CD44 and CD133 protein expression might serve as a prognostic factor for early occurrence castration-resistant prostate cancer.

BACKGROUND: The occurrence of castration-resistant prostate cancer (CRPC) varies in patients with advanced prostate cancer (PCa) undergoing androgen deprivation therapy (ADT). The rate of occurrence of CRPC may be related to the presence of prostate cancer stem cells (CSC). Thus, this study aims to evaluate the presence of CSC markers (CD44 and CD133) in histopathology tissue at the time of diagnosis and their correlation with the occurrence of CRPC in patients with advanced PCa within 2 years of ADT. METHOD: A retrospective case-control study was conducted to evaluate the incidence of CRPC within 2 years. The inclusion criteria were patients with PCa who had received treatment with ADT and a first-generation anti-androgen (AA) for 2 years. We classified patients based on whether they developed CRPC within 2 years (CRPC) of the therapy or did not experience CRPC within 2 years (non-CRPC) of the therapy. We performed immunohistochemical (IHC) staining for CD44 and CD133 on the prostate biopsy tissue samples. RESULTS: Data were collected from records spanning 2011-2019. We analyzed a total of 65 samples, including 22 patients with CRPC and 43 patients with non-CRPC who had received treatment with LHRH agonists and AA for up to 2 years. Our findings showed a significant H-score difference in CD44 protein expression between CRPC prostate adenocarcinoma samples 869 (200-1329) and non-CRPC 524 (154-1166) (p = 0.033). There was no significant difference in CD133 protein expression between the two groups (p = 0.554). However, there was a significant difference in the nonoccurrence of CRPC between the high expressions of both CD44 and CD133 groups with other expressions of CD44/CD133 groups (25% vs. 75%; p = 0.011; odds ratio = 4.29; 95% confidence interval [1.34, 13.76]). CONCLUSION: This study found a low expression of at least one CD44/CD133 protein in the patients without early occurrence of CRPC. This result might suggest that CD44/CD133 may function as a potential prognostic marker for PCa, especially in a low expression, to identify patients who have a better prognosis regarding the occurrence of early CRPC.

Emerging progressive atypical acute kidney injury in young children linked to ethylene glycol and diethylene glycol intoxication.

BACKGROUND: There had been a sudden surge of unusually severe and rapidly progressing acute kidney injury (AKI) incidence in Indonesia since August 2022 which did not correspond to the rise of COVID-19 incidence. We suspected this was related to ethylene glycol (EG) and diethylene glycol (DEG) intoxication. This study is aimed at describing the clinical and laboratory characteristics of AKI related to D(EG) intoxication in order to spread awareness of the possibility of intoxication in cases of rapidly progressing AKI with unknown etiology. METHODS: We conducted a cross-sectional study by collecting secondary data from the pediatric AKI registry at a national referral hospital in Jakarta, Indonesia. Data on children admitted from January to November 2022 with diagnosis of stage 3 AKI based on KDIGO criteria were included. Data regarding demographics, symptoms prior to anuria, laboratory results, infection panel including COVID-19 status, treatment administered, and mortality were analyzed. RESULTS: Sixteen patients tested positive for EG and DEG, all with history of consuming syrup-based medications. High anion gap metabolic acidosis was observed in majority of patients with mean pH 7.33 ± 0.07 and mean anion gap 15.6 ± 7.8 mEq/L. No patient had high osmolal gap (mean osmolal gap 3.46 ± 4.68). One deceased patient, who had kidney biopsy performed, showed severe damage and calcium oxalate crystals in the kidney tissue. Mortality was recorded in six patients (37.5%). CONCLUSION: Careful history taking of patient's clinical course, including consumption of syrup-based medications and laboratory findings, might aid clinicians to establish a working diagnosis of D(EG) intoxication without needing to wait for blood toxicology test. Early diagnosis and therapy are crucial to prevent substantial mortality.

Rituximab, Mycophenolic Acid, and Calcineurin Inhibitors Achieve Long-Term Remission in Pediatric Focal Segmental Glomerulosclerosis with Steroid-Resistant and Frequently Relapsing Nephrotic Syndrome: A Report of Two Cases.

Studies investigating the effect of rituximab in children with nephrotic syndrome (NS) due to focal segmental glomerulosclerosis (FSGS) have reported conflicting results, with some concluding that patients may require additional immunosuppressive therapy to achieve and/or maintain long-term remission. We report successful treatment of pediatric FSGS with rituximab infusions, followed by maintenance immunosuppression with mycophenolic acid (MPA) and a calcineurin inhibitor (CNI) in 1 patient with refractory steroid-resistant NS (SRNS), and one with frequently relapsing NS (FRNS). Case 1 is a patient with refractory SRNS due to FSGS. MPA and tacrolimus induced complete remission within 6 months following rituximab treatment. Remission was maintained for over 2 years, and the patient's kidney function and body height also returned to normal ranges within this time. Case 2 is a patient with FRNS due to FSGS, who was treated with rituximab followed by MPA and cyclosporine, which successfully prevented relapses for 18 months, that is, at the end point of the observation. Our case report demonstrates that rituximab and a combination of CNIs and MPA can be effective in achieving complete remission in pediatric refractory SRNS and sustaining remission in pediatric FSGS with FRNS and SRNS for several years. This treatment regimen has the advantage of eliminating the need for long-term high-dose steroid treatments, allowing 1 patient to achieve normal growth and recover from other adverse steroid effects.

HPV Infection is Associated with FoxM1 Overexpression in Dysplastic Changes of Sinonasal Inverted Papilloma.

BACKGROUND: This study aims to describe the factors associated with dysplastic changes in sinonasal inverted papilloma (SIP) including somatic EGFR mutation, FoxM1 expression, HPV status, and their association with dysplastic changes. METHODS: A cross-sectional, analytical study was conducted comprising 34 samples of histologically-confirmed diagnosis of SIP. The samples were further grouped into 2 groups: 20 samples without associated dysplastic changes, and 14 samples with associated dysplastic changes. The numbers of FoxM1 positively-expressed cells, EGFR mutation, and HPV status were compared among two groups using appropriate comparative statistics. RESULTS: There was statistically-significant difference of FoxM1 expression between SIP and SIP with dysplasia (10% vs 100%; p<0.001). EGFR mutation was identified in 6 samples (30.0%) of the SIP and 5 samples (35.7%) of SIP with dysplasia. No difference of EGFR mutant proportion among two groups. HPV DNA was detected in 5 samples (25.0%) of SIP versus 9 samples (64.3%) of SIP with dysplasia. There was significant difference of HPV status among two groups (p=0.022). The high-risk subtypes were found in most HPV positive samples (57.1%), while low-risk subtypes and out panel subtypes were found 14.3% and 21.4%, respectively. CONCLUSIONS: FoxM1 was overexpressed in SIP with malignant transformation. FoxM1 along with HPV status is associated with dysplastic changes in the SIP. FoxM1 immunostaining is potential to be a biomarker of malignant transformation in SIP.

Renal cell carcinoma with early skin metastasis and partial response on tyrosine kinase inhibitor: A case report.

INTRODUCTION AND IMPORTANCE: Renal cell carcinoma (RCC) skin metastasis is a rare disease. However, there are no data on the effect of a Tyrosine Kinase Inhibitor (TKI) on its treatment. CASE PRESENTATION: A 54-year-old male patient with renal cell carcinoma developed subcutaneous metastasis three months after radical nephrectomy and there was no discoloration or pain. Furthermore, an excision biopsy confirmed the metastatic lesion, and pazopanib was initiated as a treatment method. After 1-month of treatment, the patient developed ulceration and subsided after treatment was stopped. Similarly, a follow-up PET scan was performed almost a year after stopping the treatment, which showed improvement over metastatic pulmonary lesions. CLINICAL DISCUSSION: Renal cell carcinoma (RCC) major metastases were observed in pulmonary, costal, and skin. Tumor burden and location of metastasis influences progression free-survival of RCC patients treated with TKI. CONCLUSION: In this case, TKI treatment showed a long-term partial response, despite its lack of continuous therapy.

Retroperitoneoscopic proximal ureter resection and ureteroureterostomy as an alternative management for upper tract urothelial carcinoma: A case report.

Radical nephroureterectomy (RNU) with bladder cuff removal is the treatment of choice for upper tract urothelial carcinoma (UTUC). Partial ureterectomy (PU) with ureteroureterostomy in this case has shown a good result. We herein report an elderly woman with adenocarcinoma colon complaining gross intermittent hematuria and solid ureteral mass on NCCT. Patient declined RNU, so we performed PU with ureteroureterostomy. Histology examination showed high-grade infiltrating urothelial carcinoma with negative margin. Four cycles of Gemcitabine and cisplatin were given. Routine follow up and evaluation were done without any mass progression. PU and ureteroureterostomy with adjuvant chemotherapy are an alternative procedure for UTUC.

Case Report: High-grade anterior prostate cancer previously undetected by transrectal biopsy, diagnosed with MRI-US fusion transperineal robotic prostate biopsy.

Seventy percent of anterior prostate cancer cases are diagnosed during rebiopsy. MRI-US fusion transperineal robotic prostate biopsy is an emerging diagnostic method and might be an effective one in diagnosing prostate cancers in difficult sites such as the anterior zone. We report a case of a high grade anterior prostate cancer previously undetected by transrectal biopsy, diagnosed with MRI-US fusion transperineal robotic prostate biopsy. This case report suggests that MRI-US fusion transperineal robotic prostate biopsy might be valuable in diagnosing prostate cancer especially in difficult sites - the anterior region in this case - and might be an imperative diagnostic method in suspicious cases with prior negative biopsy.

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.

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.

A Modified Regimen of Methylprednisolone, Cyclophosphamide, and Mycophenolic Acid for Severe IgA Vasculitis with Nephritis in a Child.

IgA vasculitis with nephritis (IgAVN), which was formerly known as Henoch-Schonlein purpura nephritis, commonly manifests with mild symptoms. However, in rare circumstances, IgAVN in children can progress to kidney failure. Despite the successful treatment of severe IgAVN with a combination of immunosuppressive medications including corticosteroids, no consensus has been established for IgAVN treatment. Here, we present a case of severe IgAVN in an eight-year-old Indonesian boy who was treated with simultaneous methylprednisolone, cyclophosphamide, and mycophenolic acid. He experienced recovery of kidney function within one month, while proteinuria resolved in five months, and hematuria resolved within a year after treatment initiation. No recurrences were noted during the two-year follow-up. Although our immunosuppressive regimen may seem very potent, it was shown to have tolerable side effects and could be beneficial for kidney recovery. Importantly, they have also been shown to prevent progression to chronic kidney disease in children with severe IgAVN.

Experience of the first 6 years of pediatric kidney transplantation in Indonesia: A multicenter retrospective study.

BACKGROUND: Pediatric kidney transplantation was only introduced in Indonesia in 2013. We therefore aimed to assess the characteristics and outcomes of transplants performed from its inception to January 2019. METHOD: The study had a dual-center retrospective design. We examined the records of kidney transplant recipients and then calculated patient and graft survival rates by Kaplan-Meier survival analysis with 95% confidence intervals (95% CI). RESULTS: In total, 12 kidney transplantations were performed in eleven children during the study period; among these, ten were boys, and nine had renal failure caused by congenital anomaly of the kidney or urinary tract. All donors were living, and all recipients were on dialysis at the time of transplantation, when their median age was 14.5 years (range, 8-19 years). Three patients died of infection in the first year of follow-up and two lost their allograft by the time of their last follow-up (median, 13 months; range, 4-69 months). The 1-year patient survival rate was therefore 68.18% (95% CI, 29.72%-88.61%), which remained unchanged at 3 and 5 years. However, the non-death-censored graft survival rates at 1, 3, and 5 years were 68.18% (95% CI, 29.72%-88.61%), 51.14% (95% CI, 14.5%-79.46%), and 25.57% (95% CI, 1.38%-64.78%), respectively. CONCLUSION: Patient and graft survival rates after pediatric kidney transplantation in Indonesia are lower than those reported in other countries. Closer patient follow-up and stricter adherence to guidelines could improve transplant outcomes, but we must seek to improve the balance between infection and rejection.

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.

Delayed Admission and Management of Pediatric Acute Kidney Injury and Multiple Organ Dysfunction Syndrome in Children with Multiple Wasp Stings: A Case Series.

Multiple wasp stings may cause fatal complications, such as anaphylactic reactions, intravascular hemolysis, rhabdomyolysis, acute kidney injury (AKI), increased levels of liver enzymes, clotting abnormalities, or even death. AKI-related mortality due to multiple wasp stings may reach 25%, occurring within the early onset of disease; therefore, renal function should be continuously monitored within the first few days following the stings. Herein, we report 2 cases of AKI due to multiple stings of wasp (Vespa affinis). In both cases, delayed hospital admissions and gradual loss of kidney function along with hemolysis and anemia without rhabdomyolysis were observed. Diuresis was reduced on the 10th day following the stings in the first case, whereas it occurred on the 5th day in the second case. Both cases had biopsy results of acute tubular injury and acute interstitial nephritis. The first case improved with intermittent hemodialysis, whereas the second required continuous renal replacement therapy and plasma exchange because hemolysis was more severe, which was presumably caused by a greater number of stings and larger amount of toxins involved. Multiple organ dysfunction syndrome was also observed in the second case; hence, high-dose steroid therapy was administered to alleviate interstitial fibrosis. Both cases showed that although AKI occurring after multiple wasp stings usually have fatal consequences. Administering fluid treatment and steroid therapy and selecting accurate renal replacement therapy modalities during the few first days after the stings may result in favorable long-term outcomes.

Diagnostic Determinants of Proliferative Lupus Nephritis Based on Clinical and Laboratory Parameters: A Diagnostic Study.

BACKGROUND: proliferative lupus nephritis (LN) has higher prevalence and worse prognosis than non-proliferative LN. Renal biopsy plays an important role in diagnosis and therapy of LN, but there are some obstacles in its implementation. A diagnostic scoring system for proliferative LN is necessary, especially for cases in which renal biopsy cannot be performed. This study aimed to develop a diagnostic scoring system of proliferative LN based on its diagnostic determinants including hypertension, proteinuria, hematuria, eGFR, anti-dsDNA antibody, and C3 levels. METHODS: a cross-sectional study with total sampling method was conducted. Our subjects were adult LN patients who underwent renal biopsy in Cipto Mangunkusumo Hospital between January 2007 and June 2017. RESULTS: from a total of 191 subjects with biopsy-proven LN in this study, we found a proportion of proliferative LN of 74.8%. There were 113 subjects included for analysis of proliferative LN determinants. The multivariate analysis demonstrated that determinants for proliferative LN were hypertension (OR 3.39; 95% CI 1.30-8.84), eGFR <60ml/min/1.73m2 (OR 9.095; 95% CI 1.11-74.68), and low C3 levels (OR 3.97; 95% CI 1.41-11.17). After further analysis, we found that hypertension, eGFR <60ml/min/1.73m2, low C3 levels, and hematuria were essential components of the diagnostic scoring system on proliferative LN. The scoring system was tested with ROC curve and an AUC of 80.4% was obtained (95% CI 71.9-89). CONCLUSION: the proportion of proliferative LN in biopsy-proven LN patients of Cipto Mangunkusumo Hospital is 74.8%. Components of scoring system for proliferative LN consist of hypertension, eGFR <60ml/min/1.73m2, low C3 levels, and hematuria.

A rare case of primary cardiac lymphoma and the role of early surgical debulking: a case report.

BACKGROUND: Primary cardiac lymphoma (PCL) is a very rare disease and is most commonly found among immunocompromised patients. Its cardiac manifestations are non-specific, leading to delayed diagnosis and poor prognosis. However, chemotherapy could improve survival, which makes early and prompt diagnosis very crucial. This is a report of a rare case of PCL found on a 73-year-old man who benefit from early debulking surgery. CASE SUMMARY: A 73-year-old man presented with worsening dyspnoea over the last 2 months. A 7.2 × 10.2 cm intramural tumour was found extending from the right atrium to the right ventricle. It was considered that the tumour could cause sudden death due to its size and extension. Therefore, surgical debulking with biopsy and valve repair was done. Cytology examination from the resected specimen demonstrated diffuse large B-cell lymphoma non-germinal centre B-cell like type. He was discharged 2 weeks after the surgery in stable condition and referred to internal medicine department for chemotherapy. However, he chose palliative home care and died 44 days after surgery. DISCUSSION: In cases of PCL with concerning tumour size and symptoms due to cardiac obstruction, early surgical debulking could improve haemodynamics, prevent sudden death, and confirm immunopathological diagnosis needed in determining further chemotherapy, which is proven to improve survival.