[A Case of Small Cell Carcinoma of the Urethra].

We report a case of small cell carcinoma of the urethra with inguinal lymph node metastases. A 50- year-old female patient presented with gross hematuria. Cystoscopy and computed tomography (CT) revealed a tumor surrounding the urethra and an inguinal lymphadenopathy. Biopsy of the urethral tumor demonstrated small cell carcinoma. Four courses of chemotherapy with etoposide and cisplatin, followed by 66 Gy of irradiation achieved complete remission. Unfortunately, 14 months later, positroemission-CT scan revealed recurrence of inguinal lymph node metastases. Although seven courses of chemotherapy with nogitecan were carried out, a new metastatic bone tumor developed. Amrubicin was administered as a third-line treatment, but was canceled after one course because of side effects. The patient died at 39 months after diagnosis. Small cell carcinoma of urethra with metastases has extremely poor prognosis, as is demonstrated by this case.

[A Case of Intra-Abdominal Testicular Cancer Occurring from an Overlooked Intra-Abdominal Testis in Undescended Testicular Surgery].

Here, we report an adult case of intra-abdominal testicular cancer after surgical treatment of an undescended testis in infancy. A 36-year-old male patient was accidentally diagnosed with a tumor in the pelvic cavity by ultrasonographic examination. He had hematuria and the human chorionic gonadotropin beta subunit level was slightly elevated. T2-weighedmagnetic resonance imaging revealed a well-defined and highly intense mass. Since these findings suggested intra-abdominal testicular cancer, laparoscopic surgery was performed to remove the mass. Laparoscopy revealed an intra-abdominal tumor accompanied by a looping vas deferens entering the left inguinal canal. The distal part of the looping vas had already been removed from the external inguinal ring. The pathological findings revealed a pT1 seminoma. The patient has been recurrence-free for 12 months. The present case implies the importance of careful investigation and treatment for intra-abdominal testicular cancer, since intra-abdominal testis might have been overlooked at the time of surgery for undescended testis.

[Testicular Malignant Sertoli Cell Tumor with Long-Term Survival After Pulmonary Metastasectomy: A Case Report].

A 45-year-old man was referred to our hospital with a complaint of right scrotal discomfort. With a diagnosis of testicular tumor, right orchiectomy was performed. The tumor was histologically diagnosed as malignant Sertoli cell tumor pT1N0M0. A pulmonary nodule appeared, 53 months after the operation, and increased in size there after. Thoracoscopic left upper lobectomy was performed 64 months after the operation, and the pathological diagnosis was metastasis of malignant Sertoli cell tumor. No recurrence has been observed for 94 months after the resection of the metastatic lesion.

Eleven-year retrospective study characterizing patients with severe brain damage and poor neurological prognosis -role of physicians' attitude toward life-sustaining treatment.

BACKGROUND: Severe brain hemorrhage/infarction and cardiac arrest constitute the most critical situations leading to poor neurological prognosis. Characterization of these patients is required to offer successful end-of-life care, but actual practice is affected by multiple confounding factors, including ethicolegal issues, particular in Japan and Asia. The aim of this study is to evaluate the clinical courses of patients with severe brain damage and to assess the preference of end-of-life care for these patients in Japanese hospitals. METHODS: A retrospective observational study was conducted between 2008 and 2018. All intracranial hemorrhage/infarction and cardiac arrest out-patients (n = 510) who were admitted to our two affiliated hospitals and survived but with poor neurologic outcomes were included. Demographic characteristics as well as prognosis and treatment policies were also assessed. RESULTS: Patients were divided into two categories; cases with absent brainstem reflex (BSR) (BSR[-]) and those with preserved BSR (BSR[ +]). The survival rate was higher and the length of hospitalization was longer in patients with BSR[ +] than in those with BSR[-]. Among three life-sustaining policies (i.e., aggressive treatment, withdrawal of treatment, and withholding of treatment), withholding of treatment was adopted to most patients. In BSR[-], the proportion of three treatment policies performed at the final decision did not differ from that at the initial diagnosis on neurological status (p = 0.432). In contrast, this proportion tended to be altered in BSR[ +] (p = 0.072), with a decreasing tendency of aggressive treatment and a modest increasing tendency of withdrawal of treatment. Furthermore, the requests from patients' families to withdraw life-sustaining treatment, including discontinuation of mechanical ventilation, increased, but actual implementation of withdrawal by physicians was less than half of the requests. CONCLUSIONS: BSR constitutes a crucial determinant of mortality and length of hospitalization in comatose patients with severe brain damage. Although the number of withdrawal of life-sustaining treatment tends to increase over time in BSR[ +] patients, there are many more requests from patients' families for withdrawal. Since physicians has a tendency to desist from withdrawing life-sustaining treatment, more in-depth communication between medical staff and patients' families will facilitate mutual understanding over ethicolegal and religious issues and may thus improve end-of-life care.

Profiling the tackle and its injury characteristics in premier New Zealand club rugby union players over a complete season.

OBJECTIVES: RugbySmart is a safe tackle technique education programme. Our objective was to identify whether the RugbySmart-recommended safe tackle technique was exhibited by club rugby players and whether tackle-related injuries showed poor tackle technique characteristics. METHODS: The prospective cohort design enabled 28 senior club based amateur male rugby union players from New Zealand to be followed over 18 matches in the 2017 rugby season. Game video analysis by three analysts provided categorisation of tackle technique into type, approach, foot contact, leading foot and rear foot position, face and head position. Injuries were diagnosed by the same sports medicine physician. RESULTS: In the 18 matches, 28 players completed a combined total of 3006 tackles, with only six tackle-related injuries sustained. Notable findings included: (1) forwards complete more tackles than backs; (2) shoulder tackles were the most prevalent tackle; (3) good tackle technique as promoted by RugbySmart was demonstrated in 57.9% of all tackles and (4) of the six tackle-related injuries, two occurred despite RugbySmart desired tackle techniques. CONCLUSION: This is the first study to investigate whether players were performing the recommended 'safe tackle technique' proposed by New Zealand Rugby's RugbySmart programme. As two of six tackle-related injuries occurred despite the RugbySmart preferred technique being performed, further technique analysis and a larger sample are needed to determine what techniques reduce risk of injury during tackles. As only 57.9% of tackles were performed with RugbySmart head and foot positions, further research and education regarding tackle technique recommendations are needed.

Clinical, pathological, and therapeutic features of newly diagnosed prostate cancer predominantly detected by opportunistic PSA screening: A survey of Shiga Prefecture, Japan.

BACKGROUND: In all the prefectures of Japan, with the exception of Shiga Prefecture, more than half of local governments have an organized prostate-specific antigen (PSA) screening system in place. However, in the Shiga Prefecture, only a single city performed PSA screening over the time period of this survey. The purpose of the present study was to determine the clinical, pathological, and therapeutic features of newly diagnosed prostate cancer in localities where a formally organized screening system was almost entirely absent. METHODS: A multicenter observational study was conducted in the Shiga Prefecture, which has the lowest rate of population-based PSA-screening in Japan. Patients' age, initial PSA, reasons for PSA testing, Gleason score, clinical stage, and primary treatments were surveyed. We stratified patients according to the reasons for PSA measurement, and compared the differences between groups subject to organized versus opportunistic screening. RESULTS: In the 2 years 2012 and 2017, 984 newly diagnosed prostate cancer patients were analyzed. Of these, 954 (97%) were opportunistically tested (i.e., not as part of an organized screening system), with the remaining 29 (3%) measured as part of an organized screening program. Patients in the former group exhibited a higher initial PSA value than in the organized screening group (median: 11.49 vs. 5.67 ng/ml). They also had worse clinical features, including higher Gleason score and TNM stage. More patients in the organized screening group were treated curatively than in the nonorganized screening group in terms of the primary treatment. The results were similar in a subanalysis of the patients of age 50-69 years. CONCLUSIONS: Organized PSA screening contributes to increasing the number of patients diagnosed with early-stage cancer who can be treated curatively.

Mapping of QTLs controlling epicotyl length in adzuki bean (Vigna angularis).

Epicotyl length (ECL) of adzuki bean (Vigna angularis) affects the efficiency of mechanized weeding and harvest. The present study investigated the genetic factors controlling ECL. An F2 population derived from a cross between the breeding line 'Tokei1121' (T1121, long epicotyls) and the cultivar 'Erimo167' (common epicotyls) was phenotyped for ECL and genotyped using simple sequence repeats (SSRs) and single-nucleotide polymorphism (SNP) markers. A molecular linkage map was generated and fifty-two segregating markers, including 27 SSRs and 25 SNPs, were located on seven linkage groups (LGs) at a LOD threshold value of 3.0. Four quantitative trait loci (QTLs) for ECL, with LOD scores of 4.0, 3.4, 4.8 and 6.4, were identified on LGs 2, 4, 7 and 10, respectively; together, these four QTLs accounted for 49.3% of the phenotypic variance. The segregation patterns observed in F5 residual heterozygous lines at qECL10 revealed that a single recessive gene derived from T1121 contributed to the longer ECL phenotype. Using five insertion and deletion markers, this gene was fine mapped to a ~255 kb region near the end of LG10. These findings will facilitate marker-assisted selection for breeding in the adzuki bean and contribute to an understanding of the mechanisms associated with epicotyl elongation.

DyP-Type Peroxidases: Recent Advances and Perspectives.

In this review, we chart the major milestones in the research progress on the DyP-type peroxidase family over the past decade. Though mainly distributed among bacteria and fungi, this family actually exhibits more widespread diversity. Advanced tertiary structural analyses have revealed common and different features among members of this family. Notably, the catalytic cycle for the peroxidase activity of DyP-type peroxidases appears to be different from that of other ubiquitous heme peroxidases. DyP-type peroxidases have also been reported to possess activities in addition to peroxidase function, including hydrolase or oxidase activity. They also show various cellular distributions, functioning not only inside cells but also outside of cells. Some are also cargo proteins of encapsulin. Unique, noteworthy functions include a key role in life-cycle switching in Streptomyces and the operation of an iron transport system in Staphylococcus aureus, Bacillus subtilis and Escherichia coli. We also present several probable physiological roles of DyP-type peroxidases that reflect the widespread distribution and function of these enzymes. Lignin degradation is the most common function attributed to DyP-type peroxidases, but their activity is not high compared with that of standard lignin-degrading enzymes. From an environmental standpoint, degradation of natural antifungal anthraquinone compounds is a specific focus of DyP-type peroxidase research. Considered in its totality, the DyP-type peroxidase family offers a rich source of diverse and attractive materials for research scientists.

Characterization of Class V DyP-Type Peroxidase SaDyP1 from Streptomyces avermitilis and Evaluation of SaDyPs Expression in Mycelium.

DyP-type peroxidases are a family of heme peroxidases named for their ability to degrade persistent anthraquinone dyes. DyP-type peroxidases are subclassified into three classes: classes P, I and V. Based on its genome sequence, Streptomyces avermitilis, eubacteria, has two genes presumed to encode class V DyP-type peroxidases and two class I genes. We have previously shown that ectopically expressed SaDyP2, a member of class V, indeed has the characteristics of a DyP-type peroxidase. In this study, we analyzed SaDyP1, a member of the same class V as SaDyP2. SaDyP1 showed high amino acid sequence identity to SaDyP2, retaining a conserved GXXDG motif and catalytic aspartate. SaDyP1 degraded anthraquinone dyes, which are specific substrates of DyP-type peroxidases but not azo dyes. In addition to such substrate specificity, SaDyP1 showed other features of DyP-type peroxidases, such as low optimal pH. Furthermore, immunoblotting using an anti-SaDyP2 polyclonal antibody revealed that SaDyP1 and/or SaDyP2 is expressed in mycelia of wild-type S. avermitilis.

Early renal dysfunction after temporary ileostomy construction.

PURPOSE: Loop ileostomy is often used to prevent complications after colorectal surgery, but it has been reported to cause renal impairment. This study aimed to evaluate the changes in the renal function after ileostomy and to compare these with the renal function after low anterior resection without ileostomy (low-ANT). METHODS: The subjects included 58 patients who underwent ileostomy construction and closure for rectal cancer. The estimated glomerular filtration rate (eGFR) was calculated at specific time points after the index surgery. In addition, we conducted a case-matched study on 147 patients who underwent low-ANT. RESULTS: The eGFR was significantly lower at 1 month after ileostomy than at the time of ileostomy construction (78.8 vs. 84.0, p < 0.0001) and did not improve after ileostomy closure. The only risk factor for a reduced eGFR was preoperative chemotherapy or chemoradiotherapy. In the case-matched study, 36 patients were allocated for each of the two groups. The number of ileostomy patients with a reduced eGFR was significantly increased 1 month after the index surgery (p = 0.005). CONCLUSIONS: The eGFR began to decrease at one month after ileostomy construction and did not improve after ileostomy closure.

Exploratory Observational Study of Extracorporeal Cardiopulmonary Resuscitation for Nonshockable Out-Of-Hospital Cardiac Arrest Occurring After an Emergency Medical Services Arrival: SOS-KANTO 2012 Study Report.

BACKGROUND: The outcomes of patients with nonshockable out-of-hospital cardiac arrest (OHCA) are poor, but may be improved by extracorporeal cardiopulmonary resuscitation (E-CPR). OBJECTIVE: To examine the effects of veno-arterial extracorporeal membranous oxygenation (ECMO) as E-CPR in patients with nonshockable OHCA after emergency medical services (EMS) arrival for whom satisfactory cardiopulmonary resuscitation (CPR) was immediately performed. METHODS: Among 16,452 patients enrolled in the SOS-KANTO 2012 study, we examined data on 531 patients aged ≥ 18 years who performed activities of daily living (ADL) well or had moderate disability before the onset of cardiac arrest (CA) and those with normal spontaneous respiration or pulse palpation upon EMS arrival. CPR was performed immediately after CA onset, and advanced life support was provided upon hospital arrival for these patients. We divided patients into ECMO and non-ECMO groups. We retrospectively analyzed background factors and clinical outcomes. RESULTS: E-CPR was performed on 38 (7.2%) patients. In the univariate analysis, the mean age of the ECMO group was lower, ADL function before onset was more favorable, mean body weight was higher, and the mean interval from onset until hospital arrival was shorter than those in the non-ECMO group. One-to 3-month survival or favorable cerebral function outcome rates were higher in the ECMO group than in the non-ECMO group. In the multivariate analysis, ECMO use and the interval from onset until hospital arrival were independent prognostic factors for favorable cerebral functional outcomes at 1 and 3 months. CONCLUSION: E-CPR may be associated with favorable outcomes in carefully selected patients with nonshockable OHCA.

Substrate N2 atom recognition mechanism in pierisin family DNA-targeting, guanine-specific ADP-ribosyltransferase ScARP.

ScARP from the bacterium Streptomyces coelicolor belongs to the pierisin family of DNA-targeting ADP-ribosyltransferases (ARTs). These enzymes ADP-ribosylate the N2 amino groups of guanine residues in DNA to yield N2-(ADP-ribos-1-yl)-2'-deoxyguanosine. Although the structures of pierisin-1 and Scabin were revealed recently, the substrate recognition mechanisms remain poorly understood because of the lack of a substrate-binding structure. Here, we report the apo structure of ScARP and of ScARP bound to NADH and its GDP substrate at 1.50 and 1.57 Å resolutions, respectively. The bound structure revealed that the guanine of GDP is trapped between N-ribose of NADH and Trp-159. Interestingly, N2 and N3 of guanine formed hydrogen bonds with the OE1 and NE2 atoms of Gln-162, respectively. We directly observed that the ADP-ribosylating toxin turn-turn (ARTT)-loop, including Trp-159 and Gln-162, plays a key role in the specificity of DNA-targeting, guanine-specific ARTs as well as protein-targeting ARTs such as the C3 exoenzyme. We propose that the ARTT-loop recognition is a common substrate-recognition mechanism in the pierisin family. Furthermore, this complex structure sheds light on similarities and differences among two subclasses that are distinguished by conserved structural motifs: H-Y-E in the ARTD subfamily and R-S-E in the ARTC subfamily. The spatial arrangements of the electrophile and nucleophile were the same, providing the first evidence for a common reaction mechanism in these ARTs. ARTC (including ScARP) uses the ARTT-loop for substrate recognition, whereas ARTD (represented by Arr) uses the C-terminal helix instead of the ARTT-loop. These observations could help inform efforts to improve ART inhibitors.

Association Between Therapeutic Hypothermia and Outcomes in Patients with Non-shockable Out-of-Hospital Cardiac Arrest Developed After Emergency Medical Service Arrival (SOS-KANTO 2012 Analysis Report).

BACKGROUND/OBJECTIVE: The outcomes of patients with non-shockable out-of-hospital cardiac arrest (non-shockable OHCA) are poorer than those of patients with shockable out-of-hospital cardiac arrest (shockable OHCA). In this retrospective study, we selected patients from the SOS-KANTO 2012 study with non-shockable OHCA that developed after emergency medical service (EMS) arrival and analyzed the effect of therapeutic hypothermia (TH) on non-shockable OHCA patients. METHODS: Of 16,452 patients who have definitive data on the 3-month outcome in the SOS-KANTO 2012 study, we selected 241 patients who met the following criteria: age ≥ 18 years, normal spontaneous respiration or palpable pulse upon emergency medical services arrival, no ventricular fibrillation or pulseless ventricular tachycardia before hospital arrival, and achievement of spontaneous circulation without cardiopulmonary bypass. Patients were divided into two groups based on the presence or absence of TH and were analyzed. RESULTS: Of the 241 patients, 49 underwent TH. Univariate analysis showed that the 1-/3-month survival rates and favorable 3-month cerebral function outcome rates in the TH group were significantly better than the non-TH group (46% vs 19%, respectively, P < 0.001, 35% vs 12%, respectively, P < 0.001, 20% vs 7%, respectively, P = 0.01). Multivariate logistic regression analysis showed that TH was a significant, independent prognostic factor for cerebral function outcome. CONCLUSIONS: In this study, TH was an independent prognostic factor for the 3-month cerebral function outcome. Even in patients with non-shockable OHCA, TH may improve outcome if the interval from the onset of cardiopulmonary arrest is relatively short, and adequate cardiopulmonary resuscitation is initiated immediately after onset.

Comparative Studies of Actin- and Rho-Specific ADP-Ribosylating Toxins: Insight from Structural Biology.

Mono-ADP-ribosylation is a major post-translational modification performed by bacterial toxins, which transfer an ADP-ribose moiety to a substrate acceptor residue. Actin- and Rho-specific ADP-ribosylating toxins (ARTs) are typical ARTs known to have very similar tertiary structures but totally different targets. Actin-specific ARTs are the A components of binary toxins, ADP-ribosylate actin at Arg177, leading to the depolymerization of the actin cytoskeleton. On the other hand, C3-like exoenzymes are Rho-specific ARTs, ADP-ribosylate Rho GTPases at Asn41, exerting an indirect effect on the actin cytoskeleton. This review focuses on the differences and similarities of actin- and Rho-specific ARTs, especially with respect to their substrate recognition and cell entry mechanisms, based on structural studies.

[A Case of Metastatic Clear Cell Renal Cell Carcinoma Showing Long-Term Complete Response after the Discontinuation of Tyrosine Kinase Inhibitor].

Randomized phase III trials demonstrated superiority of targeted therapy with tyrosine kinase inhibitors over cytokine-based therapy as first-line therapy for metastatic renal cell carcinoma. However, the rate of complete response (CR) with targeted therapy is smaller than that with cytokine-based therapy. A 47-year-old man was referred to our hospital with a 12 cm left renal tumor and polycythemia. He was diagnosed with renal cancer, cT3aN0M1, with multiple lung metastases. He underwent cytoreductive nephrectomy, with the histopathological diagnosis of clear cell renal cell carcinoma, Fuhrman nuclear grade 2, INFb, pT2b. Three months postoperatively, spontaneous regression of lung metastases was observed. Seventeen months postoperatively, a 17×13 mm retroperitoneal tumor facing the pancreas recurred. CR of the recurrent tumor was achieved by targeted therapy with sunitinib for 12 months. This CR was maintained for 32 months after the discontinuation of targeted therapy with sunitinib.

[Prostate Cancer Diagnosed during Androgen Replacement Therapy for Late-Onset Hypogonadism Treatment: A Case Report].

We report a 60-year-old man with prostate cancer diagnosed during androgen replacement therapy (ART) for late onset hypogonadism after surgery for pituitary adenoma. He was refered to the department of urology since prostate specific antigen values were elevated after 6 months of ART. After the diagnosis of prostate cancer, ART was discontinued, and robot-asssited laparoscopic radical prostatectomy with pelvic lymphadenoctomy was performed. Pathological examination revealed Gleason score 4 + 5 prostate adenocarcinoma with seminal vesicle invasion and lymph node metastasis(pT3bN1). He has stayed biochemically and radiologically disease-free 33 months postoperatively.

[Port-Site Metastasis of Prostate Cancer after Robot-Assisted Laparoscopic Prostatectomy : A Case Report].

The incidence of port-site metastasis in urologic laparoscopic surgery is low, especially in prostate cancer, with 4 reported cases to date. A 65-year-old man was introduced to our hospital presenting with gross hematuria and dysuria. His prostate-specific antigen (PSA) level was 3.1 ng/ml. He was diagnosed with poorly differentiated adenocarcinoma of the prostate, Gleason 9 (5＋4), cT3aN0M0 with non-invasive urothelial cancer of bladder (pTaN0M0, low grade). Robot-assisted laparoscopic prostatectomy was performed. Histopathological examination revealed adenocarcinoma, Gleason 9 (5＋4), pT3bN0, and surgical margins were positive. Eighteen weeks postoperatively, local recurrence, lymph node metastases, and a port-site metastasis were observed. Androgen deprivation therapy with 4 courses of induction docetaxel chemotherapy achieved a complete response on imaging study, 2 years postoperatively.

[Reactive Arthritis during the Second Course of Intravesical BCG Therapy Requiring Administration of Methotrexate : A Case Report].

Reactive arthritis, formerly called Reiter's syndrome, is one of the rare complications following intravesical instillation of Bacillus Calmette Guerin (BCG). A 58-year-old man was admitted to our hospital because of fever, hyperemia of conjunctiva, and arthralgia following the second course of intravesical instillation of BCG in the treatment of pT1 and pTis bladder cancer. We diagnosed him with reactive arthritis due to the clinical course. Reactive arthritis is usually well controlled with the discontinuation of instillation and administration of nonsteroidal anti-inflammatory drugs (NSAIDs). However, his symptoms were not improved after administration of NSAIDs, prednisolone, and isoniazid. Following initiation of methotrexate, however, there was remission. He has been free from recurrence of bladder cancer for 20 months.

[A Case of More Than Five-Year Survival of Carcinoma Associated with Anal Fistula Effectively Treated by Combined Modality Therapy].

The patient was a 56-year-old man who presented with perianal pain and a perianal abscess. After admission, he underwent debridement and colostomy due to poor control of the perianal abscess. Following a biopsy of the resected specimens, he was diagnosed with adenocarcinoma in the anorectal fistula. CT and MRI revealed that the tumor had invaded into the internal obturator muscle. Therefore, preoperative chemoradiotherapy and chemotherapy were given for locally advanced cancer. Subsequent to tumor shrinkage, we performed an abdominoperineal resection. Histopathologically, no cancer cells were detected on the surgical margin, and the effect of the preoperative therapy was judged to be Grade 1b. There has been no indication of recurrence of cancer after 5 years.

Rho GTPase Recognition by C3 Exoenzyme Based on C3-RhoA Complex Structure.

C3 exoenzyme is a mono-ADP-ribosyltransferase (ART) that catalyzes transfer of an ADP-ribose moiety from NAD(+) to Rho GTPases. C3 has long been used to study the diverse regulatory functions of Rho GTPases. How C3 recognizes its substrate and how ADP-ribosylation proceeds are still poorly understood. Crystal structures of C3-RhoA complex reveal that C3 recognizes RhoA via the switch I, switch II, and interswitch regions. In C3-RhoA(GTP) and C3-RhoA(GDP), switch I and II adopt the GDP and GTP conformations, respectively, which explains why C3 can ADP-ribosylate both nucleotide forms. Based on structural information, we successfully changed Cdc42 to an active substrate with combined mutations in the C3-Rho GTPase interface. Moreover, the structure reflects the close relationship among Gln-183 in the QXE motif (C3), a modified Asn-41 residue (RhoA) and NC1 of NAD(H), which suggests that C3 is the prototype ART. These structures show directly for the first time that the ARTT loop is the key to target protein recognition, and they also serve to bridge the gaps among independent studies of Rho GTPases and C3.