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  • Ogawa, Hiroomi  (8)
  • Shiraishi, Takuya  (8)
  • 1
    In: Surgical Case Reports, Springer Science and Business Media LLC, Vol. 7, No. 1 ( 2021-12)
    Abstract: No standard treatment for anorectal fistula cancer, such as multidisciplinary therapy, has been established due to the rarity of the disease. Herein, we investigated patients with cancer associated with anorectal fistula who underwent surgery to clarify the clinicopathological characteristics and to propose future perspectives for treatment strategies. Case presentation Seven patients with cancer associated with anorectal fistula who underwent rectal amputation in our institute were analyzed with regard to clinical characteristics, pathological findings, surgical results, and prognosis. Four cases had Crohn's disease as an underlying cause. All seven cases were diagnosed as advanced stage. Preoperative [ 18 F]-fluoro-2-deoxy- d -glucose (FDG)-positron emission tomography/computed tomography (FDG-PET/CT) showed abnormal FDG accumulation in six cases including four mucinous adenocarcinomas. Three cases that received preoperative hyperthermo-chemoradiotherapy achieved pathological R0 resection. Postoperative recurrence was observed in four cases including three with Crohn's disease and one resulting in death. Conclusions Anorectal fistula cancer is rare and difficult to be diagnosed at early stages. Mucinous adenocarcinoma associated with anorectal fistula tends to exhibit abnormal FDG accumulation by FDG-PET/CT unlike common colorectal mucinous adenocarcinoma. Preoperative hyperthermo-chemoradiotherapy may be effective in obtaining pathological complete resection.
    Type of Medium: Online Resource
    ISSN: 2198-7793
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2809613-7
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  • 2
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 11, No. 1 ( 2021-06-22)
    Abstract: Ulcerative colitis (UC) is a DNA damage-associated chronic inflammatory disease; the DNA double-strand break (DSB) repair pathway participates in UC-associated dysplasia/colitic cancer carcinogenesis. The DSB/interferon regulatory factor-1 (IRF-1) pathway can induce PD-L1 expression transcriptionally. However, the association of PD-L1/DSB/IRF-1 with sporadic colorectal cancer (SCRC), and UC-associated dysplasia/colitic cancer, remains elusive. Therefore, we investigated the significance of the PD-L1/DSB repair pathway using samples from 17 SCRC and 12 UC patients with rare UC-associated dysplasia/colitic cancer cases by immunohistochemical analysis. We compared PD-L1 expression between patients with SCRC and UC-associated dysplasia/colitic cancer and determined the association between PD-L1 and the CD8+ T-cell/DSB/IRF-1 axis in UC-associated dysplasia/colitic cancer. PD-L1 expression in UC and UC-associated dysplasia/colitic cancer was higher than in normal mucosa or SCRC, and in CD8-positive T lymphocytes in UC-associated dysplasia/colitic cancer than in SCRC. Moreover, PD-L1 upregulation was associated with γH2AX (DSB marker) and IRF-1 upregulation in UC-associated dysplasia/colitic cancer. IRF-1 upregulation was associated with γH2AX upregulation in UC-associated dysplasia/colitic cancer but not in SCRC. Multicolour immunofluorescence staining validated γH2AX/IRF-1/PD-L1 co-expression in colitic cancer tissue sections. Thus, immune cell-induced inflammation might activate the DSB/IRF-1 axis, potentially serving as the primary regulatory mechanism of PD-L1 expression in UC-associated carcinogenesis.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2615211-3
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  • 3
    In: Surgical Case Reports, Springer Science and Business Media LLC, Vol. 7, No. 1 ( 2021-12)
    Abstract: Chlamydial infection is a difficult-to-diagnose type of sexually transmitted disease that occurs mainly in young people. We report a case of bowel obstruction caused by intrapelvic adhesions formed by chlamydial infection. Case presentation This patient was a 23-year-old woman who had been suffering from acute abdominal pain. She had been previously treated several times for intrapelvic abscesses and had a history of chlamydial infection. Endometriosis was thought to be the cause of her pelvic abscess based on endoscopic findings. Computed tomography demonstrated a small bowel obstruction caused by a pelvic abscess. However, the diagnosis could not be confirmed. She underwent laparoscopic surgery and was diagnosed with bowel obstruction due to adhesion of chlamydial infection based on the intraoperative findings and Chlamydia trachomatis antibody test. She was discharged 5 days after surgery. Conclusions It is necessary to consider the possibility of chlamydial infection as a cause for lower abdominal pain and unexplained bowel obstruction in female patients.
    Type of Medium: Online Resource
    ISSN: 2198-7793
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2809613-7
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  • 4
    In: Cancer Reports, Wiley, Vol. 4, No. 4 ( 2021-08)
    Abstract: Lectin‐like oxidized LDL receptor‐1 (LOX‐1) has been identified as a new marker for functional myeloid‐derived suppressor cells (MDSCs) that exhibit an immunosuppressive phenotype in the tumor microenvironment (TME). However, the role of LOX‐1 + cells in the TME of colorectal cancer (CRC) remains unknown. Aim This study aimed to determine the expression and significance of LOX‐1 in the TME of clinical CRC specimens. Methods and results We performed immunohistochemical and genetic analyses of LOX‐1, CD8, KRAS , and BRAF in 128 resected CRC specimens and determined the expression of IFN‐γ and IL‐10 using real‐time reverse transcription‐polymerase chain reaction. We analyzed the correlation between LOX‐1, TME factors, gene alteration, clinicopathological factors, and disease prognosis. The co‐expression pattern of LOX‐1, hematopoietic markers, and a fibroblast marker was evaluated using multiplex immunofluorescence staining. Low stromal LOX‐1 expression and low intratumoral CD8 + cytotoxic T‐lymphocyte (CTL) status correlated with poor prognosis. Moreover, stromal LOX‐1‐low/CD8 + CTL‐low status was the most important independent prognostic factor of poor overall survival. Most of the LOX‐1 + stromal cells were positive for CD163 + , indicating they were CD163 + M2 macrophages. Conclusions The MDSC marker, LOX‐1, was mainly expressed by M2 macrophages in CRC tissues. LOX‐1 + macrophages and CD8 + CTLs may serve as useful biomarkers for predicting the prognosis of CRC.
    Type of Medium: Online Resource
    ISSN: 2573-8348 , 2573-8348
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2920367-3
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  • 5
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 24, No. 17 ( 2023-09-04), p. 13648-
    Abstract: Human leukocyte antigen class I (HLA-I) is considered a genetic pathogen for ulcerative colitis (UC). This study aimed to investigate the significance of DNA damage and HLA-I expression in infiltrating immune cells and immune checkpoint protein PD-L1 expression in dysplasia/colitic cancer (CC) and sporadic colorectal cancer (SCRC). We performed immunohistochemical staining for HLA-I, PD-L1, γH2AX (DNA damage marker), and immune cell markers such as CD8, FOXP3, CD68, and CD163 (in surgically resected specimens from 17 SCRC patients with 12 adjacent normal mucosa (NM) and 9 UC patients with 18 dysplasia/CC tumors. The ratio of membrane HLA-I-positive epithelial cells in UC and dysplasia/CC tissues was significantly higher than that in NM and SCRC. High HLA-I expression in dysplasia/CC was associated with high positivity of γH2AX and PD-L1 expression compared to SCRC. The infiltration of CD8-positive T cells and CD68-positive macrophages in HLA-I-high dysplasia/CC was significantly higher than in UC and SCRC. Dysplasia/CC specimens with DNA damage exhibited high levels of HLA-I-positive epithelial cells with high CD8- and CD68-positive immune cell infiltration compared to UC and SCRC specimens. Targeting DNA damage in UC may regulate immune cell infiltration, immune checkpoint proteins, and carcinogenesis by modulating DNA damage-induced HLA-I antigen presentation.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 6
    In: Surgical Case Reports, Springer Science and Business Media LLC, Vol. 6, No. 1 ( 2020-12)
    Abstract: Neuroendocrine carcinomas (NECs) of the colon are among the rarest types of colorectal cancers. Among these, large cell type neuroendocrine carcinoma (LCNEC) is particularly rare. Colorectal NEC is an aggressive disease, and there are few reports of long-term survivors. Here, we report a case of LCNEC accompanied by disseminated peritoneal leiomyomatosis that was difficult to diagnose. Case presentation The case involves a 62-year-old female found to be positive for fecal occult blood by medical examination. An endoscopy revealed a tumor in the ascending colon, and the biopsy revealed poorly differentiated cancer. Abnormal FDG accumulation with peritoneal thickening was visible on 18F-fluorodeoxyglucose positron-emission tomography (FDG-PET) and suspected to be peritoneal dissemination. Laparoscopic ileocecal resection was performed for the tumor of the ascending colon with abdominal wall invasion. At that time, numerous intra-abdominal nodules were observed, indicating peritoneal dissemination. The pathological diagnosis of the primary lesion was LCNEC, and the patient requested to undergo total peritoneal resection. After one course of chemotherapy with irinotecan plus cisplatin, she underwent total peritoneal resection, uterine annex resection, left inguinal lymph node resection, and intra-abdominal hyperthermic intraperitoneal chemotherapy with mitomycin C. Because a postoperative pathological examination revealed that the intra-abdominal nodules were leiomyomas, we diagnosed the patient with disseminated peritoneal leiomyomatosis. The left inguinal lymph node was diagnosed with a metastatic tumor. In summary, the final diagnosis was LCNEC in the ascending colon with inguinal lymph node metastasis. Postoperative chemotherapy has been administered to date. She is currently 18 months post-primary surgery and 15 months post-peritonectomy without apparent recurrence or metastatic findings. Conclusion We experienced a case of Stage IVa colorectal LCNEC accompanied by disseminated peritoneal leiomyomatosis. Although the prognosis is generally poor, multidisciplinary treatment for advanced colorectal LCNEC may result in a favorable outcome for some patients. If peritoneal dissemination is suspected during operation, sampling of the nodule to confirm the pathological diagnosis is advisable.
    Type of Medium: Online Resource
    ISSN: 2198-7793
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2809613-7
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  • 7
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 24, No. 3 ( 2023-01-30), p. 2604-
    Abstract: The mammalian target of rapamycin (mTOR) is often activated in several cancers. We focused on two mTOR regulatory mechanisms: oxaliplatin-induced mTOR signaling and L-type amino acid transporter 1 (LAT1)-induced mTOR activation. High LAT1 expression in several cancers is associated with mTOR activation and resistance to chemotherapy. However, the significance of LAT1 has not yet been elucidated in colorectal cancer (CRC) patients treated with post-operative adjuvant chemotherapy. Immunohistochemistry was conducted to examine the significance of membrane LAT1 expression in 98 CRC patients who received adjuvant chemotherapy, including oxaliplatin. In vitro analysis was performed using CRC cell lines to determine the effects of LAT1 suppression on proliferation, oxaliplatin sensitivity, and mTOR signaling. LAT1 expression was associated with cancer aggressiveness and poor prognosis in 98 CRC patients treated with adjuvant chemotherapy. We found that positive LAT1 expression correlated with shorter survival in 43 patients treated with the capecitabine-plus-oxaliplatin (CAPOX) regimen. LAT1 suppression in CRC cells inhibited the proliferation potency and oxaliplatin-induced activation of mTOR signaling, and improved oxaliplatin sensitivity. LAT1 evaluation before adjuvant treatment may therefore be a sensitive marker for oxaliplatin-based regimens. Moreover, LAT1 may be a promising target for patients with refractory CRC.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 8
    In: International Journal of Cancer, Wiley
    Abstract: Chronic inflammation caused by infiltrating immune cells can promote colitis‐associated dysplasia/colitic cancer in ulcerative colitis (UC) by activating inflammatory cytokine signalling through the IL‐6/p‐STAT3 and TNFα/NF‐κB pathways. Mucosal addressin cell adhesion molecule‐1 (MAdCAM‐1) expressed on high endothelial venules promotes the migration of immune cells from the bloodstream to the gut via interaction with α4β7 integrin expressed on the immune cells. MAdCAM‐1, has therefore drawn interest as a novel therapeutic target for treating active UC. However, the role of MAdCAM‐1‐positive endothelial cells in immune cell infiltration in dysplasia/colitic cancers remains unclear. We evaluated the expression of MAdCAM‐1, CD31 and immune cell markers (CD8, CD68, CD163 and FOXP3) in samples surgically resected from 11 UC patients with dysplasia/colitic cancer and 17 patients with sporadic colorectal cancer (SCRC), using immunohistochemical staining. We used an azoxymethane/dextran sodium sulphate mouse model (AOM/DSS mouse) to evaluate whether dysplasia/colitic cancer could be suppressed with an anti‐MAdCAM‐1 blocking antibody by preventing immune cell infiltration. The number of MAdCAM‐1‐positive vessels and infiltrating CD8 + , CD68 + and CD163 + immune cells was significantly higher in dysplasia/colitic cancer than in normal, SCRC and UC mucosa. In AOM/DSS mice, the anti‐MAdCAM‐1 antibody reduced the number, mean diameter, depth of tumours, Ki67 positivity, number of CD8 + , CD68 + and CD163 + immune cells and the IL‐6/p‐STAT3 and TNF‐α/NF‐κB signalling. Our results indicate that targeting MAdCAM‐1 is a promising strategy for controlling not only UC severity but also carcinogenesis and tumour progression by regulating inflammation/immune cell infiltration in patients with UC.
    Type of Medium: Online Resource
    ISSN: 0020-7136 , 1097-0215
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 218257-9
    detail.hit.zdb_id: 1474822-8
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