Penile carcinoma: A retrospective analysis of 93 patients at a tertiary care center in Jakarta, Indonesia.

OBJECTIVES: Penile carcinoma (PC) is a rare disease with considerable physical and psychological impact. To date, there is no data regarding PC prevalence and characteristics in Indonesia. This study aimed to analyze the characteristics of patients with PC in Indonesia and determine cumulative survival rates and time to disease progression. METHODS: This was a retrospective study of all patients diagnosed with PC at Cipto Mangunkusumo General Hospital from 1995 to 2014, with a minimum of 1 year follow-up. The outcomes of the study were cumulative survival rates and time-to-disease progression. RESULTS: Ninety-three subjects were recruited, with a mean age of 49.44 ± 13.62. Inguinal lymph node dissection (ILND) was performed in 49 (53%) patients. The mean survival in the ILND group was better compared to the non-ILND group (80.7 months vs. 67.1 months; p = 0.032). Time-to-progression in the ILND group was significantly longer than in the non-ILND group (71.7 months vs. 54.3 months; p = 0.022). No significant difference in survival between the total and partial penectomy (PP) groups was observed (p = 0.701). Time-to-progression in total penectomy (TP) was significantly longer than in PP (68 months vs. 56.0 months; p = 0.023). In Cox-regression analysis, after adjustment of other variables, history of ILND, higher stage of cancer, and older age were found to affect the survival of patients. CONCLUSION: ILND in PC led to better survival and reduced disease progression. The type of penectomy is only associated with progression but not survival. TP had a longer time to disease progression compared to PP.

Prostate cancer management in Southeast Asian countries: a survey of clinical practice patterns.

Background: Prostate cancer (PC) has a serious public health impact, and its incidence is rising due to the aging population. There is limited evidence and consensus to guide the management of PC in Southeast Asia (SEA). We present real-world data on clinical practice patterns in SEA for advanced PC care. Method: A paper-based survey was used to identify clinical practice patterns and obtain consensus among the panelists. The survey included the demographics of the panelists, the use of clinical guidelines, and clinical practice patterns in the management of advanced PC in SEA. Results: Most panelists (81%) voted prostate-specific antigen (PSA) as the most effective test for early PC diagnosis and risk stratification. Nearly 44% of panelists agreed that prostate-specific membrane antigen positron emission tomography-computed tomography imaging for PC diagnostic and staging information aids local and systemic therapy decisions. The majority of the panel preferred abiraterone acetate (67%) or docetaxel (44%) as first-line therapy for symptomatic mCRPC patients. Abiraterone acetate (50%) is preferred over docetaxel as a first-line treatment in metastatic castration-sensitive prostate cancer patients with high-volume disease. However, the panel did not support the use of abiraterone acetate in non-metastatic castration-resistant prostate cancer (nmCRPC) patients. Apalutamide (75%) is the preferred treatment option for patients with nmCRPC. The cost and availability of modern treatments and technologies are important factors influencing therapeutic decisions. All panelists supported the use of generic versions of approved therapies. Conclusion: The survey results reflect real-world management of advanced PC in a SEA country. These findings could be used to guide local clinical practices and highlight the financial challenges of modern healthcare.

Solitary fibrous tumor in the retroperitoneum: A case report.

INTRODUCTION AND IMPORTANCE: Solitary fibrous tumor (SFT) is an uncommon mesenchymal tumor that can manifest in a variety of locations, including the retroperitoneum. The most effective standard diagnostic approach and treatment is yet to be determined due to unpredictable behavior of SFT, including retroperitoneal SFT. CASE PRESENTATION: A 43-year-old female with a retroperitoneal SFT presented with a palpable mass and symptomatology. Surgical exploration disclosed a tumor encompassing the left renal artery and vein, necessitating left nephrectomy and retroperitoneal mass removal. Initial histological examination suggested rhabdomyosarcoma, but subsequent immunohistochemistry confirmed the diagnosis of retroperitoneal SFT. No adjuvant therapy was administered, and there was no detectable mass on follow-up imaging. The patient remained symptom-free. CLINICAL DISCUSSION: Retroperitoneal SFTs are difficult to diagnose due to their non-specific morphology, thus immunohistochemistry plays a crucial role in confirming its diagnosis. Surgical excision with negative resection margins continues to be the standard treatment. Recurrence rates are low in comparison to other retroperitoneal sarcomas, hence routine chemotherapy or radiation therapy is not advised. CONCLUSION: This case demonstrates the significance of contemplating SFT as the differential diagnosis of retroperitoneal tumors and the role of immunohistochemistry in confirming the diagnosis. The optimal management strategies for retroperitoneal SFTs should be determined by additional research.

Adenocarcinoma mucinosum of extrophy bladder: A rare case report.

INTRODUCTION: Bladder exstrophy is a rare congenital anomaly while, bladder adenocarcinoma mucinous type is a rare type of bladder cancer, with aggressive behavior and inadequate response to radiation and chemotherapy. In extremely rare cases, untreated bladder exstrophy could transform into bladder mucinous adenocarcinoma. CASE PRESENTATION: We report a case of a 41-year-old male with untreated bladder exstrophy that transformed into mucinous adenocarcinoma. The patient also had epispadias and a right inguinal hernia. Joint procedures were conducted to perform radical cystectomy, total penectomy and W-Pouch continent urostomy, inguinal hernia repair, osteotomy, and keystone and scrotal flap by split-thickness skin graft (STSG) for wound closure. The patient progressed well after surgery, two months after initial procedure, nephrostomies were conducted due to pouches stenosis. Due to the government's limited transportation and lockdown policy, as the Covid-19 pandemic occurred, the patient could not come to the hospital for routine follow-up and died nine-month after surgery. CLINICAL DISCUSSION: Bladder exstrophy is one of the risk factors of bladder cancer. Transformation of bladder exstrophy into mucinous adenocarcinoma is extremely rare, as the case is the first case to be discovered in Indonesia. Surgery, followed with a strict follow-up regime, is mainstay of treatment in this type of malignancy. CONCLUSION: Adenocarcinoma of mucinous type is a scarce type of bladder exstrophy malignancies. A multidiscipline approach is mandatory in these cases. Strict and regular follow up are suggested for these cases.

Molecular Phenotyping of AR Signaling for Predicting Targeted Therapy in Castration Resistant Prostate Cancer.

Castration-resistant prostate cancer (CRPC) is defined by resistance of the tumor to androgen deprivation therapy (ADT). Several molecular changes, particularly in the AR signaling cascade, have been described that may explain ADT resistance. The variety of changes may also explain why the response to novel therapies varies between patients. Testing the specific molecular changes may be a major step towards personalized treatment of CRPC patients. The aim of our study was to evaluate the molecular changes in the AR signaling cascade in CRPC patients. We have developed and validated several methods which are easy to use, and require little tissue material, for exploring AR signaling pathway changes simultaneously. We found that the AR signaling pathway is still active in the majority of our CRPC patients, due to molecular changes in AR signaling components. There was heterogeneity in the molecular changes observed, but we could classify the patients into 4 major subgroups which are: AR mutation, AR amplification, active intratumoral steroidogenesis, and combination of AR amplification and active intratumoral steroidogenesis. We suggest characterizing the AR signaling pathway in CRPC patients before beginning any new treatment, and a recent fresh tissue sample from the prostate or a metastatic site should be obtained for the purpose of this characterization.

Cystoscopy-assisted laparoscopic partial cystectomy for muscle-invasive bladder cancer: Initial experience in Cipto Mangunkusumo Hospital, Jakarta.

INTRODUCTION: We report the experience with patients of urachal adenocarcinoma of the bladder, a rare malignancy in the urinary bladder, treated with laparoscopic partial cystectomy. AIM: Solitary transitional cell carcinoma (TCC) of the dome/anterior wall of the bladder in some cases. As compared to radical surgery, partial cystectomy has a lower morbidity rate and similar oncological outcomes. We present our experience with laparoscopic partial cystectomy (LPC) in patients with urachal adenocarcinoma. CASE PRESENTATION: Until being admitted to the hospital, a 60-year-old woman had been suffering from painless, sporadic gross hematuria for the previous year. Her physical examination was undistinguished. Computed tomography revealed an enhancing firmly bordered mass on the anterior-superior aspect of the bladder wall. The patient then underwent cystoscopy and laparoscopic partial cystectomy simultaneously. CONCLUSION: Based on our first experience in LPC, we suggest that cystoscopy assisted LPC is a reasonable and safe procedure with fewer complications and does not extend the operating time. The procedure's effectiveness hinges on the patient's selection. However, many cases needed to emphasize the effectiveness and safety of LPC.

Management of bilateral Wilms' tumour: A case report.

INTRODUCTION: Wilms' tumour remains the most common renal tumour in children (6% of all pediatric malignancies) and present as one of the most challenging tasks for paediatric urologists as its management requires an advanced procedure. The ultimate goal in these cases is to preserve as much renal parenchyma as possible whilst still achieving complete tumour resection. PRESENTATION OF CASE: Here we present a six year follow up report of a bilateral Wilms' tumour case in a 19-months old boy. This patient underwent neoadjuvant chemotherapy regimen, followed by right partial nephrectomy and left radical nephrectomy. Adjuvant radiotherapy was performed following the surgery. Follow-up imaging 5 months afterward revealed a firmly heterogeneous cystic lesion consist of fat and calcification at the upper pole of the right kidney, none of which created any problem for the patient. MRI was later performed on the 19th month after the surgery, showing marked decrease in the size of the cyst. DISCUSSION: According to SIOP and NWTSG classification, the patient presented as stage V of the disease. The patient was on neoadjuvant chemotherapy (Regimen I) as recommended by NWTSG. This strategy was shown to be effective, as the tumour on the left kidney was reduced to less than 70% of the initial size. A routine follow-up using chest x-ray, abdominal ultrasonography (USG), and contrast studies such as MRI and MSCT scan, was performed in our reports. CONCLUSION: From our experience, the combination of neo-adjuvant chemotherapy, renal salvage surgery and adjuvant radiotherapy is a feasible, safe and effective option for bilateral Wilms' tumour cases.

Meta-analysis of neoadjuvant chemotherapy compared to radical cystectomy alone in improving overall survival of muscle-invasive bladder cancer patients.

BACKGROUND: Most patients with muscle-invasive bladder cancer (MIBC) developed metastasis within 2 years, even after radical cystectomy (RC). The recurrence rate of MIBC was more than 50% of the cases. A meta-analysis conducted by Yin et al. showed that neoadjuvant chemotherapy (NAC) + RC improves overall survival in MIBC compared with RC only. However, a new meta-analysis by Li et al. concluded that NAC + RC was not superior to RC only in improving overall survival. The inconsistencies of these studies required further comprehensive analysis to recommend NAC use in bladder cancer treatment. Therefore, this meta-analysis aims to analyze previous studies that compare the efficacy of NAC + RC versus RC only to improve overall survival of MIBC. METHODS: The articles were searched using Pubmed with keywords "muscle-invasive bladder cancer", "neoadjuvant chemotherapy", "cystectomy", and "overall survival". The articles that were published until June 2020 were screened. The overall survival outcome was analyzed as hazard ratio (HR) and presented in a forest plot. RESULT: Seventeen studies were included in meta-analysis with a total sample of 13,391 patients, consist of 2890 received NAC followed by RC and 10,418 underwent RC only. Two studies used methotrexate/vinblastine/doxorubicin/cisplatin (MVAC), two studies used gemcitabine/cisplatin (GC), one study used Cisplatin-based regimen, one study used MVAC or GC, one study used gemcitabine/carboplatin (GCarbo) or GC or MVAC, one study used Cisplatin/Gemcitabine or MVAC, one study used Cisplatin only, one study used Cisplatin-based (GC, MVAC) or non-Cisplatin-based (combined paclitaxel/gemcitabine/carboplatin), one study used GC, MVAC, Carboplatin, or Gemcitabine/Nedaplatin (GN), and five studies did not mention the regimen The overall survival in the NAC + RC only group was significantly better than the RC only group (HR 0.82 [0.71-0.95], p = 0.009). CONCLUSION: NAC + RC is recommended to improve overall survival in MIBC patients. A further study assessing side effects and quality of life regarding NAC + RC is needed to establish a strong recommendation regarding this therapy.

Early upregulation of AR and steroidogenesis enzyme expression after 3 months of androgen-deprivation therapy.

BACKGROUND: Androgen deprivation therapy (ADT) is a standard treatment for advanced prostate cancer (PCa). However, PCa recurrence and progression rates during ADT are high. Until now, there has been no evidence regarding when progression begins. This study evaluated the gene expression of intraprostatic androgen receptor (AR) and steroidogenic enzymes in the early stages of ADT. METHODS: Prostate tissue samples were taken from PCa patients with urinary retention who received ADT (ADT-PCa; n = 10) and were further subgrouped into ADT ≤12 months (n = 4) and ADT > 12 months (n = 6). The ADT-PCa tissues were then compared with BPH (n = 12) and primary (no treatment) PCa tissues (n = 16). mRNA for gene expression analysis of AR and steroidogenic enzymes was extracted from formalin-fixed paraffin embedded (FFPE) tissues and analyzed by real-time PCR. Protein expression was evaluated by immunohistochemistry with specific antibodies. RESULTS: AR gene expression was higher in the ADT-PCa group than in the BPH or primary PCa group. Both the ADT ≤12 and > 12 months subgroups had significantly higher relative gene expression levels of AR (p < 0.01 and 0.03, respectively) than the primary PCa group. In the ADT-PCa group, AR protein expression showed an increasing trend in the ADT ≤12 months subgroup and was significantly elevated in the ADT > 12 months subgroup compared with the PCa group (100%; p < 0.01). Half (50%) of the patients in the ADT ≤12 months subgroup were found to have upregulation of AR, and one showed upregulation beginning at 3 months of ADT. A trend toward elevated relative gene expression of SRD5A3 was also apparent in the ADT groups. CONCLUSION: AR and steroidogenic enzymes are upregulated in ADT-PCa patients as early as 3 months, without PSA elevation. Steroidogenic enzymes, particularly SRD5A3, were also upregulated before PSA rose.

TUR-P phantom for resident surgical training: food-based design as a human mimicking model of the prostate.

PURPOSE: This study would like to develop a novel model similar to human prostate in terms of its texture profile, sensation upon resection, and anatomical hallmarks for resident transurethral resection of the prostate (TUR-P) training. METHODS: Ten phantom designs were proposed, using broadly available ingredients and a homemade protocol. Three steps of evaluation and development were done: objective measurement measuring texture profile (e.g. hardness, elasticity, cohesiveness/consistency, and adhesiveness/stickiness) using TA-XT2i Texture Analyzer (Llyod Instruments, Ametek Inc) to compare the designs with human prostate, finding the most similar design to prostate; expert consensus by a panel of urologist/senior residents comparing the simulation of TUR-P on the selected design with pre-existing control phantom; and anatomical design development using 3D printing for molding. RESULTS: Texture profile analysis for mean hardness, elasticity, cohesiveness/consistency, and adhesiveness/stickiness of human prostate was 3753.4 ± 673.4, 85 ± 1.9, 0.7 ± 0.03, and 0, respectively, and design IX was the most similar to human prostate (3660.7 ± 465.6, 87.0 ± 2.5, 0.6 ± 0.05, 0). Furthermore, expert consensus showed superiority of design IX compared with pre-existing control phantom (16.95 ± 1.36 vs 8.86 ± 3.10; P < 0.001). Most of the respondents agreed that the texture, consistency, and phantom ability to mimic human prostate upon resection were similar with human prostate, though hallmarks of the prostate e.g. veromontanum, and lobes were lacking. We used these feedbacks to develop a mold, designed to produce these important anatomical hallmarks. CONCLUSION: This study developed a cost-effective prostate model from a food-based design that is similar to human prostate in terms of its texture and sensation upon TUR-P resection provided with important anatomical hallmarks.

Prognostic value of platelet to lymphocyte ratio in predicting survival of patients with metastatic castration-resistant prostate cancer receiving abiraterone acetate: An evidence-based case report and review of literature.

Platelet to lymphocyte ratio (PLR) is a candidate prognostic marker for metastatic castration-resistant prostate cancer patients receiving abiraterone acetate and evidence demonstrates that a high PLR is associated with poor survival. More studies are required to verify current findings and establish a definite cutoff point.

Effect of Pneumoperitoneum on Renal Resistive Index and Renal Function in Patients Who Have Undergone Laparoscopic Living Donor Nephrectomy: A Pilot Study.

INTRODUCTION: The use of low-pressure pneumoperitoneum during laparoscopic living donor nephrectomy (LLDN) was assumed to cause less renal damage compared to high-pressure pneumoperitoneum. This study aims to evaluate the effect of low vs high-pressure pneumoperitoneum during LLDN on renal function and renal resistive index (RRI), which has never been done before. MATERIALS AND METHODS: The subjects were divided into 2 groups, low-pressure (8-10 mmHg) and high-pressure pneumoperitoneum (12-14 mmHg). The RRI, serum creatinine, and estimated glomerular filtration rate were measured during the perioperative period. RESULTS: A total of 45 samples were analyzed in this study: 17 subjects in the low-pressure pneumoperitoneum group and 28 subjects in the high-pressure group. RRI levels remained within the normal range (< .80) with no significant difference observed between the 2 groups (P > .05) before surgery, intraoperatively, or post-surgery. The preoperative and postoperative serum creatinine and glomerular filtration rate were similar in both groups. CONCLUSIONS: The use of low-pressure pneumoperitoneum had no benefit compared to high-pressure pneumoperitoneum in preserving RRI and function in LLDN.

The importance of targeting intracrinology in prostate cancer management.

Accumulating evidence has shown that intracrinology in prostate cancer (PCa) has a pivotal role in survival of cancer cell. PCa cells are able to produce androgens from different androgen precursors, such as dehydroepiandrosterone, thereby maintaining androgen receptor signaling. Several drugs have been developed that target intracrinology, some of which are now being used as standard treatment for the so-called castrate-resistant prostate cancer (CRPC) patients. Recently, the US FDA approval has changed the indication of drugs targeting intracrinology, e.g., abiraterone and enzalutamide where it evolved from post-chemotherapy CRPC to hormone-naive metastatic PCa cases. This approval raises question whether those drugs can also be used as the first-line treatment in localized stage PCa cases. In addition, development of additional drugs targeting major components of intracrinology is ongoing. Application of these new drugs and administration of combinations of existing drugs will ultimately lead to an increase in the efficacy of such treatments as well as to reduce the toxicity of the therapy and to prevent the risk of resistance.

Recent advances in optical imaging technologies for the detection of bladder cancer.

White-light cystoscopy (WLC) is the diagnostic standard for the detection of bladder cancer (BC). However, the detection of small papillary and subtle flat carcinoma in situ lesions is not always possible with WLC. Several adjunctive optical imaging technologies have been developed to improve BC detection and resection. Photodynamic diagnosis, which requires the administering of a photoactive substance, has a higher detection rate than WLC for the detection of BC. Narrow-band imaging provides better visualization of tumors by contrast enhancement between normal mucosa and well-vascularized lesions. A technology called confocal laser endomicroscopy can be used to obtain detailed images of tissue structure. Optical coherence tomography is a high-resolution imaging process that enables noninvasive, real-time, and high-quality tissue images. Several other optical imaging technologies are also being developed to assist with the detection of BC. In this review, we provide an overview of the strengths and weaknesses of these imaging technologies for the detection of BC.

Surgical Management of Giant Genital Condyloma Acuminata by Using Double Keystone Flaps.

Condyloma acuminata in the external genitalia (genital warts) is a sexually transmitted disease that is often caused by human papillomavirus (HPV). We report a case of giant genital condyloma acuminata in a 35-year-old male patient with HIV comorbidity treated by wide surgical excision. Excision defect was covered with split thickness skin graft (STSG) and double keystone flaps. There was no complication after surgery. Ten months following surgery, there was no new condyloma lesion and the patient had normal voiding and erectile functions.

The role of HOXC6 in prostate cancer development.

BACKGROUND: Homeobox (HOX) genes, which are involved in organ development and homeostasis, have been shown to be involved in normal prostate- and PCa development. In this study, we investigate the expression levels of the HOX A-D genes in PCa. The functional relevance and potential of HOX gene as biomarkers are explored. METHODS: We evaluated HOX gene expression in prostate tissues of different grade and stage and related the outcome to clinical parameters. We analyzed AR regulation and function of HOXC6 in PCa cell lines. We developed a urine-based HOXC6 mRNA assay for diagnostic purposes. RESULTS: HOXC6 was one of the most upregulated HOX genes in all primary, metastasized, and castration-resistant PCa. HOXC6 upregulation was specific to the epithelial component of PCa, and HOXC6 was shown to be involved in epithelial cell proliferation. HOXC6 expression was not influenced by androgens nor by treatments targeting the AR signaling pathway. HOXC6 expression was not related to a prognosis after radical prostatectomy, that is, biochemical or local recurrence. We successfully developed an assay for HOXC6 mRNA detection in urine and confirmed that HOXC6 levels are higher in PCa patients. CONCLUSIONS: HOXC6 has a role in all PCa stages, particularly in PCa cell proliferation. Due to its stable expression, HOXC6 is a novel candidate biomarker for PCa not only in early detection but also for monitoring of progression or response to therapy.

Indonesian prostate cancer risk calculator (IPCRC): an application for predicting prostate cancer risk (a multicenter study).

AIM: to develop a prediction risk model of prostate cancer based on Indonesia population. METHODS: we included all benign prostate hyperthrophy (BPH) and PCa patients who had prostate biopsy and prostatectomy between January 2009 and December 2013 from 5 urology centers in Indonesia. The relationship between the possibility of PCa with the following variables including: age; PSA level, prostate volume (by transabdominal ultrasound or transrectal ultrasound) and digital rectal examination (DRE) finding. We calculated a predictive scoring equation to predict the possibility of PCa using chi-square analysis, Kolmogorov-Smirnov test, multiple logistic regression and ROC curve. Then, we designed an application for predicting prostate cancer risk called Indonesian Prostate Cancer Risk Calculator (IPCRC). RESULTS: there were 784 PCa and 1173 BPH patients were used for developing the risk calculator in our study. The mean ages, PSA and prostate volume are 66.9±8.1 years old; 72.4±248.9 ng/ml and 49.6±28.2 ml, respectively. Abnormal DRE was found in 637 PCa and 56 BPH. We included age, PSA level, abnormal DRE finding (all showed significant p<0.05 in univariate model). Additionally, although not significant, we included prostate volume (p=0.157) due to its clinical importance. The corrected ROC analysis showed AUC 0.935, sensitivity of 90.1% and specificity 80% in predicting the prostate cancer in our population. CONCLUSION: we have developed the Indonesian Prostate Cancer Risk Calculator which includes age, PSA, DRE, and prostate volume as its variables. Future prospective study to validate the risk calculator is needed.

Urologic cancer in Indonesia.

Non-communicable diseases, including cancer, start to become more common in Indonesia. According to the government statement, incidence of malignant diseases increased annually up to 8% in the last decade and these diseases become the seventh leading cause of death in Indonesia. On the basis of the latest Globocan report on cancer incidence in Indonesia, prostate cancer ranks sixth; followed by bladder (12th) and kidney (18th). More than half of patients with kidney cancer are diagnosed in the advanced stage. Besides renal cell carcinoma, there are significant number of people affected with squamous cell and transitional cell carcinoma because of kidney stones. Radical nephrectomy or cytoreductive nephrectomy was the primary treatment, mostly done as an open procedure. Transitional cell carcinoma is the commonest histology type in bladder cancer cases followed by squamous cell carcinoma, which almost always related to bladder stones. Unfortunately, >70% of our cases were diagnosed with muscle invasive bladder cancer, and ∼60% of these patients refused further radical treatment. Incidence of prostate cancer is increasing rapidly and it becomes the third most common cancer in men. However, most of our patients are diagnosed in the advanced stage. Radical prostatectomy or external beam radiotherapy is the treatment of choice in localized disease. Nearly 40% of the elderly patients are treated with primary androgen deprivation therapy. Therefore, it requires more research by the Indonesian urologists and other healthcare providers to diagnose these cancers in earlier stage as well as community education for prevention.