Hiroshi Fukushima

Tokyo Medical and Dental University | TMDU · Department of Urology

Near-infrared photoimmunotherapy (NIR-PIT) is a newly developed cancer therapy that targets cancer cells using a monoclonal antibody-photon absorber conjugate (APC) that is bound to the target cell surface. Subsequent application of low levels of NIR light results in immediate cancer cell death. The anti-tumor effect of NIR-PIT in immunocompromised...

Background and objective: Muscle-invasive bladder cancer (MIBC) is a biologically aggressive disease and its prognosis is poor. Radical cystectomy (RC) with urinary diversion and lymph node dissection is the gold standard treatment for MIBC patients. Accumulating evidence indicates that sarcopenia, the degenerative and systemic loss of skeletal mu...

Programmed cell death 1 (PD-1) blockade therapy can result in dramatic responses in some cancer patients. However, about 15% of patients receiving PD-1 blockade therapy experience rapid tumor progression, a phenomenon termed "hyperprogressive disease" (HPD). The mechanism(s) underlying HPD has been difficult to uncover because HPD is challenging to...

Near-infrared photoimmunotherapy (NIR-PIT) is a new cancer treatment that utilizes an antibody-IRDye700DX (IR700) conjugate that binds to a target followed by the application of NIR light that results in dramatic changes in solubility of the conjugate leading to rapid cell membrane damage and highly immunogenic cell death. NIR-PIT has been used cli...

Background: While the controlling nutritional status (CONUT) score and sarcopenia are objective indices of different aspects of a patient's general condition, few studies have comprehensively examined their mutual relationship in patients with advanced cancer. Methods: This retrospective study included 200 Japanese patients with advanced urothel...

Regulatory T cells (Tregs) play a crucial role in mediating immunosuppression in the tumor microenvironment. Furthermore, Tregs contribute to the lack of efficacy and hyperprogressive disease upon Programmed cell death protein 1 (PD-1) blockade immunotherapy. Thus, Tregs are considered a promising therapeutic target, especially when combined with P...

Background: Solasonine has been demonstrated to exert an inhibitory effect on bladder cancer (BC), but the potential mechanisms remain unclear. Therefore, the aim of this study is to explore the association between microRNAs (miRNAs)-mediated regulation and the anti-tumor activities of solasonine in BC. Methods: MiRNA sequencing was performed to...

Near‐infrared photoimmunotherapy (NIR‐PIT) is a new type of cancer therapy that employs antibody‐IRDye700DX conjugates (AbPCs) and near‐infrared (NIR) light at a wavelength of 689 nm, the excitation wavelength of IR700. Administered intravenously, injected AbPCs bind specifically to cells expressing the target antigen, whereupon NIR light exposure...

Introduction: F3 is a cell surface protein that plays a role in blood clotting, but recent research has revealed its implication in cancer proliferation, metastasis, angiogenesis, and immune escape. TCGA cohort analysis has shown that elevated F3 is a common feature of many cancers, and generally correlates with poor patient survival. Therefore, th...

Background Noninvasive in vivo cell tracking is valuable in understanding the mechanisms that enhance anti-cancer immunity. We have recently developed a new method called phototruncation-assisted cell tracking (PACT), that uses photoconvertible cell tracking technology to detect in vivo cell migration. This method has the advantages of not requirin...

Epidermal growth factor receptor (EGFR) has emerged as an important therapeutic target in many cancers, and overexpression of EGFR is frequently observed in hepatocellular carcinomas (HCCs). Near-infrared photoimmunotherapy (NIR-PIT) is a new anticancer treatment that selectively damages the cell membrane of cancer cells after NIR light-induced pho...

Interleukin (IL)-15 is a potent inducer of differentiation and proliferation of CD8+ T and natural killer (NK) cells, making it a promising candidate for cancer immunotherapy. However, limited efficacy of systemic monotherapy utilizing intravenous IL-15 suggests needs for alternative routes of administration or combination treatment with other ther...

Background & aims: Recently, the strength, assistance with walking, rise from a chair, climb stairs, and falls (SARC-F) questionnaire has been developed to screen patients with signs of sarcopenia. However, its clinical benefit remains uncertain in elderly patients undergoing elective major surgeries. This study aimed to explore the role of the SA...

Objectives: Recent studies suggest that the radiological infiltrative feature (r-IF) of renal tumors is strongly correlated with poor oncologic outcomes in locally advanced renal cell carcinoma (RCC). This study investigated the prognostic impact of r-IF of primary renal tumors in metastatic RCC (mRCC) in comparison with International Metastatic R...

Aim: Evaluation of lymphatic drainage can be challenging to differentiate between separate drainage basins because only one 'color' is typically employed in sentinel node studies. This study aimed to test the feasibility of multicolor in vivo lymphangiography using newly developed organic polymer dots. Materials & methods: Biocompatible, purely org...

Near-infrared photoimmunotherapy (NIR-PIT) is a new anti-cancer treatment by NIR light-induced photochemical reactions within antibody-IRdye700DX conjugates, leading to significant immunogenic cell death. The efficacy of NIR-PIT is synergistically enhanced by combining immune activating agents including immune checkpoint inhibitors and cytokines. H...

The bones are a common site for metastasis arising from solid tumors such as breast and prostate cancer. Chemotherapy, including immunotherapy, is rarely curative. Radiotherapy with pain palliation can temporize bone metastases but is generally considered a short-term solution and retreatment is difficult. Surgery is often necessary, yet recovery t...

Background Unexpected adverse pathology is a major concern in surgical management of clinically localised renal cell carcinoma (RCC). Further studies are needed to improve preoperative risk stratification. Objective To define and classify tumour shape irregularity (TSI) based on preoperative imaging, and to investigate its effect on pathological a...

Background Adrenocortical carcinoma is an aggressive tumor which often recurs despite apparent complete resection. This study assessed the long-term outcomes for patients with recurrent adrenocortical carcinoma after multimodal salvage therapy with chemotherapy, chemoradiotherapy and surgery. Methods We retrospectively reviewed medical records of...

Objectives: Accurately predicting of progression is important for patients with non-muscle-invasive bladder cancer (NMIBC). We previously reported that bladder neck involvement (BNI) was significantly associated with progression of NMIBC. In this study, we evaluated the prognostic significance of the detailed BNI location in NMIBC patients. Metho...

The immune system is recognized as an important factor in regulating the development, progression, and metastasis of cancer. Myeloid-derived suppressor cells (MDSCs) are a major immune-suppressive cell type by interfering with T cell activation, promoting effector T cell apoptosis, and inducing regulatory T cell expansion. Consequently, reducing or...

Near-infrared photoimmunotherapy (NIR-PIT) is a cell-specific cancer therapy that uses an antibody-photoabsorber (IRDye700DX, IR700) conjugate (APC) and NIR light. Intravenously injected APC binds the target cells, and subsequent NIR light exposure induces immunogenic cell death only in targeted cells. Panitumumab and cetuximab are antibodies that...

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer and conventional chemotherapy and molecular-targeted therapies show limited efficacy. Near-infrared photoimmunotherapy (NIR-PIT) is a new anti-cancer treatment that selectively damages the cell membrane of cancer cells based on NIR light-induced photochemical react...

Near-infrared photoimmunotherapy (NIR-PIT) is a novel cancer treatment modality that utilizes antibody-photoabsorber conjugates (APCs) and selectively kills target cells after irradiation with NIR light. Originally, NIR-PIT was targeted against cancer cell surface antigens, but as it became clear that NIR-PIT induced a strong immune response, an ef...

Near-infrared photoimmunotherapy (NIR-PIT) is a novel molecularly-targeted therapy that selectively kills cancer cells by systemically injecting an antibody-photoabsorber conjugate (APC) that binds to cancer cells, followed by the application of NIR light that drives photochemical transformations of the APC. APCs are synthesized by selecting a mono...

Photoconvertible tracking strategies assess the dynamic migration of cell populations. Here we develop phototruncation-assisted cell tracking (PACT) and apply it to evaluate the migration of immune cells into tumor-draining lymphatics. This method is enabled by a recently discovered cyanine photoconversion reaction that leads to the two-carbon trun...

Purpose To investigate the utility of radiomics features of diffusion-weighted magnetic resonance imaging (DW-MRI) to differentiate fat-poor angiomyolipoma (fpAML) from clear cell renal cell carcinoma (ccRCC). Materials and methods This multi-institutional study included two cohorts with pathologically confirmed renal tumors: 65 patients with ccRC...

V-domain immunoglobulin suppressor of T cell activation (VISTA) is an inhibitory immune checkpoint molecule that is broadly expressed on lymphoid and myeloid cells, including regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs). Near-infrared photoimmunotherapy (NIR-PIT) is a cancer treatment that utilizes an antibody-photoabsorb...

Photoconvertible tracking strategies examine the dynamic migration of various cell populations. Here we develop phototruncation-assisted cell tracking (PACT) and apply it to evaluate the migration of immune cells into tumor-draining lymphatics. This approach is enabled by a recently discovered cyanine photoconversion reaction that leads to the two-...

Near-infrared photoimmunotherapy (NIR-PIT) is a newly developed cancer treatment that utilizes an antibody-photoabsorber-conjugate (AbPC) combined with NIR light. The AbPC is injected and binds to the tumor whereupon NIR light irradiation causes a photochemical reaction that selectively kills cancer cells. NIR-PIT is ideal for surface-located skin...

Prognostic accuracy of the quick sequential organ failure assessment (qSOFA) score for mortality may be limited in elderly patients. Using our multi-institutional database, we classified obstructive acute pyelonephritis (OAPN) patients into young and elderly groups, and evaluated predictive performance of the qSOFA score for in-hospital mortality....

Objectives To report experience with focal brachytherapy (FB) and compare its clinical outcomes with those of radical prostatectomy (RP) in localized prostate cancer. Methods Fifty-one patients with low- to intermediate-risk prostate cancer underwent low-dose-rate FB. Survival rates free from biochemical failure (BF), additional treatment (AT) inc...

Background: Reports on the prognostic significance of serum γ-glutamyltransferase (GGT) in men with metastatic castration-resistant prostate cancer (mCRPC) are limited. In addition, GGT expression status in cancer tissues has not been well characterized regardless of cancer types. Methods: This retrospective study included 107 consecutive men wi...

Aim: We aimed to explore the association between cancer cachexia phenotypes in the early phase of treatment induction and the prognosis of advanced urothelial cancer (aUC) patients receiving pembrolizumab. Methods: This retrospective study included 31 aUC patients treated with pembrolizumab as a second- or later-line therapy. Patients were categ...

Near-infrared photoimmunotherapy (NIR-PIT) is a new cancer treatment that utilizes antibody-IRDye700DX (IR700) conjugates. The clinical use of NIR-PIT has recently been approved in Japan for patients with inoperable head and neck cancer targeting human epidermal growth factor receptor (hEGFR). Previously cytotoxic T-lymphocyte antigen 4 (CTLA4)-tar...

Objectives To evaluate the trends and safety of robot-assisted partial nephrectomy during the initial 2-year period after government approval for this type of procedure in April 2016. Methods This nationwide retrospective study included 3722 received robot-assisted partial nephrectomy cases carried out from April 2016 to March 2018 in 124 particip...

Objectives Locally advanced renal cell carcinoma is considered clinically aggressive, despite heterogeneity in survival outcomes. We investigated the clinical relevance and pathological implications of infiltrative tumor interface with normal renal parenchyma on preoperative imaging in locally advanced renal cell carcinoma. Methods A total of 77 p...

Objectives To evaluate the incidence of perioperative infections without antimicrobial prophylaxis in patients undergoing clean surgeries for adrenal and renal tumors. Methods We prospectively enrolled 1362 consecutive patients who underwent minimally invasive adrenalectomy (n = 303), radical nephrectomy (n = 499), and partial nephrectomy (n = 560...

Near-infrared photoimmunothrapy (NIR-PIT) is a cell selective cancer therapy which uses an antibody-photoabsorber conjugate (APC) and NIR light. NIR-PIT targeting epidermal growth factor receptor (EGFR) in head and neck cancer (HNC) was conditionally approved in Japan in 2020. APC-bound tumors can be detected by endoscopic fluorescence imaging whil...

Purpose To evaluate the impact of modifications to anatomical apical dissection including a puboprostatic open-collar technique, which visualizes the lateral aspect of the apex and dorsal vein complex (DVC) covering the rhabdosphincter while preserving the puboprostatic collar, on positive surgical margin (PSM) and continence recovery. Methods One...

BACKGROUND Whole‐body diffusion‐weighted MRI (WB‐DWI) is useful for assessing disease activity in castration‐resistant prostate cancer (CRPC). MET‐RADS‐P is a subjective assessment‐based reporting system proposed to standardize the interpretation of WB‐DWI. However, a quantitative evaluation of WB‐DWI has not been fully investigated. PURPOSE To in...

The therapeutic benefit of immune checkpoint inhibitor monotherapy is limited to a subset of patients in urothelial carcinoma (UC). Previous studies showed the immunogenicity of cisplatin and irradiation. Here, we investigated whether chemoradiotherapy (CRT), a combination of cisplatin and irradiation, could improve the efficacy of postirradiation...

Radiotherapy plus immune checkpoint inhibitors can potentially induce synergistic antitumor immune responses. However, little clinical evidence is established regarding their combination therapy. Here, we aimed to assess whether radiotherapy to the primary tumor impacts on the efficacy of pembrolizumab in advanced urothelial cancer. We retrospectiv...

Sarcopenia, the degenerative and systemic loss of skeletal muscle mass, is a multifactorial syndrome reflecting frailty, poor general health status, and the possible presence of cancer cachexia. Here, we aimed to investigate the effect of sarcopenia on the efficacy of pembrolizumab in patients with advanced urothelial carcinoma (aUC). This retrospe...

Introduction An association between the development of overall or specific immune-related adverse events (irAEs) and outcomes of immune checkpoint inhibitors has recently been suggested. To address this emerging association in urothelial cancer patients receiving pembrolizumab, we conducted a multicenter retrospective analysis which is the first an...

Objective To investigate the prognostic significance of contact with the renal sinus in patients with clear cell renal cell carcinoma. Methods A total of 787 pT1N0M0 clear cell renal cell carcinoma patients who had undergone radical or partial nephrectomy were reviewed retrospectively. A tumor in contact with the renal sinus was defined as a tumor...

A 38-year-old female developing pelvic lymph node recurrence (cN2) of bladder cancer was referred to our hospital. Eighteen months earlier, she had received complete transurethral resection of bladder tumor and pathological diagnosis of muscle-invasive urothelial carcinoma with micropapillary variant had been made. She had declined radical cystecto...

We herein report a rare case of nontraumatic urethral rupture. The patient presented with oliguria, perineal pain and anorexia, and a 3 cm fistula was located in the perineum. Computed tomography revealed a retroperitoneal abscess invading the urethra, and a retrograde urethrogram revealed the rupture of the membranous urethra. He had no history of...

Introduction: We aimed to evaluate the incidence and risk factors for nephrectomy-related hypertension (NR-HT) in patients with renal tumors who underwent partial nephrectomy (PN) or radical nephrectomy (RN). Patients and methods: A retrospective cross-sectional follow-up survey of postoperative home blood pressure (BP) and defined daily dose (D...

Background: Intermediate-risk non-muscle-invasive bladder cancer (NMIBC) involves heterogeneous patients, resulting in uncertainty regarding its prognosis and the indication of adjuvant therapy. Previous studies suggested a correlation between tumor location, especially bladder neck involvement (BNI), and patient prognosis of NMIBC. Objective: W...

Objective To assess the feasibility and functional/oncological outcomes of selective tetramodal bladder‐preservation therapy in elderly patients with muscle‐invasive bladder cancer. Methods This study analyzed 154 patients with non‐metastatic muscle‐invasive bladder cancer who were enrolled into the protocol. After maximal transurethral resection...

Background: There is no clear consensus regarding gender differences in the prognosis of patients with clear-cell renal cell carcinoma (ccRCC). In the present study, we investigated the prognostic value of gender in patients with non-metastatic ccRCC undergoing curative surgery using the inverse probability of treatment weighting (IPTW) method to...

Objectives To evaluate the impact of fluorodeoxyglucose uptake on positron emission tomography/computed tomography on chemosensitivity and survival in patients with metastatic urothelial carcinoma. Methods The present study assessed 51 metastatic urothelial carcinoma patients undergoing fluorodeoxyglucose positron emission tomography/computed tomo...