Genetic variations predicting progression with docetaxel and novel androgen-receptor pathway inhibitors.

Genetic variations represented by single-nucleotide polymorphisms (SNPs) could be helpful for choosing an effective treatment for patients with prostate cancer. This study investigated the prognostic and predictive values of SNPs associated with the prognoses of pharmacotherapy for prostate cancer through their pharmacological mechanisms. Patients treated with docetaxel or androgen receptor pathway inhibitors (ARPIs), such as abiraterone and enzalutamide, for castration-resistant prostate cancer were included. The SNPs of interest were genotyped for target regions. The prognostic and predictive values of the SNPs for time to progression (TTP) were examined using the Cox hazard proportional model and interaction test, respectively. Rs1045642 in ABCB1, rs1047303 in HSD3B1, rs1856888 in HSD3B1, rs523349 in SRD5A2, and rs34550074 in SLCO2A1 were differentially associated with TTP between docetaxel chemotherapy and ARPI treatment. In addition to rs4775936 in CYP19A1, rs1128503 in ABCB1 and rs1077858 in SLCO2B1 might be differentially associated with TTP between abiraterone and enzalutamide treatments. Genetic predictive models using these SNPs showed a differential prognosis for treatments. This study identified SNPs that could predict progression as well as genetic models that could predict progression when patients were treated with docetaxel versus ARPI and abiraterone versus enzalutamide. The use of genetic predictive models is expected to be beneficial in selecting the appropriate treatment for the individual patient.

Personality traits and preoperative lifestyle improvement are predictors of early weight loss after sleeve gastrectomy.

PURPOSE: This study investigated the associations of personality traits and preoperative lifestyle improvements with early weight loss after sleeve gastrectomy. METHODS: This was a single-center, retrospective study of 57 patients who underwent preoperative lifestyle intervention with a multidisciplinary team approach based on cognitive behavioral therapy before sleeve gastrectomy. All patients underwent preoperative psychological testing with the Neuroticism-Extraversion-Openness Five-Factor Inventory (NEO-FFI) and the Tokyo University Egogram New Version II (TEG II). We investigated the associations of psychological testing results and lifestyle improvements with percent total weight loss (%TWL) one year after surgery. RESULTS: The median %TWL at 1 year was 38.2% for patients with an improved lifestyle and 26.9% for those without improvement (P = 0.0008). Although TEG II factors were not associated with %TWL at 1 year, higher NEO-FFI extraversion (E) scores were significantly associated with a better %TWL at 1 year. The median %TWL at 1 year was 35.2% for patients with higher E scores and 25.4% for those with lower E scores (P = 0.0247). Lifestyle improvement and the NEO-FFI E score significantly influenced %TWL at 1 year based on a logistic regression analysis. CONCLUSION: The NEO-FFI E score and preoperative lifestyle improvement may be predictors of early weight loss after sleeve gastrectomy.

Prognostic significance of pathogenic variants in BRCA1, BRCA2, ATM and PALB2 genes in men undergoing hormonal therapy for advanced prostate cancer.

BACKGROUND: The prognostic significance of germline variants in homologous recombination repair genes in advanced prostate cancer (PCa), especially with regard to hormonal therapy, remains controversial. METHODS: Germline DNA from 549 Japanese men with metastatic and/or castration-resistant PCa was sequenced for 27 cancer-predisposing genes. The associations between pathogenic variants and clinical outcomes were examined. Further, for comparison, DNA from prostate biopsy tissue samples from 80 independent patients with metastatic PCa were analysed. RESULTS: Forty-four (8%) patients carried germline pathogenic variants in one of the analysed genes. BRCA2 was most frequently altered (n = 19), followed by HOXB13 (n = 9), PALB2 (n = 5) and ATM (n = 5). Further, the BRCA1, BRCA2, PALB2 and ATM variants showed significant association with a short time to castration resistance and overall survival (hazard ratio = 1.99 and 2.36; 95% CI, 1.15-3.44 and 1.23-4.51, respectively), independent of other clinical variables. Based on log-rank tests, the time to castration resistance was also significantly short in patients with BRCA1, BRCA2, PALB2 or ATM somatic mutations and TP53 mutations. CONCLUSIONS: Germline variants in BRCA1, BRCA2, PALB2 or ATM are independent prognostic factors of the short duration of response to hormonal therapy in advanced PCa.

[The issues behind solitary deaths of older people in central Tokyo].

Objectives　The purpose of this study was to clarify the issues behind the increasing number of solitary deaths of older people in central Tokyo.Methods　In this study a request was made to the national government for information on the 2016 vital statistics survey of ward A, one of the 23 wards of Tokyo. The entries in the death forms do not distinguish between death and post-mortem certificates. However, in the 23 wards where there is a medical examiner system, if the medical institution of the doctor who prepared the post-mortem certificate is the Tokyo-to Medical Examiner's Office, it is possible to identify that the postmortem examination was performed. If the hospital is listed, it is considered a death certificate. A descriptive analytical study was made on the relationship between the cause of death, sex, age and marital status with regard to postmortem examinations of deaths at home or in hospitals resulting from illnesses and home care deaths.Results　Of the 4,429 deaths in Ward A in 2016, 613 were found to be postmortem examinations, of which 436 (71.1%) were of individuals who were 65 years or older. Of the 757 deaths at home, 399 (52.7%) were postmortem examinations, of which 271 were deaths from illness. The number of home care deaths was 358 (47.3%). The mean age of death was 73.6 years for 145 males and 79.5 years for 123 females, out of 268 home deaths of 34 years or older identified as death from illness by postmortem examination. On the other hand, the mean age of death in 358 home care deaths was significantly older as compared to postmortem examination deaths. 65.3% of deaths at home and 54.1% of hospital deaths were due to sudden death-type diseases such as ischemic heart disease. Of the postmortem examination of home deaths from illness among the older people aged 65 years or older, 65.5% of the 110 males and 87.3% of the 110 females were single. Bereavement occurred in 27.3% of men and 52.7% of women, separation in 16.4% of men and 9.1% of women. 21.8% of men and 25.5% of women were never married.Conclusions　In the solitary deaths of older people in central Tokyo, sudden death disease is the direct cause of death and, in the background, there are bereavement from a spouse in women, separation or bereavement from a spouse in men, and being unmarried in both.

High level of phosphatidylcholines/lysophosphatidylcholine ratio in urine is associated with prostate cancer.

The altered levels of phospholipids (PLs) and lysophospholipids (LPLs) in prostate cancer (CaP) and benign tissues in our previous findings prompted us to explore PLs and LPLs as potential biomarkers for CaP. Urinary lipidomics has attracted increasing attention in clinical diagnostics and prognostics for CaP. In this study, 31 prostate tissues obtained from radical prostatectomy were assessed using high-resolution matrix-assisted laser desorption/ionization imaging mass spectrometry (HR-MALDI-IMS). Urine samples were collected after digital rectal examination (DRE), and urinary lipids were extracted using the acidified Bligh-Dyer method. The discovery set comprised 75 patients with CaP and 44 with benign prostatic hyperplasia (BPH) at Kyoto University Hospital; the validation set comprised 74 patients with CaP and 59 with BPH at Osaka University Hospital. Urinary lipidomic screening was performed using MALDI time-of-flight MS (MALDI-TOF/MS). The levels of urinary lysophosphatidylcholine (LPC) and phosphatidylcholines (PCs) were compared between the CaP and BPH groups. The (PC [34:2] + PC [34:1])/LPC (16:0) ratio was significantly higher (P < .001) in CaP tissues than in benign epithelial tissues. The urinary PCs/LPC ratio was significantly higher (P < .001) in the CaP group than in the BPH group in the discovery and validation sets.

Establishment and characterization of a novel treatment-related neuroendocrine prostate cancer cell line KUCaP13.

The prevalence of neuroendocrine prostate cancer (NEPC) arising from adenocarcinoma (AC) upon potent androgen receptor (AR) pathway inhibition is increasing. Deeper understanding of NEPC biology and development of novel therapeutic agents are needed. However, research is hindered by the paucity of research models, especially cell lines developed from NEPC patients. We established a novel NEPC cell line, KUCaP13, from tissue of a patient initially diagnosed with AC which later recurred as NEPC. The cell line has been maintained permanently in vitro under regular cell culture conditions and is amenable to gene engineering with lentivirus. KUCaP13 cells lack the expression of AR and overexpress NEPC-associated genes, including SOX2, EZH2, AURKA, PEG10, POU3F2, ENO2, and FOXA2. Importantly, the cell line maintains the homozygous deletion of CHD1, which was confirmed in the primary AC of the index patient. Loss of heterozygosity of TP53 and PTEN, and an allelic loss of RB1 with a transcriptomic signature compatible with Rb pathway aberration were revealed. Knockdown of PEG10 using shRNA significantly suppressed growth in vivo. Introduction of luciferase allowed serial monitoring of cells implanted orthotopically or in the renal subcapsule. Although H3K27me was reduced by EZH2 inhibition, reversion to AC was not observed. KUCaP13 is the first patient-derived, treatment-related NEPC cell line with triple loss of tumor suppressors critical for NEPC development through lineage plasticity. It could be valuable in research to deepen the understanding of NEPC.

[Investigation of the Risk for Biochemical Recurrence after Radical Prostatectomy Using the Length of the Positive Surgical Margin Microscopically Measured from the Surgical Specimen].

Radical prostatectomy is one of the major treatment options for patients with localized prostate cancer, and biochemical recurrence (BCR) after surgery is regarded as one of the representative indicators of the oncological outcome. The positive surgical margin (PSM) of the surgical specimen is considered to be one of the risk factors for BCR and its length (LPSM) was reported to be positively correlated with the risk for BCR. We retrospectively investigated the relationship between BCR and LPSM in 115 patients who underwent radical retropubic prostatectomy or laparoscopic radical prostatectomy without neoadjuvant hormone therapy at Shimada Municipal Hospital between 2008 and 2016. We found that the patients with a LPSM of 3 mm or longer had a higher risk for BCR than those with a LPSM shorter than 3 mm (HR 10.98, 95% confidence interval : 3.09-39.06, p <0.001), and patients with pT3 disease with a LPSM of 3 mm or longer had a higher risk for early BCR. Therefore, the LPSM may be a useful parameter to predict BCR after radical prostatectomy.

[A Case Of cT3bN2M0 Pleomorphic Giant Cell Carcinoma of the Bladder without Recurrence after Neoadjuvant Chemotherapy and Radical Cystectomy for 4 Years].

Pleomorphic giant cell carcinoma of the bladder is a highly malignant subtype and its prognosis is very poor. Among 22 previously reported cases, 14 cases were diagnosed as muscle-invasive tumors and the 10 patients died within 1.5 years after the initial diagnosis. We herein report a long-surviving patient with cT3bN2M0 pleomorphic giant cell carcinoma of the bladder without recurrence. A 73-year-old man presented with macroscopic hematuria and cystoscopy revealed a papillary nodular tumor 45 millimeters in diameter at the right bladder wall. Bilateral external iliac lymph node metastases were found on computed tomography (CT) and magnetic resonance imaging (MRI). The histopathological diagnosis of the transurethral resection specimen was pleomorphic giant cell urothelial carcinoma, high-grade, G3, pT2 or higher. The pleomorphic giant cells were composed of large epithelioid cells with single or multiple bizarre nuclei. The patient underwent 2 cycles of neoadjuvant chemotherapy using gemcitabine and cisplatin. Follow-up CT and MRI revealed disappearance of iliac lymph node matastases. Laparoscopic radical cystectomy and lymphadenectomy were performed. The histopathological diagnosis was pleomorphic giant cell urothelial carcinoma, ypT3aN0M0, RM0. Giant cells were found in 70% of the tumor. No recurrence has been found for 4 years after surgery. If neoadjuvant chemotherapy is effective, long-term survival without recurrence may be possible after radical cystectomy even in cases of muscle-invasive or N2 pleomorphic giant cell carcinoma of the bladder.

[A Case of PT1 Plasmacytoid Variant Bladder Cancer Treated by Bladder Conserving Therapy].

Plasmacytoid variant bladder cancer is a highly malignant subtype associated with a high propensity for invasion, metastasis and poor prognosis. Among approximately 100 reported cases, most were diagnosed at an advanced stage and only 10 were diagnosed at a non-muscle-invasive stage. Due to the limited data on clinical features of non-muscle-invasive plasmacytoid variant bladder cancer, its treatment has not been established. We report a long-surviving patient with pT1 plasmacytoid variant bladder cancer in whom the bladder was conserved after detailed pathological examinations of the transurethral resection (TUR) specimen and intensive follow-up. A 65-year-old man presented with macroscopic hematuria. Cystoscopy revealed a nodular tumor 11 millimeters in diameter and no metastasis was observed on computed tomography. The histopathological diagnosis of the TUR specimen was pT1 plasmacytoid variant urothelial carcinoma of the bladder. Microvascular invasion was not found by immunohistochemical staining and histopathological examination of the specimen from the second TUR indicated no residual cancer. The patient strongly desired bladder conservation and additionally underwent intravesical instillation therapy with 40 mg of mitomycin C weekly for 6 consecutive weeks. Follow-up cystoscopy demonstrated 3 small papillary tumors 12 months after intravesical instillation therapy, but histopathologically, the recurrent tumors were pTa with pTis urothelial carcinomas without plasmacytoid components. To treat pTis disease, he subsequently underwent intravesical BCG instillation therapy. The plasmacytoid variant bladder cancer has not recurred for 26 months since the initial diagnosis. Non-muscle-invasive and localized plasmacytoid variant bladder cancer may be treated with bladder conserving therapy.

[A Case of HER2-Positive Inflammatory Breast Cancer for Which Preoperative Chemotherapy with Pertuzumab Resulted in a Pathological Complete Response].

A 52-year-old woman presented with redness and swelling with a peau d'orange appearance in the whole right breast. Ultrasound revealed elevated subcutaneus fat density and a diffuse hypoechoic area. She was diagnosed with inflammatory breast cancer(T4dN2M0, Stage III B of the HER2 subtype). After 4 courses of EC treatment as primary systemic therapy, the hypoechoic area was still present. Subsequent chemotherapy with pertuzumab, trastuzumab, and docetaxel was effective, as hypoechoic area was not observed on ultrasound. She underwent mastectomy and axillary dissection, and pathological examination revealed pCR. At present, 2 years after surgery, the patient is alive with no reccurence.

Dissociable memory traces within the macaque medial temporal lobe predict subsequent recognition performance.

Functional magnetic resonance imaging (fMRI) studies have revealed that activity in the medial temporal lobe (MTL) predicts subsequent memory performance in humans. Because of limited knowledge on cytoarchitecture and axonal projections of the human MTL, precise localization and characterization of the areas that can predict subsequent memory performance are benefited by the use of nonhuman primates in which integrated approach of the MRI- and cytoarchiture-based boundary delineation is available. However, neural correlates of this subsequent memory effect have not yet been identified in monkeys. Here, we used fMRI to examine activity in the MTL during memory encoding of events that monkeys later remembered or forgot. Application of both multivoxel pattern analysis and conventional univariate analysis to high-resolution fMRI data allowed us to identify memory traces within the caudal entorhinal cortex (cERC) and perirhinal cortex (PRC), as well as within the hippocampus proper. Furthermore, activity in the cERC and the hippocampus, which are directly connected, was responsible for encoding the initial items of sequentially presented pictures, which may reflect recollection-like recognition, whereas activity in the PRC was not. These results suggest that two qualitatively distinct encoding processes work in the monkey MTL and that recollection-based memory is formed by the interplay of the hippocampus with the cERC, a focal cortical area anatomically closer to the hippocampus and hierarchically higher than previously believed. These findings will advance the understanding of common memory system between humans and monkeys and accelerate fine electrophysiological characterization of these dissociable memory traces in the monkey MTL.

In vivo support for the new concept of pulmonary blood flow-mediated CO2 gas excretion in the lungs.

To further examine the validity of the proposed concept of pulmonary blood flow-dependent CO2 gas excretion in the lungs, we investigated the effects of intramediastinal balloon catheterization-, pulmonary artery catheterization-, or isoprenaline (ISP)-induced changes in pulmonary blood flow on the end-expiratory CO2 gas pressure (PeCO2 ), the maximal velocity of the pulmonary artery (Max Vp), systemic arterial pressure, and heart rate of anesthetized rabbits. We also evaluated the changes in the PeCO2 in clinical models of anemia or pulmonary embolism. An almost linear relationship was detected between the PeCO2 and Max Vp. In an experiment in which small pulmonary arteries were subjected to stenosis, the PeCO2 fell rapidly, and the speed of the reduction was dependent on the degree of stenosis. ISP produced significant increases in the PeCO2 of the anesthetized rabbits. Conversely, treatment with piceatannol or acetazolamide induced significant reductions in the PeCO2 . Treatment with a cell surface F1/FO ATP synthase antibody caused significant reductions in the PeCO2 itself and the ISP-induced increase in the PeCO2 . Neither the PeCO2 nor SAP was significantly influenced by marked anemia [%hematocrit (Ht), 70 ∼ 47%]. On the other hand, in the presence of less severe anemia (%Ht: 100 ∼ 70%) both the PeCO2 and SAP fell significantly when the rabbits' blood viscosity was decreased. The rabbits in which pulmonary embolisms were induced demonstrated significantly reduced PeCO2 values, which was compatible with the lowering of their Max Vp. In conclusion, we reaffirm the validity of the proposed concept of CO2 gas exchange in the lungs.

[A Case of Partial Prostatectomy for Advanced Rectal Cancer Involving the Prostate in the Jack-Knife Position].

A 72-year-old man was diagnosed with advanced rectal cancer possibly involving the prostate on magnetic resonance imaging (MRI) findings. Following neoadjuvant chemoradiotherapy (CRT), he underwent curative surgery. Confirming negative surgical margin through intraoperative pathological evaluation, colorectectomy with partial prostatectomy was performed in the jack-knife position. No evidence of local recurrence of the tumor was observed one year after surgery without symptoms of the urinary tract. Partial prostatectomy is a choice to be taken into account in the treatment of advanced rectal cancer achieving both the good surgical outcome and the patient's quality of life (QOL).

[Adenocarcinoma of an augmented bladder 49 years after enterocystoplasty : a case report].

A 69-year-old man visited our hospital presenting with bladder tamponade. The patient had undergone bladder augmentation using the ileocecum and the ascending colon for an atrophy bladder due to tuberculosis 49 years previously. Cystoscopy revealed an invasive bladder tumor in the anastomotic region of the bladder and the intestine. He underwent cystourethrectomy and ileal conduit (utilizing the previous ureteroileal anastomosis). A deliberate procedure of urinary tract diversion was required because of the severe postoperative adhesion by the augmentation. The pathological diagnosis showed adenocarcinoma. The tumor spread over the intestinal tract side and the deepest part reached the adventitia of the intestinal tract. The patient is receiving additional therapy of combined modality including chemotherapy.

[Carboplatin plus irinotecan induced partial response in a patient with small cell carcinoma of the prostate; a case report].

An 80-year-old man with prostate cancer receiving hormone therapy presented with urinary retention. The computed tomographic scan showed metastases to the lung, liver, and lymph nodes, as well as increased prostate volume. Transurethral resection of the prostate (TURP) was performed, and the resected specimen was pathologically found to be a small cell carcinoma of the prostate. The patient was treated with a combination of carboplatin and irinotecan, and achieved a partial response : size reduction of the prostate and the metastatic lesions, and decreased neuron specific enolase (NSE) level. The chemotherapy with carboplatin and irinotecan is reported to have fewer serious adverse effects, and equivalent efficacy to the cisplatin/etoposide chemotherapy. Therefore, this regimen could also be a treatment option for the patients with small cell carcinoma of the prostate.

[A case of ventricular tachycardia that was probably caused by coronary artery spasm induced by pericardial manipulation].

We present a case of ventricular tachycardia (VT) that was probably caused by coronary artery spasm. A 74-year-old man was scheduled to undergo right lower lobectomy for lung cancer. Although he had never suffered from any episodes of ischemic heart disease, he had several risk factors for coronary artery disease (CAD); i. e., a history of smoking, a low high-density lipoprotein cholesterol level, and diabetes mellitus type 2. Anesthesia for one-lung ventilation was maintained by inhalation of sevoflurane (1-1.5%), the continuous intravenous infusion of remifentanil (0.1-0.15 µg x kg(-1) x min(-1)), and the intermittent administration of epidural (T4-5) 2% mepivacaine (4 ml) and 0.75% ropivacaine (5 ml). During manipulation of the pericardium, the patient's systolic blood pressure suddenly increased to 200 mmHg, followed by an ST elevation on his electrocardiogram. Despite the immediate infusion of nitroglycerin (1 mg), he developed non-sustained VT, lasting for about 30 seconds. Then, diltiazem (0.5 µg x kg(-1) x min(-1)) was continuously administered, and the infusion rate of remifentanil was increased to 0.3 µg x kg(-1) x min(-1). The patient recovered smoothly from anesthesia and his postoperative course was uneventful. Anesthesiologists should be aware of the possibility of coronary artery spasms induced by sudden modulation of the autonomic nervous system, particularly in patients who are at high risk of CAD.

Additional mutation in PROKR2 and phenotypic differences in a Kallmann syndrome/normosmic congenital hypogonadotropic hypogonadism family carrying FGFR1 missense mutation.

Congenital hypogonadotropic hypogonadism (CHH) is a genetically and clinically diverse disorder encompassing Kallmann syndrome (KS) and normosmic CHH (nCHH). Although mutations in numerous genes account for nearly 50% of CHH cases, a significant portion remains genetically uncharacterized. While most mutations follow the traditional Mendelian inheritance patterns, evidence suggests oligogenic interactions between CHH genes, acting as modifier genes to explain variable expressivity and incomplete penetrance associated with certain mutations.In this study, the proband presented with nCHH, while his son exhibited KS. We employed whole-exome sequencing (WES) to investigate the genetic differences between the two, and Sanger sequencing was used to validate the results obtained from WES.Genetic analysis revealed that both the proband and his son harboured a mutation in FGFR1 gene. Notably, an additional rare mutation in PROKR2 gene was exclusively identified in the son, which suggests the cause of the phenotypic difference between KS and nCHH.

Effects of thienopyridine class antiplatelets on bleeding outcomes following robot-assisted radical prostatectomy.

This study aimed to assess the effects of thienopyridine-class antiplatelet agents (including ticlopidine, clopidogrel, and prasugrel) on bleeding complications in patients who underwent robot-assisted radical prostatectomy. This cohort study used a database for robot-assisted radical prostatectomy at 23 tertiary centers nationwide between 2011 and 2022. Patients who received thienopyridines (thienopyridine group) were compared with those who received aspirin monotherapy (aspirin group). The primary outcome was the incidence of bleeding complications. High-grade complications were defined as Clavien-Dindo grade III or higher. The risks of these outcomes were evaluated using inverse probability of treatment weighted regression models. The study results demonstrated that thienopyridine therapy was associated with a higher risk of overall bleeding complications (OR: 3.62, 95%CI 1.54-8.49). The increased risks of the thienopyridine group were detected for low-grade bleeding complications (OR: 3.20, 95%CI 1.23-8.30) but not for high-grade bleeding complications (OR: 5.23, 95%CI 0.78-34.9). The increased risk of bleeding complications was not observed when thienopyridine was discontinued (OR: 2.52, 95%CI 0.83-7.70); however, it became apparent when it was continued perioperatively (OR: 4.35, 95%CI 1.14-16.61). In conclusion, thienopyridine increased the incidence of bleeding complications, particularly low-grade bleeding complications, following robot-assisted radical prostatectomy. These bleeding effects emerged when thienopyridine was continued perioperatively.

Functional dissociation between anterior and posterior temporal cortical regions during retrieval of remote memory.

Retrieval of remote memory is considered to differentially involve the anterior and posterior temporal neocortices. Previous neuropsychological studies suggest that the different posterior temporal cortical regions are involved in the retrieval of remote memory of different categories of stimuli, whereas the anterior region is involved more generally in remote memory retrieval. In the present study, using functional magnetic resonance imaging of human brains, we tested this dissociation by examining the more precise characteristics of the anterior and posterior temporal cortical regions. Two categories of stimuli, faces and scenes, were used for paired stimuli to be retrieved, and the brain activity during retrieval of paired stimuli that were learned immediately before the scanning was compared with that during retrieval of paired stimuli that were learned ∼8 weeks earlier. We found that the different posterior temporal cortical regions were activated during retrieval of different categories of remote memory in a category-specific manner, whereas the anterior temporal cortical region was activated during retrieval of remote memory in a category-general manner. Furthermore, by applying a multivariate pattern analysis to psychophysiological interactions during retrieval of remote memory relative to recent memory, we revealed the significant interaction from the category-specific posterior temporal cortical regions to the category-general anterior temporal region. These results suggest that the posterior temporal cortical regions are involved in representation and retrieval of category-specific remote memory, whereas the anterior cortical temporal region is involved in category-general retrieval process of remote memory.