Molecular mechanism of formation and destruction of a pseudo­capsule in clear cell renal cell carcinoma.

The process and molecular mechanisms underlying the formation and destruction of a pseudo-capsule (PC) in clear cell renal cell carcinoma (ccRCC) are poorly understood. In the present study, the PCs of surgical specimens from primary tumors and metastatic lesions in 169 patients with ccRCC, and carcinogen-induced ccRCC rat models were semi-quantified using the invasion of PC (i-Cap) score system. This was based on the relationship among the tumor, PC and adjacent normal tissue (NT) as follows: i-Cap 0, tumor has no PC and does not invade NT; i-Cap 1, tumor has a complete PC and does not invade into the PC; i-Cap 2, tumor with focal absences in the PC, which partially invades the PC but not completely through the PC; i-Cap 3, tumor crosses the PC and invades the NT; i-Cap 4, tumor directly invades the NT without a PC. The study suggested that PC formation was not observed without physical compression, and also revealed that tumor invasion into the PC was a prognostic factor for postoperative oncological outcomes. Higher i-Cap, Fuhrman grade and tumor size were independent poor prognostic factors for postoperative disease-free survival. mRNA expression arrays generated from carcinogen-induced ccRCC rat models were used to explore genes potentially associated with the formation and destruction of a PC. Subsequently, human ccRCC specimens were validated for four genes identified via expression array; the results revealed that collagen type 4A2, matrix metalloproteinase-7 and l-selectin were upregulated alongside the progression of i-Cap score. Conversely, endoglin was downregulated. In conclusion, the present study provides insights into the formation and destruction of a PC, and the results may aid the treatment and management of patients with ccRCC.

A landscape of complex tandem repeats within individual human genomes.

Markedly expanded tandem repeats (TRs) have been correlated with ~60 diseases. TR diversity has been considered a clue toward understanding missing heritability. However, haplotype-resolved long TRs remain mostly hidden or blacked out because their complex structures (TRs composed of various units and minisatellites containing >10-bp units) make them difficult to determine accurately with existing methods. Here, using a high-precision algorithm to determine complex TR structures from long, accurate reads of PacBio HiFi, an investigation of 270 Japanese control samples yields several genome-wide findings. Approximately 322,000 TRs are difficult to impute from the surrounding single-nucleotide variants. Greater genetic divergence of TR loci is significantly correlated with more events of younger replication slippage. Complex TRs are more abundant than single-unit TRs, and a tendency for complex TRs to consist of <10-bp units and single-unit TRs to be minisatellites is statistically significant at loci with ≥500-bp TRs. Of note, 8909 loci with extended TRs (>100b longer than the mode) contain several known disease-associated TRs and are considered candidates for association with disorders. Overall, complex TRs and minisatellites are found to be abundant and diverse, even in genetically small Japanese populations, yielding insights into the landscape of long TRs.

Phase-separated nuclear bodies of nucleoporin fusions promote condensation of MLL1/CRM1 and rearrangement of 3D genome structure.

NUP98 and NUP214 form chimeric fusion proteins that assemble into phase-separated nuclear bodies containing CRM1, a nuclear export receptor. However, these nuclear bodies' function in controlling gene expression remains elusive. Here, we demonstrate that the nuclear bodies of NUP98::HOXA9 and SET::NUP214 promote the condensation of mixed lineage leukemia 1 (MLL1), a histone methyltransferase essential for the maintenance of HOX gene expression. These nuclear bodies are robustly associated with MLL1/CRM1 and co-localized on chromatin. Furthermore, whole-genome chromatin-conformation capture analysis reveals that NUP98::HOXA9 induces a drastic alteration in high-order genome structure at target regions concomitant with the generation of chromatin loops and/or rearrangement of topologically associating domains in a phase-separation-dependent manner. Collectively, these results show that the phase-separated nuclear bodies of nucleoporin fusion proteins can enhance the activation of target genes by promoting the condensation of MLL1/CRM1 and rearrangement of the 3D genome structure.

The arginine transporter Can1 acts as a transceptor for regulation of proline utilization in the yeast Saccharomyces cerevisiae.

Proline is the most abundant amino acid in wine and beer, because the yeast Saccharomyces cerevisiae hardly assimilates proline during fermentation processes. Our previous studies showed that arginine induces endocytosis of the proline transporter Put4, resulting in inhibition of proline utilization. We here report a possible role of arginine sensing in the inhibition of proline utilization. We first found that two basic amino acids, ornithine, and lysine, inhibit proline utilization by inducing Put4 endocytosis in a manner similar to arginine, but citrulline does not. Our genetic screening revealed that the arginine transporter Can1 is involved in the inhibition of proline utilization by arginine. Intriguingly, the arginine uptake activity of Can1 was not required for the arginine-dependent inhibition of proline utilization, suggesting that Can1 has a function beyond its commonly known function of transporting arginine. More importantly, our biochemical analyses revealed that Can1 activates signaling cascades of protein kinase A in response to extracellular arginine. Hence, we proposed that Can1 regulates proline utilization by functioning as a transceptor possessing the activity of both a transporter and receptor of arginine.

First-line pembrolizumab for patients with early relapsing urothelial carcinoma after perioperative chemotherapy: a retrospective analysis of bladder cancer and upper urinary tract cancer.

BACKGROUND: First-line pembrolizumab is available for recurrent disease within 12 months after the receipt of platinum-based perioperative chemotherapy. However, the benefit of first-line pembrolizumab is unclear. This study evaluated the oncological outcome of patients treated with pembrolizumab compared with chemotherapy as first-line therapy for early relapsing disease after the receipt of platinum-based perioperative chemotherapy. METHODS: Data from a multicenter study included 454 patients diagnosed with unresectable or metastatic UC from November 2006 to July 2021. We identified patients with early and non-early relapsing disease. Oncological outcomes were evaluated using progression-free survival, overall survival, and survival with disease control. RESULTS: Fifty-three patients with early relapsing disease and 15 patients with non-early relapsing disease were identified. Of 53 patients with early relapsing disease, 26 (49.1%) were treated with pembrolizumab and 27 (50.9%) were treated with chemotherapy as first-line therapy. Fifteen patients with non-early relapsing disease were treated with chemotherapy. Early relapsing disease was associated with shorter progression-free survival and overall survival than non-early relapsing disease. Pembrolizumab was associated with longer progression-free survival and survival with disease control than chemotherapy in patients with early relapsing disease. There was no significant difference in overall survival between pembrolizumab and chemotherapy, but overall survival plateau with a long tail was observed in pembrolizumab. CONCLUSIONS: First-line pembrolizumab in earlier clinical settings for highly malignant tumors might improve the prognosis of patients with early relapsing disease after the receipt of platinum-based perioperative chemotherapy.

The Cdc25/Ras/cAMP-dependent protein kinase A signaling pathway regulates proline utilization in wine yeast Saccharomyces cerevisiae under a wine fermentation model.

Proline is a predominant amino acid in grape must, but it is poorly utilized by the yeast Saccharomyces cerevisiae in wine-making processes. This sometimes leads to a nitrogen deficiency during fermentation and proline accumulation in wine. In this study, we clarified that a glucose response is involved in an inhibitory mechanism of proline utilization in yeast. Our genetic screen showed that strains with a loss-of-function mutation on the CDC25 gene can utilize proline even under fermentation conditions. Cdc25 is a regulator of the glucose response consisting of the Ras/cAMP-dependent protein kinase A (PKA) pathway. Moreover, we found that activation of the Ras/PKA pathway is necessary for the inhibitory mechanism of proline utilization. The present data revealed that crosstalk exists between the carbon and proline metabolisms. Our study could hold promise for the development of wine yeast strains that can efficiently assimilate proline during the fermentation processes.

Organ-Specific and Mixed Responses to Pembrolizumab in Patients with Unresectable or Metastatic Urothelial Carcinoma: A Multicenter Retrospective Study.

To investigate the organ-specific response and clinical outcomes of mixed responses (MRs) to immune checkpoint inhibitors (ICIs) for unresectable or metastatic urothelial carcinoma (ur/mUC), we retrospectively analyzed 136 patients who received pembrolizumab. The total objective response rate (ORR) and organ-specific ORR were determined for each lesion according to the Response Evaluation Criteria in Solid Tumors version 1.1 as follows: (i) complete response (CR), (ii) partial response (PR), (iii) stable disease (SD), and (iv) progressive disease (PD). Most of the organ-specific ORR was 30−40%, but bone metastasis was only 5%. There was a significant difference in overall survival (OS) between responders and non-responders with locally advanced lesions and lymph node, lung, or liver metastases (HR 9.02 (3.63−22.4) p < 0.0001; HR 3.63 (1.97−6.69), p < 0.0001; HR 2.75 (1.35−5.59), p = 0.0053; and HR 3.17 (1.00−10.0), p = 0.049, respectively). MR was defined as occurring when PD happened in one lesion plus either CR or PR occurred in another lesion simultaneously, and 12 cases were applicable. MR was significantly associated with a poorer prognosis than that of the responder group (CR or PR; HR 0.09 (0.02−0.35), p = 0.004). Patients with bone metastases benefitted less. Care may be needed to treat patients with MR as well as patients with pure PD. Further studies should be conducted in the future.

[A Case of Refractory Intermittent Hematuria that Occurred during Paclitaxel/Ramucirumab Combination Therapy for Metastatic Gastric Cancer].

A 76-year-old male patient developed right hydronephrosis due to peritoneal and retroperitoneal dissemination after surgery for gastric cancer. A ureteral stent was inserted, and systemic chemotherapy was introduced for metastatic gastric cancer. Disease progression was observed, and paclitaxel/ramucirumab combination therapy was started as the second-line treatment. After seven courses, severe gross hematuria appeared intermittently, and refractory epistaxis was observed concurrently. No hemorrhagic lesion was found in the imaging test and urethrocystoscopy. The patient received conservative treatment, such as blood transfusion, and further examination was planned. However, hematuria and epistaxis resolved spontaneously during the course of treatment. From the clinical course, it was thought to be a hemorrhagic adverse event due to ramucirumab, and the patient's treatment was therefore changed to another drug. The patient recovered without recurrence of gross hematuria.

Response to Pembrolizumab After Dose-Reduced Cisplatin Plus Gemcitabine Chemotherapy Is Inferior to That After Carboplatin Plus Gemcitabine Chemotherapy in Cisplatin-Unfit Patients With Advanced Urothelial Carcinoma.

INTRODUCTION: Response to pembrolizumab after first-line chemotherapy is vital to prolonged survival in advanced, unresectable, and/or metastatic urothelial carcinoma (aUC). However, there are sparse clinical data on host-tumor immune modification by first-line platinum-based chemotherapy. This study investigated the association between response to first-line gemcitabine plus cisplatin (GC) or carboplatin (GCarbo) chemotherapy and response to subsequent pembrolizumab treatment. PATIENTS AND METHODS: A multicenter-derived database registered 454 patients diagnosed with aUC between 2008 and 2020. Of these, 108 patients who received first-line GC or GCarbo followed by second-line or later pembrolizumab were eligible for investigation and were classified into 3 groups: 48 receiving full-dose GC, 21 receiving dose-reduced GC, and 39 receiving GCarbo. Overall survival (OS) was calculated using the Kaplan-Meier method and compared using the log-rank test. Possible factors associated with the response to pembrolizumab were evaluated using binary logistic regression methods. RESULTS: The rate of patients undergoing surgical removal of the primary organ was higher and creatinine clearance was lower in the dose-reduced GC and GCarbo groups than in the full-dose GC groups. Pembrolizumab responders had significantly better survival benefits than nonresponders. The rate of pembrolizumab responders was much higher in first-line chemotherapy responders than in first-line chemotherapy nonresponders. In contrast to the full-dose GC and GCarbo groups, the pembrolizumab responder rate was lower, and no association was observed between response to first-line chemotherapy and response to pembrolizumab in the dose-reduced GC group. CONCLUSION: Cisplatin and carboplatin may play an important role in the antitumor immune response, which could impact the outcome of subsequent pembrolizumab treatment. Given that the rate of response to pembrolizumab after dose-reduced GC chemotherapy was relatively low, this regimen is not recommended for cis-unfit patients with aUC. Further studies are required to understand the mechanisms responsible for the cross-reactivity of platinum and immune checkpoint inhibitors.

MNX1-HNF1B Axis Is Indispensable for Intraductal Papillary Mucinous Neoplasm Lineages.

BACKGROUND & AIMS: Chromatin architecture governs cell lineages by regulating the specific gene expression; however, its role in the diversity of cancer development remains unknown. Among pancreatic cancers, pancreatic ductal adenocarcinoma (PDAC) and intraductal papillary mucinous neoplasms (IPMN) with an associated invasive carcinoma (IPMNinv) arise from 2 distinct precursors, and their fundamental differences remain obscure. Here, we aimed to assess the difference of chromatin architecture regulating the transcriptional signatures or biological features in pancreatic cancers. METHODS: We established 28 human organoids from distinct subtypes of pancreatic tumors, including IPMN, IPMNinv, and PDAC. We performed exome sequencing (seq), RNA-seq, assay for transposase-accessible chromatin-seq, chromatin immunoprecipitation-seq, high-throughput chromosome conformation capture, and phenotypic analyses with short hairpin RNA or clustered regularly interspaced short palindromic repeats interference. RESULTS: Established organoids successfully reproduced the histology of primary tumors. IPMN and IPMNinv organoids harbored GNAS, RNF43, or KLF4 mutations and showed the distinct expression profiles compared with PDAC. Chromatin accessibility profiles revealed the gain of stomach-specific open regions in IPMN and the pattern of diverse gastrointestinal tissues in IPMNinv. In contrast, PDAC presented an impressive loss of accessible regions compared with normal pancreatic ducts. Transcription factor footprint analysis and functional assays identified that MNX1 and HNF1B were biologically indispensable for IPMN lineages. The upregulation of MNX1 was specifically marked in the human IPMN lineage tissues. The MNX1-HNF1B axis governed a set of genes, including MYC, SOX9, and OLFM4, which are known to be essential for gastrointestinal stem cells. High-throughput chromosome conformation capture analysis suggested the HNF1B target genes to be 3-dimensionally connected in the genome of IPMNinv. CONCLUSIONS: Our organoid analyses identified the MNX1-HNF1B axis to be biologically significant in IPMN lineages.

Trends in risk classification at diagnosis and choice of primary therapy for prostate cancer: An analysis of 10 839 patients from the Nara Urological Research and Treatment Group registry between 2004 and 2015.

OBJECTIVE: To evaluate trends in risk classification at diagnosis and choice of primary therapy in patients diagnosed with prostate cancer. METHODS: This retrospective study included 10 839 patients who were newly diagnosed with prostate cancer between 2004 and 2015 at 23 Japanese institutions. Risk classification and primary therapies between 2004 and 2015 were evaluated. The trends in risk classification and primary therapy were evaluated using chi-squared tests for trend during four periods (2004-2006; 2007-2009; 2010-2012; and 2013-2015). Binary logistic analysis was used to evaluate the extent to which factors such as age, risk classification, and institution influenced primary therapy choice in the 2013-2015 cohort. RESULTS: The number of patients with very-low or low-risk classification (P < 0.001) and metastasis (P = 0.04) decreased and the number with intermediate-risk classification (P < 0.001) increased during the four periods. A tendency to choose radical prostatectomy as primary therapy for prostate cancer was not observed during the four periods (P = 0.90). The number of patients who chose radiation therapy (P < 0.001) and active surveillance/watchful waiting (P < 0.001) as primary therapies increased during the four periods and the number of patients who chose androgen deprivation therapy (P < 0.001) decreased. Age, institution, and risk classification significantly influenced primary therapy choice. CONCLUSIONS: We have shown the trends in risk classification of prostate cancer and primary therapy choices between 2004 and 2015 in Japan. Age, institution, and risk classification significantly influenced the decision on primary therapy for prostate cancer.

Longevity Regulation by Proline Oxidation in Yeast.

Proline is a pivotal and multifunctional amino acid that is used not only as a nitrogen source but also as a stress protectant and energy source. Therefore, proline metabolism is known to be important in maintaining cellular homeostasis. Here, we discovered that proline oxidation, catalyzed by the proline oxidase Put1, a mitochondrial flavin-dependent enzyme converting proline into ∆1-pyrroline-5-carboxylate, controls the chronological lifespan of the yeast Saccharomyces cerevisiae. Intriguingly, the yeast strain with PUT1 deletion showed a reduced chronological lifespan compared with the wild-type strain. The addition of proline to the culture medium significantly increased the longevity of wild-type cells but not that of PUT1-deleted cells. We next found that induction of the transcriptional factor Put3-dependent PUT1 and degradation of proline occur during the aging of yeast cells. Additionally, the lifespan of the PUT3-deleted strain, which is deficient in PUT1 induction, was shorter than that of the wild-type strain. More importantly, the oxidation of proline by Put1 helped maintain the mitochondrial membrane potential and ATP production through the aging period. These results indicate that mitochondrial energy metabolism is maintained through oxidative degradation of proline and that this process is important in regulating the longevity of yeast cells.

Finding long tandem repeats in long noisy reads.

MOTIVATION: Long tandem repeat expansions of more than 1000 nt have been suggested to be associated with diseases, but remain largely unexplored in individual human genomes because read lengths have been too short. However, new long-read sequencing technologies can produce single reads of 10 000 nt or more that can span such repeat expansions, although these long reads have high error rates, of 10-20%, which complicates the detection of repetitive elements. Moreover, most traditional algorithms for finding tandem repeats are designed to find short tandem repeats (<1000 nt) and cannot effectively handle the high error rate of long reads in a reasonable amount of time. RESULTS: Here, we report an efficient algorithm for solving this problem that takes advantage of the length of the repeat. Namely, a long tandem repeat has hundreds or thousands of approximate copies of the repeated unit, so despite the error rate, many short k-mers will be error-free in many copies of the unit. We exploited this characteristic to develop a method for first estimating regions that could contain a tandem repeat, by analyzing the k-mer frequency distributions of fixed-size windows across the target read, followed by an algorithm that assembles the k-mers of a putative region into the consensus repeat unit by greedily traversing a de Bruijn graph. Experimental results indicated that the proposed algorithm largely outperformed Tandem Repeats Finder, a widely used program for finding tandem repeats, in terms of sensitivity. AVAILABILITY AND IMPLEMENTATION: https://github.com/morisUtokyo/mTR.

A new diagnostic indication device of a biomarker growth differentiation factor 15 for mitochondrial diseases: From laboratory to automated inspection.

Mitochondrial diseases (MDs) are occasionally difficult to diagnose. Growth differentiation factor 15 (GDF15) has been reported as a biomarker useful for not only diagnosing MDs, but also evaluating disease severity and therapeutic efficacy. To enable the measurement of serum GDF15 concentrations at medical institutions, we developed a new latex-enhanced turbidimetric immunoassay (LTIA) as an automated diagnostic indication test for MDs. We also examined the equivalency of specificity and sensitivity in measuring serum GDF15 concentrations between a commercially available enzyme-linked immunosorbent assay (ELISA) kit and a novel LTIA device in patients with MDs, disease controls, and healthy controls. A clinical performance study used a newly developed LTIA device and an existing ELISA kit to measure the concentrations of GDF15 in 35 MD patients, 111 disease controls, and 86 healthy controls. The median (first quartile-third quartile) of serum GDF15 concentrations measured with the LTIA device was significantly higher (P < .001) in MD patients (1389.0 U/mL [869.5-1776.0 U/mL]) than in healthy controls (380.5 U/mL [330.2-471.8 U/mL]); the interquartile ranges did not overlap between MD patients and healthy controls. The areas under the curve in disease and healthy controls were 0.812 (95% confidence interval [CI]: 0.734-0.886) and 0.951 (95% CI: 0.910-0.992), respectively. The automated, high-throughput technology-based LTIA device has definite advantages over the ELISA kit in shorter processing time and lower estimated cost per sample measurement. The LTIA device of GDF15 may be a sufficiently reliable, frontline, diagnostic indicator of individuals with suspected MDs in the general population.

Trends in treatment outcomes of hydrocele in Japanese children: A single-institute experience.

OBJECTIVES: To investigate trends in treatment outcomes of surgical intervention versus observation for pediatric hydrocele. METHODS: This retrospective study included 175 patients diagnosed with hydrocele at our institution. Hydrocele was diagnosed based on medical history, physical examination and ultrasonography findings. The treatment for these patients was divided into two options: surgical intervention or careful follow up; the outcomes were investigated. RESULTS: The median age at diagnosis was 3 months, and a total of 11 patients (6%) were premature at birth. Hydrocele was diagnosed on the right side, the left side and bilaterally in 106 (61%), 46 (26%) and 23 (13%) patients, respectively. A total of 136 patients showed spontaneous improvement at the median 7 months after diagnosis, and 54 patients underwent surgical intervention. The rate of spontaneous resolution deceased with age, but spontaneous resolution was observed in patients aged >2 years. CONCLUSIONS: Our findings suggest that spontaneous resolution can be observed in patients aged >2 years, and surgical intervention can be carried out effectively and safely. Infant hydrocele should be followed up carefully for at least 1 year without surgical intervention since diagnosis. Investigation of the optimal timing of and appropriate reason for surgical intervention can lead to better management and outcomes in patients with hydrocele. Further research is warranted to support the current clinical practice.

Clinical Impact of Sarcopenia and Inflammatory/Nutritional Markers in Patients with Unresectable Metastatic Urothelial Carcinoma Treated with Pembrolizumab.

Sarcopenia is a muscle loss syndrome known as a risk factor of various carcinomas. The impact of sarcopenia and sarcopenia-related inflammatory/nutritional markers in metastatic urothelial carcinoma (mUC) treated with pembrolizumab was unknown, so this retrospective study of 27 patients was performed. Psoas muscle mass index (PMI) was calculated by bilateral psoas major muscle area at the L3 with computed tomography. The cut-off PMI value for sarcopenia was defined as ≤6.36 cm2/m2 for men and ≤3.92 cm2/m2 for women. Neutrophil-to-lymphocyte ratio (NLR) ≥ 4.0 and sarcopenia correlated with significantly shorter progression-free survival (PFS) (hazard ratio (HR) 3.81, p = 0.020; and HR 2.99, p = 0.027, respectively). Multivariate analyses identified NLR ≥ 4.0 and sarcopenia as independent predictors for PFS (HR 2.89, p = 0.025; and HR 2.79, p = 0.030, respectively). Prognostic nutrition index < 45, NLR ≥ 4.0 and sarcopenia were correlated with significantly worse for overall survival (OS) (HR 3.44, p = 0.046; HR 4.26, p = 0.024; and HR 3.92, p = 0.012, respectively). Multivariate analyses identified sarcopenia as an independent predictor for OS (HR 4.00, p = 0.026). Furthermore, a decrease in PMI ≥ 5% in a month was an independent predictor of PFS and OS (HR 12.8, p = 0.008; and HR 6.21, p = 0.036, respectively). Evaluation of sarcopenia and inflammatory/nutritional markers may help in the management of mUC with pembrolizumab.

Clinical Significance of Tumor Size, Pathological Invasion Sites Including Urinary Collecting System and Clinically Detected Renal Vein Thrombus as Predictors for Recurrence in pT3a Localized Renal Cell Carcinoma.

The recent eighth tumor-node-metastasis (TMN) staging system classifies renal cell carcinoma (RCC) with perirenal fat invasion (PFI), renal sinus fat invasion (SFI), or renal vein invasion (RVI) as stage pT3a. However, limited data are available on whether these sites have similar prognostic value or recurrence rate. We investigated the recurrence rate based on tumor size, pathological invasion sites including urinary collecting system invasion (UCSI), and clinically detected renal vein thrombus (cd-RVT) with pT3aN0M0 RCC. We retrospectively reviewed 91 patients with pT3aN0M0 RCC who underwent surgical treatment. Patients with tumor size > 7 cm, UCSI, three invasive sites (PFI + SFI + RVI), and cd-RVT showed a significant correlation with high recurrence rates (hazard ration (HR) 2.98, p = 0.013; HR 8.86, p < 0.0001; HR 14.28, p = 0.0008; and HR 4.08, p = 0.0074, respectively). In the multivariate analysis, tumor size of > 7 cm, the presence of UCSI, and cd-RVT were the independent predictors of recurrence (HR 3.39, p = 0.043, HR 7.31, p = 0.01, HR 5.06, p = 0.018, respectively). In pT3a RCC, tumor size (7 cm cut-off), UCSI, and cd-RVT may help to provide an early diagnosis of recurrence.

Unexpected presentation and surgical salvage of transplant renal artery dissection caused by vascular clamping: a case report.

BACKGROUND: Transplant renal artery dissection is a rare and serious event that can cause allograft dysfunction and activation of the renin-mediated renovascular hypertension. Most cases are induced by percutaneous transluminal angioplasty, arteriosclerotic disease, or fibromuscular dysplasia. We observed a case of transplant renal artery dissection induced by unusual causes during kidney transplantation. CASE PRESENTATION: A 35-year-old woman, whose mother donated a kidney to her, underwent ABO-incompatible living kidney transplantation. The allograft had one renal artery and vein that were anastomosed to the internal iliac artery and external iliac vein, respectively. Although careful handling was performed in all procedures including vascular clamping, Doppler ultrasonography (US) immediately after reperfusion showed an increase in the systolic blood velocity and urine output was not observed. Arterial anastomotic stenosis was suspected, but upon exploration, a renal artery dissection was detected in the middle portion of the donor artery. The part of the transplant renal artery was resected, and cold reflux was started again. At the resected part of transplant renal artery, dissection was identified. After re-anastomosis, Doppler US revealed that the blood flow of the renal artery was adequate without an increase in the systolic blood velocity, and sufficient blood flow was observed throughout the allograft. Urine output was also observed as soon as blood flow returned, and serum creatinine level decreased to 0.95 mg/dL after surgery. The cause of injury might have been vascular clamping in order to drain the air and check bleeding at the anastomosis. CONCLUSIONS: Our case reaffirmed that careful handling is needed in all procedures, including donor nephrectomy, cannulation for transplant perfusion, vascular clamping, and anastomosis, even without any evidence of arteriosclerosis. Kidney transplant recipients commonly have atherosclerosis and hypertension, which are risk factors for arterial dissection. Early diagnosis and intervention can lead to the prevention of allograft dysfunction. Therefore, close monitoring of allograft blood flow by Doppler US during surgery should be considered.

Appropriate Number of Docetaxel Cycles in Castration-Resistant Prostate Cancer Patients Considering Peripheral Neuropathy and Oncological Control.

BACKGROUND: The number of cycles of docetaxel required for castration-resistant prostate cancer (CRPC) is unclear. This study estimated peripheral neuropathy (PN) incidence and the optimal number of treatment cycles in patients receiving docetaxel for CRPC. PATIENTS AND METHODS: The study retrospectively reviewed 82 patients receiving docetaxel for CRPC at an institution between January 2005 and January 2017. Docetaxel (70 or 75 mg/m2) was administered every 3 weeks, and prednisone 5 mg or dexamethasone 0.5 mg was administered twice a day. RESULTS: PN (grade ≥2) was noted in 32 (39.0%) patients. The median cumulative dose of docetaxel associated with PN was 675 mg/m2. No factor significantly predicted the occurrence of PN. The prostate-specific antigen progression rate, prostate cancer-specific survival, and overall survival were significantly better with ≥8 cycles of docetaxel than with <8 cycles (p < 0.05). CONCLUSION: The incidence of PN is high, and 8 treatment cycles are optimal for patients receiving docetaxel for CRPC.

Clinical Significance of Postoperative Nutritional Status as a Prognostic Factor in Kidney Transplant Recipients.

BACKGROUND: Despite advancements in the management of kidney transplantation (KT), kidney transplant recipients (KTRs) have a higher risk of mortality than the age-matched general population. Improvement of long-term graft and patient survival is a significant issue. Therefore we investigated the effects of postoperative nutritional status on graft and patient survival and explored the predictive factors involved in nutritional status. METHODS: Our retrospective study included 118 KTRs who underwent KT at our hospital. Clinical and laboratory data were obtained from medical charts. The prognostic nutritional index (PNI) was used to assess nutritional status. Changes in nutritional status after KT were monitored and the effect of nutritional status on graft and patient survival was investigated. The variables involved in nutritional status were also explored. RESULTS: The KTRs in this cohort comprised 66 men and 52 women with a median age of 47 years at KT. There were 16, 32, and 22 cases of cadaveric, preemptive, and ABO-incompatible KTs, respectively. Postoperative PNI gradually improved and was stable from 6 months after KT. Although graft survival was regulated by ABO-compatibility, independent predictors for patient survival were history of dialysis, PNI, and serum-corrected calcium levels. Preemptive KT and inflammatory status contributed to PNI. CONCLUSIONS: Nutritional status of KTRs improved over time after KT and could contribute to patient survival. Optimal nutritional educational programs and interventions can lead to better outcomes in KTRs. Further studies are needed to validate our results and develop appropriate nutritional educational programs, interventions, and exercise programs.