Transurethral bipolar enucleation using a TUEB loop for large benign prostatic hyperplasia: a retrospective cohort study.

PURPOSE: We aimed to assess the efficacy and safety of transurethral enucleation with bipolar system (TUEB) regardless of the prostate size using a specially developed TUEB loop. METHODS: A total of 251 patients who underwent TUEB were categorized into two groups depending on the prostate volume (PV): small-PV (≤ 80 mL) group, 133 patients; large-PV (> 80 mL) group, 118 patients. Comparisons of background information and treatment outcomes were performed between the groups. RESULTS: Operation (113.5 vs 166.4 min), enucleation (49.4 vs 68.1 min), and morcellation (11.4 vs 26.4 min) times were longer and hemoglobin decreased significantly (0.84 vs 1.30 g/dL) in the large PV group. However, the enucleation efficiency (enucleated weight per enucleation time; 0.71 vs 0.97 g/min) and prostate-specific antigen reduction rate (24.6% vs 16.1%) were significantly better in the large-PV group, with similar enucleation rates (enucleated weight per transitional zone volume; 82% vs 81%). The International Prostate Symptom Score, uroflowmetry maximum flow rate, and post-void residual urine in both groups improved at 3, 6, and 12 months compared with baseline. No patient underwent blood transfusion. There were no differences in the frequency of postoperative clot retention, urethral stricture, or stress incontinence at 3, 6, and 12 months. CONCLUSION: TUEB using a TUEB loop resulted in high levels of satisfaction regarding the enucleation efficiency, efficacy, and safety for BPH surgery regardless of the prostate size. TUEB should be considered one of the best treatment options for large BPH that is uncontrollable with medication.

Current clinical perspective of urological oncology in the adolescent and young adult generation.

Among adolescents and young adults, hematological tumors are the most common malignancies in younger patients; however, solid tumors also increase with advancing age. The pathogenesis of some of these tumors differs from that of tumors which develop in children, or middle-aged and older adults, and special care should be taken in their treatment and management. A treatment plan that takes into consideration future fertility is necessary for testicular tumors, and an educational campaign to encourage early detection is also essential. The treatment of adolescents with advanced testicular tumors should resemble therapeutic approaches for young adults and not a pediatric regimen. Adrenal tumors often develop as part of familiar hereditary syndrome. Therefore, taking the personal and family history is very important, and genetic counseling should be also recommended. In renal tumors, the incidence of translocation renal cell carcinomas is higher. Complete resection is the only promising method for long-term prognosis because of no established treatment for translocation renal cell carcinomas with distant metastasis. Bladder tumors are often detected by symptoms of gross hematuria and are found at a relatively early stage. Along with renal tumors, oncological evaluation including cystoscopy is also considered essential for gross hematuria. Wilms tumors and rhabdomyosarcomas could be managed in accordance with pediatric protocols to improve the treatment outcomes. The dedicated cancer survivorship care for adolescents and young adults could be also indispensable to conquer cancer and maintain a better quality of life.

Single-shot compressive hyperspectral imaging with dispersed and undispersed light using a generally available grating.

Commercially available hyperspectral cameras are useful for remote sensing, but in most cases snapshot imaging is difficult due to the need for scanning. The coded aperture snapshot spectral imager (CASSI) has been proposed to simultaneously acquire a target scene's spatial and spectral dimensional data, employing a refractive prism as a disperser. This paper proposes a CASSI-based technique using a generally available diffraction grating of a Ronchi ruling and blazed grating and its improvement using the undispersed zeroth-order light. The feasibility and performance of the proposed technique are experimentally validated, and the grating parameters are identified.

Landscape of prognostic signatures and immunogenomics of the AXL/GAS6 axis in renal cell carcinoma.

BACKGROUND: Cabozantinib is an oral tyrosine kinase inhibitor in renal cell carcinoma (RCC), whose targets include oncogenic AXL and unique ligand GAS6. Critical gaps in basic knowledge need to be addressed to devise an exclusive biomarker and candidate when targeting the AXL/GAS6 axis. METHODS: To clarify the effects of the AXL/GAS6 axis on RCC, we herein performed a large-scale immunogenomic analysis and single-cell counts including various metastatic organs and histological subtypes of RCC. We further applied genome-wide mutation analyses and methylation arrays. RESULTS: Varying patterns of AXL and GAS6 expression were observed throughout primary RCC tumours and metastases. Scoring individual AXL/GAS6 levels in the tumour centre and invasive margin, namely, the AXL/GAS6 score, showed a good ability to predict the prognosis of clear cell RCC. Metastasis- and histological subtype-specific differences in the AXL/GAS6 score existed since lung metastasis and the papillary subtype were weakly related to the AXL/GAS6 axis. Cell-by-cell immunohistological assessments clarified an immunosuppressive environment in tumours with high AXL/GAS6 scores. Genomic alterations in the PI3K-mTOR pathway and DNA methylation profiling revealed distinct differences with the AXL/GAS6 score in ccRCC. CONCLUSION: The AXL/GAS6 scoring system could predict the outcome of prognosis and work as a robust biomarker for the immunogenomic state in RCC.

Efficacy, safety, and pharmacokinetics of oral valganciclovir in patients with congenital cytomegalovirus infection.

OBJECTIVES: Valganciclovir (VGCV) has been shown to improve sensorineural hearing loss (SNHL) and neurological outcomes in patients with neonatal symptomatic congenital cytomegalovirus (cCMV) infection. However, reports on the pharmacokinetics, efficacy and safety of oral VGCV are limited. The aim of this study is to evaluate the pharmacokinetics of VGCV for use in the treatment of cCMV. METHODS: This was a single-center, retrospective observational study conducted at Saitama Children's Medical Center in Japan between 2012 and 2017. CMV DNA copy number, maximum plasma VGCV concentration (Cmax), and adverse events (ADEs) during treatment were evaluated. RESULTS: A total of 26 patients with cCMV who received VGCV were included in this study. The median age at VGCV initiation was 9.5 months (range 0-46). Twenty-one patients (81%) had SNHL at baseline. Of these, five patients (19%) presented with improved SNHL, and none experienced worsened SNHL during treatment. The mean VGCV Cmax was 3.5 µg/mL (range 2-5.3), with no significant variation among individual values, and the values were maintained during treatment. Furthermore, there were no correlations between the Cmax values and age, sex, SNHL improvement or ADEs. Neutropenia (<1000/mm3) was observed in six patients (23%); however, no serious ADEs occurred. CONCLUSIONS: VGCV prevented the progression of SNHL without serious ADEs due to its stable pharmacokinetics. This study provides safety and tolerability of VGCV for the treatment of cCMV patients.

Safety and efficacy of plasma exchange via direct femoral vein puncture in autoimmune blistering diseases.

Plasma exchange (PE) is performed for patients with autoimmune blistering diseases by using multiple vascular access routes. We retrospectively examined the safety and the efficacy of PE using direct femoral vein puncture (FVP) technique, by comparing with that using double-lumen catheter (DLC). The troubles related to vascular route, such as catheter occlusion, insufficient blood flow and hematoma, were not different between the FVP group (4.6%) and the DLC group (6.7%), whereas access-related infections occurred more frequently in the DLC group (6.7%) than the FVP group (0.4%). Regarding the efficacy, the removal rate of autoantibodies in PE using the FVP technique was similar or lower, as compared with that using the DLC. These results suggest that PE with the FVP technique is able to be performed safely in patients with autoimmune blistering diseases, although the removal of autoantibodies is not superior to that using the DLC.

Small intestinal perforation due to a huge gastrointestinal stromal tumor in a kidney transplant recipient: a case report and literature review.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) in transplant recipients are very rare and only a handful of cases have been reported to date. Here we present the first known case of a huge GIST in a kidney transplant recipient with perforation of small intestine. CASE PRESENTATION: A 64-year-old male presented at our hospital with right colic pain; he had received an ABO incompatible kidney transplant 6 years earlier and was treated with cyclosporine, mycophenolate mofetil, and methylprednisolone. Radiological evaluation revealed a huge (11 cm in diameter) solitary tumor at the small intestine without distant metastasis. The small intestinal wall at the tumor location was perforated one week after diagnosis and the patient underwent emergency surgery. The pathological findings were compatible with GIST and the tumor consisted of spindle cells with positive staining for KIT, CD34, and DOG1 and negative or weak staining for desmin and S-100 protein. A mutation in exon 11 of the c-kit gene was also detected. Cyclosporine was withdrawn and imatinib mesylate (400 mg daily) was introduced. However, thereafter, we needed to decrease the dose at 300 mg daily due to severe hyponatremia. Reduced imatinib treatment was well tolerated and recurrence was not observed for 18 months after surgery. CONCLUSIONS: The occurrence of GISTs in transplant patients is rare, and huge GISTs should be resected immediately after diagnosis because gastrointestinal tract at the tumor site could be perforated. Imatinib treatment is feasible in transplant recipients under immunosuppression, although immunosuppressive drugs metabolized by CYP3A4 should be used at a reduced dosage or withdrawn.

Pre-donation BMI and preserved kidney volume can predict the cohort with unfavorable renal functional compensation at 1-year after kidney donation.

BACKGROUND: The magnitude of renal function recovery after kidney donation differs in donors with a heterogeneous background. Preoperative assessment of candidates with potentially unfavorable renal functional compensation is critical when baseline kidney function is marginal. We explored the significance of preserved kidney volume (PKV) and known preoperative risk factors for the prediction of unfavorable renal function compensation. METHODS: We enrolled 101 living donors for whom a 1-mm sliced enhanced computed tomography scan was performed preoperatively and clinical data could be collected up to 1 year after donation. The donors whose estimated glomerular filtration rate (eGFR) at 1 year after donation was 70% or higher of baseline eGFR were assigned to the "favorable renal compensation" group and the others to the "unfavorable renal compensation" group. RESULTS: Age, sex, and preoperative serum uric acid level were not significant predictors for "unfavorable renal compensation." Multivariable logistic regression analysis revealed that body mass index (BMI) and body surface area (BSA)-adjusted PKV were independent preoperative risk factors for "unfavorable renal compensation" (adjusted odds ratio, 1.342 and 0.929, respectively). Hypertension and preoperative eGFR were not independent predictors when adjusted with BMI and BSA-adjusted PKV. Receiver operative characteristic analysis revealed that the predictive equation with the two independent predictors yielded a good accuracy to detect donor candidates with unfavorable renal functional compensation (area under the curve = 0.803), and the optimal cut-off values were identified as 23.4 kg/m2 for BMI and 107.3 cm3/m2 for BSA-adjusted PKV. CONCLUSIONS: BMI and BSA-adjusted PKV may be useful to select candidates with potentially unfavorable renal function compensation before kidney donation.

Ethnic derivation of the Ainu inferred from ancient mitochondrial DNA data.

OBJECTIVES: The Ainu, the indigenous people living on the northernmost island of Japan, Hokkaido, have long been a focus of anthropological interest because of their cultural, linguistic, and physical identity. A major problem with genetic studies on the Ainu is that the previously published data stemmed almost exclusively from only 51 modern-day individuals living in Biratori Town, central Hokkaido. To clarify the actual genetic characteristics of the Ainu, individuals who are less influenced by mainland Japanese, who started large-scale immigration into Hokkaido about 150 years ago, should be examined. Moreover, the samples should be collected from all over Hokkaido. MATERIALS AND METHODS: Mitochondrial DNA haplogroups of 94 Ainu individuals from the Edo era were successfully determined by analyzing haplogroup-defining polymorphisms in the hypervariable and coding regions. Thereafter, their frequencies were compared to those of other populations. RESULTS: Our findings indicate that the Ainu still retain the matrilineage of the Hokkaido Jomon people. However, the Siberian influence on this population is far greater than previously recognized. Moreover, the influence of mainland Japanese is evident, especially in the southwestern part of Hokkaido that is adjacent to Honshu, the main island of Japan. DISCUSSION: Our results suggest that the Ainu were formed from the Hokkaido Jomon people, but subsequently underwent considerable admixture with adjacent populations. The present study strongly recommends revision of the widely accepted dual-structure model for the population history of the Japanese, in which the Ainu are assumed to be the direct descendants of the Jomon people.

Relationship between the skeletal maturation of the distal attachment of the patellar tendon and physical features in preadolescent male football players.

PURPOSE: The aim of this study was to compare ultrasonography stages of the tibial tuberosity development and physical features. METHODS: This study examined 200 knees in 100 male football players aged 10-15 years. Tibial tuberosity development on ultrasonography was divided into 3 stages: Sonolucent stage (stage S), Individual stage (stage I), and Connective stage (stage C). Age, height, quadriceps and hamstring muscle tightness, and muscle strength in knee extension and flexion were determined. These findings were compared with the respective stages of development. RESULTS: The tibial tuberosity was stage S in 27 knees, stage I in 69 knees, and stage C in 104 knees, with right and left sides at the same stage in 95 %. Average age and height significantly increased with advancing tibial tuberosity development. Quadriceps tightness increased with tibial tuberosity development. Hamstring tightness decreased with development. The strength of both knee extension and flexion increased with advancing development, with a greater change seen in knee extension, hamstring/quadriceps ratio: stage C, 0.74; stage A, 0.64; stage E, 0.53. CONCLUSIONS: Osgood-Schlatter pathogenesis reportedly involves increased quadriceps tightness with rapidly increasing femoral length during tibial tuberosity development. In this study, it was confirmed that quadriceps tightness increased, yet hamstring tightness decreased, suggesting that quadriceps tightness is not due to femoral length alone. Other factors, including muscle strength, may be involved. The study shows that thigh muscle tightness and thigh muscle performance change with the skeletal maturation of the distal attachment of the patellar tendon. These results add new information to the pathogenesis of Osgood-Schlatter disease.

Decreased activities of daily living is a strong risk factor for liver injury by anti-tuberculosis drugs.

BACKGROUND AND OBJECTIVE: We evaluated the association between activities of daily living and drug-induced liver injury by anti-tuberculosis drugs. METHODS: This retrospective cohort study included adult inpatients with newly diagnosed smear-positive lung tuberculosis treated with standard regimen in two hospitals. (n = 346; 63.6 ± 20.3 years old; 106 (30.6%) females). Activities of daily living was divided into 'independent' (Barthel Index (BI) 80-100, 60.4%) and 'decreased' (BI 0-75, 39.6%) categories. Liver injury was defined as the withdrawal or change of treatment regimen on the basis of the following criteria: serum transaminase concentrations were more than three times the upper limit of normal range with jaundice and/or hepatitis symptoms, or more than five times the upper limit of the normal range. RESULTS: Compared with 'independent' patients, patients with 'decreased' activities of daily living had odds ratios for liver injury of 4.2 (P < 0.001) in univariate analysis and 5.7 (P = 0.002) in logistic regression analysis after adjusting for other risk factors. CONCLUSIONS: Decreased activity of daily living is a strong risk factor for liver injury among adult inpatients with newly diagnosed smear-positive lung tuberculosis treated using a standard regimen.

Outcomes and failure factors in surgical treatment for osteochondritis dissecans of the capitellum.

BACKGROUND: Osteochondritis dissecans (OCD) of the capitellum is an intra-articular lesion and one of the leading causes of permanent elbow disability. The treatment of advanced capitellar OCD remains challenging because of the limited potential of the articular cartilage for self-repair. The purpose of this study was to investigate the outcome of surgical treatment for OCD of the capitellum. METHODS: From 2000 to 2010, 32 male patients who had advanced lesions of capitellar OCD were treated operatively. The mean age of the patients was 14.4 years at the time of surgery. Twenty-nine patients played baseball and 3 played other sports. The lesions were of the centralized type in 9 patients, the lateral type in 4 patients, and the widespread type in 19 patients. For the surgical procedure, osteochondral peg fixation was selected for 13 patients and osteochondral autograft transplantation for 19 patients. Clinical outcome was measured with the elbow rating system including range of motion, and the number of patients who returned to active sports participation within 1 year after surgery was determined. RESULTS: The mean total arc of elbow motion increased from 123±17 degrees preoperatively to 132±14 degrees postoperatively. The mean clinical score improved significantly from 133±24 to 177±27. Within the first year after surgery, 81.3% of the patients returned to active sports playing. However, 4 of 8 patients (50%) in which osteochondral peg fixation was performed for lesions of the lateral widespread type required reoperation. CONCLUSIONS: Our results indicate that osteochondral peg fixation and osteochondral autograft transplantation may improve elbow rating score, and may facilitate a return to active sports participation. However, osteochondral peg fixation may be insufficient for lesions of the widespread type because of their poor stability. The large lateral condyle lesions had a worse outcome, and future studies will need to develop improved treatment for these defects. LEVEL OF EVIDENCE: Level IV (case series).

[Comparison of drug-induced hepatitis occurring in elderly and younger patients during anti-tuberculosis treatment with a regimen including pyrazinamide].

BACKGROUND: In Japan, tuberculosis (TB) patients aged over 80 years are usually treated with a regimen not including pyrazinamide (PZA) because of the risk of drug-induced hepatitis. PURPOSES: The purpose of this study was to investigate the occurrence of drug-induced hepatitis in TB patients over 80 years of age, who are treated with a regimen including PZA, and compare the findings with those of younger patients. [Methods] Thirty-six patients with pulmonary tuberculosis, who were admitted to Yokohama City University Hospital between June 2011 and March 2012 were included. They were treated with isoniazid, rifampicin, ethambutol, and PZA and had their liver function assessed once a week for 2 months. RESULTS: Hepatitis occurred in 4 of 28 (14.3%) patients aged under 80 years and in 1 of 8 (12.5%) patients aged over 80 years. CONCLUSION: There was no difference in the frequency of drug-induced hepatitis between patients aged under and over 80 years. We conclude that elderly patients aged over 80 years should be treated with a short course regimen that includes PZA.

Functional improvements in ß-conglycinin by edible bioconjugation with carboxymethyl dextran.

ß-Conglycinin was conjugated with carboxymethyl dextran (CMD) by the Maillard reaction to improve its function. The ß-conglycinin-CMD conjugate was purified by dialysis. Conjugation was confirmed by SDS-PAGE with CBB and PAS staining. Composition of the ß-conglycinin-CMD was ß-conglycinin:CMD = 1:2.7 (molar ratio) which was confirmed by BCA method and phenol sulfuric acid method. Solubility of ß-conglycinin in the range of pH 2.0-7.0 was much improved by conjugation with CMD. Emulsifying property of ß-conglycinin at pH 7 and in presence of salt was improved by conjugation with CMD. Immunogenicity of ß-conglycinin was reduced by conjugation with CMD. Conjugation method performed in this study was considered to be valuable in that it can be used in food processing.

Efficacy and Safety of Dietary Undenatured Type II Collagen on Joint and Motor Function in Healthy Volunteers: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study.

Prevalence of osteoarthritis (OA) is increasing alarmingly worldwide. Slowing down the progression of OA and diverse locomotive organ disorders is gaining interest in improving the quality of life (QOL) and extending healthy life-span. In a pilot study, intake of a small amount of undenatured type II collagen exhibited suppression of damage to the articular cartilage via oral immune tolerance. It also demonstrated improvement of knee and joint flexibility and mobility with continued intake of undenatured type II collagen (NEXT-II®) derived from chicken sternum cartilage. This randomized, double-blind, placebo-controlled, parallel-group clinical investigation (RCT) evaluated the efficacy and safety of 12 weeks of regular intake of NEXT-II® on joint and motor function in healthy Japanese male and female participants (aged 20 to <75 years).Sixty-four participants were randomized to receive either NEXT-II® (undenatured type II collagen 3.2 mg/d) or placebo over a period of 12 consecutive weeks. Efficacy on joint and motor functions were evaluated measuring knee passive range of motion as the primary outcome; the Japan Knee Osteoarthritis Measure (JKOM), Visual Analog Scale (VAS) for knee discomfort, and motor functions (10-meter walking and stair-climbing test) as the secondary outcomes; and Japan Low back pain Evaluation Questionnaire (JLEQ) and VAS for lower back discomfort as the exploratory outcomes.Fifty-eight participants (placebo = 28; NEXT-II® group = 30) completed the study. In the assessment of knee passive range of motion, significant improvements in "flexion" and "flexible angle (range)" were observed in the NEXT-II® group at 4, 8, and 12 weeks of treatment. NEXT-II® induced significant improvements in JKOM, VAS for knee and lower back discomfort, 10-meter walking test, stair-climbing test, and JLEQ.Results demonstrate that undenatured type II collagen is safe and efficacious in improving knee flexibility and mobility, reducing knee and lower back pain, and enhancing motor function.

Effect of Dietary Pyrroloquinoline Quinone Disodium Salt on Cognitive Function in Healthy Volunteers: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study.

BACKGROUND: Cognitive dysfunctions are increasing alarmingly around the world, and researchers are exploring preventive measures for improving brain performance. Pyrroloquinoline quinone (PQQ), a naturally occurring coenzyme in foods, exhibits potent antioxidant activity, and improves diverse functions which include mitochondrial activation, growth, repair, protection of nerve cells by increased expression of nerve growth factor (NGF) and NGF receptors; and suppression of fibril formation and aggregation of amyloid ß. OBJECTIVE: This randomized, double-blind, placebo-controlled, parallel-group clinical investigation (RCT) evaluated the efficacy and safety of PQQ disodium salt powder (mnemoPQQ®) for improved cognitive function after 12 weeks of supplementation in healthy Japanese male and female (age 40 to <80 Y). METHODS: 64 healthy subjects were randomly assigned to receive either mnemoPQQ® (PQQ disodium salt: 21.5 mg/day) or a placebo over a period of 12 weeks. The efficacy of mnemoPQQ® on cognitive performance (memory, attention, judgment, and cognitive flexibility) was examined using Cognitrax as the primary outcome (primary endpoint), and forgetfulness questionnaire (DECO: Deterioration Cognitive Observee) and Mini-Mental State Examination-Japanese (MMSE-J) as the secondary outcome (secondary endpoint). RESULTS: A total of 58 subjects (placebo = 31; Age = 70.91 ± 3.06 Y; mnemoPQQ® group = 27; Age = 72.10 ± 3.77 Y) completed the study over a period of 12 weeks of supplementation. Significant improvements were observed on the Cognitrax's cognitive function domain score on "composite memory", "verbal memory", "reaction time", "complex attention", "cognitive flexibility", "executive function", and "motor speed" in the mnemoPQQ® group as compared to the placebo group. The DECO and the MMSE-J scores were also significantly improved in the mnemoPQQ® group. No adverse events were observed. CONCLUSIONS: Study demonstrates that supplementation of PQQ disodium salt is useful in improving memory, attention, judgment, and cognitive function, in middle-aged to elderly population, who feel they have become more forgetful because of aging.

Unique characteristics of tertiary lymphoid structures in kidney clear cell carcinoma: prognostic outcome and comparison with bladder cancer.

BACKGROUND: The aims of this study were (1) to clarify the impact of tertiary lymphoid structure (TLS) status on the outcome and immunogenomic profile of human clear cell renal cell carcinoma (ccRCC) and (2) to determine phenotypic differences in TLSs between different types of genitourinary cancer, that is, urinary ccRCC and bladder cancer. METHODS: We performed a quantitative immunohistological analysis of ccRCC tissue microarrays and conducted integrated genome mutation analysis by next-generation sequencing and methylation array analysis. Since the tumor immune microenvironment of ccRCC often differs from that of other cancer types, we analyzed the phenotypic differences in TLSs between ccRCC and in-house bladder cancer specimens. RESULTS: Varying distribution patterns of TLSs were observed throughout ccRCC tumors, revealing that the presence of TLSs was related to poor prognosis. An analysis of genomic alterations based on TLS status in ccRCC revealed that alterations in the PI3K-mTOR pathway were highly prevalent in TLS-positive tumors. DNA methylation profiling also revealed distinct differences in methylation signatures among ccRCC samples with different TLS statuses. However, the TLS characteristics of ccRCC and bladder cancer markedly differed: TLSs had the exact opposite prognostic impact on bladder cancer as on ccRCC. The maturity and spatial distribution of TLSs were significantly different between the two cancer types; TLSs were more mature with follicle-like germinal center organization and likely to be observed inside the tumor in bladder cancer. Labeling for CD8, FOXP3, PD-1, and PD-L1 showed marked differences in the diversity of the immune microenvironment surrounding TLSs. The proportions of CD8-, FOXP3-, and PD-L1-positive cells were significantly higher in TLSs in bladder cancer than in TLSs in ccRCC; rather the proportion of PD-1-positive cells was significantly higher in TLSs in ccRCC than in TLSs in bladder cancer. CONCLUSION: The immunobiology of ccRCC is unique, and various cancerous phenomena conflict with that seen in other cancer types; therefore, comparing the TLS characteristics between ccRCC and bladder cancer may help reveal differences in the prognostic impact, maturity and spatial distribution of TLSs and in the immune environment surrounding TLSs between the two cancers.

Profiling the inhibitory receptors LAG-3, TIM-3, and TIGIT in renal cell carcinoma reveals malignancy.

A cutting edge therapy for future immuno-oncology is targeting a new series of inhibitory receptors (IRs): LAG-3, TIM-3, and TIGIT. Both immunogenomic analyses and diagnostic platforms to distinguish candidates and predict good responders to these IR-related agents are vital in clinical pathology. By applying an automated single-cell count for immunolabelled LAG-3, TIM-3, and TIGIT, we reveal that individual IR levels with exclusive domination in each tumour can serve as valid biomarkers for profiling human renal cell carcinoma (RCC). We uncover the immunogenomic landscape associated with individual IR levels in human RCC tumours with metastases in various organs and histological subtypes. We then externally validate our results and devise a workflow with optimal biomarker cut-offs for discriminating the LAG-3, TIM-3, and TIGIT tumour profiles. The discrimination of LAG-3, TIM-3, and TIGIT profiles in tumours may have a broad impact on investigations of immunotherapy responses after targeting a new series of IRs.

[Case of intravascular lymphoma diagnosed by transbronchial lung biopsy, with transient spontaneous remission].

A 70-year-old man visited hospital because of intermittent fever (about 38 degrees C) and night sweat. He had a history of smoking of 1 pack a day for 35 years. He had no abnormal findings on physical examination, but had abnormal laboratory findings, including elevated C-reactive protein, lactate dehydrogenase and soluble interleukin-2 receptor levels. Although malignant lymphoma was suspected, his symptoms and laboratory findings resolved spontaneously. However, intermittent fever and night sweat reoccurred 19 months after his first presentation, and he visited our hospital with dyspnea the following month. On physical examination, he had no abnormal findings. A chest radiograph showed no abnormal findings, but chest and abdominal CT images revealed diffuse ground-glass opacities in both lung fields, and splenomegaly. Transbronchial lung biopsy (TBLB) confirmed a diagnosis of intravascular large B-cell lymphoma. Spontaneous remission is rare in aggressive lymphomas, including intravascular lymphomas (IVL). We report a case of IVL, with symptoms which resolved spontaneously, and reoccurred 19 months later with diffuse interstitial shadows on chest CT images, and in which a diagnosis of IVL was confirmed by TBLB.

Successful Treatment of End-stage Renal Disease in a Patient With Chronic Myeloid Leukemia by Kidney Transplantation and Tyrosine Kinase Inhibitors: A Case Report.

Consensus regarding kidney transplantation feasibility in patients with chronic myeloid leukemia (CML) well controlled by tyrosine kinase inhibitors has not yet been achieved. Here, we report a patient with CML well controlled by tyrosine kinase inhibitors who developed end-stage renal disease during treatment and underwent kidney transplantation. CML activity has been carefully and successfully controlled for 4 years post-transplant. Very cautious dose adjustment and temporary cessation of nilotinib were required because kidney function fluctuated in reference to the doses of nilotinib.