Tamotsu Sagawa, Shutaro Oiwa, Masahiro Hirakawa, Nozomi Minagawa, Makoto Yoshida, Riku Miyaishi, Atsushi Uesugi, Yutaro Okazaki, Kentaro Kawamura, Yoshiaki Maeda, Hiroyuki Nagashima and Koshi Fujikawa : Pathological Complete Response Following mFOLFOX6 Plus Zolbetuximab and Conversion Surgery in Initially Unresectable CLDN18.2-Positive Advanced Gastric Cancer: A Case Report, Journal of Gastrointestinal Cancer, 57, 1, 2026.
(要約)
Zolbetuximab plus platinum-fluoropyrimidine chemotherapy has emerged as an important first-line treatment option for patients with claudin 18.2 (CLDN18.2)-positive, HER2-negative advanced gastric or gastroesophageal junction adenocarcinoma. However, pathological complete response after zolbetuximab-based induction therapy followed by conversion surgery has rarely been documented, particularly in patients with peritoneal dissemination and malignant ascites. A man in his early 50s with Eastern Cooperative Oncology Group performance status 0 was referred to our hospital with scirrhous-type gastric cancer. Initial evaluation revealed initially unresectable advanced gastric cancer with peritoneal dissemination and cytologically confirmed malignant ascites. Gastric biopsy showed poorly differentiated adenocarcinoma with signet-ring cell features. The tumor was HER2 IHC 1+, strongly CLDN18.2-positive by the VENTANA CLDN18 (43-14 A) RxDx Assay, with 90% of viable tumor cells showing 2+/3 + membranous staining, proficient mismatch repair, and PD-L1 CPS ≥ 10. First-line mFOLFOX6 plus zolbetuximab was administered every 2 weeks without dose reduction or treatment delay. After six cycles, computed tomography and esophagogastroduodenoscopy showed marked improvement. After nine cycles, conversion surgery with total gastrectomy, D2 lymph node dissection, and Roux-en-Y reconstruction was performed. Intraoperative lavage cytology was negative. Final pathology showed ypT0N0, 0/20 lymph nodes, and TRG 1a/Grade 3, consistent with pathological complete response. This case suggests that mFOLFOX6 plus zolbetuximab may induce deep radiological, endoscopic, cytological, and pathological responses and may enable R0 conversion surgery in carefully selected patients with CLDN18.2-positive initially unresectable advanced gastric cancer.
(キーワード)
CLDN18.2 / Conversion surgery / Gastric cancer / Malignant ascites / mFOLFOX6 / Pathological complete response / Zolbetuximab
Tamotsu Sagawa, Kengo Umehara, Miho Izumi, Masahiro Hirakawa, Shutaro Oiwa, Hayato Watabe, Atsushi Uesugi, Makoto Yoshida, Hiroyuki Nagashima and Koshi Fujikawa : Real-world implementation of a standardized administration protocol for zolbetuximab-associated nausea and vomiting: a retrospective supportive-care cohort study, Supportive Care in Cancer, 34, 8, 2026.
(要約)
Zolbetuximab frequently causes infusion-related nausea and vomiting, which may lead to infusion interruption in routine practice. We developed and implemented a standardized institutional protocol for zolbetuximab administration and chemotherapy-induced nausea and vomiting (CINV) management. This single-center retrospective descriptive cohort study included all consecutive eligible patients with unresectable or recurrent, HER2-negative, CLDN18.2-positive advanced gastric, or gastroesophageal junction adenocarcinoma who received zolbetuximab-containing chemotherapy between June 2024 and December 2025. The protocol incorporated structured antiemetic prophylaxis and real-time nausea assessment using the Wong-Baker FACES® Rating Scale (FRS). FRS ≥ 3 was used as an institutional operational threshold for temporary interruption and stepwise re-initiation; it was not intended to be formally equivalent to CTCAE grade 2 nausea. Seventeen consecutive patients were included, and no eligible patients were excluded after screening. During cycle 1, the acute-phase total control (TC) rate was 70.6% (12/17; 95% CI, 44.0-89.7). TC rates during the delayed, ultra-delayed, and overall phases were 70.6%, 82.4%, and 70.6%, respectively. Complete response rates were 100.0% in the acute phase and remained above 94% across all phases. Temporary infusion interruption occurred in 4 patients (23.5%); 3 interruptions (17.6%) were attributed to nausea and 1 (5.9%) to severe epigastric pain. All planned infusions were completed. Serum albumin showed a transient decline during early cycles followed by gradual recovery. In this small, non-comparative retrospective cohort, protocol-based zolbetuximab administration was feasible in routine practice, and all patients completed the planned cycle 1 infusion. Albumin findings and survival outcomes should be interpreted as exploratory and hypothesis-generating.
(キーワード)
Antiemetic prophylaxis / Chemotherapy-induced nausea and vomiting / Claudin 18.2 / Gastric cancer / Supportive care / Zolbetuximab
Tamotsu Sagawa, Masahiro Hirakawa, Shutaro Oiwa, Atsushi Uesugi, Makoto Yoshida, Hiroyuki Nagashima and Koshi Fujikawa : Clinical Outcomes of Second-Line FOLFIRI Plus Ramucirumab According to Prior Biologic Exposure in Metastatic Colorectal Cancer: A Retrospective Comparison of Prior Bevacizumab and Prior Anti-EGFR Cohorts, Journal of Gastrointestinal Cancer, 57, 1, 2026.
(要約)
Ramucirumab plus FOLFIRI is an established second-line treatment option for metastatic colorectal cancer (mCRC) after oxaliplatin-based first-line therapy. However, real-world data comparing outcomes according to prior biologic exposure are limited. We retrospectively reviewed patients with mCRC who received second-line FOLFIRI plus ramucirumab after oxaliplatin- and fluoropyrimidine-based first-line therapy combined with either bevacizumab or an anti-EGFR antibody. Efficacy, safety, and subsequent treatment patterns were evaluated. Among 135 screened patients, 85 were included: 55 in the prior bevacizumab group and 30 in the prior anti-EGFR group. The prior anti-EGFR group was enriched for RAS wild-type tumors (100.0% vs. 12.7%) and left-sided primary tumors (90.0% vs. 58.2%). The objective response rate was 9.1% versus 33.3%, median progression-free survival was 6.1 versus 7.9 months, and median overall survival was 19.8 months (95% CI, 14.0-27.5) versus 31.5 months (95% CI, 11.0-37.8), respectively. Adverse events were manageable in both groups, without a marked increase in severe proteinuria in the prior bevacizumab group. Second-line FOLFIRI plus ramucirumab showed clinically meaningful activity and manageable toxicity after either prior biologic strategy. The more favorable outcomes observed in the prior anti-EGFR cohort should be interpreted as hypothesis-generating because of baseline biologic imbalance and potential confounding.
(キーワード)
Anti-EGFR antibody / Bevacizumab / FOLFIRI / Metastatic colorectal cancer / Ramucirumab / Real-world study
Shutaro Oiwa, Tamotsu Sagawa, Hayato Watabe, Masahiro Hirakawa, Atsushi Uesugi, Makoto Yoshida, Hiroyuki Nagashima and Koshi Fujikawa : Surgical Intervention After Zolbetuximab-Based Chemotherapy for CLDN18.2-Positive Gastric and Gastroesophageal Junction Adenocarcinoma: A Case Series, Journal of Gastrointestinal Cancer, 57, 1, 2026.
(要約)
Zolbetuximab, a monoclonal antibody targeting claudin-18 isoform 2 (CLDN18.2), has demonstrated survival benefits when combined with platinum-based chemotherapy in patients with CLDN18.2-positive gastric and gastroesophageal junction (GEJ) adenocarcinoma. However, evidence regarding surgical intervention following zolbetuximab-based chemotherapy remains limited. We report four patients with CLDN18.2-positive, HER2-negative gastric or GEJ adenocarcinoma who underwent surgical intervention following zolbetuximab-based chemotherapy. Three patients initially had unresectable or marginally resectable disease and subsequently underwent conversion-intent or response-adapted surgical intervention after tumor regression and improvement of non-curative factors. One patient underwent pulmonary metastasectomy for metachronous oligometastatic disease after sustained systemic disease control. Zolbetuximab was administered in combination with mFOLFOX6 or CAPOX for a median of seven cycles. Macroscopic complete resection was achieved in three patients, whereas one patient had microscopic residual disease. No unexpected perioperative complications attributable to zolbetuximab were observed. These findings suggest that zolbetuximabbased chemotherapy may allow surgical intervention in carefully selected patients; however, the survival benefit of this approach remains unproven and requires further study. Zolbetuximab-based chemotherapy may facilitate conversion-intent or response-adapted surgical intervention, including metastasectomy, in carefully selected patients with CLDN18.2-positive gastric and GEJ adenocarcinoma. A biomarker-driven, response-adapted multidisciplinary strategy may help identify candidates for surgery following CLDN18.2-targeted therapy, but larger studies are required to determine whether this approach improves survival outcomes.
(キーワード)
CLDN18.2 / Conversion-intent surgery / Gastric cancer / Gastroesophageal junction cancer / Response-adapted surgery / Zolbetuximab
Akira Shibata, Michihiro Ono, Shutaro Oiwa, Atsushi Uesugi, Seiya Saito, Makoto Usami, Tomoyuki Abe, Masahiro Yoshida, Masahiro Maeda and Kohichi Takada : Successful Management of Suspected Epstein-Barr Virus-Associated Hemophagocytic Lymphohistiocytosis in BRAF-Mutant Cholangiocarcinoma Following Treatment With Immune Checkpoint Inhibitors and BRAF/MEK Inhibitors: A Case Report, Cancer Reports, 9, 3, e70504, 2026.
(要約)
The BRAF V600E mutation is a rare genetic alteration in cholangiocarcinoma for which sequential therapy with immune checkpoint inhibitors (ICIs) and BRAF/MEK inhibitors may be effective. However, the full spectrum of adverse events associated with the sequential use of these agents remains unclear. Hemophagocytic lymphohistiocytosis (HLH) is a fatal cytokine release syndrome that can be triggered by a cytokine storm. A 49-year-old man underwent left lateral hepatectomy and adjuvant chemotherapy for cholangiocarcinoma and subsequently developed lymph node recurrence. The patient initially received systemic chemotherapy with gemcitabine, cisplatin, and S-1; however, due to disease progression, the regimen was switched to gemcitabine, cisplatin, and durvalumab. After these treatments, a BRAF V600E mutation was identified through comprehensive gene panel testing, leading to the initiation of BRAF and MEK inhibitors. However, 3 months later, the patient presented to the emergency department of Steel Memorial Muroran Hospital with fever and fatigue in June 2024. He was initially diagnosed with septic shock but was unresponsive to broad-spectrum antibiotics. Laboratory tests revealed elevated ferritin levels, elevated soluble interleukin-2 receptor levels, and Epstein-Barr Virus (EBV)-DNA. HLH was diagnosed, and multidisciplinary treatment, including steroid pulse therapy, was initiated. The patient's condition improved dramatically, and he survived. We report a rare case of cholangiocarcinoma with suspected EBV-associated HLH that developed after sequential therapy with an ICI and BRAF/MEK inhibitors. Clinicians should consider HLH as a differential diagnosis in patients with a history of ICI therapy who present with severe unexplained inflammation or shock. Prompt diagnosis and multidisciplinary management are crucial to prevent death.
Atsushi Uesugi, Kumiko Kamada, Keiko Kudoh and Naito Kurio : Recurrent Ameloblastoma of the Mandibular Ramus Resected Using a Modified High Perimandibular Approach: A Case Report, Case Reports in Dentistry, 2026, 1, 2026.
Kumiko Kamada, Atsushi Uesugi, Naoyuki Fukuda, Natsumi Takamaru and Naito Kurio : Alveolar Ridge Bone Augmentation Using Carbonate Apatite Granules as a Novel Bone Substitute for Orthodontic Tooth Movement: A Report of the First Case, Curēus, 17, 9, e91521, 2025.
10.
栗尾 奈愛, 鎌田 久美子, 上杉 篤史, 常松 貴明, 工藤 保誠 : 頬粘膜に発生した基底細胞腺腫の1例, Journal of Oral Health and Biosciences, 37, 1, 18-23, 2024年.
(要約)
Basal cell adenoma (BCA) is a rare type of benign salivary gland tumor. It frequently occurs in the parotid glands but rarely in the minor salivary grands. We report a rare case of BCA of the buccal mucosa. A 81-year-old man presented to our department with a mass of his left side of buccal mucosa. Intraoral examination revealed an elastic-hard, mobile, well-circumscribed submucosal mass covered with normal mucosa, measuring about 15 mm in diameter. Ultrasonography showed well-defined hypoechoic area and slight blood flow. Clinical diagnosis was a benign buccal tumor. The tumor excision was performed under intravenous sedation. Since the tumor had distinct capsule and no adhesion with surrounding tissue, it was easily resected. Histopathological examination revealed that the tumor was encapsulated by thin fibrous connective tissue. Some tumor nests presented with biphasic tubular structure composed of inner luminal cells and outer basaloid and myoepithelial cells. Immunohistochemical examination revealed that the basaloid and the myoepithelial cells were positive for p63 and the luminal cells and the stromal cells were positive for S-100. Ki-67 labeling index was less than 1%. Histopathological diagnosis was BCA. The postoperative course was uneventful. Tumor recurrence has not been observed over 3 years.
Atsushi Uesugi, Fumihiko Tsushima, Youji Miyamoto and Hiroyuki Harada : Pollen food allergy syndrome caused by Japanese radish: A case report, Indian Journal of Dermatology, 68, 1, 123, 2023.
(要約)
Pollen food allergy syndrome (PFAS) is a food allergy that manifests as hypersensitivity symptoms of the oropharyngeal mucosa on ingesting specific foods, and findings resemble herpetic gingivostomatitis. Few reports of PFAS caused by consuming radishes are found in the literature. A 31-year-old man presented to our department with stomatitis and pharyngeal pain. He had no history of allergies. Herpetic gingivostomatitis was suspected. He was admitted to the emergency room a few days later complaining of oral and epigastric pain. Symptoms were similar to those reported previously. He reported frequently consuming raw Japanese radish ( L.) which gave rise to his symptoms. Japanese radish was suspected as the allergen. The skin-prick test confirmed the diagnosis of PFAS. PFAS can be diagnosed easily once the food-causing symptoms are identified. Upon encountering widespread erosion in the oral cavity, it is essential to consider PFAS as the possible cause.
(キーワード)
herpetic gingivostomatitis / Japanese radish / pollen food allergy syndrome / Raphans sativus L. / skin prick test
山村 佳子, 鴨居 耕平, 工藤 景子, 栗尾 奈愛, 鎌田 久美子, 横田 美保, 上杉 篤史, 宮本 洋二 : A Case of Ameloblastoma Removed Using a Three-dimensional Transparent Plastic Jaw Model Which Can Visualize Internal Jawbone Structures, Journal of Oral Health and Biosciences, 35, 1, 9-13, 2022年.
(キーワード)
ameloblastoma / three-dimensional jaw model / three-dimensional printer / visualization
Fumihiko Tsushima, Jinkyo Sakurai, Atsushi Uesugi, Yu Oikawa, Toshimitu Ohsako, Yumi Mochizuki, Hideaki Hirai, Kou Kayamori and Hiroyuki Harada : Malignant transformation of oral lichen planus: a retrospective study of 565 Japanese patients, BMC Oral Health, 21, 1, 298, 2021.
(要約)
Oral lichen planus (OLP) is a chronic inflammatory oral mucosa disease that is recognized as an oral potentially malignant disorder. However, the potentially malignant nature of OLP remains unclear. We designed this study to examine the demographic and clinical characteristics of patients with OLP and evaluate the associated malignant transformation rate. A total of 565 patients with a clinical and histopathological diagnosis of OLP who presented at our department between 2001 and 2017 were retrospectively studied. Patients who had clinical and histopathological features of oral lichenoid lesions (OLLs) classified as oral lichenoid contact lesions, oral lichenoid drug reactions and oral lichenoid lesions of graft-versus-host disease were excluded. The study population included 123 men and 442 women aged 21-93 years (mean ± standard deviation, 60.5 ± 11.8). The 565 patients were followed up for a duration of 55.9 ± 45.3 months, during which 4 (0.7%) patients developed squamous cell carcinoma (SCC). In three of these 4 patients who developed SCC, the clinical type of OLP was the red type. Our results suggested that OLP was associated with a low risk of malignant transformation. We recommend regular follow-up for OLP patients and clear differentiation of oral epithelial dysplasia and OLLs to enable early detection of malignant transformation. Further investigation of the clinical risk factors associated with malignant transformation is necessary.
Atsushi Uesugi, K. Mochida, H. Harada and H. Imai : Ossifying fibroma arising from the zygomatic arch: A case report, Journal of Stomatology, Oral and Maxillofacial Surgery, 121, 3, 288-291, 2019.
(要約)
Ossifying fibroma (OF) is a rare type of tumor characterized by fibrous tissue proliferation with cementum- or bone-like hard tissue formation. Since its first report by Montgomery in 1927, several cases of OF have been reported; however, no cases of OF arising from the zygomatic arch have been reported. Herein, we report a case of OF arising from the zygomatic arch. A 70-year-old female visited our department in February 2017 because of a gradually growing osseous protrusion in the right zygomatic region, which she was aware of since the previous 6 months. A 3.3cm×3.2-cm area of swelling was observed in the region. Computed tomography confirmed the presence of a granulated lesion on the surface of the right zygomatic arch. Accordingly, benign bone tumor was diagnosed, and tumor resection was subsequently performed. Histopathological analysis revealed irregularly arranged bone trabeculae, an increased number of fibroblasts, and collagen fibers between the bone trabeculae; accordingly, OF was diagnosed. No clinical or radiographic evidence of recurrence was observed during the 1.5-year follow-up period. A granulated lesion was present on the surface of the right zygomatic arch, and the boundary between the lesion and surrounding bone was clear. Resection of the lesion from the zygomatic arch was relatively easy. Thus, OF was diagnosed. If OF is suspected, a risk of recurrence persists; therefore, shaving the area including the bones surrounding the lesion may be necessary. Although detailed causes of OF and osteoma remain unknown, past trauma has been indicated as a common etiology. However, compared with the frequency of fractures in the zygomatic arch, the frequency of OF and osteoma is rare; thus, the etiology of OF and osteoma remains to be fully elucidated.
Yuri Kuribayashi, Fumihiko Tsushima, Ichi Kei Morita, Kanako Matsumoto, Jinkyo Sakurai, Atsushi Uesugi, Kiyoshi Sato, Seiichiro Oda, Kei Sakamoto and Hiroyuki Harada : Long-term outcome of non-surgical treatment in patients with oral leukoplakia, Oral Oncology, 51, 11, 1020-1025, 2015.
(要約)
The standard treatments for oral leukoplakia range from careful observation to complete resection. No surgical intervention is chosen for several supposable reasons. Surgical treatment and no surgical treatment for oral leukoplakia have no defined basis for comparisons, and few studies have reported on the long-term outcomes of oral leukoplakia without surgery. This study aimed to identify the important factors using a long-term wait-and-see policy in patients with oral leukoplakia. In total, 237 lesions from 218 patients selected for non-surgical therapy between 2001 and 2010 were analyzed. On the basis of long-term follow-up data, lesions were classified as unchanged, reduced, disappeared, expanded, and malignantly transformed. In total, 135 (57.0%) lesions remained unchanged, 30 (12.7%) lesions were characterized by a reduction in size or clinical severity, and 44 (18.6%) lesions had disappeared. Another 17 (7.2%) lesions resulted in spread or clinical deterioration, and 11 (4.6%) lesions developed oral squamous cell carcinoma. We demonstrated a cumulative malignant transformation rate of 11.6% in 10years without resection. The lesions that were nonhomogeneous, and higher degree of epithelial dysplasia, located on the tongue were likely to progress into cancer. In addition, 32.5% of lesions without surgical treatment were reduced or disappeared. There is a possibility that removal of considerable irritation for a long time contributes to the treatment of this disease. The development of appropriate treatments for oral leukoplakia is required, which will enable successful differentiation between surgical and observation cases.
Tomohiko Tsuruta, Ichi Ken Kozaki, Atsushi Uesugi, Mayuko Furuta, Akira Hirasawa, Issei Imoto, Nobuyuki Susumu, Daisuke Aoki and Johji Inazawa : miR-152 is a tumor suppressor microRNA that is silenced by DNA hypermethylation in endometrial cancer, Cancer Research, 71, 20, 6450-6462, 2011.
(要約)
The etiology and development of human cancers that remain little understood might be enlightened by defining tumor suppressor microRNAs (TS-miRNA). In this study, we identified TS-miRNAs silenced by aberrant DNA hypermethylation in endometrial cancer. Functional screening of 327 synthetic miRNAs in an endometrial cancer cell proliferation assay identified 103 miRNAs that inhibited cell growth. We then determined the sequence, DNA methylation status, and expression levels of these miRNAs in endometrial cancer cell lines and primary tumors. These determinations led to the identification of miR-152 as a candidate TS-miRNA gene in endometrial cancer. Epigenetic silencing documented in miR-152 was consistent with its location at 17q21.32 in intron 1 of the COPZ2 gene, which is also silenced often in endometrial cancer by DNA hypermethylation, and also with evidence that miR-152 targets the DNA methyltransferase DNMT1. Notably, restoration of miR-152 expression in endometrial cancer cell lines was sufficient to inhibit tumor cell growth in vitro and in vivo. We identified E2F3, MET, and Rictor as novel candidate targets of miR-152, suggesting how its epigenetic silencing can drive endometrial carcinogenesis. Our findings define a central role for miR-152 in endometrial cancer, and they also suggest its use in new therapeutic strategies to treat this cancer.
Atsushi Uesugi, Ichi Ken Kozaki, Tomohiko Tsuruta, Mayuko Furuta, Ichi Kei Morita, Issei Imoto, Ken Omura and Johji Inazawa : The tumor suppressive microRNA miR-218 targets the mTOR component rictor and inhibits AKT phosphorylation in oral cancer, Cancer Research, 71, 17, 5765-5778, 2011.
(要約)
The incidence of oral squamous cell carcinoma (OSCC) is rising rapidly in developed countries, posing a growing challenge due to the poor management of this type of malignancy at present. In this study, we profiled tumor suppressive microRNAs (miRNAs) that are silenced by DNA hypermethylation in OSCC using a function-based screening approach. This approach employed a cell proliferation assay for 327 synthetic miRNAs in two OSCC cell lines. Among the 110 miRNAs identified in this set that exhibited inhibitory properties, we compared DNA methylation and expression status in a wider panel of OSCC cell lines and primary tumor tissues, resulting in the identification of miR-218 and miR-585 as functionally significant miRNA genes that are frequently silenced in OSCC by DNA hypermethylation. Ectopic expression of miR-218 and miR-585 in OSCC cells lacking endogenous expression reduced cell growth in part through caspase-mediated apoptosis. Notably, miR-218 reduced levels of the rapamycin-insensitive component of mTOR, Rictor, in a manner associated with a suppression of Akt S473 phosphorylation. Together our findings define miR-585 as a tumor suppressive function that is often epigenetically silenced in OSCC, and they identify Rictor as a novel target of miR-218, suggesting that activation of the mTOR-Akt signaling pathway induced by Rictor contributes centrally to oral carcinogenesis.
Atsushi Uesugi, Fumihiko Tsushima, Makoto Kodama, Takeshi Kuroshima, Jinkyo Sakurai and Hiroyuki Harada : Oral granuloma in a pediatric patient with chronic graft-versus-host disease: a case report, World Journal of Clinical Cases, 8, 22, 5663-5669, 2020.
(要約)
Oral mucositis is often observed with graft-versus-host disease (GVHD); however, the occurrence of oral granuloma is rare. The rapid increase in granulomatous lesions should be distinguished from malignant tumors in patients with GVHD because malignant diseases can develop in those patients. This case is the youngest pediatric patient with granuloma associated with GVHD. The patient was a 1-year and 5-mo-old girl who presented to our department for the management of oral nodules. At the age of 5 mo, she was diagnosed with primary immunodeficiency disease, cord blood transplant was performed at 11 mo and bone marrow transplant at 1 year of age. After transplantation, GVHD and oral mucositis developed, and tacrolimus was administered. Interestingly, nodules appeared on the lower lip and buccal mucosa, which spontaneously disappeared. Then, a new nodule appeared on the left lateral border of the tongue. Resection was performed and the histopathological diagnosis was granuloma. The origin of these nodules were considered to be the fibroblasts activated under inflammation caused by GVHD because the calcineurin inhibitor tacrolimus acted on their proliferation. It is very important to distinguish oral granulomatous lesions from malignancies if GVHD is present at the base and if immunosuppressive agents and steroids are being administered.