Local radiotherapy for chemotherapy-refractory Kaposi's sarcoma in an HIV-infected patient: A case report and literature review.

Human immunodeficiency virus-associated Kaposi's sarcoma (HIV-KS) is a well-documented vascular tumor with a pathogenesis involving human herpesvirus-8 (HHV-8) infection. While antiretroviral therapy (ART) and chemotherapy are effective for treating most KS cases, some become refractory. In this report, we present a case of a 58-year-old man with refractory HIV-KS treated with ART and chemotherapy. Chemotherapy was eventually discontinued due to an adverse reaction, and the patient presented with painful plantar lesions that impaired ambulation. With the exclusion of visceral metastases, localized radiotherapy was administered, which resulted in significant cosmetic and functional improvements. The patient regained ambulation and lived independently, receiving additional radiotherapy as needed. This case underscores the potential use of radiotherapy for the treatment of ART-resistant KS, particularly when the patient is unresponsive to conventional chemotherapy. It also highlights the need for future research in this area.

Progress in Natural Killer T Cell-Based Immunotherapy for Cancer: Use of Allogeneic and Gene-Edited Cells.

Immune cell therapy has received attention in the clinical setting. However, current chimeric antigen receptor T cell therapies require individualized manufacturing based on patient cells, resulting in high costs and long processing times. Allogeneic immune cell therapy, which involves the use of immune cells from other donors, is emerging as a promising alternative that offers multiple advantages, including off-the-shelf availability, standardized manufacturing, and potentially stronger effector functions. Natural killer T (NKT) cells are a type of T cell that can be activated without being restricted by HLA, indicating their potential use in allogeneic cell immunotherapy. They exhibit cytotoxic activity against various cancer targets. However, their low frequency in blood limits their use in ex vivo amplification for treatment. This has led researchers to focus on allogeneic NKT cells as a potential treatment agent. In this study, we review the research on NKT cell-based immunotherapy and focus on the recent progress in clinical trials related to NKT cell-based immunotherapy worldwide. NKT cell-based therapy is not limited to specific cancer types and has been investigated in many ways worldwide over the past decade. Some clinical trials targeting NKT cells have shown promising results; however, the number of trials is low compared to those using T and natural killer cells. The use of allogeneic NKT cells may revolutionize the treatment of cancer and other diseases. However, further research and clinical trials are necessary to fully understand their efficacy, safety, and long-term benefits.

Anti-Vα24Jα18 TCR Antibody Tunes iNKT Cell Responses to Target and Kill CD1d-negative Tumors in an FcγRII (CD32)-dependent Manner.

Invariant natural killer T (iNKT) cells play an essential role in antitumor immunity by exerting cytotoxicity and producing massive amounts of cytokines. iNKT cells express invariant T-cell receptors (TCR) to recognize their cognate glycolipid antigens such as α-galactosylceramide (α-GalCer) presented on CD1d. We recently reported that iNKT cells recognize CD1d-negative leukemia cell line K562 in a TCR-dependent manner. However, it remains controversial how iNKT cells use TCRs to recognize and exhibit cytotoxic activity toward CD1d-negative tumors cells without CD1d restriction. Here, we report that iNKT cells exerted cytotoxicity toward K562 cells via a carried over anti-Vα24 TCR mAb from positive selection by magnetic bead sorting. We found that addition of the anti-Vα24Jα18 TCR mAb (6B11 mAb) rendered iNKT cells cytotoxic to K562 cells in an FcγRII (CD32)-dependent manner. Moreover, iNKT cells treated with 6B11 mAb became cytotoxic to other CD32+ cell lines (U937 and Daudi). In addition, iNKT cells treated with 6B11 mAb suppressed K562 cell growth in a murine xenograft model in vivo. These data suggest that anti-iNKT TCR mAb treatment of iNKT cells can be applied as a therapeutic strategy to treat CD32+ cancers such as leukemia, lymphoma, and lung cancer. SIGNIFICANCE: Our findings unveiled that iNKT cells recognize and kill CD1d-negative target tumors via the anti-iNKT TCR mAb bound to CD32 at the tumor site, thereby bridging iNKT cells and CD1d-negative tumors. These findings shed light on the therapeutic potential of anti-iNKT TCR mAbs in NKT cell-based immunotherapy to treat CD1d-negative CD32+ cancers.

High IL2RA/CD25 expression is a prognostic stem cell biomarker for pediatric acute myeloid leukemia without a core-binding factor.

CD25 is an aberrant marker expressed on the leukemic stem cell (LSC) surface and an immunotherapy target in acute myeloid leukemia (AML). However, the clinical prevalence and significance of CD25 expression in pediatric AML are unknown. High IL2RA/CD25 expression in pediatric AML showed a stem cell-like phenotype, and elevated CD25 expression was associated with lower overall survival (p < .001) and event-free survival (p < .001) in the Japanese Pediatric Leukemia/Lymphoma Study Group AML-05 study. This finding was reproduced in AML without a core-binding factor in the Children's Oncology Group study cohort. High CD25 expression has prognostic significance in pediatric AML.

Sitafloxacin- Versus Moxifloxacin-Based Sequential Treatment for Mycoplasma Genitalium Infections: Protocol for a Multicenter, Open-Label Randomized Controlled Trial.

BACKGROUND: Mycoplasma genitalium is an emerging sexually transmitted pathogen associated with increasing antibiotic resistance. The current treatment guidelines recommend moxifloxacin-sequential therapy for macrolide-resistant Mgenitalium or strains with unknown resistance profiles. However, it is unclear whether sitafloxacin, a 4th-generation fluoroquinolone antibiotic, is effective against resistant strains. OBJECTIVE: This study aims to assess and compare the efficacy and safety of sitafloxacin- and moxifloxacin-based treatment regimens for managing Mgenitalium infections. METHODS: We will conduct this randomized controlled trial at multiple centers in Japan. Eligible participants include adults aged 18 years or older with a confirmed Mgenitalium infection, as determined through the nucleic acid amplification test. Patients will be randomly assigned using a stratified approach based on the treatment facility and infection site. The interventions comprise oral sitafloxacin (200 mg) daily for 7 days (with optional pretreatment of oral doxycycline, 200 mg, daily for up to 7 days), with a control group receiving oral doxycycline (200 mg) daily for 7 days followed by moxifloxacin (400 mg) daily for another 7 days. The primary outcome is the treatment success rate with a superiority margin of 10%, as confirmed through the nucleic acid amplification test. Secondary outcomes encompass changes in the bacterial load at the urogenital or rectal sites and the emergence of posttreatment-resistant mutant strains. RESULTS: Enrollment commenced in June 2023 and will conclude in December 2024, with findings anticipated by 2025. The expected success rates fall within the range of 80% for sitafloxacin and 42% for moxifloxacin against Mgenitalium carrying the G248T (S83I) mutation, based on previous studies. Accordingly, with a 5% significance level (2-sided) and 80% statistical power, we aim to recruit 50 participants per group, factoring in a 10% expected dropout rate. CONCLUSIONS: This study will provide valuable insights into the efficacy and safety of sitafloxacin- versus moxifloxacin-based sequential therapy in treating Mgenitalium infections. These findings have the potential to influence clinical guidelines, favoring more effective therapeutic choices. The multicenter approach enhances the robustness of this study. However, a limitation is the potential insufficiency of statistical power to detect posttreatment-resistant mutant strains in each group, rendering posttreatment-resistance mutations a notable concern. In the future, we may need to increase the sample size to enhance power. TRIAL REGISTRATION: Japan Registry of Clinical Trials (jRCTs031230111); https://jrct.niph.go.jp/en-latest-detail/jRCTs031230111. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/52565.

Prevalence of Asymptomatic Mpox among Men Who Have Sex with Men, Japan, January-March 2023.

We prospectively assessed asymptomatic monkeypox virus infections among men who have sex with men in Tokyo, Japan, during the initial phase of the mpox epidemic. Our findings suggest that asymptomatic infections were likely underestimated and were comparable in magnitude to symptomatic infections, highlighting the need to improve testing accessibility among high-risk populations.

Detection of foaling using a tail-attached device with a thermistor and tri-axial accelerometer in pregnant mares.

It is desirable to attend to the mare at the time of foaling in order to assist fetal delivery and prevent complications. The early detection of the onset of labor is an important issue for the equine industry. The purpose of this study was to examine the applicability of a sensor for foaling detection using the data of surface temperature (ST), roll angle (rotation about the y-axis) and y-axis (long axis of the tail) acceleration which were collected from a multimodal device attached to the ventral tail base of the mare. The data were collected every 3 minutes in 17 pregnant mares. Roll angle differences from the reference values and the mare's posture (standing or recumbent) confirmed by video were compared and associated. Cohen's kappa coefficient was 0.99 when the threshold was set as ± 0.3 radian in roll angle differences. This result clearly showed that the sensor data can accurately distinguish between standing and recumbent postures. The hourly sensor data with a lower ST (LST < 35.5°C), a recumbent posture determined by the roll angle, and tail-raising (TR, decline of 200 mg or more from the reference value in y-axis acceleration) was significantly higher during the last hour prepartum than 2-120 hours before parturition (P < 0.01). The accuracy of foaling detection within one hour was verified using the following three indicators: LST; lying down (LD, change from standing to recumbent posture); and TR. When LST, LD and TR were individually examined, even though all indicators showed that sensitivity was 100%, the precision was 13.1%, 8.1% and 2.8%, respectively. When the data were combined as LST+LD, LST+TR, LD+TR and LST+LD+TR, detection of foaling improved, with precisions of 100%, 32.1%, 56.7% and 100%, respectively. In conclusion, the tail-attached multimodal device examined in this present study is useful for detecting foaling.

Effectiveness of sitafloxacin monotherapy for quinolone-resistant rectal and urogenital Mycoplasma genitalium infections: a prospective cohort study.

BACKGROUND: Mycoplasma genitalium has a tendency to develop macrolide and quinolone resistance. OBJECTIVES: We investigated the microbiological cure rate of a 7 day course of sitafloxacin for the treatment of rectal and urogenital infections in MSM. PATIENTS AND METHODS: This open-label, prospective cohort study was conducted at the National Center for Global Health and Medicine, Tokyo, Japan from January 2019 to August 2022. Patients with M. genitalium urogenital or rectal infections were included. The patients were treated with sitafloxacin 200 mg daily for 7 days. M. genitalium isolates were tested for parC, gyrA and 23S rRNA resistance-associated mutations. RESULTS: In total, 180 patients (median age, 35 years) were included in this study, of whom 77.0% (97/126) harboured parC mutations, including 71.4% (90/126) with G248T(S83I) in parC, and 22.5% (27/120) harboured gyrA mutations. The median time to test of cure was 21 days. The overall microbiological cure rate was 87.8%. The cure rate was 100% for microbes harbouring parC and gyrA WTs, 92.9% for microbes harbouring parC G248T(S83I) and gyrA WT, and 41.7% for microbes harbouring parC G248T(S83I) and gyrA with mutations. The cure rate did not differ significantly between urogenital and rectal infection (P = 0.359). CONCLUSIONS: Sitafloxacin monotherapy was highly effective against infection caused by M. genitalium, except strains with combined parC and gyrA mutations. Sitafloxacin monotherapy can be used as a first-line treatment for M. genitalium infections in settings with a high prevalence of parC mutations and a low prevalence of gyrA mutations.

Regeneration of invariant natural killer T (iNKT) cells: application of iPSC technology for iNKT cell-targeted tumor immunotherapy.

Invariant natural killer T (iNKT) cells are a subset of innate-like T cells restricted by a major histocompatibility complex (MHC) class I-like molecule, CD1d. iNKT cells express an invariant T cell receptor (TCR) encoded by Vα14 Jα18 in mice and Vα24 Jα18 in humans and are activated by recognizing glycolipid antigens, such as α-galactosylceramide (αGalCer), presented by CD1d. iNKT cells exhibit anti-tumor activity via their NK-like cytotoxicity and adjuvant activity. Although iNKT cell-targeted immunotherapy is a conceptually promising approach, we still found a technical hurdle for its clinical implementation which is mainly due to the low frequency of iNKT cells, particularly in humans. To compensate for this, we proposed to generate adequate numbers of clinically competent NKT cells from induced pluripotent stem cells (iPSCs) for cancer immunotherapy. Toward this goal, we first obtained the proof of concept (POC) for this approach in mice. We developed a technology to differentiate iPSCs into iNKT cells (iPSC-iNKT cells) and found iPSC-iNKT cells efficiently rejected a syngeneic experimental thymoma by inducing antigen-specific CD8 T cells. After achieving the POC in mice, we developed human iPSC-iNKT cells, which had a high correlation in their gene expression profiles with parental iNKT cells. Human iPSC-iNKT cells also exhibited anti-tumor activity and adjuvant activity for human NK cells in vivo. Based on this supporting evidence for the anti-tumor activity of human iPSC-iNKT cells, we began to generate good manufacturing practice (GMP)-grade iPSC-iNKT cells. As of now, the first-in-human clinical trial of iPSC-iNKT cell therapy is ongoing as a single-agent, dose-escalation study for patients with advanced head and neck cancer. Demonstration of the safety of iPSC-iNKT cell therapy may allow us to improve the strategy by further reinforcing the therapeutic activity of iPSC-iNKT, cells either by gene-editing or combinatorial use with other immune cell products such as dendritic cells. Sixteen years after the establishment of the iPSC technology, we are reaching the first checkpoint to evaluate the clinical efficacy of iPSC-derived immune cells.

Combination of Amoxicillin 3000 mg and Probenecid Versus 1500 mg Amoxicillin Monotherapy for Treating Syphilis in Patients With Human Immunodeficiency Virus: An Open-Label, Randomized, Controlled, Non-Inferiority Trial.

BACKGROUND: Amoxicillin plus probenecid is an alternative to intramuscular benzathine penicillin G for treating syphilis in the United Kingdom. Low-dose amoxicillin is an alternative treatment option used in Japan. METHODS: We conducted an open-label, randomized, controlled, non-inferiority trial between 31 August 2018, and 3 February 2022, to compare 1500 mg low-dose amoxicillin monotherapy with the combination of 3000 mg amoxicillin and probenecid (non-inferiority margin 10%). Patients with human immunodeficiency virus (HIV) infection and syphilis were eligible. The primary outcome was the cumulative serological cure rate within 12 months post-treatment, measured using the manual rapid plasma reagin card test. Secondary outcomes included safety assessment. RESULTS: A total of 112 participants were randomized into 2 groups. Serological cure rates within 12 months were 90.6% and 94.4% with the low-dose amoxicillin and combination regimens, respectively. Serological cure rates for early syphilis within 12 months were 93.5% and 97.9% with the low-dose amoxicillin and combination regimens, respectively. Non-inferiority of low-dose amoxicillin compared with amoxicillin plus probenecid overall and for early syphilis was not confirmed. No significant side effects were detected. CONCLUSIONS: This is the first randomized controlled trial to demonstrate a high efficacy of amoxicillin-based regimens for treating syphilis in patients with HIV infection, and the non-inferiority of low-dose amoxicillin compared with amoxicillin plus probenecid was not seen. Therefore, amoxicillin monotherapy could be a good alternative to intramuscular benzathine penicillin G with fewer side effects. However, further studies comparing with benzathine penicillin G in different populations and with larger sample sizes are needed. TRIALS REGISTRATION: (UMIN000033986).

[Cancer Immunotherapy Using Allogeneic NKT Cells].

We have developed autologous NKT cell-targeted immunotherapy for lung cancer and head and neck cancer at Chiba University. We induce α-galactosylceramide(αGalCer)-pulsed antigen-presenting cells(APCs)from patients' peripheral blood mononuclear cells(PBMCs)in vitro and give them back to the patients. We transferred them intravenously to patients with lung cancer and demonstrated the potential to improve survival time. For patients with head and neck cancer, we transferred them via the nasal submucosa with ex vivo expanded autologous NKT cells. We demonstrated an increased response rate compared with αGalCer-pulsed APCs alone. This suggested that combination therapy of αGalCer-pulsed APCs and NKT cells can increase the response rate. However, NKT cells circulate at less than 0.1% in human PBMCs. Producing enough autologous NKT cells for adoptive immunotherapy is tough. Furthermore, the immunologic function of patient-derived NKT cells can vary among patients. Because stable cell production in number and nature is essential to show effective treatment results, the development of NKT cell-targeted immunotherapy is moving forward using allogeneic NKT cells worldwide. In this circumstance, we, RIKEN and Chiba University, have been developing allogeneic induced pluripotent stem cell(iPS cell)- derived NKT cell therapy. The phase Ⅰ clinical trial of iPS cell-derived NKT cell therapy for head and neck cancer is ongoing.

[Pre-Operative Factors Affecting Trifecta Achievement in the Initial Series of Robot-Assisted Partial Nephrectomy].

We investigated pre-operative factors affecting trifecta achievement in robot-assisted partial nephrectomy (RAPN). We retrospectively analyzed 81 patients who underwent RAPN from December 2016 to September 2021 with final malignant pathologies. Trifecta was defined as negative resection margin (RM),warm ischemic time (WIT) less than 25 minutes, and no severe perioperative complications (Clavien-Dindo＜III). Factors affecting trifecta achievement were analyzed using sex, age, body mass index, RENAL nephrometry score (low or moderate/high complexity), surgical approach (transabdominal or retroperitoneal), tumor diameter and surgical experiences of each surgeon. Negative RM, WIT less than 25 minutes, and no severe complications were obtained in 75 (93%), 65 (80%), and 79 patients (98%), respectively. The trifecta was achieved in 60 patients (74%). In multivariate regression analysis, surgical experience (OR:0.92, 95% CI : 0.86-0.99) was significantly associated with trifecta achievement. Receiver operating characteristic curve analysis identified 9 cases as the optimal cut-off values for the predication of trifecta achievement (AUC＝0.69,p ＝0.11). The achievement of WIT less than 25 minutes (65 vs 90%, p＜0.01) and trifecta (58 vs 84%,p ＜0.05) were significantly lower in surgical experiences less than 9 cases than in 9 or greater. We conclude that surgical experience in RAPN is an important factor affecting WIT and trifecta achievement in the initial series.

Effect of tenofovir-based HIV pre-exposure prophylaxis against HBV infection in men who have sex with men.

BACKGROUND AND AIMS: Men who have sex with men (MSM) are vulnerable to contracting HBV as a sexually transmitted infection. We evaluated the incidence of HBV infection (HBI) and the prophylactic effect of tenofovir-based pre-exposure prophylaxis (PrEP) on HBI in an MSM cohort. METHODS AND RESULTS: MSM who were older than 16 years were enrolled from January 2018 and followed up until June 2021 and tested for HIV, bacterial sexually transmitted infections, and HBsAg/ HBsAb and HBcAb every 3 months based on inclusion criteria, including HBsAg, HBcAb, HBsAb, and HIV negativity at enrollment. HBI was defined as seroconversion of HBsAg or HBcAb status. The log-rank test was used to evaluate the prophylactic effect of PrEP against HBI. As a substudy, individuals excluded from the main study due to HBs Ab positivity were evaluated for HBI incidence. Among 1577 MSM, 786 participants (546 PrEP nonusers, 131 daily PrEP users, and 109 event-driven PrEP users) met the criteria and were included. The annual incidence of HBV among PrEP nonusers (3.8%, 21 infections, with 559.5 person-years) was significantly higher ( p = 0.018, log-rank test) than that among daily PrEP users [0.77%, 1 infection (admitted nonadherence), with 129.3 person-years] and event-driven PrEP users (no infection with 93.8 person-years). Although the incidence of HBI and HIV infection decreased with PrEP use, the incidence of other sexually transmitted infections was higher in both daily and event-driven PrEP users. The annual incidence of HBV among HBsAb-positive and HBcAb-negative PrEP nonusers was 1.8% (3 infections, with 167.5 person-years). CONCLUSIONS: Tenofovir-based PrEP prevented HBI among MSM in a real-world setting.

In situ scanning electron microscopy of hydrogen embrittlement by near atmospheric-pressure hydrogen microplasma jet.

Elucidation of microstructures responsible for hydrogen embrittlement is hoped for research and development of high-strength low-alloy steel. For this purpose, a novel in situ scanning electron microscopy method of hydrogen embrittlement was developed by using a near atmospheric-pressure hydrogen microplasma jet excited by pulsed glow discharge. By the developed method, propagations of hydrogen embrittlement cracks in typical martensitic steel, Japanese Industrial Standards SCM435 steel, were successfully observed at frame rates at least up to 10.2 Hz with the same image quality as in high vacuum. The hydrogen microplasma jet neither elevated the specimen temperature nor damaged the specimen surface. Strain evolution prior to the crack propagations was also successfully observed in conjunction with the digital image correlation technique. It was found that a small electron scattering cross section of the hydrogen molecule, a large density of hydrogen ions in the near atmospheric-pressure microplasma jet, and stabilization of the glow discharge by the electron beam of the scanning electron microscope play a crucial role in the realization of the in situ observations.

A phase III clinical trial evaluating efficacy and safety of minimal residual disease-based risk stratification for children with acute myeloid leukemia, incorporating a randomized study of gemtuzumab ozogamicin in combination with post-induction chemotherapy for non-low-risk patients (JPLSG-AML-20).

The purpose of this study is to establish a treatment with appropriate intensity for children (<16 years old at diagnosis) with de novo acute myeloid leukemia (excluding acute promyelocytic leukemia and myeloid leukemia associated with Down syndrome) according to a risk stratification based on recurrent leukemic cytogenetic abnormalities and flow-cytometric minimal residual disease at end of initial induction chemotherapy and to validate the safety and efficacy of gemtuzumab ozogamicin (GO)-combined post-induction chemotherapy for the non-low-risk (non-LR) patients. The primary endpoint of this phase III study is three-year disease-free survival rate, which will be compared between the GO and non-GO arms of the non-LR (intermediate-risk and high-risk [HR]) patients. All HR patients will be allocated to allogeneic hematopoietic stem cell transplantation in first remission. This trial has been registered at the Japan Registry of Clinical Trials (jRCTs041210015).

Identification of asymptomatic Entamoeba histolytica infection by a serological screening test: A cross-sectional study of an HIV-negative men who have sex with men cohort in Japan.

BACKGROUND: Amebiasis, caused by Entamoeba histolytica, is spreading in developing countries and in many developed countries as a sexually transmitted infection. Here, we evaluated the efficacy of serological screening to identify asymptomatic E. histolytica infection as a potential epidemiological control measure to limit its spread. METHODOLOGY/PRINCIPAL FINDINGS: This cross-sectional study was carried out between January and March 2021 in an HIV-negative men who have sex with men (MSM) cohort at the National Center for Global Health and Medicine. Serological screening was performed using a commercially available ELISA kit. For seropositive individuals, we performed stool polymerase chain reaction (PCR) to determine current E. histolytica infection. We performed E. histolytica serological screening of 312 participants. None had a history of E. histolytica infection prior to the study. The overall E. histolytica seropositivity was 6.7% (21/312), which was similar to that found by the rapid plasma reagin test (17/312). We identified current infection in 8 of 20 seropositive participants (40.0%) by stool PCR. CONCLUSIONS/SIGNIFICANCE: Our serological screening approach constitutes a potentially practical epidemiological strategy. Active epidemiological surveys, in combination with an effective screening strategy for asymptomatically infected individuals, should be applied to help reduce sexually transmitted E. histolytica infections.

A four-year observation of HIV and sexually transmitted infections among men who have sex with men before and during pre-exposure prophylaxis in Tokyo.

BACKGROUND: Pre-exposure prophylaxis (PrEP) with tenofovir/emtricitabine (TDF/FTC) has been recommended worldwide. We evaluated the safety and efficacy of daily PrEP with TDF/FTC in Tokyo. METHODS: This single-center, single-arm study was performed with 124 men who have sex with men (MSM) between January 2017 and March 2021. MSM who entered into an MSM cohort from January 2017 through March 2018 and had a pre-PrEP observational period of 1 year were eligible and recruited to the study between April 2018 and March 2019 and followed for 2 years. The primary outcome was the incidence of HIV infection (per 100 person-years). Secondary outcomes were the incidence of sexually transmitted infections and adverse events, and the rate of retention and adherence to PrEP. RESULTS: There were 309 MSM registered in the cohort (mean age, 36.6 years); 124 fulfilled the criteria and were included in the study. The remaining patients were continuously followed. There was a significant decrease in incidental HIV infection among PrEP users (0 infections, 235.5 person-years) compared to non-PrEP users (11 infections [3.4%/year], 318.9 person-years; p = 0.01). The average adherence rate was consistently greater than 95%, and the retention rate at two years was approximately 80%. CONCLUSIONS: The present study showed a high prophylactic effect against HIV infection, retention, and adherence to PrEP. PrEP is feasible and highly recommended in Japan. TRIAL REGISTRATION: UMIN Clinical Trials Registry (UMIN000031040, www.umin.ac.jp), Japan Registry of Clinical Trials (jRCTs031180134).

Electrocautery ablation therapy for anal intraepithelial carcinoma: A study protocol.

BACKGROUND: Anal cancer is a human papillomavirus-related cancer. Screening with high-resolution anoscopy (HRA) and subsequent therapeutic intervention are increasingly recognized as the standard procedure for anal cancer. Generally, lesions suspected as being high-grade squamous intraepithelial lesions are biopsied and treated if they are grade 2 or 3 anal intraepithelial neoplasia (AIN). According to several studies, electrocautery ablation for grade 2 or 3 AIN is highly effective. However, relapse within and outside the targeted areas after the intervention is a clinical problem. In Japan, electrocautery ablation is not available at most facilities. Therefore, this study aims to investigate the efficacy and safety of electrocautery ablation. METHODS: This single-arm, open-label, pilot intervention study will investigate the efficacy and safety of electrocautery ablative therapy using high-frequency medical devices. Patients diagnosed with grade 2 or 3 AIN will be included and will receive ablation treatment. Then, they will be followed up at 3 and 6 months after the procedure for HRA-guided sextant biopsy. To reduce the possibility of missed lesions before and after the intervention, we will perform HRA-guided sextant biopsy routinely. In this study, a sextant biopsy is defined as at least 6 biopsies in all directions, regardless of abnormal findings under HRA. The primary outcome is the recurrence rate at 6 months, and the secondary outcomes are the adverse event and recurrence rates at 3 months. CONCLUSION: This pilot study will provide data on the effectiveness and safety of electrocautery ablation as a treatment for grade 2 or 3 AIN.

Progressive Cytopenia Developing during Treatment of Cryptococcosis in a Patient with HIV Infection and Bone Marrow Cryptococcal Infection.

Cytopenia is a common complication in patients with human immunodeficiency virus (HIV) infection. Identifying the cause is demanding because of the wide range of possible diagnoses. We herein report an HIV-infected patient with disseminated cryptococcosis involving multiple organs including the blood, brain, lungs, and bone marrow, who developed progressive pancytopenia after initiation of anti-fungal treatment with liposomal amphotericin-B (L-AMB) and flucytosine (5FC). The pancytopenia persisted despite early 5FC discontinuation. A bone marrow biopsy revealed cryptococcal infiltration and the blood examination findings recovered quickly after resuming L-AMB. Thus, this HIV-infected patient's pathological findings and clinical course suggested that the primary cause of the pancytopenia was bone marrow cryptococcosis.

Anal human papillomavirus infection and its relationship with abnormal anal cytology among MSM with or without HIV infection in Japan.

Anal high-risk human papillomavirus (hr-HPV) infection is widely considered a cause of anal cancer. However, epidemiological data are quite limited in Japan. This study investigated anal HPV infections and cytological abnormalities among MSM with or without HIV infection. Anal swabs were obtained, and cytological results were examined. Hybrid capture-based methodology was used for hr-HPV genotyping. The exclusion criterion was a history of vaccination against HPV. 644 subjects participated, and the overall prevalence of hr-HPV was 59.7% (95% CI 54.7-62.3), HIV-infected had higher prevalence than HIV-uninfected (68.9% vs 40.6%) p < .001. Among hr-HPV-infected participants, 82.8% (312/377) were infected with at least one of 9 valent vaccine-covered hr-HPV genotypes. From regression analysis, detection of abnormal cytology correlated positively with HIV infection (OR 2.17 [95% CI 1.51-3.13]), number of hr-HPV genotypes infected (OR 1.83 [1.59-2.10]), history of STI (OR 1.58 [1.14-2.22]) and No. of lifetime sexual partners (OR 1.56 [1.10-2.21]), albeit multivariate analysis identified the number of detected hr-HPV genotypes (adjusted OR 1.78 [1.54-2.06]) as the independent risk factor for abnormal cytology. High rates of anal hr-HPV infection, especially 9-valent HPV vaccine-preventable hr-HPV were detected among our MSM participants in Japan. HPV vaccination should also be encouraged for MSM in Japan.