Economical Evaluation of Prostate Cancer Treatment Using Intensity-Modulated Radiation Therapy, 3-Dimensional Conformal Radiation Therapy and Radical Prostatectomy: A Systematic Review.

OBJECTIVES: Prostate cancer is a common form of cancer among men worldwide. The objective of this study was to conduct a systematic review of the economic evaluations of prostate cancer treatment strategies. METHODS: This systematic review was conducted using multiple electronic databases up to May 2021. English-language economic evaluation studies that compared intensity-modulated radiation therapy (IMRT), 3-dimensional conformal radiation therapy (3DCRT), and radical prostatectomy (RP) were included. The studies were evaluated using the Consolidated Health Economic Evaluation Reporting Standards checklist. The search yielded 1151 potentially relevant publications, which were screened based on the title and abstract. After the removal of duplicates, 55 studies remained, and 9 studies were screened in full text. Finally, textual data were analyzed manually using by-content analysis method. RESULTS: All studies were cost-effective and evaluated quality-adjusted life year as the efficacy indicator. The studies were conducted from either payers' or health systems' perspectives, and the time horizon varied from 5 to 20 years. We included only full economic evaluation studies. The use of IMRT in comparison with 3DCRT was evaluated in 6 studies, based on which IMRT increased health and reduced side effects of treatment. According to incremental cost-effectiveness ratio (ICER) results, IMRT was more cost-effective than 3DCRT. Three studies evaluated the use of RP in comparison with radiotherapy. Based on these studies, radiotherapy was more effective than RP. CONCLUSION: IMRT was found to be more cost-effective than 3DCRT in all 6 studies compared with the threshold. Radiotherapy was found to be more effective than RP. However, long-term clinical trial studies are needed to confirm these findings and to provide more definitive conclusions.

Renal vein thrombosis due to metastatic germ cell tumor, report of a case with a very rare clinical scenario.

BACKGROUND: Renal metastasis is a rare manifestation of germ cell tumors. Extension of malignant lesions into the renal vein can complicate the scenario. CASE: This report presents a 35-year-old man with primary stage IS NSGCT. Fourteen months after radical orchiectomy he presented with metastasis in the lung, kidney, and para-aortic lymph nodes. He received multiple lines of salvage treatments including chemotherapy and surgery. Intraoperative exploration during radical nephrectomy and retroperitoneal lymphadenectomy revealed intra-renal vein involvement with a prominent teratomatous component. CONCLUSION: Defining the exact extent of malignant lesions, especially endovascular lesions, is very important to clarify how advanced the malignant lesions are. The surgeons must be aware of the risk factors that predict vascular involvement, and therefore, providing intraoperative access to vascular surgery procedures when needed.

The In Vitro Pro-inflammatory Functions of the SP/NK1R System in Prostate Cancer: a Focus on Nuclear Factor-Kappa B (NF-κB) and Its Pro-inflammatory Target Genes.

Prostate cancer is one of the main global health threats for men which is in close association with chronic inflammation. Neuropeptide substance P (SP), acting through neurokinin receptor (NK-1R), induces various pro-inflammatory responses which are strongly involved in the pathogenesis of several diseases as well as cancer. Therefore, we aimed to investigate the pro-inflammatory functions of the SP/NK1R complex in prostate cancer and the therapeutic effects of its inhibition by NK-1R antagonist, aprepitant, in vitro. MTT assay was conducted for the cytotoxicity assessment of aprepitant in prostate cancer cells. The protein expression levels were evaluated by Western blot assay. Quantitative real-time PCR (qRT-PCR) was applied to measure mRNA expression levels of pro-inflammatory cytokines. Concurrently, the protein concentrations of pro-inflammatory cytokines were also analyzed by enzyme-linked immunosorbent assay. We observed that SP increased the levels of pro-inflammatory cytokines (IL-1ß, IL-6, and TNF-α), while treatment with aprepitant reduced the effects of SP. We also indicated that SP increased the protein levels of nuclear factor-kappa B (NF-κB), as the main regulator of inflammatory processes, and also an NF-κB target gene, cyclooxygenase 2 (COX-2) in prostate cancer cells, while treatment with aprepitant reversed these effects. Taken together, our findings highlight the importance of the SP/NK1R system in the modulation of pro-inflammatory responses in prostate cancer cells and suggest that aprepitant may be developed as a novel anti-inflammatory agent for the management of cancer-associated inflammation.

Selection of reference genes for RT-qPCR analysis of rice with Rhizoctonia solani infection and biocontrol PGPR/KSi application.

BACKGROUND: Rhizoctonia solani (AG1 IA) is an important pathogen of rice (Oryza sativa L.) that causes rice sheath blight (RSB). Since control of RSB by breeding and fungicides have had limited success, novel strategies like biocontrol with plant growth-promoting rhizobacteria (PGPR) can be an effective alternative. METHOD AND RESULTS: Seven commonly used reference genes (RGs), 18SrRNA, ACT1, GAPDH2, UBC5, RPS27, eIF4a and CYP28, were evaluated for their stability in rice-R. solani-PGPR interaction for real-time quantitative PCR (RT-qPCR) analysis. Different algorithms were examined, Delta Ct, geNorm, NormFinder, BestKeeper, and comprehensive ranking by RefFinder, to evaluate RT-qPCR of rice in tissues infected with R. solani and treated with the PGPR strains, Pseudomonas saponiphilia and Pseudomonas protegens, with potassium silicate (KSi) alone or in combination with each PGPR strain. RG stability was affected for each treatment and treatment-specific RG selection was suggested. Validation analysis was done for nonexpressor of PR-1(NPR1) for each treatment. CONCLUSION: Overall, ACT1 was the most stable RG with R. solani infection alone, GAPDH2 with R. solani infection plus KSi, UBC5 with R. solani infection plus P. saponiphilia, and eIF4a with R. solani infection plus P. protegens. Both ACT1 and RPS27 were the most stable with the combination of KSi and P. saponiphilia, while RPS27 was the most stable with the combination of KSi and P. protegens.

Translation, Linguistic Validation, and Cultural Adaptation of the Bladder Cancer Index (BCI) Questionnaire Into the Persian (Farsi) Language and Comparing it With WHO Quality of Life Questionnaire: An Observational Study.

Objective: Whether ileal conduit diversion (ICD) or orthotopic neobladder (ONB) urinary diversion provides better quality of life (QoL) is still under debate. The Bladder Cancer Index (BCI) is a specific tool for bladder cancer (BCa) patients, providing reliable results in previous studies. A validated Farsi version of the BCI concerning cultural aspects could help Farsi-speaking clinicians gain more reliable feedback on QoL following urinary diversion. Materials and methods: Based on WHO suggestions, we translated the BCI questionnaire into the Persian language. Then, we performed a cross-sectional study on BCa patients who underwent ICD or ONB urinary diversion. We compared their QoL via BCI and WHO questionnaires. Chi-square and independent t-tests were used where appropriate. Results: The content validity ratio and the content validity indexes were 1 and 0.8-1.0, respectively. Of 57 participants, six patients (10.5%) were women. The ICD was performed for 38 (66.7%) and ONB diversion for 19 (33.3) participants. The mean age of ICD and ONB was 68.71 ± 7.40 and 64.28 ± 8.34 years, respectively (p-value: 0.055). In all sub-domains of BCI, except bowel habits, the mean scores were higher in the ICD group. A significant difference between ICD and ONB groups was found regarding urinary function (p-value<0.001). There was no significant difference between ICD and ONB groups in none of the domains of the WHO questionnaire. Conclusion: The QoL of ICD and ONB patients did not differ significantly. Even ICD may be superior in ritual purification, while the psychological status of ONB patients was better.

Does Renal Mass with Venous Thrombosis always Indicate Renal Cell Carcinoma? A Case Series.

Intravascular tumor extension in the major renal veins or their tributaries, as a rare but important clinical entity that can change the disease stage, prognosis, and approach to treatment. There is limited literature on the obstruction of renal vein and IVC by tumor thrombus in other types of renal tumors that are not of RCC type. We presented four different renal tumor cases with the presence of gross renal vein or IVC thrombosis. Although the incidence of renal vein and IVC tumor thrombus might be suggestive of (often diagnosed as) RCC, the possibility of other non-RCC renal tumors should be included in the differential diagnosis.

Bone scan with technetium 99m-methyl diphosphonate, the missing link in the initial staging of muscle-invasive bladder carcinoma.

BACKGROUND: Accurate staging is crucial to determine the type of treatment for patients with bladder cancer (BCa), especially in high-risk cases. We aimed to assess the role of bone scan in the initial staging of muscle-invasive bladder carcinoma (MIBC). MATERIAL AND METHODS: Forty-five patients with MIBC were referred to our tertiary clinic to perform a technetium 99m-methyl diphosphonate (Tc99m-MDP) bone scan from January 2019 to March 2020. The patients underwent bone scintigraphy with pelvic SPECT/CT before radical cystectomy. Whole-body scanning was performed 4 hours after Tc99m-MDP injection in both anterior and posterior views. Since the most common bone involvement site in these patients is the pelvic bones and the spine, pelvic SPECT/CT was performed in all patients. RESULTS: Frequency of skeletal metastasis was 26.7%. Only 19% of the metastases were detected by previous pelvic CT/MRI images performed for routine staging. All the reported skeletal metastases by previous anatomical imaging methods were detected in the bone scan. There was no statistically significant correlation between bone metastasis and the patient's age, lymph nodes metastasis (LNM), hydronephrosis, and muscle-invasive type. The mean serum calcium level was 8.7 ± 0.57 in patients with bone metastasis and 8.87 ± 0.99 in patients without bone metastasis, which was not statistically significant. CONCLUSION: Bone scan has higher diagnostic performance than conventional imaging methods for detecting bone metastases. It changed the management plan in 8.8% of our patients, so we conclude that performing a whole-body bone scan in the initial staging of MIBC would be helpful.

Renal Tumors in Pregnancy: A Case Report Focusing on the Timing of the Surgery and Patient Positioning.

Management of renal mass during pregnancy is challenging. There is no consensus regarding the fundamental timing issues (which trimester) of the interventions and patient positioning during the procedures. We present three pregnant women with renal mass and their management, focusing on patient positioning and timing of surgical intervention. All patients were positioned supine with a 30-degree rotation to the left lateral without signs of compromising fetal circulation. This report's three major takeaway points are the following: (1) Renal mass biopsy might be more beneficial in pregnant women than the normal population (unless CT findings suggest vascular angiomyolipomas) to achieve a definite diagnosis and avoid unnecessary interventions during pregnancy. (2) Surgical interventions, if indicated, should be performed as soon as possible and are applicable in all trimesters of pregnancy. (3) A minimum of 15-degree left lateral tilt (for both right- and left-sided renal masses) can provide enough venous return during the nephrectomy.

Sentinel lymph node mapping in post chemotherapy nonseminoma testicular cancer patients undergoing retroperitoneal lymph node dissection: A series of nine cases.

OBJECTIVES: Testicular germ cell cancers are the most common solid malignancy among young men at the age ranging between 14 and 35 years. In this study, we evaluated the feasibility of sentinel lymph node mapping using intraoperative injection of radiotracer in nonseminomatous testicular cancer patients with history of orchiectomy who were candidate for retroperitoneal lymph node dissection (RPLND) in post-chemotherapy setting. METHODS: Nine consecutive cases were included in the study. Technetium-99m-labelled phytate was injected in two divided doses in the stump of the spermatic cord, through transabdominal approach. A hand-held gamma probe was used for radio-guided retroperitoneal sentinel lymph node detection intraoperatively and confirming the location of the sentinel lymph nodes. RESULTS: Detection rate and the false negative rate were estimated as the main indices. The detection rate was 6/9 (66%) and the false negative rate was 0/2 (0%). Location of the dissected sentinel lymph nodes were interaortocaval (2 patients), internal iliac (1 patient), external iliac (1 patient), common iliac (2 patients), and paraaortic (1 patient). CONCLUSION: Sentinel lymph node mapping technique seems to be feasible and promising in post chemotherapy non-seminoma testis cancer patients who are candidate for RPLND; however, further larger studies are needed to increase and standardize the detection rate.

Prostate-Specific Membrane Antigen Radioguided Surgery for Salvage Pelvic Lymph Node Dissection in a Man With Prostate Cancer.

ABSTRACT: A 75-year-old man with evidence of recurrent prostate cancer on 68Ga-prostate-specific membrane antigen (PSMA) PET/CT after radical prostatectomy was referred to our department for 99mTc-PSMA radioguided surgery. Intraoperatively, lymph nodes with high count rates were localized using a handheld gamma probe. High-count specimens were resected from the exact locations as reported by 68Ga-PSMA PET/CT. The total prostate-specific antigen value decreased 6 weeks after surgery. Our case shows the feasibility of radioguided surgery with 99mTc-PSMA for salvage lymphadenectomy in prostate cancer.

Prognostic Significance of Substance P and Neurokinin-1 Receptor in Bladder Cancer.

Background: Bladder cancer is one of the most common genitourinary cancers with significant mortality. Finding reliable tumor markers and potential drug targets can improve early diagnosis, prognosis, and more effective therapeutic protocols. Previous studies have reported the involvement of the substance P (SP)/neurokinin-1 receptor (NK-1R) system in cancers. The potential prognostic role and the interaction of SP and NK-1R in bladder tumor are yet to be elucidated. Methods: Serum samples from 22 primarily diagnosed patients with bladder cancer as well as 22 healthy controls were examined for SP level using ELISA method. Tissue distribution of NK-1R in tumor samples and their adjacent normal tissues was evaluated through immunohistochemistry. Results: Serum SP levels in patients with bladder cancer were higher than the healthy group (p< 0.001) and had a significant correlation with NK-1R staining intensity (p< 0.001), percentage of stained cells (p< 0.001), and NK-1R tissue distribution. Also, the immunoreactivity of NK-1R in cancer samples increased significantly without correlation with tumor characteristics. However, no significant association was found between SP and NK-1R levels with clinical characteristics including tumor size (p= 0.33), tumor stage (p= 0.29), grade (p= 0.93), NK-1R staining intensity (p= 0.53), and percentage of stained cells (p= 0.32). Discussion: According to our findings, despite the lack of association between SP and NK-1R with clinical characteristics of bladder cancer, their serum levels were higher in patients with bladder cancer. Further studies are needed to confirm the potential prognostic role of SP and NK-1R in bladder cancer.

Adult Wilms with Biphasic Pattern; A Case Report.

BACKGROUND: Wilms' tumor, nephroblastoma, is an extremely uncommon kidney tumor of adulthood. We reported a woman with a huge kidney mass diagnosed with nephroblastoma. CASE PRESENTATION: A 39-year-old female was assessed due to right flank pain. CT scan revealed a mass measuring 128×100 mms involving the upper portion of the right kidney. The patient underwent nephrectomy, and the diagnosis of adult Wilms' tumor was confirmed based on the morphological and immunohistochemical findings. CONCLUSION: In adult patients with flank pain and renal mass, the diagnosis of Wilms' tumor should be pronounced in the absence of histopathologic features of renal cell carcinoma.

Sentinel lymph node biopsy in upper tract urothelial cancers: an experience with intraoperative radiotracer injection.

BACKGROUND: The feasibility of the sentinel node mapping in upper tract urothelial cancers (UTUC) was evaluated, using a radiotracer as the mapping material. MATERIAL AND METHODS: To identify the sentinel lymph nodes, 37 MBq of [99mTc] phytate was injected in five patients with the renal pelvis or ureter cancer, who were candidates for ureterectomy and lymphadenectomy. The radiotracer was injected in a peritumoral fashion following the surgical exposure of the tumour. The sentinel lymph nodes were detected using a handheld gamma probe. RESULTS: By intraoperatively injecting the radiotracer immediately after surgical exposure of the tumour, at least one sentinel lymph node could be detected in each patient, and the detection rate was 100%. The location of sentinel nodes was in the paracaval, renal hill, retro-aortic, para-aortic, common iliac, and external iliac areas, which was dependent on the tumour location. No false-negative case was identified. CONCLUSIONS: Sentinel node mapping is feasible in UTUC. Injection technique (intra-vesical approach vs peri-tumoral injection after exposure of the tumour) and location of the tumour (proximal vs distal) may affect the technique's feasibility.

Bowel visualization on the lymphoscintigraphy images of a bladder cancer patient due to inadvertent injection of the tracer in the rectal wall.

The effectiveness of the sentinel lymph node mapping in patients with Urothelial carcinoma of the bladder is under investigation. Single photon emission computed tomography (SPECT/CT) and intraoperative sentinel node biopsy using gamma probe are performed to detect the exact location of the sentinel lymph node to be dissected during the surgery. In this case report, a 73-year old man with high grade urothelial carcinoma was referred to our nuclear medicine department for SPECT/CT, four hours after injection of the radiotracer through cystoscopy. SPECT/CT could not reveal any sentinel node; however, one sentinel lymph node was detected and harvested in the right external iliac region during surgery. SPECT/CT revealed unusual accumulation of tracer in large bowel which was due to severe adhesion of rectum and bladder, and inadvertent injection of the radiotracer into the rectal wall. During the sentinel lymph node procedure, the tracer should be injected with extreme caution and lymphoscintigraphy post injection may help detection of any injection failures.

Effects of Sertraline on Spermatogenesis of Male Rats and its Reversibility after Terminating the Drug.

PURPOSE: The purpose of this research was to studding the effects of Sertraline on spermatogenesis of male rats and whether these probable effects are constant or provisional after terminating the drug. MATERIALS AND METHODS: In this study, 32  two-month old male Wistar albino rats were equally divided into the Sertraline-treated and the control groups. The drug group was gavaged with Sertraline daily while the control group was gavaged with water at the same volume. After 80 days, half of the rats in each group were selected randomly for hormonal evaluations and bilateral orchiectomy. Histological and hormonal evaluations were performed. The remaining half of rats were kept alive for 90 more days without intervention and then underwent hormonal evaluation and bilateral orchiectomy in a similar fashion. RESULTS: There was no difference between the testes histology and pathology of the sertraline-treated and the control groups.  There was a significant decrease in serum FSH in the Sertraline-treated group compared to the control group (P <0.05). However, this decline appeared to be reversible following termination of exposure to Sertraline. FSH returned to pretreatment levels in the remaining treated rats following 90 days of treatment cessation.  Conclusion: Within the time-frame studied, Sertraline can induce transitory changes in serum FSH of male rats without concomitant spermatogenic changes within the testes.  This hormonal change appears to be reversible following withholding of Sertraline. The long-term effect of Sertraline usage on hormonal status and spermatogenesis in rats needs further investigation.

Sentinel lymph node biopsy in muscle-invasive bladder cancer: single-center experience.

OBJECTIVE: In this study, the validity of sentinel node biopsy procedure as our index test was assessed and compared with bilateral pelvic lymphadenectomy for staging and detecting the regional lymph nodes metastasis in patients with muscle-invasive bladder cancer (MIBC). METHODS: Consecutive series of cases with T1-T4 urothelial MIBC were included. Following the injection of radiotracer, sentinel nodes were sought using a handheld gamma probe and all hot nodes were harvested. Bilateral pelvic lymphadenectomy was done for all patients following sentinel node biopsy. The tumor specimen, sentinel nodes, and excised lymph nodes were evaluated histopathologically. Same as the other midline tumors, detection rate and false negative rates were calculated using patient basis and side basis methods. RESULTS: By evaluating each patient as a unit of analysis, sentinel nodes were detected in 35 of 41 patients (85%), 13/16 (81%) of the neoadjuvant chemotherapy (NAC) and 22/25 (88%) of the no-neoadjuvant chemotherapy (No-NAC) participants. The false negative rate was 3/7 (42%): 1/3 (33%) for NAC, and 2/4 (50%) for No-NAC patients. By evaluating each hemipelvis as a unit of analysis, sentinel nodes were detected in 53 of 82 hemipelves (65%), 19/32 (66%) of the NAC, and 34/50 (68%) of the No-NAC hemipelves. No false-negative result was found by assessing each hemipelvis as a unit of analysis. CONCLUSIONS: Sentinel node biopsy is a feasible method for lymph node staging in MIBC, including patients with a history of NAC. To optimize the sensitivity, the decision regarding the lymphadenectomy is best to be based on the pathological status of sentinel node harvested from each hemipelvis separately as the unilateral finding of a sentinel node, does not rule out the possibility of metastatic involvement of contralateral pelvic lymph nodes.

Sentinel Node Biopsy in Urothelial Carcinoma of the Bladder: Systematic Review and Meta-Analysis.

OBJECTIVES: To determine the application of sentinel node biopsy in urothelial carcinoma of the bladder, we performed a systematic review and meta-analysis. METHODS: Pooled false negative rate and detection rate were presented using Meta-Disc (version 1.4), and comprehensive meta-analysis (version 2). Publication bias and heterogeneity were assessed using funnel plot, Cochrane Q test, and I2 index. RESULTS: The pooled detection rate was 91% (95% CI 87-93%) and pooled sensitivity was 79% (95% CI 0.69-0.86%). When the neoadjuvant chemotherapy group of patients was omitted, the pooled sensitivity changed to 82% (95% CI 74-88%), and the Cochrane Q and I2 statistics were 15.44 and 48.2%, respectively. The pooled sensitivity of studies that included > 50% of pT 3 or 4 patients was 70% (59-80), by omitting studies that enrolled > 50% of patients at pT stage of 3 or 4, the pooled sensitivity increased to 93% (81-98). CONCLUSIONS: Although the studies on SN biopsy of muscle invasive bladder cancer patients resulted in a high detection rate and sensitivity, further validated multicenter trials with larger sample size are essential to confirm the reliability and accuracy of this approach and obtain a standardized method. We showed that pT1 or pT2 bladder cancer patients with clinically negative lymph nodes are the most appropriated group for sentinel lymph node mapping.

Urinary Canthariasis Due to Tenebrio molitor Larva in a Ten-Year-Old Boy.

Canthariasis is a human disease caused by infestation of beetle larvae. We report here an unusual cause of urogenital infection due to Tenebrio molitor in a 10-year-old boy suffering from severe and intermittent suprapubic pain from Nehbandan City, Northeastern Iran in 2018. After 9 months, three larvae were excreted. Keratinization of bladder wall was observed in histopathology. All laboratory evaluations were normal except for presence of microscopic hematuria. This report implicated that T. molitor could infest bladder accidentally and cause canthariasis and clinical symptoms that may lead to severe pain and bladder inflammation and hyperemia.

Is There a Role for Genetic Information in Risk Assessment and Decision Making in Prostate Cancer?

OBJECTIVES: Prostate cancer is a neoplasm with a variable natural history and clinical behavior. There is much debate on the use of inherited genetic information in clinical application including risk assessment and treatment decisions. This study was performed to evaluate the relationship between clinical parameters of prostate cancer (PSA, Gleason score, and metastasis) and expression of NKX3.1, AMACR, TMPRSS2-ERG, ERG, and SPINK1 genes. METHODS: Newly diagnosed cases of prostate cancer were selected for this study. Thirty four tissue samples were obtained via open radical prostatectomy and 9 samples were obtained via needle biopsy. Each tissue sample was sectioned into two parts, one used for detection of malignant changes and Gleason score determination, and the other immersed in RNA later solution (Qiagen). The expression of NKX3.1, AMACR, TMPRSS2-ERG, ERG, and SPINK1 genes were assessed by real-time PCR assay. Correlation between expression of each gene and PSA level, Gleason score, and presence of metastasis were examined. RESULTS: A total number of 43 specimens were studied, from which 9 were obtained from patients with metastatic prostate cancer. The expression of five examined genes had no correlation with PSA level and Gleason score. The expression of AMACR decreased in metastatic prostate cancer (P = 0.02). The expression of other genes showed no difference between metastatic and non-metastatic tumors (P > 0.1). CONCLUSIONS: Genetic information combined with clinical data can be useful in risk assessment and treatment planning. Based on the results of the current study, the decreased expression of AMACR was a sign of poor prognosis.