Gastric metastasis of renal cell carcinoma treated with endoscopic resection: A case report.

Gastric metastasis of renal cell carcinoma (RCC) is rarely encountered. The time interval between the primary diagnosis of RCC and the occurrence of gastric metastasis tends to occur after more than 10 years. Clinicians should be diligent in checking the general symptoms of patients for more than 10 years.

Systemic amyloid A amyloidosis of the bladder after transurethral resection of urothelial carcinoma.

Introduction: Amyloid A amyloidosis of the bladder is not a major disease. We report a patient with systemic amyloid A amyloidosis of the bladder after transurethral resection of urothelial carcinoma. Case presentation: An 87-year-old Japanese man had bladder carcinoma. He was followed up regularly with cystoscopy. Cystoscopy revealed multiple polypoid tumors 6 months after the first transurethral resection of urothelial carcinoma. Pathologic specimens contained the amyloid A component. He had hypertrophic cardiomyopathy, valvular disorders, and arrhythmias. His cardiac disease may have resulted from amyloid A amyloidosis. We speculated the patient had systemic amyloid A amyloidosis of the heart and bladder. Conclusion: We determined the type of amyloidosis via a biopsy of the bladder tumors. Our patient had cardiac disease. Therefore, systemic amyloid A amyloidosis could have caused his cardiac disease. The pathologic findings of bladder tumors can contribute to detecting systemic amyloid A amyloidosis.

Stilbene analogs of resveratrol improve insulin resistance through activation of AMPK.

Resveratrol (RSV), 3,5,4'-trihydroxy-trans-stilbene, is known to have many beneficial physiological activities. We have synthesized several stilbene analogues and have reported that the hydroxyl group in the 4' position of RSV exhibited strong radical scavenging action. Using stilbene analogs, we investigated the structure of RSV to explain its protective effect against obesity and type 2 diabetes. All six analogs used in this study inhibited the differentiation of 3T3-L1 adipocytes. 3-Hydroxy-trans stilbene (3(OH)ST), and 3,4'-dihydroxy-trans stilbene (3,4'(OH)2ST) increased glucose uptake and induced adenosine monophosphate kinase (AMPK) phosphorylation in C2C12 myotubes independently of insulin. An in vivo study using mice fed high-fat diets indicated that 3(OH)ST was more effective than RSV in improving insulin resistance. In conclusion, RSV and its derivatives, particularly 3(OH)ST, inhibited adipocyte differentiation and enhanced glucose uptake in the myotubes, resulting in a reduction of obesity and an improvement in glucose tolerance in vivo.

[Neobladder-rectal fistula as early postoperative complication of radical cystectomy and orthotopic neobaldder construction].

We report a case of neobladder-rectal fistula that developed as an early postoperative complication of radical cystectomy and orthotopic neobladder construction procedures. A 75-year-old man underwent a radical cystectomy and orthotopic neobladder construction using Studer's method for locally invasive bladder cancer (cT2N0M0). The patient had severe watery diarrhea on postoperative day 20, and was diagnosed with a neobladder-rectal fistula based on cystography findings. We inserted a Foley catheter into the neobladder, and performed conservative treatment. Four months after development of the fistula, cystography revealed that it had spontaneously closed. A neobladder-rectal fistula is an extremely rare complication, with no other known reports. Herein, we present this case of neobladder-rectal fistula and discuss its formation, diagnosis and treatment, along with reference to previous reports of neobladder-vaginal fistulas.

Predictors of Long-Term Urinary Incontinence After Robot-Assisted Laparoscopic Prostatectomy.

Introduction: Urinary incontinence is a major complication after radical prostatectomy. We analyzed the predictors of urinary incontinence after robot-assisted radical prostatectomy. Material and Methods: One hundred twenty-one patients, whose urinary continence status was evaluable at 3 months, 6 months, and 12 months after robot-assisted radical prostatectomy, were included from October 2016 to September 2021. Data were retrospectively collected from electronic medical records. The continence status was evaluated by interviewing the patients about the number of urinary pads used per day. We compared the patients' age, body mass index, prostate volume, membranous urethral length on preoperative magnetic resonance imaging, surgeon experience, and pathological findings between patients with and without regained continence at 12 months after robot-assisted radical prostatectomy. Results: The urinary continence rates were 30%, 57.8% and 79.3% at 3 months, 6 months, and 12 months, respectively, after robot-assisted radical prostatectomy. Twelve months after robot-assisted radical prostatectomy, 96 patients had regained continence and did not require urinary pads, whereas 25 patients had persistent urinary incontinence and required urinary pads. Membranous urethral length and surgeon experience were significantly different between patients with and without regained continence at 12 months after robot-assisted radical prostatectomy (P=0.05). However, no significant differences existed in age, body mass index, prostate volume, and pathological findings between patients with and without regained continence at 12 months after robot-assisted radical prostatectomy. Conclusion: Membranous urethral length and surgeon experience are predictors of urinary incontinence after robot-assisted radical prostatectomy. Measuring the membranous urethral length is recommended before performing the operation.

Localized Amyloid A amyloidsis of ureter: A case report.

Amyloidosis of the ureter is a rare disease, distinguishing it from a neoplasm is difficult. A 64-year-old Japanese woman suffered from macrohematuria and left side hydronephrosis with ultrasound in 2014. Retrograde pyelography revealed no ureter tumor at that time. The patient had macrohematuria, left side hydronephrosis, and ureteral stenosis in the left ureter on retrograde pyelography. She was suspected of having a ureter tumor when she was 71 years old in 2021. The patient underwent ureteroscopy with biopsy. Pathological specimens contained the amyloid A component, based on immunohistochemistry staining. We diagnosed the patient with amyloid A amyloidosis of the ureter.

Do the oxidative stress biomarkers predict COVID-19 outcome? An in-hospital cohort study.

In SARSCoV-2 infections, excessive activation of the immune system dramatically elevates reactive oxygen species levels, harms cell structures, and directly increases disease severity and mortality. We aimed to evaluate whether plasma oxidative stress biomarker levels could predict mortality in adults admitted with Coronavirus Disease 2019 (COVID-19), considering potential confounders. We conducted a cohort study of 115 adults (62.1 ± 17.6 years, 65 males) admitted to a Brazilian public hospital for severely symptomatic COVID-19. Serum levels of α-tocopherol, glutathione, superoxide dismutase, 8-hydroxy-2'-deoxyguanosine, malondialdehyde, and advanced oxidation protein products were quantified at COVID-19 diagnosis using real-time polymerase chain reaction. Serum levels of α-tocopherol, glutathione, superoxide dismutase, and advanced oxidation protein products differed significantly between survivors and non-survivors. Serum glutathione levels below 327.2 µmol/mL were associated with a significant risk of death in COVID-19 patients, even after accounting for other factors (adjusted hazard ratio = 3.12 [95% CI: 1.83-5.33]).

[Usage of gastric antisecretory drugs in palliative care of lung cancer patients].

Non-steroidal anti-inflammatory drugs(NSAID)and steroids are important drugs that are the most frequently prescribed medications for the relief of cancer pain. However, there is overwhelming evidence that these drugs cause various forms of gastric mucosal injury. Based on clinical experience, gastric antisecretory drugs such as the proton pump inhibitor(PPI)and the histamine-H2 receptor antagonist(H2RA)are widely used to avoid the gastrointestinal problems caused by NSAID and steroids. There are individual differences in how physicians use PPI and H2RA. In the present study, we retrospectively examined PPI and H2RA usage in the palliative care of 83 lung cancer patients, who were routinely prescribed an NSAID alone (single group)or a combination of an NSAID with a steroid(combination group). We also administered a questionnaire survey to 25 prescribing physicians specializing in respiratory medicine. The proportion of physicians prescribing a PPI prophylactically in the combination group was significantly higher than that of the single group. According to answers in the questionnaire survey, PPI prescribed by physicians in the single group was determined by the performance status and history of gastrointestinal problems in patients. Regardless of such factors, in the combination group, PPI was deliberately prescribed with steroids. Further investigation is needed to examine the clinical effects of PPI in palliative care, so as to establish more appropriate use of both PPI and H2RA.

Urinary Tract Infection in Hemodialysis-Dependent End-Stage Renal Disease Patients.

INTRODUCTION: The aim of this study was to analyze urinalysis findings and urinary bacterial culture in hemodialysis-dependent end-stage renal disease patients. The research goal was to understand the proportion, risk factors, and the causative organisms of urinary tract infection in hemodialysis-dependent end-stage renal disease patients. MATERIALS AND METHODS: Between May 2020 and June 2021, this study included 100 hemodialysis-dependent end-stage renal disease patients (50 male patients and 50 female patients). The urine underwent microscopic examination, pyuria was defined as ≥5 white blood cells per high-power field, and urinary bacterial cultures were conducted for patients with pyuria. Bacteriuria was defined as ≥104 colony-forming units/mL in men and ≥105 colony-forming units/mL in women. Daily urine output was investigated by oral listening. Postvoiding residual urine volume was measured. RESULTS: Fifty-six percent of male patients and 30% of female patients had normosthenuria, 24% of male patients and 38% of female patients had pyuria, and 20% of male patients and 32% of female patients had a urinary tract infection. A comparison of normosthenuria and urinary tract infection revealed no statistically significant difference in age, time on dialysis, daily urine output, and postvoiding residual urine volume. The proportion of female patients among those with normosthenuria was 34.8%, whereas the proportion of female patients among those with UTI was 61.5%. Urinary bacterial cultures showed that the major causative organisms were Escherichia coli (45%; 18/40 cultures) and extended spectrum beta-lactamase-producing Escherichia coli (17.5%; 7/40 cultures). CONCLUSION: The incidence of urinary tract infection was higher in female patients than in male patients. The proportion of resistant bacteria as the causative organisms was high in hemodialysis-dependent end-stage renal disease patients. Urinary bacterial culture should be checked while patients are able to void urine.

Efficacy of Cabozantinib in Metastatic Papillary Renal Cell Carcinoma Following Ineffective Treatment With Initial Therapy of Nivolumab and Ipilimumab.

Sunitinib is listed as first-line therapy for non clear-cell renal cell carcinoma (RCC) in several guidelines. However, in the era of immunotherapy, there is an urgent need for updated evidence for the treatment of metastatic non clear-cell RCC. Herein, we present three cases of patients with type 2 papillary RCC who were effectively treated with cabozantinib. The first case was a 48-year-old woman who underwent radical nephrectomy (pT3aN0M0). The tumor relapsed in the retroperitoneum 3 months postoperatively and was unresponsive to first-line nivolumab plus ipilimumab (NI). After the use of cabozantinib, the tumors drastically shrunk in 2 weeks, and complete response was achieved 3 months later. The second case was a 55-year-old man who underwent radical nephrectomy (pT3aN2M1). Metastatic lesions continued to grow with first-line NI, and cabozantinib was used as the second-line therapy. All metastatic lesions had shrunk by 50% after 4 months. The third case was a 36-year-old man with multiple tumors in the left solitary kidney and iliopsoas muscle metastasis. First-line therapy with NI was ineffective; subsequently, second-line axitinib was used for 5 months, and the disease was identified as progressive. Cabozantinib was started as third-line therapy. Multiple tumors shrunk in 2 weeks. There is little evidence concerning the treatment of papillary RCC. We experienced low efficacy of NI for first-line treatment of papillary RCC for three patients who were subsequently effectively treated with cabozantinib. Cabozantinib inhibits multiple tyrosine kinase receptors, which may suppress aggressive tumor progression of type 2 papillary RCC. Cabozantinib or combination with immuno-oncological drugs may be a promising treatment option for papillary RCC.

Profiling of Androgen-Dependent Enhancer RNAs Expression in Human Prostate Tumors: Search for Malignancy Transition Markers.

INTRODUCTION: Although the ability of androgens to promote prostate cancer development has been known for decades, the molecular mechanisms of androgen receptor (AR) signaling in the tumorigenesis remain unclear. Enhancer RNAs (eRNAs) transcribed from strong enhancers, or super-enhancers (SEs), have recently emerged as a novel class of regulatory non-coding RNAs (ncRNAs) that facilitate transcription, including that of androgen target genes, through chromatin looping to position enhancers proximate to the promoters. The aim of this study was to assess androgen-dependent transcription in prostate tumors of eRNAs (designated as KLK3eRNAs) from the SE of the KLK3 gene encoding the prostate-specific antigen (PSA) protein, a clinical marker of prostate carcinogenesis. MATERIALS AND METHODS: The androgen-induced KLK3eRNAs were identified in the LNCaP human prostate cancer cell line. The expressions of these KLK3eRNAs together with KLK3 and AR mRNA transcripts were assessed by qRT-PCR in prostate tumor samples from five prostate cancer patients. RESULTS: Androgen-induced KLK3eRNAs have been identified in the LNCaP cells, and their expression was further analyzed in tumors of prostate cancer patients. Transcripts of the tested KLK3eRNAs have been detected in all clinical samples, but their expression patterns differed between individual tumor specimens. We found a statistically significant correlation between the levels of the KLK3 and AR mRNAs with those of the previously reported KLK3eRNAs, while such correlation was not observed for novel KLK3eRNAs described in our recent report. CONCLUSION: Presented data suggest that prostate tumor development may associate with epigenetic reorganization in the KLK3 genomic regulatory elements reflected by changes of the KLK3eRNA expression. Our findings support a potential of eRNAs profiling to be used as diagnostic marker.

Albumin-to-Alkaline Phosphatase Ratio as a Novel Prognostic Marker of Nivolumab Monotherapy for Previously Treated Metastatic Renal Cell Carcinoma.

BACKGROUND/AIM: The relationship between albumin-to-alkaline phosphatase ratio (AAPR) and the outcome of patients with metastatic renal cell carcinoma (mRCC) treated with immune checkpoint inhibitors remains unresolved. We aimed to clarify the prognostic role of AAPR in nivolumab monotherapy for previously treated mRCC. PATIENTS AND METHODS: We retrospectively evaluated 60 patients with mRCC treated with nivolumab after failure of at least one molecular targeted therapy. The patients were stratified into two groups based on the baseline AAPR. The threshold of AAPR was determined using receiver-operating characteristics and Youden index analyses. Overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) of nivolumab therapy were compared between the high and low AAPR groups. RESULTS: The threshold of AAPR was set at 0.3, and 20 patients (33%) were assigned to the low AAPR group. The median OS and PFS were significantly lower in the low AAPR group than those in the high group (OS: 8.3 months vs. not reached, p<0.0001; PFS: 2.9 vs. 10.4 months, p=0.0006). Moreover, ORR was significantly lower in the low AAPR group than in the high group (16% vs. 45%, p=0.0397). Multivariate analyses further showed that AAPR was an independent factor for OS [HR=0.27 (95% CI=0.09-0.77), p=0.0151] but not for PFS (p=0.174). CONCLUSION: Baseline AAPR was significantly associated with outcome in patients with mRCC receiving nivolumab monotherapy and may, therefore, constitute an effective prognostic factor for nivolumab treatment.

Does repeated hydrodistension with transurethral fulguration for interstitial cystitis with Hunner's lesion cause bladder contraction?

Objective: To evaluate the effect of repeated bladder hydrodistension with transurethral resection or fulguration (TUF) of Hunner's lesions on bladder capacity and interstitial cystitis (IC) symptoms. TUF for Hunner's lesion is recommended in several IC/BPS guidelines, although recurrence is highly probable. Patients and methods: The study cohort comprised 44 IC patients with Hunner's lesions who underwent multiple bladder hydrodistensions with TUF and electrocautery (EC) at our institution between July 2005 and June 2018. We analysed their frequency-volume chart, O'Leary Sant Interstitial Cystitis Symptom Index (ICSI), Interstitial Cystitis Problem Index (ICPI), and visual analogue scale (VAS) for pain, before and at 2, 6, and 12 months after surgery. Results: The 44 Hunner-type IC patients underwent a total of 117 surgeries. Patients were divided into three groups based upon the number of hydrodistensions with TUF they underwent. Group 1 (n = 44), Group 2 (n = 44) and Group 3 (n = 21) underwent one, two, and three surgeries, respectively. At 6 months after surgery, the mean average voided volume (AVV) and maximum voided volume (MVV) were 157 mL and 228 mL in Group 1; 203 mL, 283 mL in Group 2; and 193 mL, 264 mL in Group 3. The AVV in Group 2 (P < 0.01) and Group 3 (P < 0.03), and the MVV in Group 2 (P < 0.02) increased significantly compared to Group 1. ICSI, ICPI and VAS pain score in groups 2 (P < 0.003, P < 0.01, P < 0.05) and 3 (P < 0.001, P < 0.001, P < 0.001) decreased significantly compared to Group 1. Conclusion: Repeated hydrodistension and TUF with EC of Hunner's lesions for recurrent Hunner-type IC patients improved their symptoms. There was a tendency toward an increase in bladder capacity and repeated hydrodistension with TUF did not appear to be a direct cause of bladder contraction. Abbreviations: AVV: average voided volume; BPS: bladder pain syndrome; EC: electrical cautery; IC: interstitial cystitis; ICPI: Interstitial Cystitis Problem Index; ICSI: Interstitial Cystitis Symptom Index; MVV: maximum voided volume; TUF: transurethral fulguration; TUR: transurethral resection; VAS: visual analogue scale.

Multiple myeloma with testicular involvement: A case report.

A case of multiple myeloma with testicular involvement is rare. We report a 72-year-old male with testicular infiltration as extramedullary disease of IgD λ-type multiple myeloma. The patient received systemic treatment, which included high orchiectomy, anticancer chemotherapy, and radiation therapy for bone metastasis. Eight months after the initial diagnosis, he remains alive. The testis is a rare location for extramedullary disease of multiple myeloma. Testicular involvement of multiple myeloma indicates a poor prognosis. The particular treatment strategy for extramedullary disease in multiple myeloma remains unclear. Testicular involvement of multiple myeloma is reviewed and discussed in this paper.

Deficiency of emerin contributes differently to the pathogenesis of skeletal and cardiac muscles in LmnaH222P/H222P mutant mice.

Laminopathies are tissue-selective diseases that affect differently in organ systems. Mutations in nuclear envelopes, emerin (Emd) and lamin A/C (Lmna) genes, cause clinically indistinguishable myopathy called Emery-Dreifuss muscular dystrophy (EDMD) and limb-girdle muscular dystrophy. Several murine models for EDMD have been generated; however, emerin-null (Emd) mice do not show obvious skeletal and cardiac muscle phenotypes, and Lmna H222P/H222P mutant (H222P) mice show only a mild phenotype in skeletal muscle when they already have severe cardiomyopathy. Thus, the underlying molecular mechanism of muscle involvement due to nuclear abnormalities is still unclarified. We generated double mutant (Emd-/-/LmnaH222P/H222P; EH) mice to characterize dystrophic changes and to elucidate interactions between emerin and lamin A/C in skeletal and cardiac muscles. As H222P mice, EH mice grow normally and have breeding productivity. EH mice showed severer muscle involvement compared with that of H222P mice which was an independent of cardiac abnormality at 12 weeks of age. Nuclear abnormalities, reduced muscle fiber size and increased fibrosis were prominent in EH mice. Roles of emerin and lamin A/C in satellite cells function and regeneration of muscle fiber were also evaluated by cardiotoxin-induced muscle injury. Delayed increases in myog and myh3 expression were seen in both H222P and EH mice; however, the expression levels of those genes were similar with control and regenerated muscle fiber size was not different at day 7 after injury. These results indicate that EH mouse is a suitable model for studying skeletal muscle involvement, independent of cardiac function, in laminopathies and an interaction between emerin and lamin A/C in different tissues.

Degarelix treatment is compatible with diabetes and antithrombotic therapy in patients with prostate cancer.

INTRODUCTION: Therapeutically induced androgen deficiency (AD) is a standard treatment for patients with prostate cancer, but it is often associated with various adverse effects (AEs) that may lead to discontinuation. Some AEs may depend on the patient's health condition, while others may be due to complications of the drug delivery method. Degarelix is a gonadotropin-releasing hormone (GnRH) antagonist widely used for the treatment of androgen-dependent prostate cancer. This study aimed to ascertain the following: 1) the compatibility of degarelix treatment with diabetes and 2) any specific causal associations of degarelix injections with increased blood clotting and antithrombotic therapy requirements. PATIENTS AND METHODS: The medical records of 162 patients with prostate cancer who had undergone degarelix treatment were retrospectively examined. The association of a medical history of diabetes and anticoagulant co-treatment with degarelix treatment discontinuation was analyzed statistically. RESULTS: Rapid and significant decreases in prostate-specific antigen (PSA) levels during the course of degarelix treatment were detected for patients with prostate cancer regardless of clinical state. During the 27 months of treatment, 68 subjects (48%) ceased degarelix treatment, owing to several reasons, mainly financial issues. Among these subjects, 19 had diabetes, while 35 were treated with antithrombotics. Extensive statistical analysis indicated that there were no causal associations between degarelix treatment discontinuation and preexisting diabetes or antithrombotic therapy. CONCLUSION: Our study suggests that preexisting diabetes and antithrombotic therapy were not significant factors for the discontinuation of degarelix treatment in patients with prostate cancer.

Central command increases muscular oxygenation of the non-exercising arm at the early period of voluntary one-armed cranking.

This study aimed to examine whether central command increases oxygenation in non-contracting arm muscles during contralateral one-armed cranking and whether the oxygenation response caused by central command differs among skeletal muscles of the non-exercising upper limb. In 13 male subjects, the relative changes in oxygenated-hemoglobin concentration (Oxy-Hb) of the non-contracting arm muscles [the anterior deltoid, triceps brachii, biceps brachii, and extensor carpi radialis (ECR)] were measured during voluntary one-armed cranking (intensity, 35-40% of maximal voluntary effort) and mental imagery of the one-armed exercise for 1 min. Voluntary one-armed cranking increased (P < 0.05) the Oxy-Hb of the triceps, biceps, and ECR muscles to the same extent (15 ± 4% of the baseline level, 17 ± 5%, and 16 ± 4%, respectively). The greatest increase in the Oxy-Hb was observed in the deltoid muscle. Intravenous injection of atropine (10-15 µg/kg) and/or propranolol (0.1 mg/kg) revealed that the increased Oxy-Hb of the arm muscles consisted of the rapid atropine-sensitive and delayed propranolol-sensitive components. Mental imagery of the exercise increased the Oxy-Hb of the arm muscles. Motor-driven passive one-armed cranking had little influence on the Oxy-Hb of the arm muscles. It is likely that central command plays a role in the initial increase in oxygenation in the non-contracting arm muscles via sympathetic cholinergic vasodilatation at the early period of one-armed cranking. The centrally induced increase in oxygenation may not be different among the distal arm muscles but may augment in the deltoid muscle.

Perioperative outcomes of laparoscopic radical nephrectomy for renal cell carcinoma in patients with dialysis-dependent end-stage renal disease.

The aims of this study were: (i) to analyze the perioperative outcomes of laparoscopic radical nephrectomy for renal cell carcinoma in patients with dialysis-dependent end-stage renal disease and (ii) to reveal perioperative management problems that are unique to these patients. Between June 2004 and June 2011, laparoscopic radical nephrectomy was performed in 39 patients who had renal cell carcinoma and dialysis-dependent end-stage renal disease. The operative outcomes of these patients were compared with the operative outcomes of 104 non-end-stage renal disease patients with sporadic renal cell carcinoma who underwent laparoscopic radical nephrectomy during the same period. Laparoscopic surgery was completed in thirty-eight end-stage renal disease patients. One patient was converted to open surgery because of an intraoperative injury to the inferior vena cava. This patient was excluded from the analysis. The mean operative time was 240 min; blood loss, 157 mL; and postoperative hospital stay, 9.6 days. Postoperative complications were observed in six patients, as follows: retroperitoneal hematoma and abscess in one patient, thrombosis of the arteriovenous fistula in three patients, pneumonia in one patient, and gastrointestinal bleeding in one patient. Eleven patients required blood transfusions. There was no significant difference between the end-stage renal disease patients and the non-end-stage renal disease patients in the mean operative time or the amount of blood loss. In conclusion, laparoscopic radical nephrectomy is feasible for dialysis-dependent end-stage renal disease patients, as well as for non-end-stage renal disease patients; however, end-stage renal disease patients may have a higher probability of experiencing non-life-threatening complications.