathomorphological indicators of tumor malignancy and expression of RCAS1 on CAFs and TAMs. Higher Treg frequencies were observed in early phase of tumor growth (pTa-pT2), in larger tumors, with more aggressive type of invasion, and with expression of RCAS1. The later phase of tumor development, accompanied by a nonclassic differentiations and pT3-pT4 advancement, had lower number of tumor infiltrating lymphocytes (TILs) and lower Treg frequency. Furthermore, in pT2-pT4 tumors, a decreased post-surgery Treg frequency was associated with poorer prognosis: patients with the lowest frequency of Tregs died first. These findings strongly suggest that the Treg frequencies at later phase of tumor growth, associated with a low anti-tumor response, represent a new and important prognostic indicator in urinary bladder cancer.

Radiofrequency ablation of small renal masses as an alternative to nephron-sparing surgery: preliminary results.

INTRODUCTION: Radical endoscopic minimal-invasive treatment methods, such as thermal ablation, are sought as an alternative to standard radical surgical treatment of kidney neoplasms. We analysed patients who could be qualified for radical treatment due to T1a renal tumour. MATERIAL AND METHODS: Twenty-three patients out of 129 who underwent radiofrequency thermal ablation of kidney tumours in the years 2003-2010 were analysed. The inclusion criteria were age below 70 years, lack of major comorbidities (ASA score 1, 2), and competent contralateral kidney. In all cases tumour size was below 4 cm. All patients were followed up with computed tomography (CT) and ultrasonography (USG) every 6 months for 3 years. RESULTS: In 20 patients kidney tumour was biopsied before radiofrequency ablation (RFA) and 10 of these biopsies were positive and revealed cancer. Six patients required additional treatment due to recurrence visible in CT - 3 with a positive biopsy result, 1 with negative and 2 without biopsy. Three of them were treated with a second session of RFA, 1 with radical nephrectomy and 2 with partial nephrectomy. No disease dissemination was observed and all patients who received additional treatment remain disease free. CONCLUSIONS: The RFA can be safely used in selected patients with T1a tumour as an alternative to partial nephrectomy. Careful follow-up is required after thermal ablation and allows early detection and successful treatment of recurrences.

Lymph node dissection during laparoscopic (LRC) and open (ORC) radical cystectomy due to muscle invasive bladder urothelial cancer (pT2-3, TCC).

AIM: The aim of the study was to compare the number of nodes dissected during laparoscopic and open radical cystoprostatectomy in men or anterior exenteration in women due to muscle invasive bladder urothelial cancer (IBC). MATERIAL AND METHODS: Fifty-one patients treated with laparoscopic radical cystectomy (LRC) and 63 with open radical cystectomy (ORC) were compared. The LRC group consisted of 47 pT2 tumours and 4 pT3, while the ORC group was composed of 27 pT2 tumours and 36 pT3. During ORC external, internal, common iliac and obturator lymph nodes were removed separately, but were added and analysed together for each side. Nodes dissected from one side during ORC were compared to en bloc dissected nodes in the LRC group. RESULTS: There were no complications associated with extended pelvic lymph node dissection during LRC or ORC. There were significant differences in the mean number of resected lymph nodes between LRC and ORC for pT2 tumours. The laparoscopic approach allowed about 8-9 more lymph nodes to be removed than open surgery in the pT2 group. In 15% of patients with pT2 disease treated with open radical cystectomy node metastases were observed. Active disease was detected in 18% of nodes resected laparoscopically due to pT2 disease. Fourty-seven percentage of patients with pT3 disease treated with open surgery were diagnosed as harbouring metastatic lymph nodes. The laparoscopic group with pT3 disease was too small to analyse. CONCLUSIONS: We have found that laparoscopic radical cystectomy can be performed without any compromise in lymph node dissection. The technique of lymph node dissection (LND) during laparoscopic cystectomy (LRC) resulted in sufficient resected lymphatic tissue, especially in patients with bladder-confined tumours with a low volume of lymph nodes.