Noninvasive Carcinoma Research Articles

Urothelial Cancer: A Case Report of Macroscopic Hematuria

A 67 year - old male patient with painless macroscopic haematuria of 3 weeks of evolution being his only symptom. Auxiliary laboratory exams were non-conclusive. In the histopathological study of the lesion, renal pelvis with scant epithelium with atypia consistent with low-grade non-invasive urothelial carcinoma. The patient underwent a right nephroureterectomy as treatment for his condition.

International Society of Urological Pathology (ISUP) Consensus Conference on Current Issues in Bladder Cancer. Working Group 2: Grading of Mixed Grade, Invasive Urothelial Carcinoma Including Histologic Subtypes and Divergent Differentiations, and Non-Urothelial Carcinomas.

The 2022 International Society of Urological Pathology (ISUP) Consensus Conference on Urinary Bladder Cancer Working Group 2 was tasked to provide evidence-based proposals on the applications of grading in noninvasive urothelial carcinoma with mixed grades, invasive urothelial carcinoma including subtypes (variants) and divergent differentiations, and in pure non-urothelial carcinomas. Studies suggested that predominantly low-grade noninvasive papillary urothelial carcinoma with focal high-grade component has intermediate outcome between low- and high-grade tumors. However, no consensus was reached on how to define a focal high-grade component. By 2004 WHO grading, the vast majority of lamina propria-invasive (T1) urothelial carcinomas are high-grade, and the rare invasive low-grade tumors show only limited superficial invasion. While by 1973 WHO grading, the vast majority of T1 urothelial carcinomas are G2 and G3 and show significant differences in outcome based on tumor grade. No consensus was reached if T1 tumors should be graded either by the 2004 WHO system or by the 1973 WHO system. Because of the concern for underdiagnosis and underreporting with potential undertreatment, participants unanimously recommended that the presence of urothelial carcinoma subtypes and divergent differentiations should be reported. There was consensus that the extent of these subtypes and divergent differentiations should also be documented in biopsy, transurethral resection, and cystectomy specimens. Any distinct subtype and divergent differentiation should be diagnosed without a threshold cutoff, and each type should be enumerated in tumors with combined morphologies. The participants agreed that all subtypes and divergent differentiations should be considered high-grade according to the 2004 WHO grading system. However, participants strongly acknowledged that subtypes and divergent differentiations should not be considered as a homogenous group in terms of behavior. Thus, future studies should focus on individual subtypes and divergent differentiations rather than lumping these different entities into a single clinicopathological group. Likewise, clinical recommendations should pay attention to the potential heterogeneity of subtypes and divergent differentiations in terms of behavior and response to therapy. There was consensus that invasive pure squamous cell carcinoma and pure adenocarcinoma of the bladder should be graded according to the degree of differentiation. In conclusion, this summary of the International Society of Urological Pathology Working Group 2 proceedings addresses some of the issues on grading beyond its traditional application, including for papillary urothelial carcinomas with mixed grades and with invasive components. Reporting of subtypes and divergent differentiation is also addressed in detail, acknowledging their role in risk stratification. This report could serve as a guide for best practices and may advise future research and proposals on the prognostication of these tumors.

Cutaneous squamous cell carcinoma of the lip successfully treated with rhenium-188 brachytherapy.

Cutaneous squamous cell carcinoma (SCC) is the second most common form of skin cancer. In most cases, non-invasive SCC has a good prognosis and is curable by surgical resection. Nevertheless, a small percentage of patients pose specific management problems due to the technical difficulty of maintaining function and aesthetics because of the size or location of the tumor. An emerging therapeutic approach with high-dose brachytherapy using a nonsealed rhenium-188 resin, commercially known as Rhenium-Skin Cancer Therapy®, has been shown to be highly effective in non-invasive carcinoma, up to a thickness of 2-3 mm.

The Potent Anti-Tumor Effects of Rhodiola Drinking Are Associated with the Inhibition of the mTOR Pathway and Modification of Tumor Metabolism in the UPII-Mutant Ha-Ras Model.

Background: SHR-5 has been used as an "adaptogen" for enhancing physical and mental performance and for fighting stress in the healthy population. The purpose of this study is to determine the chemopreventive efficacy of SHR-5 for superficial bladder cancer and to investigate the underlying mechanisms of action. Methods: UPII-mutant Ha-ras bladder-cancer-transgenic mice, that developed low-grade and noninvasive papillary transitional urothelial cell carcinoma, were fed with 1.25 and 6.25 mg/mL SHR-5 in drinking water for 6 months. The survival of the mice, obstructive uropathy, tumor burden and morphology, and proliferation were evaluated by pathological, molecular, metabolic, and statistical analyses. Results: Approximately 95% or more of the male UPII-mutant Ha-ras mice that drank SHR-5 daily survived over 6 months of age, while only 33.3% of those mice that drank normal water survived over 6 months of age (p < 0.0001); SHR-5 drinking exposure also reduced tumor-bearing bladder weight and urinary tract obstruction and inhibited mTOR signaling in neoplastic tissues. Global metabolic analysis revealed that SHR-5 resulted in increased phenolic metabolites and decreased CoA, a critical metabolic cofactor for lipid metabolism. Conclusions: Our findings highlight the potential of SHR-5 as an anti-aging agent for bladder cancer prevention through reshaping tumor metabolism via the inhibition of the mTOR signaling. Global metabolomics profiling provides a unique and efficient tool for studying the mechanisms of complex herb extracts' action.

Multicenter study to evaluate the efficacy and standardize radiofrequency ablation therapy for early breast cancer.

e12570 Background: Early-stage breast cancer is increasingly detected by screening mammography, and we aim to establish radiofrequency ablation therapy (RFA) as a minimally invasive, cost-efficient, and cosmetically acceptable local treatment. In our Phase I study, localized tumors with a maximum diameter of 2 cm, preoperatively diagnosed by imaging and histopathology, were treated with RFA. A 90% complete ablation rate was confirmed histopathologically. Our phase II multicenter study of RFA without resection for early breast cancer will evaluate the long-term safety and efficacy of RFA as well as its cosmetic results, which are a perceived advantage of this technique. Methods: From Nov. 2009 to Nov. 2012, 58 patients with early-stage breast cancer received non-surgical RFA therapy. Patients had localized solitary N0 tumors with a maximum diameter of 1 cm. In our experimental therapy, a radiofrequency electrode needle is inserted through the skin into the breast lesion under imaging guidance, followed by thermal ablation with radiofrequency waves. RFA will be conducted under general anesthesia. The Cool-tip™ RF Ablation Single Electrode Kit (Medtronic, CO, USA) will be used to standardize the evaluation of the ablation effect. They underwent RFA and SNB under general anesthesia and adjuvant therapy and breast radiation. Follow-up evaluation for residual tumor at 3, 6, and 12 months after RFA included clinical examination, diagnostic imagings and vacuum-assisted biopsy. Surgical resection was recommended for patients with suspected residual disease or incomplete ablation. The primary endpoint was the frequency of adverse events. Secondary endpoints included the complete ablation rate and ipsilateral breast relapse-free rate. Results: The follow-up period ranged from 15 to 109 months (median, 85 months). The 57 patients completed the non-surgical RFA procedure and underwent diagnostic imaging and needle biopsy after 3 months. Seven patients with suspected incomplete ablation underwent surgical resection; incomplete ablation was confirmed in 5 (8.6%, 2 with invasive and 3 with non-invasive ductal carcinoma). During subsequent follow-up, 1 patient each was diagnosed with contralateral breast cancer and ipsilateral breast tumor relapse. No distant recurrence was documented. Cosmetic results were excellent in 94% of patients. Conclusions: Our phase II multicenter study of RFA without resection for early breast cancer will evaluate the long-term safety and efficacy of RFA as well as its cosmetic results, which are a perceived advantage of this technique. Clinical trial information: UMIN000008675 .

A canine case of bladder urothelial carcinoma (transitional cell carcinoma) treated with a chemotherapeutic agent, a molecular targeted drug, and cyclooxygenase inhibitors

A 4-year-old neutered male Scottish Terrier, weighing 10.4 kg, presented with hematuria for the past 10 days. Ultrasonography revealed multiple masses in the apex and trigone of the bladder. A catheter biopsy was performed, and the histopathological diagnosis was non-invasive urothelial carcinoma (transitional cell carcinoma) with low to medium grade pathological malignancy. Treatments with piroxicam alone, vinblastine and firocoxib, toceranib and firocoxib, and firocoxib alone resulted in a partial response or stable disease. The patient showed no regional lymph node metastasis or distant metastases, maintained stable disease, and had an excellent quality of life at 1681 days after the start of treatment.

HER2/neu expression status of post BCG recurrent non-muscle-invasive bladder urothelial carcinomas in relation to their primary ones.

Transurethral resection (TUR) followed by adjuvant therapy is still the treatment of choice of Non-Muscle-Invasive Bladder Urothelial Carcinoma (NMIBUC). However, recurrence is one of the most troublesome features of these lesions. Early second resection and adjuvant BCG therapy has been shown to improve the outcome. To evaluate the prognostic value of C-erbB-2 (HER2/neu) expression status in Non-Muscle-Invasive Bladder Urothelial Carcinoma cases, before and after intravesical Bacillus Calmette Guerin (BCG immunotherapy). HER2/neu expression was studied in 120 (Ta-T1) Non-Muscle-Invasive Urothelial Carcinoma cases. The expression was evaluated and compared to the expression after Bacillus Calmette Guerin (BCG) immunotherapy. HER2/neu expression in low and high grade of the Non- Muscle-Invasive Urothelial Carcinoma was (38%) and (83%) respectively. The difference of the expression rates by tumor grade was statistically significant. In recurring lesions post BCG therapy, C-erbB-2 expression was markedly decreased (31.6%) when compared to its expression before therapy (65%). The HER2/neu expression increased as the tumor grade rose. The reduction in expression following BCG treatment in Non-Invasive transitional cell carcinoma cases could reflect a reduction of the potential malignancy of the tumor.

"ThermoTRP" Channel Expression in Cancers: Implications for Diagnosis and Prognosis (Practical Approach by a Pathologist).

Temperature-sensitive transient receptor potential (TRP) channels (so-called "thermoTRPs") are multifunctional signaling molecules with important roles in cell growth and differentiation. Several "thermoTRP" channels show altered expression in cancers, though it is unclear if this is a cause or consequence of the disease. Regardless of the underlying pathology, this altered expression may potentially be used for cancer diagnosis and prognostication. "ThermoTRP" expression may distinguish between benign and malignant lesions. For example, TRPV1 is expressed in benign gastric mucosa, but is absent in gastric adenocarcinoma. TRPV1 is also expressed both in normal urothelia and non-invasive papillary urothelial carcinoma, but no TRPV1 expression has been seen in invasive urothelial carcinoma. "ThermoTRP" expression can also be used to predict clinical outcomes. For instance, in prostate cancer, TRPM8 expression predicts aggressive behavior with early metastatic disease. Furthermore, TRPV1 expression can dissect a subset of pulmonary adenocarcinoma patients with bad prognosis and resistance to a number of commonly used chemotherapeutic agents. This review will explore the current state of this rapidly evolving field with special emphasis on immunostains that can already be added to the armoire of diagnostic pathologists.

P16 expression in urothelial carcinoma: Experience from a tertiary care center in coastal South India.

Urothelial carcinomas (UC) account for 6 and 2% of all cancers in men and women, respectively. Human papillomavirus (HPV) is one of the causative agents in cancers of the uterine cervix and head and neck. The role of HPV is also being studied in cancers of the urinary bladder, penis, and prostate. As p16-INK4a is a surrogate marker for high-risk HPVE7 oncoprotein, this study aims to highlight the utility of p16 immunohistochemistry (IHC) in the evaluation of HPV-associated UC. A retrospective study was conducted on UC of the bladder received in the Pathology department between January 2013 and December 2018. Bladder biopsies from non-neoplastic lesions served as controls. IHC was done for the detection of the p16 antigen. The p16 staining was recorded as positive, when there was strong staining in >50% of tumor nuclei. The p16 positive and negative tumors were compared based on age, gender, tumor size, grade, and muscle invasion. P value <0.05 was considered statistically significant. The expression of p16 was analyzed in 72 UC and compared with 20 non-neoplastic cases, of which 26.4% of the cases showed p16 expression. The p16 expression was absent in the non-neoplastic lesions. While the majority (87.5%) of the low-grade tumors were negative for p16 expression, 43.8% high-grade tumors were positive. Similarly, a larger proportion of invasive carcinomas (38.8%) expressed p16 as compared to non-invasive carcinomas (13.8%). Thus, p16 expression showed a significant association with grade and stage in these malignancies (P < 0.05). The p16 expression was associated with high-grade and muscle-invasive UC. The p16 was absent in all non-neoplastic and precursor lesions. Thus, it can provide essential information not only about HPV association but also on the prognostic implications for the patients.

Quantitative Nuclear Grading: An Objective, Artificial Intelligence–Facilitated Foundation for Grading Noninvasive Papillary Urothelial Carcinoma

In nonmuscle invasive bladder cancer, grade drives important treatment and management decisions. However, grading is complex and qualitative, and it has considerable interobserver and intraobserver variability. Previous literature showed that nuclear features quantitatively differ between bladder cancer grades, but these studies were limited in size and scope. In this study, we aimed to measure morphometric features relevant to grading criteria and build simplified classification models that objectively distinguish between the grades of noninvasive papillary urothelial carcinoma (NPUC). We analyzed 516 low-grade and 125 high-grade 1.0-mm diameter image samples from a cohort of 371 NPUC cases. All images underwent World Health Organization/International Society of Urological Pathology 2004 consensus pathologist grading at our institution that was subsequently validated by expert genitourinary pathologists from 2 additional institutions. Automated software segmented the tissue regions and measured the nuclear features of size, shape, and mitotic rate for millions of nuclei. Then, we analyzed differences between grades and constructed classification models, which had accuracies up to 88% and areas under the curve as high as 0.94. Variation in the nuclear area was the best univariate discriminator and was prioritized, along with the mitotic index, in the top-performing classifiers. Adding shape-related variables improved accuracy further. These findings indicate that nuclear morphometry and automated mitotic figure counts can be used to objectively differentiate between grades of NPUC. Future efforts will adapt the workflow to whole slides and tune grading thresholds to best reflect time to recurrence and progression. Defining these essential quantitative elements of grading has the potential to revolutionize pathologic assessment and provide a starting point from which to improve the prognostic utility of grade.

Mitomycin Gel (UGN-101) as a Kidney-sparing Treatment for Upper Tract Urothelial Carcinoma in Patients with Imperative Indications and High-grade Disease

BackgroundIntracavitary UGN-101 is approved for the treatment of low-grade noninvasive upper tract urothelial carcinoma (UTUC). Post-commercialization studies underscore the benefit of UGN-101 administration for patients with imperative indications for whom radical nephroureterectomy (RNU) is not a viable option. ObjectiveTo describe the use, efficacy, and safety of UGN-101 in patients with UTUC with imperative indications for renal preservation, including high-grade disease. Design, setting, and participantsPatients receiving UGN-101 with imperative indications were retrospectively analyzed using a multicenter centralized registry from 15 high-volume academic and community centers. Outcome measurements and statistical analysisWe defined imperative indications as patients with a solitary kidney, the presence of chronic kidney disease (CKD) with a glomerular filtration rate <30 ml/min, bilateral UTUC, and patients unfit for or unwilling to undergo surgical extirpation. Tumor characteristics, disease progression/recurrence, and adverse events were recorded on a per–renal-unit basis. Results and limitationsUGN-101 was instilled into 52 renal units (38%) in 48 patients for imperative indications, including 29 patients (56%) with a solitary kidney, 11 kidneys (21%) in the setting of bilateral UTUC, six patients (12%) with CKD, and six patients (12%) who were unfit for or unwilling to undergo RNU. Twelve renal units had biopsy-proven high-grade papillary disease. Tumors were completely ablated before induction therapy in 34% of cases, while 66% had tumor present. Following induction therapy, 17 patients (40%) had no evidence of disease (NED) on ureteroscopy, 88% of whom maintained this status at median follow-up of 10.8 mo. In the cohort with high-grade disease, five patients (45%) had NED at initial post-induction primary disease evaluation. Adverse events included pyelonephritis (8%), ureteral stenosis (8%), anemia (6%), and acute renal failure (4%). Limitations include the retrospective study design, the lack of long-term follow up, and patient selection bias. ConclusionsIntracavitary therapy with UGN-101 in patients with UTUC and imperative indications shows promise as a kidney-sparing treatment modality. While long-term follow-up is needed, this intracavitary treatment may help in prolonging time to RNU and delaying the morbidity of hemodialysis in this comorbid population. Patient summaryWe reviewed results for patients with cancer in the upper urinary tract and an additional condition that would not allow kidney removal who received treatment with a gel called UGN-101. Our results suggest that UGN-101 shows promise as a kidney-sparing treatment. It may delay the time until kidney removal is needed in these patients and avoid the negative effects associated with dialysis.

Urinary Bladder Cancer-Epidemiological and Histopathological Study

Urinary bladder cancer is the main reason for morbidity and mortality throughout the world. Urothelial carcinoma is a common primary tumor of urinary bladder (90%). To investigate the epidemiological and histopathological aspects in Libyan patients suffering from urinary bladder cancer, we performed a study on 39 bladder cancer biopsies from transurethral resection of bladder tumor (TURBT) and cystoscopic samples obtained from Oncology Department- Al Hawari Hospital, over the period of (2021- May 2022), Tiba Medical Laboratory (2021- July 2022), and Alnoon Medical laboratory (2019- January 2022) at Benghazi, Libya. Of the 39 cases, 34 (87.2%) were diagnosed in men, and 5 (12.8%) were found in women, the men/ women ratio being of 6.8/1. The highest incidence of bladder tumors was recorded in individuals aged between 61 and 80 years old. In this age group, there were admitted 24 patients with bladder cancer, representing 61.5%. The most common pathological types of urinary bladder carcinoma found was Invasive Urothelial Carcinoma TCC (48.72%) followed by noninvasive Urothelial Carcinoma TCC (46.15%), and Squamous Cell Carcinoma SCC in (5.13%). A case of SCC on top of Schistosomiasis was also seen. Grade III was found in 51.2% of our patients and 43.5% of them had stage II. This study has highlighted upon the importance of histopathological study in evaluating urinary bladder cancer. Cystoscopic studies and biopsies help in early detection of bladder neoplasms and they form the mainstay of the diagnosis and follow up. The objects of this work were to assess epidemiological features of the bladder cancer in Benghazi - Libya with regard to frequency, age and sex distribution. Furthermore, to describe the Histopathological features of the urinary bladder cancer, particularly Transitional Cell Carcinoma (TCC) in urinary bladder biopsies.

Monte Carlo simulation of handheld probes to detect non-invasive ductal carcinoma from diffuse optical reflectance signals

To identify the malignancy in human breast, hand-held optical probes are simulated using the Monte Carlo method. These devices were used to scan different tissue equivalent numerical breast phantoms to detect the embedded cancerous tissues in them. The phantoms were simulated with glandular tissues embedded with ductal carcinoma of size 5 mm and 2 mm diameter at various depths. Two optical probes namely dual side detector (DSD) probe and a single side detector (SSD) probe are designed through which one million light photons of wavelengths 600 nm and 800 nm respectively were passed into the numerical phantoms. The photons that were backscattered from the phantoms were received by the detectors in both probes. They were measured as signals and both probes were able to detect the presence of the embedded cancerous tissues at different depths. The results indicate that the probes with a light source at 800 nm could detect deep-seated inhomogeneities. The absolute value of Peak Intensity (|PI|) and Full Width at Half Maximum (FWHM) would be indicative of their location and approximate size of the embedded tissues. The |PI| decreases with the size and depth of the embedded tissue, and the FWHM increases with depth. The results show that the designed probes are capable of detecting small variations in tissues.

Frequent Telomerase Reverse Transcriptase Promoter and Fibroblast Growth Factor Receptor 3 Mutations Support the Precursor Nature of Papillary Urothelial Hyperplasia of the Urinary Bladder

The precursor nature of papillary urothelial hyperplasia of the urinary bladder is uncertain. In this study, we investigated the telomerase reverse transcriptase (TERT) promoter and fibroblast growth factor receptor 3 (FGFR3) mutations in 82 patients with papillary urothelial hyperplasia lesions. Thirty-eight patients presented with papillary urothelial hyperplasia and concurrent noninvasive papillary urothelial carcinoma, and 44 patients presented with de novo papillary urothelial hyperplasia. The prevalence of the TERT promoter and FGFR3 mutations is compared between de novo papillary urothelial hyperplasia and those with concurrent papillary urothelial carcinoma. Mutational concordance between papillary urothelial hyperplasia and concurrent carcinoma was also compared. The TERT promoter mutations were detected in 44% (36/82) of papillary urothelial hyperplasia, including 23 (23/38, 61%) papillary urothelial hyperplasia with urothelial carcinoma and 13 (13/44, 29%) de novo papillary urothelial hyperplasia. The overall concordance of TERT promoter mutation status between papillary urothelial hyperplasia and concurrent urothelial carcinoma was 76%. The overall FGFR3 mutation rate of papillary urothelial hyperplasia was 23% (19/82). FGFR3 mutations were detected in 11 patients with papillary urothelial hyperplasia and concurrent urothelial carcinoma (11/38, 29%) and 8 patients with de novo papillary urothelial hyperplasia (8/44, 18%). Identical FGFR3 mutation status was detected in both papillary urothelial hyperplasia and urothelial carcinoma components in all 11 patients with FGFR3 mutations. Our findings provide strong evidence of a genetic association between papillary urothelial hyperplasia and urothelial carcinoma. High frequency of TERT promoter and FGFR3 mutations suggests the precursor role of papillary urothelial hyperplasia in urothelial carcinogenesis.

GATA3 Expression in Human Tumors: A Tissue Microarray Study on 16,557 Tumors

Introduction: GATA3 is a transcription factor involved in epithelial cell differentiation. GATA3 immunostaining is used as a diagnostic marker for breast and urothelial cancer but can also occur in other neoplasms. Methods: To evaluate GATA3 in normal and tumor tissues, a tissue microarray containing 16,557 samples from 131 different tumor types and subtypes and 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry. Results: GATA3 positivity was found in 69 different tumor types including 23 types (18%) with at least one strongly positive tumor. Highest positivity rates occurred in noninvasive papillary urothelial carcinoma (92–99%), lobular carcinoma (98%), carcinoma of no special type of the breast (92%), basal cell carcinoma of the skin (97%), invasive urothelial carcinoma (73%), T-cell lymphoma (23%), adenocarcinoma of the salivary gland (16%), squamous cell carcinoma of the skin (16%), and colorectal neuroendocrine carcinoma (12%). In breast cancer, low GATA3 staining was linked to high pT stage (p = 0.03), high BRE grade (p < 0.0001), HER2 overexpression (p = 0.0085), estrogen and progesterone receptor negativity (p < 0.0001 each), and reduced survival (p = 0.03). Conclusion: Our data demonstrate that GATA3 positivity can occur in various tumor entities. Low levels of GATA3 reflect cancer progression and poor patient prognosis in breast cancer.

Significance of tumor-associated neutrophils, lymphocytes, and neutrophil-to-lymphocyte ratio in non-invasive and invasive bladder urothelial carcinoma.

Tumor-infiltrating neutrophils and lymphocytes play essential roles in promoting or combating various neoplasms. This study aimed to investigate the association between tumor-infiltrating neutrophils and lymphocytes and the neutrophil-to-lymphocyte ratio in the progression of urothelial carcinoma. A total of 106 patients diagnosed with urothelial carcinoma were was. Pathological examination for tumor grade and stage and for tumor-infiltrating neutrophils, both CD4 and CD8+ T lymphocytes, as well as the neutrophil- to-lymphocyte ratio were evaluated. The presence of neutrophils and the neutrophil-to-lymphocyte ratio correlated with high-grade urothelial neoplasms. In both low- and high-grade tumors, the lymphocytes increased during progression from a non-invasive neoplasm to an early-invasive neoplasm. CD8+ T lymphocytes increased in low-grade non-muscle-invasive tumors compared to non-invasive tumors. Additionally, there was a significant decrease in CD8+ T lymphocytes during progression to muscle-invasive tumors. Our results suggest that tumor-infiltrating neutrophils and CD8+ T lymphocytes have a significant effect on tumor grade and progression.

A Case of a 77-year-old Woman with Noninvasive Ductal Carcinoma of the Breast Incidentally Discovered after Acute Mastistis

A Case of a 77-year-old Woman with Noninvasive Ductal Carcinoma of the Breast Incidentally Discovered after Acute Mastistis

Immunohistochemical expression of CXCL5 as a valuable prognostic marker in urinary bladder urothelial carcinoma

Abstract Background and aim Urothelial carcinoma (UC) is the most common histologic subtype of bladder carcinoma. Detection of novel biomarkers that could predict UC progression and prognosis represents an active focus of research in the oncology field. CXCL5 is a member of the CXC chemokine family. It has been implicated in progression of many cancers, but its prognostic value in UC remains unclear. This study aimed to evaluate the immunohistochemical expression of CXCL5 in noninvasive and invasive UC of the urinary bladder and to correlate its expression with different studied clinicopathological characteristics to evaluate its potential prognostic value. Patients and methods A total of 60 specimens of primary invasive and noninvasive urothelial bladder carcinomas were included in this study. Paraffin-embedded tissue blocks were prepared from the specimens. Two serial tissue sections were obtained from each specimen. One tissue section was stained by hematoxylin and eosin stain and examined to confirm diagnosis, histologic subtype, tumor grade, muscle invasion, and presence or absence of bilharzial infestation, and the second tissue section was subjected to immunohistochemical using anti-human CXCL5 antibody. Results Studying the association between CXCL5 expression and different clinicopathologic parameters in urothelial bladder carcinoma revealed a statistically significant correlation between its expression and poor prognostic indicators. CXCL5 expression is significantly correlated with poorly differentiated (P=0.025), advanced stage (P=0.039), and invasive tumors (P=0.002). Conclusion The current study revealed that CXCL5 overexpression in urothelial bladder carcinoma is strongly associated with adverse prognostic factors. CXCL5 might be considered as a reliable biomarker in predicting tumor progression and poor prognosis.

HDR-brachytherapy for accelerated partial breast irradiation: Long-term experience from a Japanese institution.

We investigated the long-term oncological outcome of high-dose-rate (HDR) multicatheter interstitial brachytherapy (MIB) for adjuvant accelerated partial breast irradiation (APBI) after breast conserving surgery in Japanese patients. Between June 2002 and October 2011, 86 breast cancer patients were treated at National Hospital Organization Osaka National Hospital (trial number of the local institutional review board, 0329). Median age was 48 years (range, 26-73 years). Eighty patients had invasive and 6 patients non-invasive ductal carcinoma. Tumor stage distribution was pT0 in 2, pTis in 6, pT1 in 55, pT2 in 22, and pT3 in one patient, respectively. Twenty-seven patients had close/positive resection margins. Total physical HDR dose was 36-42 Gy in 6-7 fractions. At a median follow-up of 119 months (range, 13-189 months), the 10-year local control (LC) and overall survival rate was 93% and 88%, respectively. Concerning the 2009 Groupe Européen de Curiethérapie-European Society for Therapeutic Radiology and Oncology risk stratification scheme, the 10-year LC rate was 100%, 100%, and 91% for patients considered as low-risk, intermediate-risk, and high-risk, respectively. According to the 2018 American Brachytherapy Society risk stratification scheme, the 10-year LC rate was 100% and 90% for patients 'acceptable' and 'unacceptable' for APBI, respectively. Wound complications were observed in 7 patients (8%). Risk factors for wound complications were the omission of prophylactic antibiotics during MIB, open cavity implantation, and V100 ≥ 190 cc. No grade ≥ 3 late complications (CTCVE version 4.0) were observed. Adjuvant APBI using MIB is associated with favorable long-term oncological outcomes in Japanese patients for low-risk, intermediate-risk, and acceptable groups of patients.

CD47 expression in urothelial carcinoma and its correlation with histopathological findings.

The incidence of bladder cancers (BCs) is increasing day by day in both males and females with increased smoking. New treatment protocols are required due to the long follow-up times and high recurrence rates. CD47 (integrin-associated protein) is a membrane receptor that is effective in normal and pathophysiological events such as apoptosis, proliferation, adhesion, and immunity. Phagocytosis of both normal and tumor cells is prevented, by binding to the ligand signal regulatory protein-1 (SIRP-1)α on macrophages. Anti-CD47 antibodies can eliminate the binding and may be effective in treatment. The study included 194 cases with urothelial carcinoma (UC) who underwent transurethral resection (TUR) of the bladder and had been followed up for one year. Cytoplasmic and membranous staining was preferred for CD47-positive staining. Staining results were compared with tumor grades, pathologic tumor stage, recurrence, and metastasis grade. The prevalence and intensity of CD47 staining in BCs were evaluated in this study. High-grade tumors were stained more pronouncedly compared with low-grade tumors and normal epithelium. The prevalence of CD47 staining was significant in pT2 (Pathological tumor stage 2, invades of muscularis propria) tumors, and its correlation with pTa (Pathological tumor stage a, noninvasive papillary carcinoma) tumors was significant ( P < 0.001). In the intensity evaluation, there was a significant difference between pTa and pT2 and between pT1 (Pathological tumor stage 1, invades lamina propria) and pT2 ( P = 0.003). CD47 is expressed strongly in high-grade tumors. The prevalence and intensity of CD47 staining are high in pathologic tumor stage, recurrence, and distant metastases and are considered poor prognostic markers. We believe that anti-CD47 antibodies can be used as an alternative to the current treatment or in combination with other medications, and the systemic side effects that may occur with intravesical treatment can be prevented.