Analysis of prostate cancer localization toward improved diagnostic accuracy of transperineal prostate biopsy

PurposeDelineating the precise localization of prostate cancer is important in improving the diagnostic accuracy of prostate biopsy.MethodsIn Juntendo University Nerima Hospital, initial 12-core or repeat 16-core biopsies were performed using a transrectal ultrasound guided transperineal prostate biopsy method. We step-sectioned prostates from radical prostatectomy specimens at 5-mm intervals from the urethra to the urinary bladder and designated five regions: the (1) Apex, (2) Apex-Mid, (3) Mid, (4) Mid-Base, and (5) Base. We then mapped prostate cancer localization on eight zones around the urethra for each of those regions.ResultsProstate cancer was detected in 93 cases of 121 cases (76.9%) in the Apex, in 115 cases (95.0%) in the Apex-Mid, in 101 cases (83.5%) in the Mid, in 71 cases (58.7%) in the Mid-Base, and in 23 cases (19.0%) in the Base. In 99.2% of all cases, prostate cancers were detected from the Apex to Mid regions. For this reason, transperineal prostate biopsies have routinely been prioritized in the Apex, Apex-Mid, and Mid regions, while the Base region of the prostate was considered to be of lesser importance. Our analyses of prostate cancer localization revealed a higher rate of cancer in the posterior portion of the Apex, antero-medial and postero-medial portion of the Apex-Mid and antero-medial and postero-lateral portion of the Mid. The transperineal prostate biopsies in our institute performed had a sensitivity of 70.9%, a specificity of 96.6%, a positive predictive value (PPV) of 92.2% and a negative predictive value (NPV) of 85.5%.ConclusionsThe concordance of prostate cancer between prostatectomy specimens and biopsies is comparatively favorable. According to our study, the diagnostic accuracy of transperineal prostate biopsy can be improved in our institute by including the anterior portion of the Apex-Mid and Mid regions in the 12-core biopsy or 16-core biopsy, such that a 4-core biopsy of the anterior portion is included

Studies on Artificial Pregnancy in Rat : 1. Survival of Ova Transferred into the Uterus of Rat

子宮内に移植したラット受精卵の生存性を知るためにこの研究を行なった. donorおよびrecipientには体重200～240gのWister系の雌ラットを用い,膣栓を確認した日を妊娠または偽妊娠第1日とし,卵の培養および移植条件を確かめるために3日の4細胞卵を同期化したrecipientの子宮に移植した. 40時問の子宮生体培養の後に卵を回収し,卵の分割状態を観察した結果,供試ラットのすべてに正常な分割卵が認められた. 卵の灌流および培養液として生理食塩水:ラット不活血清(2:1)を用いた. 妊娠5日目の受精卵を採取後30℃で2時間培養した後に同期化した偽妊娠ラットの子宮内に移植した. recipientは妊娠16日目に開腹して胎児の発育状態とその数などを観察したが胎児の生存率は3.8%にすぎなかった. 次に,採卵後移植までの時間を20分以内とし,子宮に注入する液量を考慮して5日目卵を同期化した子宮に移植した. この場合には着床率は80%であり,移植卵に対する胎児の生存率は46%であった. この結果から卵採取後移植までの培養時間と注入液量が高い受胎率を得るための最も基本的な条件であることが推論された

Differential involvement of LUBAC‐mediated linear ubiquitination in intestinal epithelial cells and macrophages during intestinal inflammation

Disruption of the intestinal epithelial barrier and dysregulation of macrophages are major factors contributing to the pathogenesis of inflammatory bowel diseases (IBDs). Activation of NF-κB and cell death are involved in maintaining intestinal homeostasis in a cell type-dependent manner. Although both are regulated by linear ubiquitin chain assembly complex (LUBAC)-mediated linear ubiquitination, the physiological relevance of linear ubiquitination to intestinal inflammation remains unexplored. Here, we used two experimental mouse models of IBD (intraperitoneal LPS and oral dextran sodium sulfate [DSS] administration) to examine the role of linear ubiquitination in intestinal epithelial cells (IECs) and macrophages during intestinal inflammation. We did this by deleting the linear ubiquitination activity of LUBAC specifically from IECs or macrophages. Upon LPS administration, loss of ligase activity in IECs induced mucosal inflammation and augmented IEC death. LPS-mediated death of LUBAC-defective IECs was triggered by TNF. IEC death was rescued by an anti-TNF antibody, and TNF (but not LPS) induced apoptosis of organoids derived from LUBAC-defective IECs. However, augmented TNF-mediated IEC death did not overtly affect the severity of colitis after DSS administration. By contrast, defective LUBAC ligase activity in macrophages ameliorated DSS-induced colitis by attenuating both infiltration of macrophages and expression of inflammatory cytokines. Decreased production of macrophage chemoattractant MCP-1/CCL2, as well as pro-inflammatory IL-6 and TNF, occurred through impaired activation of NF-κB and ERK via loss of ligase activity in macrophages. Taken together, these results indicate that both intraperitoneal LPS and oral DSS administrations are beneficial for evaluating epithelial integrity under inflammatory conditions, as well as macrophage functions in the event of an epithelial barrier breach. The data clarify the cell-specific roles of linear ubiquitination as a critical regulator of TNF-mediated epithelial integrity and macrophage pro-inflammatory responses during intestinal inflammation

Profile of Blood Glucose in Diabetic Patient Suffered from Diabetic Foot Osteomyelitis with Effective Low Carbohydrate Diet

The case was 52-year-old female with type 2 diabetes mellitus (T2DM) for 10-years. She complained of the decreased sensation of right lower foot, and revealed diabetic foot infection (DFI) and/or diabetic foot osteomyelitis (DFO) at right 1st proximal phalanx. Various data included body mass index (BMI) 33.3 kg/m2, HbA1c 11.4%, blood glucose 430 mg/dL, WBC 12100 /μL, C-reactive Protein (CRP) 13.5 mg/dL. On admission (day 1), she was started by 4 times of injection (Aspart and Glargin) with glucose profile 200-500 mg/dL. Surgical amputation of the right toe was performed between 1st metatarsal and proximal phalanx (day 17). Then, blood glucose profile decreased moderately. After discharge of the hospital, super-Low Carbohydrate Diet (LCD) was started without Aspart (day 37). Consequently, glucose profile was normalized with HbA1c 6.3% on (day 77). Consequently, LCD was evaluated to be effective for glucose variability in this case and some related discussion was described

Percutaneous coronary intervention strategy for acute coronary syndrome caused by spontaneous coronary artery dissection for relieving ongoing ischemia—Case series and literature review

AbstractAlthough spontaneous coronary artery dissection (SCAD) is one of the causes of acute coronary syndrome (ACS) or sudden cardiac death, its standard management, especially primary percutaneous coronary intervention (PCI) in ACS patients with ongoing ischemia, has not been established. We experienced three ACS patients with SCAD who were treated with a different strategy of primary PCI. Each PCI strategy led to different clinical and procedural results. We describe here such PCI strategies and results, and also discuss the literature regarding primary PCI strategies for SCAD-induced ACS patients with ongoing ischemia.<Learning objective: SCAD is a cause of ACS. However, the treatment strategy of primary PCI for SCAD has not been fully investigated. We used different PCI strategies for three SCAD patients with ongoing ischemia. Our case series suggested that plain old balloon angioplasty is an acceptable option to avoid coronary stenting because the majority of patients were young menstruating women. Coronary vasospasm might be associated with SCAD. Treatment with vasodilators could be a potential pharmacological option for avoiding recurrence of SCAD.

Construction of possible integrated predictive index based on EGFR and ANXA3 polymorphisms for chemotherapy response in fluoropyrimidine-treated Japanese gastric cancer patients using a bioinformatic method

Selected genetic and clinical parameters of gastric cancer patients. (XLS 33 kb

Amino-terminal enhancer of split gene AES encodes a tumor and metastasis suppressor of prostate cancer

A major cause of cancer death is its metastasis to the vital organs. Few effective therapies are available for metastatic castration-resistant prostate cancer (PCa), and progressive metastatic lesions such as lymph nodes and bones cause mortality. We recently identified AES as a metastasis suppressor for colon cancer. Here, we have studied the roles of AES in PCa progression. We analyzed the relationship between AES expression and PCa stages of progression by immunohistochemistry of human needle biopsy samples. We then performed overexpression and knockdown of AES in human PCa cell lines LNCaP, DU145 and PC3, and determined the effects on proliferation, invasion and metastasis in culture and in a xenograft model. We also compared the PCa phenotypes of Aes/Pten compound knockout mice with those of Pten simple knockout mice. Expression levels of AES were inversely correlated with clinical stages of human PCa. Exogenous expression of AES suppressed the growth of LNCaP cells, whereas the AES knockdown promoted it. We also found that AES suppressed transcriptional activities of androgen receptor and Notch signaling. Notably, AES overexpression in AR-defective DU145 and PC3 cells reduced invasion and metastasis to lymph nodes and bones without affecting proliferation in culture. Consistently, prostate epithelium-specific inactivation of Aes in Ptenflox/flox mice increased expression of Snail and MMP9, and accelerated growth, invasion and lymph node metastasis of the mouse prostate tumor. These results suggest that AES plays an important role in controlling tumor growth and metastasis of PCa by regulating both AR and Notch signaling pathways

Simultaneous excitation of the snake-like oscillations and the m/n = 1/1 resistive interchange modes around the iota = 1 rational surface just after hydrogen pellet injections in LHD plasmas

Two types of oscillation phenomena are found just after hydrogen ice pellet injections in the Large Helical Device (LHD). Oscillation phenomena appear when the deposition profile of a hydrogen ice pellet is localized around the rotational transform ι = 1 rational surface. At first, damping oscillations (type-I) appear only in the soft X-ray (SX) emission. They are followed by the second type of oscillations (type-II) where the magnetic fluctuations and density fluctuations synchronized to the SX fluctuations are observed. Both oscillations have poloidal/toroidal mode number, m/n = 1/1. Since the type-II oscillations appear when the local pressure is large and/or the local magnetic Reynold\u27s number is small, it is reasonable that type-II oscillations are caused by the resistive interchange modes. Because both types of oscillations appear simultaneously at slightly different locations and with slightly different frequencies, it is certain that type-I oscillations are different from type-II oscillations, which we believe is the MHD instability. It is possible that type-I oscillations are caused by the asymmetric concentration of the impurities. The type-I oscillations are similar to the impurity snake phenomena observed in tokamaks though type-I oscillations survive only several tens of milliseconds in LHD

IRIS plus panitumumab for metastatic CRC

Background Irinotecan plus S-1 (IRIS) is the only oral fluoropyrimidine-based regimen reported to be non-inferior to FOLFIRI and widely used in clinical practice for metastatic colorectal cancer (mCRC) patients. However, the combination of IRIS plus an anti-EGFR agent has not been evaluated previously. This study aimed to investigate the feasibility and efficacy of IRIS with panitumumab as second-line therapy for wild-type KRAS mCRC. Methods Main inclusion criteria were patients with wild-type KRAS mCRC refractory to one prior chemotherapy regimen for mCRC, ECOG PS 0-2, and age ≥ 20 years. Patients received panitumumab (6mg/kg) and irinotecan (100mg/m2) on days 1 and 15 and S-1 (40-60 mg according to body surface area) twice daily for 2 weeks, repeated every 4 weeks. The primary endpoint was the feasibility of the therapy. The secondary endpoints were response rate (RR), progression-free survival (PFS), and overall survival (OS). Results A total of 36 patients received protocol treatment in eight centers. Of these, 23 patients (63.9%) completed protocol treatment, demonstrating achievement of the primary endpoint. The most frequent grade 3/4 toxicities were diarrhea (16.7%), acne-like rash (13.9%), and neutropenia (11.1%). The overall RR was 33.3% (12/36). Of these 4 five underwent conversion surgery. Median PFS and OS were 9.5 months (95% CI 3.5-15.4 months) and 20.1 months (95% CI 16.7-23.2 months), respectively. Conclusion IRIS plus panitumumab has an acceptable toxicity profile and a promising efficacy in patients with previously treated wild-type KRAS mCRC. Accordingly, this regimen can be an additional treatment option for second-line chemotherapy in wild-type KRAS mCRC