Activation of Yes-Associated Protein Is Indispensable for Transformation of Kidney Fibroblasts into Myofibroblasts during Repeated Administration of Cisplatin.

Cisplatin is a potent chemotherapy medication that is used to treat various types of cancer. However, it can cause nephrotoxic side effects, which lead to acute kidney injury (AKI) and subsequent chronic kidney disease (CKD). Although a clinically relevant in vitro model of CKD induced by repeated administration of low-dose cisplatin (RAC) has been established, its underlying mechanisms remain poorly understood. Here, we compared single administration of high-dose cisplatin (SAC) to repeated administration of low-dose cisplatin (RAC) in myofibroblast transformation and cellular morphology in a normal rat kidney fibroblast NRK-49F cell line. RAC instead of SAC transformed the fibroblasts into myofibroblasts as determined by α-smooth muscle actin, enlarged cell size as represented by F-actin staining, and increased cell flattening as expressed by the semidiameter ratio of attached cells to floated cells. Those phenomena, as well as cellular senescence, were significantly detected from the time right before the second administration of cisplatin. Interestingly, inhibition of the interaction between Yes-associated protein (YAP) and the transcriptional enhanced associated domain (TEAD) using Verteporfin remarkedly reduced cell size, cellular senescence, and myofibroblast transformation during RAC. These findings collectively suggest that YAP activation is indispensable for cellular hypertrophy, senescence, and myofibroblast transformation during RAC in kidney fibroblasts.

Superiority of magnetic resonance imaging in small renal mass diagnosis where image reports mismatches between computed tomography and magnetic resonance imaging.

PURPOSE: To analyze malignancy of computed tomography (CT) and magnetic resonance imaging (MRI) results in the same renal mass. MATERIALS AND METHODS: We retrospectively reviewed 1,216 patients who underwent partial nephrectomy from January 2017 to December 2021 in our institute. Patients who had both CT and MRI reports prior to surgery were included. We compared the diagnostic accuracy between the CT and the MRI. The patients were divided into two groups according to the consistency of reports: the 'Consistent group' and the 'Inconsistent group'. The Inconsistent group was further divided into two subgroups. Group 1 is the case that showed benign findings on CT but malignancy on MRI. Group 2 is the cases of malignancy on CT but benign on MRI. RESULTS: 410 patients were identified. Benign lesion was identified in 68 cases (16.6%). The sensitivity, specificity and diagnostic accuracy of MRI was 91.2%, 36.8%, and 82.2% respectively, whereas that of CT was 84.8%, 41.2%, and 77.6% respectively. Consistent group were 335 cases (81.7%) and inconsistent group were 75 cases (18.3%). The mean mass size was significantly smaller in the inconsistent group compared to the consistent group (consistent group vs. inconsistent group: 2.31±0.84 cm vs.1.84±0.75 cm, p<0.001). Also, the Group 1 had higher odds of malignancy compared to Group 2 in the renal mass size 2-4 cm (odds ratio, 5.62 [1.02-30.90]). CONCLUSIONS: Smaller mass size affects the discrepancy of CT and MRI reports. In addition, MRI showed better diagnostic performance in mismatch cases in the small renal masses.

Robotic ureter reconstruction using the native ureter to treat long-segment ureteral stricture of the transplant kidney utilizing Indocyanine green: The first Korean experience.

PURPOSE: Ureteral strictures are a common complication after kidney transplantation. Open reconstruction is preferred for long-segment ureteral strictures that cannot be resolved endoscopically; however, it is known to have the potential to fail. We report 2 successful cases of robotic reconstruction surgery of a transplant ureter using the native ureter with the aid of intraoperative Indocyanine green (ICG). MATERIALS AND METHODS: Patients were placed in semi-lateral position. Using Da Vinci Xi, the transplant ureter was dissected, and the stricture site was identified. End-to-side anastomosis of the native ureter to the transplant ureter was performed. ICG was utilized to identify the course of the transplant ureter and confirm the vascularity of the native ureter. RESULTS: Case 1: A 55-year-old female underwent renal transplantation at another hospital. She had recurrent febrile urinary tract infections (UTIs) and a ureteral stricture requiring percutaneous nephrostomy (PCN). The PCN and ureteral stent were removed successfully after surgery. The patient had only 1 febrile UTI episode after surgery. Case 2: A 56-year-old female underwent renal transplantation at another hospital. She had acute pyelonephritis 1-month post-transplantation, and a long-segment ureteral stricture was identified. She developed a UTI with anastomosis site leakage in the early postoperative period, which resolved with conservative treatment. The PCN and ureteral stent were removed 6 weeks after surgery. CONCLUSIONS: Robotic surgery for managing long-segment ureteral stricture after kidney transplantation is safe and feasible. The use of ICG during surgery to identify the ureter course and its viability can improve the success.

Effectiveness of Bariatric Surgery Targeting Opioid Prescriptions (BSTOP) protocol on postoperative pain control.

BACKGROUND: Surgical pain management is a critical component in the success of bariatric procedures. With the opioid epidemic, there have been increased efforts to decrease opioid use. In 2019, the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program developed the BSTOP protocol, a multimodal perioperative pain management regimen to minimize opioid use. The objective of this study is to evaluate the effectiveness of the BSTOP protocol on patients' need for opioid medications during their perioperative care. METHODS: This is a single-institution prospective cohort study on patients who underwent bariatric surgery from 10/2019 to 5/2021. Data was collected on morphine equivalent dose of opioids during different stages of inpatient and outpatient care. BSTOP was implemented on 7/2020. Primary outcomes were total inpatient and outpatient opioid use as well as hospital length of hospital stay (LOS). Gabapentin was removed from the protocol between 10/20/2020 and 12/31/2020 due to side effects; it was re-implemented on 1/1/2021 due to observed spikes in opioid use during its absence. RESULTS: 1264 patients who had bariatric surgery between 10/2019 and 5/2021 were included in the study, with 409 patients before (pre-BSTOP) and 855 patients after BSTOP implementation. There was a 36% reduction in total inpatient opiate use and a 57% reduction in total outpatient opiate use. LOS also significantly decreased, from 1.53 to 1.28 days. 179 patients received BSTOP without gabapentin. These patients used more opioids in the post-anesthesia care unit and on the inpatient floors compared to pre-BSTOP and BSTOP with gabapentin patients. With total inpatient and outpatient opioid use, patients on BSTOP without gabapentin used fewer opioids than those pre-BSTOP. However, those on BSTOP without gabapentin used more opioids than those with gabapentin. CONCLUSION: The BSTOP protocol significantly reduced inpatient and outpatient opioid use as well as LOS. Gabapentin is a crucial component of the BSTOP protocol.

Repeated Administration of Cisplatin Transforms Kidney Fibroblasts through G2/M Arrest and Cellular Senescence.

Cisplatin is a potent chemotherapeutic used for the treatment of many types of cancer, but it has nephrotoxic side effects leading to acute kidney injury and subsequently chronic kidney disease (CKD). Previous work has focused on acute kidney tubular injury induced by cisplatin, whereas the chronic sequelae post-injury has not been well-explored. In the present study, we established a kidney fibroblast model of CKD induced by repeated administration of cisplatin (RAC) as a clinically relevant model. In NRK-49F rat kidney fibroblasts, RAC upregulated α-smooth muscle actin (α-SMA) and fibronectin proteins, suggesting that RAC induces kidney fibroblast-to-myofibroblast transformation. RAC also enhanced cell size, including the cell attachment surface area, nuclear area, and cell volume. Furthermore, RAC induced p21 expression and senescence-associated ß-galactosidase activity, suggesting that kidney fibroblasts exposed to RAC develop a senescent phenotype. Inhibition of p21 reduced cellular senescence, hypertrophy, and myofibroblast transformation induced by RAC. Intriguingly, after RAC, kidney fibroblasts were arrested at the G2/M phase. Repeated treatment with paclitaxel as an inducer of G2/M arrest upregulated p21, α-SMA, and fibronectin in the kidney fibroblasts. Taken together, these data suggest that RAC transforms kidney fibroblasts into myofibroblasts through G2/M arrest and cellular senescence.

2-Mercaptoethanol protects against DNA double-strand breaks after kidney ischemia and reperfusion injury through GPX4 upregulation.

BACKGROUND: Kidney ischemia reperfusion injury (IRI) is characterized by tubular cell death. DNA double-strand breaks is one of the major sources of tubular cell death induced by IRI. 2-Mercaptoethanol (2-ME) is protective against DNA double-strand breaks derived from calf thymus and bovine embryo. Here, we sought to determine whether treatment with 2-ME attenuated DNA double-strand breaks, resulting in reduced kidney dysfunction and structural damage in IRI. METHODS: Kidney IRI or sham-operation in mice was carried out. The mice were treated with 2-ME, Ras-selective lethal 3, or vehicle. Kidney function, tubular injury, DNA damage, antioxidant enzyme expression, and DNA damage response (DDR) kinases activation were assessed. RESULTS: Treatment with 2-ME significantly attenuated kidney dysfunction, tubular injury, and DNA double-strand breaks after IRI. Among DDR kinases, IRI induced phosphorylation of ataxia telangiectasia mutated (ATM) and ataxia telangiectasia and Rad3 related (ATR), but IRI reduced phosphorylation of other DDR kinases including ataxia telangiectasia and Rad3 related, checkpoint kinase 1 (Chk1), Chk2, and Chinese hamster cells 1 (XRCC1). Treatment with 2-ME enhanced phosphorylation of ATM and ATM-mediated effector kinases in IRI-subjected kidneys, suggesting that 2-ME activates ATM-mediated DDR signaling pathway. Furthermore, 2-ME dramatically upregulated glutathione peroxidase 4 (GPX4) in IRI-subjected kidneys. Inhibition of GPX4 augmented adverse IRI consequences including kidney dysfunction, tubular injury, DNA double-strand breaks, and inactivation of ATM-mediated DDR signaling pathway after IRI in 2-ME-treated kidneys. CONCLUSIONS: We have demonstrated that exogenous 2-ME protects against DNA double-strand breaks after kidney IRI through GPX4 upregulation and ATM activation.

Clinical Implications for da Vinci SP Partial Nephrectomy in High-Complexity Tumors: Propensity Score-Matching Analysis.

Purpose: To compare surgical outcomes between robot-assisted laparoendoscopic single-site (R-LESS) surgery using the da Vinci Si or Xi system and the da Vinci SP system for partial nephrectomy. Materials and Methods: From 2008 to 2020, 66 partial nephrectomies were performed using a single-site robotic approach: 44 used the da Vinci Xi or Si system (R-LESS group) and 22 used the da Vinci SP system (SP group). After 1:1 propensity score matching, surgical outcomes were compared between groups. Results: Median patient age was 51.5 years. Median tumor size was 2.1 cm and was not significantly different between groups. Median operation time was longer in the R-LESS group (R-LESS vs SP: 180 vs 155 minutes, p = 0.034), but median warm ischemic time was comparable between groups. Estimated blood loss was higher in the R-LESS group (R-LESS vs SP: 215 vs 20 mL, p < 0.001). Median operation time was significantly shorter in the SP group in patients with moderate- to high-complexity tumors (R-LESS vs SP: 200 vs 172 minutes, p = 0.035). Rates of trifecta achievement were similar between groups (63.6% in both groups, p = 1.00). Conclusions: R-LESS and da Vinci SP methods are both feasible approaches for single-site incision robotic partial nephrectomy. The da Vinci SP platform allows "true" single-site surgery without additional ports and provides a wider working space. It was associated with better performance than R-LESS partial nephrectomy. In complex tumors, operation time was shorter with SP partial nephrectomy than with R-LESS partial nephrectomy, suggesting that the SP method is especially advantageous for managing complex renal tumors.

Mitochondrial metabolic reprogramming by SIRT3 regulation ameliorates drug resistance in renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) alters metabolic signals frequently, leading to mitochondrial dysfunction, such as increase of glycolysis and accumulation of lipid. Sirtuin3 (SIRT3) is a key factor for the regulation of both mitochondrial integrity and function. SIRT3 is downregulated and contributes in both cancer development and progression in ccRCC. The aim of this study is to investigate SIRT3-regulated mitochondrial biogenesis in ccRCC. SIRT3 overexpression alone reduced glucose uptake rate and enhanced membrane potential in mitochondria. ccRCC with overexpressed SIRT3 further improved the lethal effects when combined with anticancer drugs (Resveratrol, Everolimus and Temsirolimus). Cell viability was markedly decreased in a dose-dependent manner when treated with resveratrol or mTOR inhibitors in SIRT3 overexpressing ccRCC. In conclusion, SIRT3 improved mitochondrial functions in ccRCC through metabolic reprogramming. Mitochondrial reprogramming by SIRT3 regulation improves the sensitivity to anticancer drugs. The combination of SIRT3 and resveratrol functioned synergistically lethal effect in ccRCC.

Anesthesia for Pituitary Surgery.

Anesthesia for pituitary surgery is tailored to each individual patient and the type of tumor they have. Anesthetic considerations include difficult airways, hormonal and electrolyte abnormalities, cardiac abnormalities, the potential for catastrophic hemorrhage, and the importance of a smooth extubation. The anesthesiologist is able to assist the surgeons by keeping the patient motionless and lowering the blood pressure to minimize surgical bleeding. Postoperative nausea and vomiting are also of greater importance than usual, as the Valsalva movements associated with retching could cause bleeding and disruption of the surgical site.

Evaluation of the Surgical Margin Threshold for Avoiding Recurrence after Partial Nephrectomy in Patients with Renal Cell Carcinoma.

PURPOSE: An adequate minimal surgical margin for partial nephrectomy (PN) has not yet been conclusively established. Therefore, we aimed to compare PN recurrence rates according to surgical margin status and to establish an adequate minimal surgical margin. MATERIALS AND METHODS: We retrospectively studied patients with clinically localized renal cell carcinoma who underwent PN between 2005 and 2014. Surgical margin width (SMW) was assessed for all surgical tissues and divided into three groups: SMW <1 mm, SMW ≥1 mm, and positive surgical margin (PSM). The data were analyzed using the Kaplan-Meier method with log-rank tests and multivariate Cox regression models. RESULTS: Of 748 patients (median age, 55 years; interquartile range, 46-64 years; 220 female), 704 (94.2%) and 44 (5.8%) patients had negative and PSMs, respectively. Recurrence-free survival was significantly lower in patients with PSMs (p<0.001) and was not significantly different between SMW ≥1 mm and <1 mm groups (p=0.604). PSM was a significant predictor of recurrence (hazard ratio: 8.03, 95% confidence interval: 2.74-23.56, p<0.001), in contrast to SMW <1 mm (p=0.680). CONCLUSION: A PSM after PN significantly increases the risk of recurrence. We discovered that even a submillimeter safety surgical margin may be enough to prevent recurrence. To maximize normal renal parenchyma preservation and to avoid cancer recurrence in renal parenchymal tumor patients, PN may be a safe treatment, except for those with a PSM in the final pathology.

Future Platforms of Robotic Surgery.

Among the various robotic devices that exist for urologic surgery, the most common are synergistic telemanipulator systems. Several have achieved clinical feasibility and have been licensed for use in humans: the standard da Vinci, Avatera, Hinotori, Revo-i, Senhance, Versius, and Surgenius. Handheld and hands-on synergistic systems are also clinically relevant for use in urologic surgeries, including minimally invasive and endoscopic approaches. Future trends of robotic innovation include an exploration of more robust haptic systems that offer kinesthetic and tactile feedback; miniaturization and microrobotics; enhanced visual feedback with greater magnification and higher fidelity detail; and autonomous robots.

Anti-cancer effects of the aqueous extract of Orostachys japonica A. Berger on 5-fluorouracil-resistant colorectal cancer via MAPK signalling pathways in vitro and in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Orostachys japonica A. Berger, also known as Wa-song in Korea, has traditionally been used as a folk medicine, but the potential anti-cancer effects of aqueous extract of Orostachys japonica (OJe) have not yet been thoroughly investigated. AIM OF THE STUDY: To evaluate the anti-cancer effects of OJe, its possible mechanisms of action were investigated in 5-fluorouracil (5-FU) resistant SNU-C5/5-FUR colorectal cancer cells. MATERIALS AND METHODS: The functional compounds of OJe were identified with high performance liquid chromatography. The anti-cancer effects of OJe in SNU-C5/5-FUR cells were investigated by a cell viability assays, flow cytometry analysis, and a subcutaneous xenograft model employing BALB/c-nude mice. Possible signalling pathways were assayed with Western blotting. RESULTS: OJe (250 µg/ml) showed anti-cancer effects in SNU-C5/5-FUR cells, that were mediated via apoptosis as well as cell cycle arrest at the G0/G1 phase. Gallic acid and (-)-epicatechin, the major functional components of OJe, induced cell cycle arrest. OJe treatment (250 mg/kg, p.o.) produced a significant anti-proliferative effect in the xenograft model via decreased ß-catenin/GSK3ß and increased p27 expression. OJe treatment significantly activated ERK and p38 both in vitro and in vivo. CONCLUSIONS: These results suggest that OJe has anti-proliferative effects on 5-FU-resistant colorectal cancer cells via regulation of MAPK signalling pathways.

Predicting Insignificant Prostate Cancer: Analysis of the Pathological Outcomes of Candidates for Active Surveillance according to the Pre-International Society of Urological Pathology (Pre-ISUP) 2014 Era Versus the Post-ISUP2014 Era.

PURPOSE: To analyze the difference in the prediction accuracy with an active surveillance (AS) protocol between two eras (pre-International Society of Urological Pathology [pre-ISUP]-2014 vs. post-ISUP2014). MATERIALS AND METHODS: We retrospectively analyzed 118 candidates for AS who underwent radical prostatectomy between 2009 and 2017. We divided our patients into two groups (group 1 [n=57], operation date 2009-2015; group 2 [n=61], operation date 2016-2017). Pathologic slides in group 1 were reviewed to distinguish men with cribriform pattern (CP) because the determination of Gleason scores in old era had been based on pre-ISUP2014 classification. Postoperative outcomes in the two eras were analyzed twice: first, all men in group 1 vs. group 2; second, the remaining men after excluding those with CPs in group 1 vs. group 2. RESULTS: The proportion of men with insignificant prostate cancer (iPCa) was significantly lower in group 1 than in group 2 (36.8% vs. 57.4%, p=0.040). After excluding 11 men with CPs from group 1, those remaining (46 men) were compared again with group 2. In this analysis, the proportion of men with iPCa was similar between the two groups (old vs. contemporary era: 41.3% vs. 57.4%, p=0.146). Nine of 11 men with CP had violated the criteria for iPCa in the earlier comparison. CONCLUSIONS: The accuracy of the AS protocol has been affected by the coexistence of CPs and pure Gleason 6 tumors in the pre-ISUP2014 era. We suggest to use only contemporary (post-ISUP2014) data to analyze the accuracy with AS protocols in future studies.

Intraoperative Thrombolysis of Massive Pulmonary Embolus During Spine Surgery: Case Report of Survival Complicated by Massive Bleeding and Review of the Literature.

BACKGROUND: Pulmonary embolism (PE) is a known risk of lumbar spinal fusion surgery that can lead to sudden and unexpected death. Treatment often involves systemic anticoagulation when the risk of potentially fatal hemodynamic deterioration is judged to outweigh the risk of epidural hematoma and paralysis. Acute massive PE with obstruction of more than 50% of the pulmonary arterial tree causes right heart failure, hypotension, and often rapid death, and may require aggressive medical intervention with thrombolytic agents, such as alteplase, although in the postoperative period this entails an extremely high risk of bleeding and the associated potential neurologic morbidity. CASE DESCRIPTION: We report the first case, to our knowledge, of intraoperative thrombolytic therapy during spine surgery in a 68-year-old woman who developed a massive PE with cardiac arrest while undergoing lumbar instrumented fusion surgery in the prone position and detail the postoperative course that was complicated by severe bleeding. CONCLUSIONS: Our experience is that chemical thrombolysis can be a lifesaving option to address pending circulatory arrest, but that severe bleeding is a likely consequence. If used to treat an intraoperative emergency, a smaller than standard dose of thrombolytic should be considered.

Cisplatin nephrotoxicity is induced via poly(ADP-ribose) polymerase activation in adult zebrafish and mice.

Cisplatin is a well-known chemotherapy medication used to treat numerous cancers. However, treatment with cisplatin in cancer therapy has major side effects, such as nephrotoxic acute kidney injury. Adult vertebrate kidneys are commonly used as models of cisplatin-induced nephrotoxic acute kidney injury. Embryonic zebrafish kidney is more simplified and is composed simply of two nephrons and thus is an excellent model for the investigation of cisplatin nephrotoxicity. Here, we developed a novel model to induce cisplatin nephrotoxicity in adult zebrafish and demonstrated that intraperitoneal injection of cisplatin caused a decline in kidney proximal tubular function based on fluorescein-labeled dextran uptake and alkaline phosphatase staining. We also showed that cisplatin induced histological injury of the kidney tubules, quantified by tubular injury scores on the periodic acid-Schiff-stained kidney sections. As shown in a mouse model of cisplatin-induced nephrotoxicity, the activation of poly(ADP-ribose) polymerase (PARP), an enzyme implicated in cisplatin-induced cell death, was markedly increased after cisplatin injection in adult zebrafish. Furthermore, pharmacological inhibition of PARP using a specific PARP inhibitor PJ 34 hydrochloride (PJ34) or 3-aminobenzamide ameliorated kidney proximal tubular functional and histological damages in cisplatin-injected adult zebrafish kidneys. Administration of a combination of PARP inhibitors PJ34 and 3-aminobenzamide additively protected renal function and histology in zebrafish and mouse models of cisplatin nephrotoxicity. In conclusion, these data suggest that adult zebrafish are not only suitable for drug screening and genetic manipulation but also useful as a simplified but powerful model to study the pathophysiology of cisplatin nephrotoxicity and establish new therapies for treating human kidney diseases.

Yeast Extract Induces Apoptosis and Cell Cycle Arrest via Activating p38 Signal Pathway in Colorectal Cancer Cells.

The microbiome has recently become a key interest for cancer research. Anti-tumor effects of reinforced clostridium media (RCM) were investigated for all ingredients of RCM, which showed that yeast extract could be a candidate for this phenomenon. MTT assay, cell counting, cell death analysis, cell cycle analysis, and Western blotting were done on colorectal cancer cells with or without 5-fluorouracil resistance (SNU-C5 and SNU-C5/5-FUR). Yeast extract treatment showed dose- and time-dependent anti-tumor effects on SNU-C5 and SNU-C5/5-FUR. Anti-tumor effects were related to G0/G1 phase arrest with increased p21, reactive oxygen species scavenger activities, and decreased free iron. Yeast extract treatment significantly increased apoptosis, which was effectively blocked with the PARP inhibitor. Anti-tumor effects of yeast extract were correlated with the increased phosphorylation of p38 and p53. These results suggest that yeast extract might inhibit the proliferation of colorectal cancer cells via the activation of the p38-p53-p21 cascade.

Urethral duplication in male children: A study of 12 cases.

PURPOSE: To present our experience in urethral duplication focusing on detailed surgical management. METHODS: We retrospectively reviewed the records of 12 male patients treated for urethral duplication between 2005 and 2017. Evaluations included ultrasound, retrograde urethrography, cystoscopy, and voiding cystourethrography. RESULTS: The age at presentation ranged from birth to 11 years. All 12 cases were classified using the Effmann classification. Case 1-4 patients with type I underwent excision of the dorsal accessory urethra by stripping technique. In case 5 patient(type IA) with two adjacent apical urethras, the septum was opened to form a single channel. Case 6 patient with type IB underwent visual internal urethrotomy near bulbous urethra to combine urethra into one channel. Five patients classified as type II (one with a type IIA1, and four with type IIA2 urethras). Urethral duplication was incidentally found during epispadias repair in case 7 patient with type IIA1, which was corrected by ventral plication, and excision of the dorsal epispadial urethra with stripping technique just below pubic bone. Case 8 patient with type IIA2 also required dorsal urethral excision with stripping technique. The two Y-type patients (case 10, 11) underwent urethrourethrostomy with a single-stage buccal mucosa tube graft, followed by repetitive surgeries owing to urethral stricture. One type III patient presented with penile inflammation and suprapubic pain, and underwent excision of both the dorsal urethra and nonfunctional anterior bladder. CONCLUSIONS: Urethral duplication requires individualized surgical approaches based on the anatomical and functional characteristics. Because prognosis is variable depending on type and accompanied anomalies, these should be taken into account when planning a comprehensive workup and surgical management. LEVEL OF EVIDENCE: Level IV.

Incidentally found cystic lymphangioma of the adrenal gland in an elderly male cadaver.

Adrenal cystic lymphangiomas are extremely rare entities that are often identified incidentally, with less than 60 cases reported to date. We found a protruding ovoid mass consisting of a multiloculated cystic lesion within right adrenal gland in the cadaver of a 75-year-old Korean man. The epithelial cells lining the adrenal cyst were diffusely positive for cluster of differentiation 31 and podoplanin, and negative for pan-cytokeratin. The histopathological diagnosis confirmed a cystic lymphangioma arising from the adrenal gland. Post-mortem findings of the present case are discussed based on the clinicopathological features of adrenal cystic lymphangiomas.

Yeast extract inhibits the proliferation of renal cell carcinoma cells via regulation of iron metabolism.

The microbiome has recently attracted research interest in a variety of subjects, including cancer. In the present study, it was determined that reinforced clostridium media (RCM) for microbiome culture, exerts antitumor effects on renal cell carcinoma cells when compared to the microbiome 'X'. The antitumor effects of RCM were investigated for all ingredients of RCM, and the results revealed that yeast extract could be a candidate for the ingredient driving this phenomenon. Further experiments including MTT assay, cell counting, cell death analysis, cell cycle analysis and western blotting were conducted with yeast extract on renal cell carcinoma cells (Caki­1 and Caki­2) and normal human proximal tubular cells (HK­2). As a result, yeast extract exhibited dose­dependent antitumor effects on Caki­1 and Caki­2, but only slight effects on HK­2. In addition, yeast extract only exhibited slight effects on necrosis, autophagy, or apoptosis of Caki­1 and Caki­2. Yeast extract produced cell cycle arrest with an increased G0/G1 fraction and a decreased S fraction, and this was considered to be related to the decreased cyclin D1. Although yeast extract treatment increased anti­oxidant activities, the antitumor effects of yeast extract were also related to iron metabolism, based on the decreased transferrin receptor and increased ferritin. In addition, decreased GPX4 may be related to iron­dependent cell death, particularly in Caki­2. These results revealed that yeast extract may inhibit proliferation of renal cell carcinoma cells by regulating iron metabolism. Since an increased iron requirement is a classic phenomenon of cancer cells, yeast extract may be a candidate for adjuvant treatment of renal cell carcinoma.

Changes in Clinical Characteristics of Patients with an Initial Diagnosis of Prostate Cancer in Korea: 10-Year Trends Reported by a Tertiary Center.

BACKGROUND: The Korea Central Cancer Registry reported that incidence rates of prostate cancer have not increased continuously. We used recent trends in the incidence of prostate cancer to generate a preliminary report of the Korean population with prostate cancer. METHODS: Patients initially diagnosed with prostate cancer by prostate biopsy from 2006 to 2015 at our tertiary center were selected. All patients were categorized according to age (< 65, 65-75, > 75 years), time period (2006-2010 vs. 2011-2015), and risk classification. Patients with insufficient data were excluded from the analysis. RESULTS: Of 675 patients (median prostate-specific antigen [PSA], 9.09 ng/mL), those with a Gleason score (GS) of 6 (32.3%) comprised the largest proportion in our cohort. The proportion with a GS of 8 increased for those aged 65-75 years, despite the lack of increase in PSA. Treatment patterns changed for those with very low to low risk cancer. The overall survival (OS) rate and the cancer-specific survival (CSS) rate for all patients at 5 years were 87% and 90%, respectively. Patients with a low body mass index (BMI; ≤ 23 kg/m²) had worse median OS and CSS rates. CONCLUSION: Significant differences in risk classifications and initial treatments were found between 2006-2010 and 2011-2015. Although PSA did not change, the GS did change. Lower BMI (≤ 23 kg/m²) had worse effects on OS and CSS rates for Korean prostate cancer patients.