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Suda T. Targeting therapy for hepatocellular carcinoma by delivering microRNAs as exosomal cargo. World J Gastroenterol 2024; 30:2369-2370. [PMID: 38813056 PMCID: PMC11130577 DOI: 10.3748/wjg.v30.i17.2369] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2024] [Revised: 03/06/2024] [Accepted: 04/11/2024] [Indexed: 04/30/2024] [Imported: 07/30/2024] Open
Abstract
Exosomes, the smallest extracellular vesicles, have gained significant attention as key mediators in intercellular communication, influencing both physiological and pathological processes, particularly in cancer progression. A recent review article by Wang et al was published in a timely manner to stimulate future research and facilitate practical developments for targeted treatment of hepatocellular carcinoma using exosomes, with a focus on the origin from which exosomes derive. If information about the mechanisms for delivering exosomes to specific cells is incorporated, the concept of targeted therapy for hepatocellular carcinoma using exosomes could be more comprehensively understood.
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Kamimura K, Kanefuji T, Suda T, Yokoo T, Zhang G, Aoyagi Y, Liu D. Liver lobe-specific hydrodynamic gene delivery to baboons: A preclinical trial for hemophilia gene therapy. MOLECULAR THERAPY. NUCLEIC ACIDS 2023; 32:903-913. [PMID: 37346981 PMCID: PMC10280096 DOI: 10.1016/j.omtn.2023.05.018] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/20/2023] [Accepted: 05/10/2023] [Indexed: 06/23/2023] [Imported: 09/11/2023]
Abstract
Hydrodynamics-based gene transfer has been successfully employed for in vivo gene delivery to the liver of small animals by tail vein injection and of large animals using a computer-assisted and image-guided protocol. In an effort to develop a hydrodynamic gene delivery procedure clinically applicable for gene therapy, we have evaluated the safety and effectiveness of a lobe-specific hydrodynamic delivery procedure for hepatic gene delivery in baboons. Reporter plasmid was used to assess the gene delivery efficiency of the lobe-specific hydrodynamic gene delivery, and plasmid-carrying human factor IX gene was used to examine the pattern of long-term gene expression. The results demonstrated liver lobe-specific gene delivery, therapeutic levels of human factor IX gene expression lasting for >100 days, and the efficacy of repeated hydrodynamic gene delivery into the same liver lobes. Other than a transient increase in blood concentration of liver enzymes right after the injection, no significant adverse events were observed in animals during the study period. The results obtained from this first non-human primate study support the clinical applicability of the procedure for lobe-specific hydrodynamic gene delivery to liver.
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Suda T, Yokoo T, Kanefuji T, Kamimura K, Zhang G, Liu D. Hydrodynamic Delivery: Characteristics, Applications, and Technological Advances. Pharmaceutics 2023; 15:pharmaceutics15041111. [PMID: 37111597 PMCID: PMC10141091 DOI: 10.3390/pharmaceutics15041111] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2023] [Revised: 03/20/2023] [Accepted: 03/23/2023] [Indexed: 04/03/2023] [Imported: 09/11/2023] Open
Abstract
The principle of hydrodynamic delivery was initially used to develop a method for the delivery of plasmids into mouse hepatocytes through tail vein injection and has been expanded for use in the delivery of various biologically active materials to cells in various organs in a variety of animal species through systemic or local injection, resulting in significant advances in new applications and technological development. The development of regional hydrodynamic delivery directly supports successful gene delivery in large animals, including humans. This review summarizes the fundamentals of hydrodynamic delivery and the progress that has been made in its application. Recent progress in this field offers tantalizing prospects for the development of a new generation of technologies for broader application of hydrodynamic delivery.
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Suda T, Sugimoto A, Kanefuji T, Abe A, Yokoo T, Hoshi T, Abe S, Morita S, Yagi K, Takahashi M, Terai S. Gravity assistance enables liver stiffness measurements to detect liver fibrosis under congestive circumstances. World J Hepatol 2022; 14:778-790. [PMID: 35646263 PMCID: PMC9099107 DOI: 10.4254/wjh.v14.i4.778] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Revised: 12/30/2021] [Accepted: 03/06/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND As survival has been prolonged owing to surgical and medical improvements, liver failure has become a prognostic determinant in patients with congestive heart diseases. Congestive hepatopathy, an abnormal state of the liver as a result of congestion, insidiously proceed toward end-stage liver disease without effective biomarkers evaluating pathological progression. Regular measurements of shear wave elastography cannot qualify liver fibrosis, which is a prognosticator in any type of chronic liver disease, in cases of congestion because congestion makes the liver stiff without fibrosis. We hypothesized that the effects of congestion and fibrosis on liver stiffness can be dissociated by inducing architectural deformation of the liver to expose structural rigidity. AIM To establish a strategy measuring liver stiffness as a reflection of architectural rigidity under congestion. METHODS Two-dimensional shear wave elastography (2dSWE) was measured in the supine (Sp) and left decubitus (Ld) positions in 298 consecutive cases as they were subjected to an ultrasound study for various liver diseases. Regions of interest were placed at twelve sites, and the median and robust coefficient of variation were calculated. Numerical data were compared using the Mann-Whitney U or Kruskal-Wallis test followed by Dunn's post-hoc multiple comparisons. The inferior vena cava (IVC) diameters at different body positions were compared using the Wilcoxon matched pairs signed rank test. The number of cases with cardiothoracic ratios greater than or not greater than 50% was compared using Fisher's exact test. A correlation of 2dSWE between different body positions was evaluated by calculating Spearman correlation coefficients. RESULTS The IVC diameter was significantly reduced in Ld in subjects with higher 2dSWE values in Ld (LdSWE) than in Sp (SpSWE) (P = 0.007, (average ± SD) 13.9 ± 3.6 vs 13.1 ± 3.4 mm) but not in those with lower LdSWE values (P = 0.32, 13.3 ± 3.5 vs 13.0 ± 3.5 mm). In 81 subjects, SpSWE was increased or decreased in Ld beyond the magnitude of robust coefficient of variation, which suggests that body postural changes induced an alteration of liver stiffness significantly larger than the technical dispersion. Among these subjects, all 37 with normal SpSWE had a higher LdSWE than SpSWE (Normal-to-Hard, SpSWE - LdSWE (∆2dSWE): (minimum-maximum) -0.74 - -0.08 m/sec), whereas in 44 residual subjects with abnormal SpSWE, LdSWE was higher in 27 subjects (Hard-to-Hard, -0.74 - -0.05 m/sec) and lower in 17 subjects (Hard-to-Soft, 0.04 - 0.52 m/sec) than SpSWE. SpSWE was significantly correlated with ∆2dSWE only in Hard-to-Soft (P < 0.0001). ∆2dSWE was larger in each lobe than in the entire liver. When Hard-to-Hard and Hard-to-Soft values were examined for each lobe, fibrosis-4 or platelet counts were significantly higher or lower only for Hard-to-Soft vs Normal-to-Hard cases. CONCLUSION Gravity alters the hepatic architecture during body postural changes, causing outflow blockage in hepatic veins. A rigid liver is resistant to structural deformation. Stiff-liver softening in the Ld position suggests a fibrous liver.
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Suda T, Yoshikawa S, Kanefuji T, Abe S, Hoshi T, Morita S, Yagi K, Terai S. Suppression of Noncoding RNAs as Shared Early Genetic Events in Multistep Hepatocarcinogenesis. Hepatology 2021; 74:3542-3545. [PMID: 34322887 PMCID: PMC9291528 DOI: 10.1002/hep.32077] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2020] [Revised: 07/18/2021] [Accepted: 07/24/2021] [Indexed: 02/05/2023]
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Motegi S, Yokoo T, Nozawa R, Azumi R, Kawata Y, Ogawa K, Setsu T, Mizuno KI, Nishino K, Umezu H, Kawai H, Suda T, Terai S. Long-term survival of 11 years with multidisciplinary therapy for hepatocellular carcinoma metastasis to the ovary and peritoneum: a case report. Clin J Gastroenterol 2021; 14:1211-1220. [PMID: 33978943 PMCID: PMC8298212 DOI: 10.1007/s12328-021-01434-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Accepted: 05/02/2021] [Indexed: 02/07/2023]
Abstract
We herein report a rare case of HCC metastases to the ovary and peritoneum in a 61-year-old female patient who has achieved 11-year survival with multidisciplinary therapy. The patient was diagnosed with HCC during balloon angioplasty performed for Budd-Chiari syndrome in 1994 and underwent partial hepatectomy twice. Five years after the second hepatectomy, allochronic recurrence of a single nodule detected in S8 was treated by radiofrequency ablation, followed by percutaneous ethanol injection therapy and stereotactic body radiotherapy. However, her α-fetoprotein level rose to 1862 ng/mL within one year and computed tomography revealed a large pelvic tumor suggesting HCC metastasis to the ovary. The subsequent laparotomy revealed one 11-cm left ovarian tumor, one small right ovarian nodule, and numerous peritoneal nodules. Bilateral salpingo-oophorectomy and peritoneal resection of as many nodules as possible were performed. Combination therapy with intravenous 5-fluorouracil plus cisplatin and ramucirumab monotherapy effectively suppressed tumor progression with maintenance of hepatic functional reserve, and she has achieved long-term survival of 11 years, illustrating that multidisciplinary therapy with favorable hepatic functional reserve maintenance can contribute to long-term survival in HCC with extrahepatic spread.
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Suda T, Iguchi R, Ishiyama T, Kanefuji T, Hoshi T, Abe S, Morita S, Yagi K. A Superinfection of Salmonella typhi and Hepatitis E Virus Causes Biphasic Acute Hepatitis. Intern Med 2021; 60:1717-1722. [PMID: 33431734 PMCID: PMC8222138 DOI: 10.2169/internalmedicine.6458-20] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
A 47-year-old Japanese man was referred to our hospital because of a sustained high fever with diarrhea 12 days after a flight from India. Liver enzymes were elevated with rose spots, hepatosplenomegaly, relative bradycardia, and acute cholecystitis. A liver biopsy depicted the dense infiltration of lymphocytes and Kupffer cells in sinusoids and the granulomatous formation in the parenchyma. The liver damage was initially resolved with the administration of ceftriaxone for 16 days but flared up 1 week later. Laboratory tests yielded positive reactions for Salmonella typhi and hepatitis E virus RNA. The pathophysiological presentations of concurrent typhoid and type E hepatitis are discussed.
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Morita S, Sugawara S, Suda T, Hoshi T, Abe S, Yagi K, Terai S. Conversion of percutaneous transhepatic biliary drainage to endoscopic ultrasound-guided biliary drainage. DEN OPEN 2021; 1:e6. [PMID: 35310153 PMCID: PMC8828224 DOI: 10.1002/deo2.6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/16/2020] [Revised: 01/28/2021] [Accepted: 01/30/2021] [Indexed: 02/05/2023]
Abstract
INTRODUCTION Percutaneous transhepatic biliary drainage (PTBD) is a useful alternative treatment for malignant biliary obstruction (MBO) when patients have difficulty with endoscopic transpapillary drainage. We examined the feasibility of conversion of PTBD to endoscopic ultrasound-guided biliary drainage (EUS-BD) in patients with MBO unsuited for endoscopic transpapillary biliary drainage. METHODS This retrospective study included patients who underwent conversion of PTBD to EUS-BD between March 2017 and December 2019. Eligible patients had unresectable MBO, required palliative biliary drainage, and were not suited for endoscopic transpapillary drainage. Initial PTBD had been performed for acute cholangitis or obstructive jaundice in all patients. EUS-BD was performed following improvements in cholangitis. Sixteen patients underwent conversion of PTBD to EUS-BD. We evaluated technical success, procedure time, clinical success (defined as subsequent external catheter removal), adverse events (AEs), time to recurrent biliary obstruction (TRBO), and re-intervention rates. RESULTS Technical success was achieved in all patients (100%). The median procedure time was 45.0 minutes (interquartile range [IQR] 30.0-50.0 minutes). Clinical success was achieved in all patients (100%). There were mild early AEs in two patients (12.5%) (acute cholangitis: 1, bile peritonitis: 1), which improved with antibiotic administration alone. Recurrent biliary obstruction (RBO) occurred in six patients (37.5%). Kaplan-Meier analysis revealed a 50% TRBO of 95 days (IQR 41-246 days). Endoscopic treatment was possible in all RBO cases, and repeat PTBD was not required. CONCLUSIONS Conversion of PTBD to EUS-BD for the management of MBO is both feasible and safe. This approach is expected to be widely practiced at centers with little experience in EUS-BD.
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Kamimura K, Suda T, Fukuhara Y, Okuda S, Watanabe Y, Yokoo T, Osaki A, Waguri N, Ishikawa T, Sato T, Aoyagi Y, Takamura M, Wakai T, Terai S. Adipose most abundant 2 protein is a predictive marker for cisplatin sensitivity in cancers. Sci Rep 2021; 11:6255. [PMID: 33737617 PMCID: PMC7973578 DOI: 10.1038/s41598-021-85498-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2020] [Accepted: 02/28/2021] [Indexed: 02/07/2023] Open
Abstract
Cisplatin (CDDP) is one of the chemotherapeutic drugs being used to treat various cancers. Although effective in many cases, as high doses of CDDP cause cytotoxic effects that may worsen patients' condition, therefore, a marker of sensitivity to CDDP is necessary to enhance the safety and efficiency of CDDP administration. This study focused on adipose most abundant 2 (APM2) to examine its potential as a marker of CDDP sensitivity. The relationship of APM2 expression with the mechanisms of CDDP resistance was examined in vitro and in vivo using hepatocellular carcinoma (HCC) cells, tissues and serum of HCC patients (n = 71) treated initially with intrahepatic arterial infusion of CDDP followed by surgical resection. The predictability of serum APM2 for CDDP sensitivity was assessed in additional 54 HCC patients and 14 gastric cancer (GC) patients. APM2 expression in CDDP-resistant HCC was significantly higher both in serum and the tissue. Bioinformatic analyses and histological analyses demonstrated upregulation of ERCC6L (DNA excision repair protein ERCC6-like) by APM2, which accounts for the degree of APM2 expression. The serum APM2 level and chemosensitivity for CDDP were assessed and cut-off value of serum APM2 for predicting the sensitivity to CDDP was determined to be 18.7 µg/mL. The value was assessed in HCC (n = 54) and GC (n = 14) patients for its predictability of CDDP sensitivity, resulted in predictive value of 77.3% and 100%, respectively. Our study demonstrated that APM2 expression is related to CDDP sensitivity and serum APM2 can be an effective biomarker of HCC and GC for determining the sensitivity to CDDP.Trial registration: This study was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000028487).
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Morita S, Sugawara S, Suda T, Prasetyo D, Hoshi T, Abe S, Yagi K, Terai S. Transcatheter Arterial Embolization Using Microspheres for Palliating Pain from Bone Metastasis in a Patient with Cholangiocellular Carcinoma. Intern Med 2021; 60:241-246. [PMID: 32921687 PMCID: PMC7872818 DOI: 10.2169/internalmedicine.5351-20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
A 72-year-old man with intractable left shoulder pain due to bone metastasis from cholangiocellular carcinoma was admitted to our hospital. Computed tomography showed an osteoblastic metastatic lesion of the left scapula. Since the pain persisted even after the administration of opioids and external irradiation, microspheres were injected through a catheter; the catheter tip was placed at the arteries feeding the metastatic lesion. After the intervention, the shoulder pain was alleviated without any procedure-related complications, leading to a reduction in the opioid dose. This case suggests the efficacy of transcatheter arterial embolization using microspheres for palliating pain from bone metastasis.
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Yamamoto A, Suda T, Yamauchi Y, Kondo S, Okazaki N, Takahashi K, Watanabe T, Makuuchi Y, Ota Y, Nagakawa Y, Seshimo A, Katsumata K, Itoi T, Tsuchida A. [A Case of Histological Response of Grade 3 Achieved by Preoperative Chemotherapy with S-1/Oxaliplatin(SOX)]. Gan To Kagaku Ryoho 2021; 48:139-141. [PMID: 33468747 DOI: pmid/33468747] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Histological response of Grade 3 is relatively rare in gastric cancer patients but has recently been observed occasionally. We report the histological response of Grade 3 achieved by S-1/oxaliplatin(SOX)therapy. A 66-year-old man had suffered from epigastralgia when hungry. After 1 month, he visited the department of gastroenterology of our hospital. Upper gastrointestinal endoscopy revealed a type 3 tumor at the lesser curvature of middle gastric body, and poorly differentiated adenocarcinoma was detected by the biopsy examination. Abdominal/pelvic enhanced CT showed wall thickening of the lower gastric body, enlarged regional lymph nodes and para-aortic lymph nodes(No. 16b1). We diagnosed it with Stage Ⅳ. He received 4 courses of SOX therapy. After chemotherapy, upper gastrointestinal endoscopy revealed a residual tumor, although biopsy showed no cancer cells. Abdominal/pelvic enhanced CT showed significantly reduced lymph nodes despite the thickening of the gastric wall. PET-CT revealed indistinct para-aortic lymph nodes. Distal gastrectomy, D2 dissection without para-aortic lymph nodes dissection, and Billroth Ⅰ reconstruction were performed. Histological findings showed no cancer cells in the main lesion or lymph nodes, with only previous cancer cells suspected. The histological response was Grade 3. SOX therapy might be employed in the future as chemotherapy before conversion surgery for Stage Ⅳ gastric cancer.
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Morita S, Sugawara S, Suda T, Prasetyo D, Kobayashi Y, Hoshi T, Abe S, Yagi K, Terai S. Stent Placement for Malignant Inferior Vena Cava Syndrome in a Patient with Recurrent Colon Cancer. Intern Med 2020; 59:2885-2890. [PMID: 32727985 PMCID: PMC7725633 DOI: 10.2169/internalmedicine.5033-20] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
A 70-year-old man was admitted to our hospital with gait disturbance due to marked edema of the lower limbs for more than 6 months. He had been receiving systemic chemotherapy over two years for multiple recurrence after sigmoid colon cancer resection. Contrast-enhanced computed tomography demonstrated severe inferior vena cava (IVC) stenosis due to compression by lymph node metastases, i.e. IVC syndrome. As increased doses of diuretic agents failed to improve the edema, IVC stent placement was performed. This led to significant improvement of the edema and complete gait normalization. This case demonstrates the efficacy of IVC stent placement for IVC syndrome.
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Morita S, Suda T, Kishi Y, Iwasaki T, Hiraoka N, Nagayama I, Hoshi T, Abe S, Yagi K, Hasegawa G, Ikarashi T, Terai S. Synchronous Double Bile Duct Cancers with Distinct Genetic Features. Intern Med 2020; 59:2129-2134. [PMID: 32493852 PMCID: PMC7516326 DOI: 10.2169/internalmedicine.4613-20] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
A 69-year-old man was referred to our hospital because of appetite loss. Imaging showed a nodular tumor in the perihilar bile duct and a second flat lesion in the distal bile duct. Right hepatopancreaticoduodenectomy was performed, and the histopathological findings demonstrated that the perihilar and distal lesions were moderately and poorly differentiated adenocarcinoma, respectively, and anatomically separated. Furthermore, the resected specimens showed no pancreaticobiliary maljunction. Histological and TP53 gene analyses in a rare case of synchronous double bile duct cancers suggest that there are various genetic pathways through which bile duct cancer develops, highlighting the complexity of its pathogenesis.
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Mayanagi S, Takahashi N, Mitsumori N, Arigami T, Natsugoe S, Yaguchi Y, Suda T, Kinami S, Ohi M, Kawakubo H, Sato Y, Takeuchi H, Aikou T, Kitagawa Y. Sentinel node mapping for post-endoscopic resection gastric cancer: multicenter retrospective cohort study in Japan. Gastric Cancer 2020; 23:716-724. [PMID: 31927674 PMCID: PMC7305252 DOI: 10.1007/s10120-019-01038-3] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2019] [Accepted: 12/27/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND Standard gastrectomy with systematic lymphadenectomy as an additional surgery after endoscopic resection (ER) causes a deterioration in long-term quality of life. If the sentinel lymph node (SN) basin concept can be applied in post-ER gastric cancer, minimal surgery can be applied without reducing the curability. This retrospective multicenter cohort study aimed to verify the validity of the SN basin concept in post-ER gastric cancer. PATIENTS AND METHODS Individual data of 132 patients who underwent SN mapping after ER were collected from 8 university hospitals in Japan from 2001 to 2016. Tracers were injected endoscopically in the submucosal layer at four sites around the post-ER scar. We compared the SN basin distribution of post-ER gastric cancer with that of 275 patients with non-ER gastric cancer. RESULTS Two cases of SN were unidentified, both involving a single tracer (SN detection rate: 98.5%). Nine cases (6.8%) of lymph node metastasis were found, of which eight had a metastatic lymph node within the SNs and one had a non-SN metastasis within the SN basin. The diagnostic sensitivity of SN mapping for lymph node metastasis was 88.9% in post-ER group and 95.7% in non-ER group (P = 0.490); the accuracy was 99.2% and 99.6% (P = 0.539), respectively. Regarding the SN basin, no significant intergroup differences were found regardless of the primary tumor location. CONCLUSIONS Our findings clarified the feasibility of SN mapping based on the SN basin concept in patients with gastric cancer who previously underwent ER.
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Iwasaki K, Ota Y, Yamada E, Takahashi K, Watanabe T, Makuuchi Y, Suda T, Osaka Y, Seshimo A, Katsumata K, Tsuchida A. Primary malignant melanoma of the esophagus with multiple lymph node metastases: A case report and literature review. Medicine (Baltimore) 2020; 99:e18573. [PMID: 32481357 DOI: 10.1097/md.0000000000018573] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
RATIONALE Primary malignant melanoma of the esophagus (PMME) is a very rare malignancy accounting for only 0.1% to 0.2% of all malignant esophageal lesions. Presently, there are no standard strategies or clear guidelines for PMME treatment. PATIENT CONCERNS Herein, we report a patient who had PMME with multiple lymph node metastases (LNMs) who was treated successfully by esophagectomy. In March 2018, a 74-year-old man with symptoms of continuous dysphagia was referred to our hospital. DIAGNOSIS Upper gastrointestinal endoscopic examination revealed melanin pigmentation in the middle thoracic esophagus and a pigmented polypoid mass in the lower esophagus. Histopathological examination of the endoscopic biopsy specimen revealed malignant melanoma. Contrast-enhanced computed tomography showed a 3 cm tumor lesion with several enlarged lymph nodes without distant metastasis. The preoperative diagnosis based on the TNM classification was cT2N2M0 stage III. INTERVENTIONS The patient underwent esophagectomy with lymph node dissection. OUTCOMES Histopathological examination showed that the tumor extended to the submucosal layer of the esophageal wall, with multiple LNMs. Although multiple LNMs were detected, computed tomography scan 15 months after surgery showed no recurrence. Additionally, we analyzed the relationship between the overall survival and the clinicopathological factors including LNMs in 48 previously reported cases of PMME that were surgically treated. LESSONS To our knowledge, this is the first report on the effect of LNMs on the prognosis of PMME patients. The analysis revealed the prognostic value of the TNM stage. Early tumor detection and esophagectomy with lymph node dissection may play as key factors for achieving a better overall survival of PMME patients.
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Iwasaki K, Suda T, Takano Y, Ohno Y, Yamada E, Okazaki N, Takahashi K, Watanabe T, Makuuchi Y, Ota Y, Osaka Y, Seshimo A, Katsumata K, Tsuchida A. Postoperative outcomes of gastric carcinoma with lymphoid stroma. World J Surg Oncol 2020; 18:102. [PMID: 32438924 PMCID: PMC7243312 DOI: 10.1186/s12957-020-01878-9] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2020] [Accepted: 05/13/2020] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Gastric carcinoma with lymphoid stroma (GCLS) is a rare subtype of gastric cancer. There have been several reports demonstrating the favorable prognosis of early GCLS without lymph node metastasis (LNM) compared with gastric adenocarcinomas. However, it remains unknown whether advanced GCLS (AGCLS) with LNM has a similar prognosis and clinicopathological features. This study aimed to assess the clinicopathological features of GCLS of all stages. METHODS We retrospectively assessed 375 patients who were pathologically diagnosed with gastric cancer and underwent curative surgical resection at Tokyo Medical University, Japan, between September 2013 and October 2019. Of these patients, 357 (95.2%) patients were pathologically diagnosed with gastric adenocarcinomas, and 18 (4.8%) patients were diagnosed with GCLS. The GCLS patients (n = 18) were compared with the gastric adenocarcinoma patients (non-GCLS patients, control) (n = 357) in terms of their clinicopathological features and clinical outcome. RESULTS The GCLS patients showed significantly predominant upper gastric locations (P = 0.003), lower number of LNM (P = 0.01), and better overall survival rate than the non-GCLS patients (P = 0.029). The predominant upper gastric locations (P = 0.0002), lower number of LNM (P = 0.003), and better overall survival rate (P = 0.04) were significantly correlated in the AGCLS with LNM patients compared with the advanced non-GCLS with LNM patients. For survival analyses, surgical procedure, tumor location, and numbers of positive LNM were adjusted by 1:1 propensity score matching. After adjustment, the overall survival rate was significantly higher in the AGCLS group than in the advanced non-GCLS group (P = 0.03). CONCLUSION AGCLS has distinct clinicopathological features and clinical behavior that are similar to those of early GCLS. AGCLS with LNM patients showed a significantly lower number of LNM and a better survival rate than advanced non-GCLS with LNM patients. To our knowledge, this study is the first report to describe the clinicopathological features of AGCLS.
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Takahashi K, Sato S, Ota Y, Watanabe T, Tachibana S, Suda T, Makuuchi Y, Iwasaki K, Nagakawa Y, Osaka Y, Seshimo A, Katsumata K, Tsuchida A. [A Case of Local Remnant Esophageal Cancer after Chemotherapy Getting Complete Response by Radiotherapy]. Gan To Kagaku Ryoho 2020; 47:510-512. [PMID: 32381932 DOI: pmid/32381932] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
This is a case of a 72-year-old woman who presented without anymajor complaint. An anemia was indicated during follow-up for diabetes at the internal medicine unit and an upper gastrointestinal endoscopy(GS)was performed. A type 2 tumor was detected in the middle thoracic esophagus and biopsyrevealed a squamous cell carcinoma. A tumor was detected in the middle thoracic esophagus bycervical thoracoabdominal computed tomography(CT)scan and no invasion of surrounding organs was noted. The lymph node 104R had enlarged significantlybut no distant metastasis was observed. The patient was diagnosed with advanced esophageal cancer, Mt, type 2, cT2N2M0, stage Ⅱ. For preoperative chemotherapy, CDDP plus 5-FU(FP)therapywas administered. Lung metastasis was found on CT examination and surgical resection was not indicated. Hence, 4 courses of docetaxel plus CDDP plus 5-FU(DCF)therapywere administered. Following treatment, lung and lymph node metastases disappeared on the image. However, the main tumor remained at the GS. Radiotherapy was administered as a local additional treatment. Thereafter, GS showed mucous membrane redness and white spots of the lesion. Biopsyfrom the same site showed no malignant findings. The patient has remained malignancy-free since 18 months.
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Ohara N, Kobayashi M, Ikeda Y, Hoshi T, Morita S, Kanefuji T, Yagi K, Suda T, Takada T, Hasegawa G, Sato Y, Hirano K, Kosugi SI. Non-insulin-dependent Diabetes Mellitus Induced by Immune Checkpoint Inhibitor Therapy in an Insulinoma-associated Antigen-2 Autoantibody-positive Patient with Advanced Gastric Cancer. Intern Med 2020; 59:551-556. [PMID: 31708539 PMCID: PMC7056377 DOI: 10.2169/internalmedicine.3208-19] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
A 70-year-old man with insulinoma-associated antigen-2 autoantibodies developed diabetes mellitus (DM) without ketoacidosis after starting nivolumab to treat advanced gastric cancer. He subsequently exhibited preserved insulin-secretion capacity for over one year. Immune checkpoint inhibitors (ICIs) infrequently cause type 1 DM associated with the rapid loss of insulin secretion and ketoacidosis as an immune-related adverse event. ICIs may also cause non-insulin-dependent DM by inducing insulin resistance if there is islet autoantibody-related latent beta-cell dysfunction. The present case highlights the importance of testing blood glucose levels regularly to diagnose DM in patients treated with ICIs, even if they do not have diabetic ketoacidosis.
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Makuuchi Y, Suda T, Kuboyama Y, Sugiyama Y, Takahashi K, Seshimo A, Katsumata K, Tsuchida A. [Efficacy of Palliative Radiotherapy in Hemorrhage Control in Patients with Unresectable Gastric Cancer]. Gan To Kagaku Ryoho 2020; 47:316-318. [PMID: 32381974 DOI: pmid/32381974] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
We report the case of an 80-year-old man with unresectable, advanced gastric cancer and pulmonary cancer because of multiple liver metastases. The serum hemoglobin level declined to 5.3 g/dL during fourth-line chemotherapy. Radiation therapy of 30 Gy was administered in 10 fractions. After radiation treatment was completed, the serum hemoglobin level increased to 8.5g/dL. No new adverse event was observed. Subsequently, the progression of anemia stopped, and oral intake became possible. Thus, palliative radiation therapy is useful for hemorrhage control in unresectable, advanced gastric cancer patients with a poor general condition and difficult surgical treatment.
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Orimoto N, Suda T, Takahashi K, Iwasaki K, Watanabe T, Makuuchi Y, Ota Y, Nagakawa Y, Seshimo A, Katsumata K, Tsuchida A. [Administering Ramucirumab Safely after Inserting an Intestinal Stent, Due to Peritoneal Metastasis of Gastric Cancer-A Case Report]. Gan To Kagaku Ryoho 2020; 47:313-315. [PMID: 32381973] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The recent phase Ⅲ trials REGARD and RAINBOW have shown survival benefits and acceptable safetyprofiles of ramucirumab( RAM)alone and RAM plus paclitaxel. Based on this result, RAM is recommended as a secondarytreatment for advanced and recurrent gastric cancer bythe Japanese Gastric Cancer Association. Although the frequencyis not high, gastrointestinal perforation has been reported as a serious side effect. RAM is a human anti-vascular endothelial growth factor receptor 2(VEGFR-2)monoclonal antibodythat acts on vascular endothelial cells to inhibit angiogenesis. The detailed mechanism has not been elucidated, but it is thought that the ischemic state and delayed wound healing due to the inhibition of vascular endothelial growth factors could be the cause of perforation. Thus, the usage of angiogenesis inhibitors such as RAM while intestinal stents are placed, mayincrease the risk of gastrointestinal perforation. We report a case in which RAM was administrated with no adverse events after multiple gastrointestinal metal stents being inserted.
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Mizusawa T, Kamimura K, Sato H, Suda T, Fukunari H, Hasegawa G, Shibata O, Morita S, Sakamaki A, Yokoyama J, Saito Y, Hori Y, Maruyama Y, Yoshimine F, Hoshi T, Morita S, Kanefuji T, Kobayashi M, Terai S. Methotrexate-related lymphoproliferative disorders in the liver: Case presentation and mini-review. World J Clin Cases 2019; 7:3553-3561. [PMID: 31750337 PMCID: PMC6854407 DOI: 10.12998/wjcc.v7.i21.3553] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2019] [Revised: 06/19/2019] [Accepted: 07/27/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Immunosuppression is effective in treating a number of diseases, but adverse effects such as bone marrow suppression, infection, and oncogenesis are of concern. Methotrexate is a key immunosuppressant used to treat rheumatoid arthritis. Although it is effective for many patients, various side effects have been reported, one of the most serious being methotrexate-related lymphoproliferative disorder. While this may occur in various organs, liver involvement is rare. Information on these liver lesions, including clinical characteristics, course, and imaging studies, has not been summarized to date.
CASE SUMMARY We present a case of 70-year-old woman presented with a 2-wk history of fever and abdominal pain. She had had rheumatoid arthritis for 5 years and was being treated with medication including methotrexate. Contrast-enhanced computed tomography revealed multiple low density tumors in the liver and the histological analyses showed significant proliferation of lymphocytes in masses that were positive on immunohistochemical staining for CD3, CD4, CD8, and CD79a but negative for CD20 and CD56. Staining for Epstein-Barr virus-encoded RNA was negative. And based on these findings, the liver tumors were diagnosed as Methotrexate-related lymphoproliferative disorders. A time-dependent disappearance of the liver tumors after stopping methotrexate supported the diagnoses.
CONCLUSION The information obtained from our case and a review of 9 additional cases reported thus far assist physicians who may face the challenge of diagnosing and managing this disorder.
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Morita S, Suda T, Terai S. Gastric Metastasis From Uveal Melanoma. Clin Gastroenterol Hepatol 2019; 17:A20. [PMID: 29609062 DOI: 10.1016/j.cgh.2018.03.033] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2018] [Accepted: 03/27/2018] [Indexed: 02/07/2023]
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Yokoo T, Kanefuji T, Suda T, Nagayama I, Hoshi T, Abe S, Morita S, Kamimura H, Kamimura K, Tsuchiya A, Takamura M, Yagi K, Terai S. Rational arrangement of measuring shear wave speed in the liver. World J Gastroenterol 2019; 25:2503-2513. [PMID: 31171893 PMCID: PMC6543244 DOI: 10.3748/wjg.v25.i20.2503] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2018] [Revised: 11/18/2018] [Accepted: 12/28/2018] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Shear wave speed has been widely applied to quantify a degree of liver fibrosis. However, there is no standardized procedure, which makes it difficult to utilize the speed universally.
AIM To provide procedural standardization of shear wave speed measurement.
METHODS Point shear wave elastography (pSWE) was measured in 781 patients, and two-dimensional shear wave elastography (2dSWE) was measured on the same day in 18 cases. Regions-of-interest were placed at 12 sites, and the median and robust coefficient-of-variation (CVR) were calculated. A residual sum-of-square (Σdi2) was computed for bootstrap values of 1000 iterations in 18 cases with each assumption of 1 to 12 measurements. The proportion of the Σdi2 (%Σdi2) was calculated as the ratio of Σdi2 to pSWE after converting it based on the correlation between pSWE and 2dSWE.
RESULTS The CVR showed a significantly broader distribution in the left lobe (P < 0.0001), and the smallest CVR in the right anterior segment that covered 95% cases was 40.4%. pSWE was significantly higher in the left lobe than in the right lobe (1.63 ± 0.78 m/s vs 1.61 ± 0.78 m/s, P = 0.0004), and the difference between the lobes became further discrete when the subjects were limited to the cases with a CVR less than 40.4% in any segment (1.76 ± 0.80 m/s vs 1.70 ± 0.82 m/s, P < 0.0001). The highest values of the CVR in every 0.1 m/s interval were plotted in convex upward along pSWE and peaked at 1.93 m/s. pSWE and 2dSWE were significantly correlated (P < 0.0001, r = 0.95). In 216000 resamples from 18 cases, the %Σdi2 of 12 sites was 8.0% and gradually increased as the acquisition sites decreased to reach a significant difference with a %Σdi2 of 7 sites (P = 0.027).
CONCLUSION These data suggest that shear wave speed should be measured at 8 or more sites of spreading in both lobes.
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Morita S, Suda T, Terai S. Submucosal painting for gastroduodenal stent placement. Dig Endosc 2019; 31:e64-e65. [PMID: 30664261 DOI: 10.1111/den.13349] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2018] [Accepted: 01/15/2019] [Indexed: 02/08/2023]
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Katayanagi S, Katsumata K, Mori Y, Narahara K, Shigoka M, Matsudo T, Enomoto M, Suda T, Ishizaki T, Hisada M, Nagakawa Y, Tsuchida A. GSTP1 as a potential predictive factor for adverse events associated with platinum-based antitumor agent-induced peripheral neuropathy. Oncol Lett 2019; 17:2897-2904. [PMID: 30854066 PMCID: PMC6365892 DOI: 10.3892/ol.2019.9907] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2018] [Accepted: 10/26/2018] [Indexed: 02/07/2023] Open
Abstract
Glutathione S-transferase (GST) exhibits antidotal effects on numerous drugs, including platinum-based antineoplastic drugs. Furthermore, GST Pi 1 (GSTP1) polymorphism is associated with peripheral neuropathy. In the present study, it was determined whether GSTP1 can predict adverse events associated with platinum-based antitumor agent-induced peripheral neuropathy among Japanese patients. The subjects included 122 patients, among whom 105 patients had colorectal, 16 had gastric, and one patient had pancreatic cancer. It was indicated that wild type (AA) GSTP1 was expressed in 99 patients (81.1%), whereas heterozygous (AG) and homozygous (GG) GSTP1 polymorphisms were present in 22 (18.0%) and 1 (0.8%) patients, respectively. Among patients with colorectal cancer, the expression of homozygous GSTP1 was observed in 88 patients (83.8%), whereas that of heterozygous GSTP1 was observed in 17 patients (16.2%). Peripheral neuropathy of grade ≥3 occurred in 10 patients (9.5%) receiving mFOLFOX therapy (a biweekly cycle consisting of a 2-h infusion of 85 mg/m2 oxaliplatin and 200 mg/m2 leucovorin followed by a bolus administration of 400 mg/m2 5-fluorouracil and a continuous 48-h infusion of 2,400 mg/m2 5-fluorouracil) for colorectal cancer, which included 6 patients with the AA allele (6.8%) and 4 patients with the AG allele (23.5%). The number of peripheral neuropathy cases of grade ≥3 was increased among patients with the AG allele, compared with patients with the AA allele (P=0.032). In patients with gastric cancer, the AA and AG types of GSTP1 were expressed in 11 (68.8%) and 5 (31.2%) patients, respectively. Cisplatin, administered to patients with gastric cancer, did not induce peripheral neuropathy. The aforementioned indicated that GSTP1 genetic polymorphism is associated with peripheral neuropathy induced by oxaliplatin treatment for colorectal cancer, and therefore serves as a predictive marker. Furthermore, early dose reduction or drug withdrawal should be implemented depending on the severity of peripheral neuropathy as a potential method for reducing the number of patients discontinuing the drug, due to adverse events involving peripheral neuropathy.
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