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1.
Dig Surg ; 40(5): 143-152, 2023.
Article in English | MEDLINE | ID: mdl-37527628

ABSTRACT

INTRODUCTION: Several studies have indicated that sarcopenia affects the short- and long-term outcomes of cancer patients, including those with gastric cancer. In recent years, sarcopenic obesity and its effects have been reported in cancer patients. This study aimed to evaluate the impact of sarcopenic obesity on postoperative complications in patients with gastric cancer undergoing gastrectomy. METHODS: This single-center, retrospective study included 155 patients who underwent curative gastrectomy for gastric cancer from January 2015 to July 2021. Sarcopenia was defined by the psoas muscle index (<6.36 cm2/m2 in men and <3.92 cm2/m2 in women), which measures the iliopsoas muscle area at the lumbar L3 level using computed tomography. Obesity was defined by body mass index (≥25). Patients with both sarcopenia and obesity were defined as the sarcopenic obesity group and others as the non-sarcopenic obesity group. Severe postoperative complications were defined as Clavien-Dindo classification grade IIIa or higher. RESULTS: Of the 155 patients, 26 (16.8%) had sarcopenic obesity. The incidence of severe postoperative complications was significantly higher in the sarcopenic obesity group (30.8% vs. 10.9%; p = 0.014). Multivariate analysis indicated that sarcopenic obesity was an independent risk factor for severe postoperative complications (odds ratio, 3.950; 95% confidence interval, 1.390-11.200; p = 0.010). CONCLUSION: Sarcopenic obesity is an independent risk factor for severe postoperative complications.

2.
Gan To Kagaku Ryoho ; 50(8): 923-925, 2023 Aug.
Article in Japanese | MEDLINE | ID: mdl-37608422

ABSTRACT

We investigated the gastric and esophageal cancer cases treated with immune checkpoint inhibitors and chemotherapy at our hospital. Out of 17 gastric cancer cases, 9 were treated with nivolumab(Nivo)plus S-1/oxaliplatin(SOX), 5 with Nivo plus 5-fluorouracil/Leucovorin/oxaliplatin(FOLFOX), and 3 with Nivo plus capecitabine/oxaliplatin(CapeOX), yielding a response rate of 35.3%. We also treated 3 cases of esophageal cancer. Two of these were treated with Nivo plus cisplatin/5- fluorouracil(CF)and 1 case with pembrolizumab(Pembro)plus CF, with a response rate of 33.3%. The incidence of Grade 3 or higher adverse events was 29.4% in gastric cancer and 33.3% in esophageal cancer, and no serious immune-related adverse events were observed. Further case accumulation and long-term studies are required to evaluate efficacy and adverse events in clinical practice.


Subject(s)
Esophageal Neoplasms , Stomach Neoplasms , Upper Gastrointestinal Tract , Humans , Immune Checkpoint Inhibitors , Stomach Neoplasms/drug therapy , Esophageal Neoplasms/drug therapy , Oxaliplatin , Nivolumab , Hospitals
3.
J Vis Exp ; (197)2023 Jul 14.
Article in English | MEDLINE | ID: mdl-37522726

ABSTRACT

Conventional bone regeneration therapy using mesenchymal stem cells (MSCs) is difficult to apply to bone defects larger than the critical size because it does not have a mechanism to induce angiogenesis. Implanting artificial cartilage tissue fabricated from MSCs induces angiogenesis and bone formation in vivo via endochondral ossification (ECO). Therefore, this ECO-mediated approach may be a promising bone regeneration therapy in the future. An important aspect of the clinical application of this ECO-mediated approach is establishing a protocol for preparing enough cartilage to be implanted to repair the bone defect. It is especially not practical to design a single mass of grafted cartilage of a size that conforms to the shape of the actual bone defect. Therefore, the cartilage to be transplanted must have the property of forming bone integrally when multiple pieces are implanted. Hydrogels may be an attractive tool for scaling up tissue-engineered grafts for endochondral ossification to meet clinical requirements. Although many naturally derived hydrogels support MSC cartilage formation in vitro and ECO in vivo, the optimal scaffold material to meet the needs of clinical applications has yet to be determined. Hyaluronic acid (HA) is a crucial component of the cartilage extracellular matrix and is a biodegradable and biocompatible polysaccharide. Here, we show that HA hydrogels have excellent properties to support in vitro differentiation of MSC-based cartilage tissue and promote endochondral bone formation in vivo.

4.
Kyobu Geka ; 76(6): 438-442, 2023 Jun.
Article in Japanese | MEDLINE | ID: mdl-37258021

ABSTRACT

Giant atria may trigger respiratory failure, which often requires surgical intervention. We report a patient who presented with respiratory failure due to bilateral giant atria. The patient was a 75-year-old woman with rheumatic heart disease. She had undergone mitral valve replacement and tricuspid annuloplasty at another hospital 17 years ago but recently developed respiratory dysfunction. Compression to the lungs by enlarged atria was diagnosed as the main cause of respiratory dysfunction. Hence, the anterior-to-posterior left atrial wall was plicated by para-annular and superior-half plication, respectively, and the right atrial wall was excised into an ellipse shape. Tricuspid valvuloplasty was performed on four sets of eight artificial chordae with CV5 sutures and an annuloplasty ring. Respiratory failure was alleviated after the surgery.


Subject(s)
Atrial Fibrillation , Mitral Valve Insufficiency , Respiratory Insufficiency , Tricuspid Valve Insufficiency , Female , Humans , Aged , Mitral Valve/surgery , Tricuspid Valve/surgery , Tricuspid Valve Insufficiency/surgery , Respiratory Insufficiency/etiology , Respiratory Insufficiency/surgery , Heart Atria/surgery , Mitral Valve Insufficiency/surgery
5.
PLoS One ; 18(2): e0281345, 2023.
Article in English | MEDLINE | ID: mdl-36730328

ABSTRACT

Engineered cartilage tissue from differentiated mesenchymal stem cells (MSCs) can generate bone in vivo through endochondral ossification (ECO). This ECO-mediated approach has the potential to circumvent the severe problems associated with conventional MSC-based bone tissue engineering techniques that lack mechanisms to induce angiogenesis. Hyaluronic acid (HA) is a key component in the cartilage extracellular matrix. However, the ECO-supporting properties of HA remain largely unclear. This study aimed to compare the ability of HA and collagen hydrogels to support in vitro differentiation of MSC-based hypertrophic cartilage tissues and to promote endochondral bone formation in vivo. Following the chondrogenic and hypertrophic differentiation in vitro, both HA and collagen constructs accumulated sulfated glycosaminoglycan (sGAG) and type 1, type II, and type X collagen. However, HA hydrogels exhibited a more uniform distribution of sGAG, type 1 collagen, type X collagen, and osteocalcin proteins; in addition, the cells embedded in the hydrogels had more rounded cell morphologies than those in the collagen constructs. At week 5 of in vitro culture, two to three constructs were implanted into a subcutaneous pocket in nude mice and harvested after 4 and 8 weeks. Both HA and collagen constructs promoted endochondral bone formation with vascularization and bone marrow development; however, the HA constructs fused to form integrated bone tissues and the bone marrow developed along the space between the two adhered grafts in all implanted pockets (n = 5). In the collagen constructs, the integration was observed in 40% of the pockets (n = 5). Microcomputer CT analysis revealed that the bone volume of HA constructs was larger than that of collagen constructs. In conclusion, compared to collagen hydrogels, HA hydrogels had superior potential to generate integrated bone with vascularization and bone marrow development. This study provides valuable insights for applying ECO-mediated bone tissue engineering approaches for the repair of critical-sized bone defects.


Subject(s)
Mesenchymal Stem Cells , Osteogenesis , Mice , Animals , Hyaluronic Acid/metabolism , Hydrogels/metabolism , Mice, Nude , Tissue Engineering/methods , Collagen/metabolism , Chondrogenesis
6.
J Neurosurg Pediatr ; 31(5): 488-495, 2023 05 01.
Article in English | MEDLINE | ID: mdl-36840735

ABSTRACT

OBJECTIVE: Monitoring the intraoperative motor evoked potentials (MEPs) in pediatric craniotomy is challenging because of its low detection rate, which makes it unreliable. Tetanic stimulation of the peripheral nerves of the extremities and pudendal nerves prior to transcranial electrical stimulation (TES) or direct cortical stimulation (DCS) amplifies the MEPs. The authors investigated the effects of MEP amplification following tetanic stimulation of the median and tibial nerve or the pudendal nerve in pediatric patients undergoing craniotomy. METHODS: This prospective observational study included 15 patients ≤ 15 years of age (mean age 8.9 ± 4.9 years) undergoing craniotomy. MEPs were obtained with TES (15 cases) or DCS (8 cases)-conventional MEP without tetanic stimulation (c-MEP) and MEP following tetanic stimulation of the unilateral median and tibial nerves (mt-MEP) or following tetanic stimulation of the pudendal nerve (p-MEP) were used. Compound muscle action potentials were elicited from the abductor pollicis brevis, gastrocnemius, tibialis anterior, and abductor hallucis longus muscles. The authors compared the identification rate and the rate of amplitude increase of each MEP. RESULTS: For both TES and DCS, the identification and amplitude increase rates were significantly higher in cases without preoperative hemiparesis for p-MEPs than in those for c-MEPs and mt-MEPs. In comparison to patients with preoperative hemiparesis, p-MEPs displayed a higher identification rate, with fewer false negatives in DCS cases. CONCLUSIONS: In pediatric craniotomy, the authors observed the amplification effect of MEPs with pudendal nerve tetanic stimulation and the amplification effect of DCS on MEPs without increasing false negatives. These findings suggested the likelihood of more reliable intraoperative MEP monitoring in pediatric cases.


Subject(s)
Pudendal Nerve , Humans , Child , Child, Preschool , Adolescent , Evoked Potentials, Motor/physiology , Tibial Nerve/physiology , Craniotomy , Paresis , Electric Stimulation
7.
ACS Nano ; 17(3): 2235-2244, 2023 02 14.
Article in English | MEDLINE | ID: mdl-36655866

ABSTRACT

Extracellular vesicles (EVs) have promising potential as biomarkers for early cancer diagnosis. The EVs have been widely studied as biological cargo containing essential biological information not only from inside vesicles such as nucleic acids and proteins but also from outside vesicles such as membrane proteins and glycolipids. Although various methods have been developed to isolate EVs with high yields such as captures based on density, size, and immunoaffinity, different measurement systems are needed to analyze EVs after isolation, and a platform that enables all-in-one analysis of EVs from capture to detection in multiple samples is desired. Since a nanowire-based approach has shown an effective capability for capturing EVs via surface charge interaction compared to other conventional methods, here, we upgraded the conventional well plate assay to an all-in-one nanowire-integrated well plate assay system (i.e., a nanowire assay system) that enables charge-based EV capture and EV analysis of membrane proteins. We applied the nanowire assay system to analyze EVs from brain tumor organoids in which tumor environments, including vascular formations, were reconstructed, and we found that the membrane protein expression ratio of CD31/CD63 was 1.42-fold higher in the tumor organoid-derived EVs with a p-value less than 0.05. Furthermore, this ratio for urine samples from glioblastoma patients was 2.25-fold higher than that from noncancer subjects with a p-value less than 0.05 as well. Our results demonstrated that the conventional well plate method integrated with the nanowire-based EV capture approach allows users not only to capture EVs effectively but also to analyze them in one assay system. We anticipate that the all-in-one nanowire assay system will be a powerful tool for elucidating EV-mediated tumor-microenvironment crosstalk.


Subject(s)
Brain Neoplasms , Extracellular Vesicles , Nanowires , Humans , Extracellular Vesicles/metabolism , Biomarkers/metabolism , Brain Neoplasms/diagnosis , Membrane Proteins/metabolism , Tumor Microenvironment
8.
Cancer Med ; 12(6): 7116-7126, 2023 03.
Article in English | MEDLINE | ID: mdl-36478416

ABSTRACT

BACKGROUND: Rituximab, high-dose methotrexate (HD-MTX), procarbazine and vincristine (R-MPV), has significantly prolonged the survival of patients with primary central nervous system lymphoma (PCNSL), but predictive factors for response to R-MPV have not yet been investigated. Herein, we investigated the correlation of MYD88 L265P and CD79B Y196 mutations, which are the most frequently found molecular alterations in PCNSL, with prognosis of patients with PCNSL treated with R-MPV. METHODS: We investigated the long-term clinical course and status of MYD88 and CD79B genes in 85 patients with PCNSL treated with R-MPV or HD-MTX treatment, and the correlation of these genetic mutations with prognosis. RESULTS: R-MPV achieved an excellent tumor control rate (61.6% and 69.9% of 5-year progression-free and overall survival rates, respectively). While MYD88 L265P mutation had no significant effect on survival, patients with CD79B Y196 mutations exhibited prolonged survival (p < 0.05). However, the association of CD79B Y196 mutation with a better prognosis was not observed in the HD-MTX cohort, which indicated that CD79B Y196 mutation was a predictive marker for a favorable response to R-MPV. Furthermore, we established an all-in-one rapid genotyping system for these genetic mutations. CONCLUSIONS: In conclusion, CD79B Y196 mutation is a potent predictive marker for favorable response to R-MPV in PCNSL. The rapid identification of MYD88 L265P and CD79B Y196 mutations can be helpful not only for the accurate molecular diagnosis of PCNSL but also for the prediction of response to R-MPV.


Subject(s)
Central Nervous System Neoplasms , Lymphoma, Large B-Cell, Diffuse , Humans , Lymphoma, Large B-Cell, Diffuse/drug therapy , Myeloid Differentiation Factor 88/genetics , Myeloid Differentiation Factor 88/metabolism , Mutation , Rituximab/therapeutic use , Central Nervous System/metabolism , Central Nervous System/pathology , Central Nervous System Neoplasms/drug therapy , Central Nervous System Neoplasms/genetics , Methotrexate/therapeutic use , CD79 Antigens/genetics
9.
Surgery ; 173(2): 450-456, 2023 02.
Article in English | MEDLINE | ID: mdl-36481063

ABSTRACT

BACKGROUND: Tumor stiffness measurement using magnetic resonance elastography can assess tumor mechanical properties and predict hepatocellular carcinoma recurrence. This study aimed to investigate preoperative tumor stiffness on magnetic resonance elastography as a predictor of overall survival and recurrence-free survival in patients with solitary nodular hepatocellular carcinoma who underwent curative resection. METHODS: Seventy-eight patients with solitary nodular hepatocellular carcinoma who underwent preoperative magnetic resonance elastography and curative resection were retrospectively analyzed. Potential associations of tumor stiffness and other clinicopathological variables with overall survival and recurrence-free survival were analyzed in both univariate and multivariate Cox proportional hazards analyses. The optimal tumor stiffness cutoff value was determined using the minimal P value approach. RESULTS: In multivariate analysis, tumor stiffness (hazard ratio 1.31; 95% confidence interval, 1.07-1.59; P = .008) and vascular invasion (hazard ratio 2.62; 95% confidence interval, 1.27-5.17; P = .010) were independent predictors of recurrence-free survival. For overall survival, tumor stiffness (hazard ratio, 1.33; 95% confidence interval, 1.02-1.76; P = .037) was the only independent predictor. The optimal tumor stiffness cutoff value was 5.81 kPa for both overall survival and recurrence-free survival. Patients with tumor stiffness ≥5.81 kPa had a significantly greater risk of death (hazard ratio 6.10; 95% confidence interval, 2.11-21.90; P < .001) than those with tumor stiffness <5.81 kPa. CONCLUSION: Preoperative tumor stiffness as measured by magnetic resonance elastography was a predictor of overall survival and recurrence-free survival in hepatocellular carcinoma patients who underwent curative resection. Higher tumor stiffness was associated with higher risk of recurrence and death.


Subject(s)
Carcinoma, Hepatocellular , Elasticity Imaging Techniques , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/surgery , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/surgery , Liver Neoplasms/pathology , Retrospective Studies , Prognosis , Neoplasm Recurrence, Local/diagnostic imaging , Neoplasm Recurrence, Local/surgery , Hepatectomy
10.
SAGE Open Med Case Rep ; 10: 2050313X221112363, 2022.
Article in English | MEDLINE | ID: mdl-35899248

ABSTRACT

We present a case of redo stentless valve operation in a 73-year-old man who underwent aortic valve replacement via the subcoronary approach with a freestyle aortic bioprosthesis 23 years ago at our institution. He was referred for surgery because an echocardiogram showed severe aortic regurgitation due to structural valve deterioration, and aortic valve replacement was planned. Severe circumferential calcification and adhesion were noted during the surgery between the freestyle and native roots. Redo-aortic valve replacement was successful despite the technical difficulty. In stentless valve reoperations following aortic valve replacement via the subcoronary method, the planning of valve-in-valve transcatheter aortic valve implantation and sutureless valve implantation may be a practical and safe strategy.

11.
World J Hepatol ; 14(5): 1016-1024, 2022 May 27.
Article in English | MEDLINE | ID: mdl-35721290

ABSTRACT

BACKGROUND: Portal vein thrombosis (PVT) after liver resection is rare but can lead to life-threatening liver failure. This prospective study evaluated patients using contrast-enhanced computed tomography (E-CT) on the first day after liver resection for early PVT detection and management. AIM: To evaluate patients by E-CT on the first day after liver resection for early PVT detection and immediate management. METHODS: Patients who underwent liver resection for primary liver cancer from January 2015 were enrolled. E-CT was performed on the first day after surgery in patients undergoing anatomical resection, multiple resections, or with postoperative bile leakage in the high-risk group for PVT. When PVT was detected, anticoagulant therapy including heparin, warfarin, and edoxaban was administered. E-CT was performed monthly until PVT resolved. RESULTS: The overall incidence of PVT was 1.57% (8/508). E-CT was performed on the first day after surgery in 235 consecutive high-risk patients (165 anatomical resections, 74 multiple resections, and 28 bile leakages), with a PVT incidence of 3.4% (8/235). Symptomatic PVT was not observed in the excluded cohort. Multivariate analyses revealed that sectionectomy was the only independent predictor of PVT [odds ratio (OR) = 12.20; 95% confidence interval (CI): 2.22-115.97; P = 0.003]. PVT was found in the umbilical portion of 75.0% (6/8) of patients, and sectionectomy on the left side showed the highest risk of PVT (OR = 14.10; 95%CI: 3.17-62.71; P < 0.0001). CONCLUSION: Sectionectomy on the left side should be chosen with caution as it showed the highest risk of PVT. E-CT followed by anticoagulant therapy was effective in managing early-phase PVT for 2 mo without adverse events.

12.
J Surg Case Rep ; 2022(2): rjac035, 2022 Feb.
Article in English | MEDLINE | ID: mdl-35145631

ABSTRACT

Obturator hernia (OH) is a relatively rare disease and there are various surgical procedures for treating it. We report the case of a patient with an OH who underwent laparoscopic-assisted modified Kugel herniorrhaphy. The patient was a 74-year-old woman admitted to our hospital with nausea and abdominal distension. A diagnosis of intestinal obstruction was made because abdominal computed tomography revealed incarcerated right OH. No apparent strangulation findings were observed, and reduction was performed under ultrasound guidance. Laparoscopic-assisted modified Kugel herniorrhaphy for OH was performed. There were no signs of the bowel necrosis. Pneumoperitoneum was temporarily discontinued, and the OH was repaired by the modified Kugel herniorrhaphy. Laparoscopy confirmed that the direct Kugel patch was placed at the appropriate position. Laparoscopic-assisted modified Kugel herniorrhaphy is considered to be safe and useful for patients with OH and is considered as one of the treatment options.

13.
Quant Imaging Med Surg ; 11(8): 3792-3796, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34341750

ABSTRACT

High dorsal resection (HDR) of the liver is a systematic resection technique for hepatocellular carcinoma (HCC) arising in the caudate lobe. HDR is rarely performed, as the procedure requires a high level of operative skill, knowledge of liver anatomy and is performed in patients with limited hepatic function. Between 2002 and 2012, we performed HDR on 9 patients. The median operation time was 534 min (range, 349-903 min), and the median blood loss volume was 430 mL (range, 94-4,530 mL). The severe morbidity rate was 11.1%, but there was no operative mortality, and the median hospitalization was 13 days (range, 8-93 days). The overall survival was 49.7 months (range, 3.1-89.0 months). Despite the hard-to-approach anatomic location, HDR can be carried out safely with good survival compared to other segments.

14.
Cancer Res ; 81(18): 4861-4873, 2021 09 15.
Article in English | MEDLINE | ID: mdl-34333454

ABSTRACT

Isocitrate dehydrogenase-mutant low-grade gliomas (IDHmut-LGG) grow slowly but frequently undergo malignant transformation, which eventually leads to premature death. Chemotherapy and radiotherapy treatments prolong survival, but can also induce genetic (or epigenetic) alterations involved in transformation. Here, we developed a mathematical model of tumor progression based on serial tumor volume data and treatment history of 276 IDHmut-LGGs classified by chromosome 1p/19q codeletion (IDHmut/1p19qcodel and IDHmut/1p19qnoncodel) and performed genome-wide mutational analyses, including targeted sequencing and longitudinal whole-exome sequencing data. These analyses showed that tumor mutational burden correlated positively with malignant transformation rate, and chemotherapy and radiotherapy significantly suppressed tumor growth but increased malignant transformation rate per cell by 1.8 to 2.8 times compared with before treatment. This model revealed that prompt adjuvant chemoradiotherapy prolonged malignant transformation-free survival in small IDHmut-LGGs (≤ 50 cm3). Furthermore, optimal treatment differed according to genetic alterations for large IDHmut-LGGs (> 50 cm3); adjuvant therapies delayed malignant transformation in IDHmut/1p19qnoncodel but often accelerated it in IDHmut/1p19qcodel. Notably, PI3K mutation was not associated with malignant transformation but increased net postoperative proliferation rate and decreased malignant transformation-free survival, prompting the need for adjuvant therapy in IDHmut/1p19qcodel. Overall, this model uncovered therapeutic strategies that could prevent malignant transformation and, consequently, improve overall survival in patients with IDHmut-LGGs. SIGNIFICANCE: A mathematical model successfully estimates malignant transformation-free survival and reveals a link between genetic alterations and progression, identifying precision medicine approaches for optimal treatment of IDH-mutant low-grade gliomas.


Subject(s)
Cell Transformation, Neoplastic/genetics , DNA Mutational Analysis/methods , Glioma/genetics , Glioma/pathology , Isocitrate Dehydrogenase/genetics , Models, Theoretical , Mutation , Adult , Biomarkers, Tumor , DNA Copy Number Variations , Disease Management , Disease Progression , Female , Gene Expression Profiling , Glioma/mortality , Glioma/therapy , Humans , Male , Middle Aged , Phenotype , Polymorphism, Single Nucleotide , Prognosis , Treatment Outcome , Tumor Burden
15.
Neuro Oncol ; 23(11): 1936-1948, 2021 11 02.
Article in English | MEDLINE | ID: mdl-34214169

ABSTRACT

BACKGROUND: Recent comprehensive studies have revealed several molecular alterations that are frequently found in meningiomas. However, effective treatment reagents targeting specific molecular alterations have not yet been identified because of the limited number of representative research models of meningiomas. METHODS: We performed organoid cultures using meningioma cells and meningioma tumor tissues. Using immunohistochemistry and molecular analyses consisting of whole-exome sequencing, RNA-seq, and DNA methylation analyses, we compared the histological findings and molecular profiling of organoid models with those of parental tumors. Further, using these organoid models together with a public database of meningiomas, we explored molecular alterations, which are a potent treatment target for meningioma. RESULTS: We established 18 organoid models comprising of two malignant meningioma cells (HKBMM and IOMM-Lee), 10 benign meningiomas, four malignant meningiomas, and two solitary fibrous tumors (SFTs). The organoids exhibited consistent histological features and molecular profiles with those of the parental tumors. Using a public database, we identified that upregulated forkhead box M1 (FOXM1) was correlated with increased tumor proliferation. Overexpression of FOXM1 in benign meningioma organoids increased organoid proliferation; depletion of FOXM1 in malignant organoids decreased proliferation. Additionally, thiostrepton, a FOXM1 inhibitor combined with radiation therapy, significantly inhibited the proliferation of malignant meningioma organoid models. CONCLUSIONS: An organoid model for meningioma enabled us to elucidate the tumor biology of meningioma along with potent treatment targets for meningioma.


Subject(s)
Forkhead Box Protein M1/genetics , Meningeal Neoplasms , Meningioma , Humans , Meningeal Neoplasms/genetics , Meningioma/genetics , Organoids
16.
ACS Appl Mater Interfaces ; 13(15): 17316-17329, 2021 Apr 21.
Article in English | MEDLINE | ID: mdl-33793202

ABSTRACT

There are no accurate mass screening methods for early detection of central nervous system (CNS) tumors. Recently, liquid biopsy has received a lot of attention for less-invasive cancer screening. Unlike other cancers, CNS tumors require efforts to find biomarkers due to the blood-brain barrier, which restricts molecular exchange between the parenchyma and blood. Additionally, because a satisfactory way to collect urinary biomarkers is lacking, urine-based liquid biopsy has not been fully investigated despite the fact that it has some advantages compared to blood or cerebrospinal fluid-based biopsy. Here, we have developed a mass-producible and sterilizable nanowire-based device that can extract urinary microRNAs efficiently. Urinary microRNAs from patients with CNS tumors (n = 119) and noncancer individuals (n = 100) were analyzed using a microarray to yield comprehensive microRNA expression profiles. To clarify the origin of urinary microRNAs of patients with CNS tumors, glioblastoma organoids were generated. Glioblastoma organoid-derived differentially expressed microRNAs (DEMs) included 73.4% of the DEMs in urine of patients with parental tumors but included only 3.9% of those in urine of noncancer individuals, which suggested that many CNS tumor-derived microRNAs could be identified in urine directly. We constructed the diagnostic model based on the expression of the selected microRNAs and found that it was able to differentiate patients and noncancer individuals at a sensitivity and specificity of 100 and 97%, respectively, in an independent dataset. Our findings demonstrate that urinary microRNAs extracted with the nanowire device offer a well-fitted strategy for mass screening of CNS tumors.


Subject(s)
Central Nervous System Neoplasms/urine , MicroRNAs/urine , Nanowires , Urinalysis/instrumentation , Central Nervous System Neoplasms/genetics , Gene Expression Profiling , Glioblastoma/genetics , Glioblastoma/urine , Humans , MicroRNAs/genetics , Oligonucleotide Array Sequence Analysis
17.
Surgery ; 170(1): 167-172, 2021 07.
Article in English | MEDLINE | ID: mdl-33752906

ABSTRACT

BACKGROUND: Liver stiffness measurement using magnetic resonance elastography can assess the severity of liver fibrosis, which is significantly associated with recurrence after curative resection for hepatocellular carcinoma. The aim of this prospective study was to investigate whether preoperative liver stiffness measurement by magnetic resonance elastograhy can predict recurrence after curative resection for hepatocellular carcinoma. METHODS: Patients who underwent preoperative liver stiffness measurement and curative resection for hepatocellular carcinoma were enrolled in this study. Potential associations between liver stiffness measurement, along with other clinical and pathologic variables, and intrahepatic hepatocellular carcinoma recurrence were analyzed. RESULTS: In total, 156 patients were included in this study. During a median follow-up period of 25.1 months (range, 6.0-60.5 months), 72 (46.1%) patients with hepatocellular carcinoma had an intrahepatic recurrence. The median disease-free period after resection was 17.9 months (range, 1.0-60.5 months). In the multivariate analysis, liver stiffness measurement (hazard ratio, 1.27; 95% confidence interval, 1.11-1.43; P <.001) and vascular invasion (hazard ratio, 1.96; 95% confidence interval, 1.15-3.25; P = .013) were identified as independent predictors of recurrence. When the optimal cutoff point was set at 4.53 kPa using the minimal P value approach, the disease-free period after curative resection in 71 patients with a liver stiffness measurement value ≥4.53 kPa (11.3 months [range, 2.0-60.5 months]) was significantly shorter than that of 85 patients with a liver stiffness measurement value <4.53 kPa (22.5 months [range, 1.1-60.5 months]; P <.001). CONCLUSION: Liver stiffness measurement using magnetic resonance elastography is a useful preoperative predictor of intrahepatic recurrence after curative resection for hepatocellular carcinoma.


Subject(s)
Carcinoma, Hepatocellular/diagnostic imaging , Elasticity Imaging Techniques , Hepatectomy , Liver Neoplasms/diagnostic imaging , Liver/pathology , Neoplasm Recurrence, Local/epidemiology , Adult , Aged , Aged, 80 and over , Carcinoma, Hepatocellular/surgery , Female , Humans , Incidence , Liver/diagnostic imaging , Liver Neoplasms/surgery , Male , Middle Aged , Prognosis , Proportional Hazards Models , Prospective Studies , Risk Factors
18.
Ann Surg ; 273(6): e222-e229, 2021 06 01.
Article in English | MEDLINE | ID: mdl-31188213

ABSTRACT

OBJECTIVE: To propose an algorithm for resecting hepatocellular carcinoma (HCC) in the caudate lobe. BACKGROUND: Owing to a deep location, resection of HCC originating in the caudate lobe is challenging, but a plausible guideline enabling safe, curable resection remains unknown. METHODS: We developed an algorithm based on sublocation or size of the tumor and liver function to guide the optimal procedure for resecting HCC in the caudate lobe, consisting of 3 portions (Spiegel, process, and caval). Partial resection was prioritized to remove Spiegel or process HCC, while total resection was aimed to remove caval HCC depending on liver function. RESULTS: According to the algorithm, we performed total (n = 43) or partial (n = 158) resections of the caudate lobe for HCC in 174 of 201 patients (compliance rate, 86.6%), with a median blood loss of 400 (10-4530) mL. Postoperative morbidity (Clavien grade ≥III b) and mortality rates were 3.0% and 0%, respectively. After a median follow-up of 2.6 years (range, 0.5-14.3), the 5-year overall and recurrence-free survival rates were 57.3% and 15.3%, respectively. Total and partial resection showed no significant difference in overall survival (71.2% vs 54.0% at 5 yr; P = 0.213), but a significant factor in survival was surgical margin (58.0% vs 45.6%, P = 0.034). The major determinant for survival was vascular invasion (hazard ratio 1.7, 95% CI 1.0-3.1, P = 0.026). CONCLUSIONS: Our algorithm-oriented strategy is appropriate for the resection of HCC originating in the caudate lobe because of the acceptable surgical safety and curability.


Subject(s)
Algorithms , Carcinoma, Hepatocellular/surgery , Hepatectomy/methods , Liver Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged
19.
Surg Today ; 51(5): 727-732, 2021 May.
Article in English | MEDLINE | ID: mdl-33034741

ABSTRACT

BACKGROUND: The surgical indications for liver metastasis from bile duct cancer remain contentious, because surgery is generally thought unlikely to improve survival. However, recent reports show that long-term survival has been achieved with liver resection of metastasis from recurrent bile duct cancer in selected patients. METHODS: Liver resection for liver metastasis from bile duct cancer was proposed only when the following criteria were met: liver-only metastasis, a solitary tumor, and no increase in the number of lesions during 3 months of observation. This study aimed to validate our criteria and to analyze which factors impact on survival. RESULT: Between 2003 and 2017, 164 patients underwent pathologically curative resection for bile duct cancer. Recurrence developed in 98 of these patients, as liver-only metastasis in 25. Eleven of these 25 patients underwent liver resection (liver resection group), and 14 did not (non-liver resection group). The median overall survival was longer in the liver resection group than in all the patients (44 months vs. 17.8 months, respectively p = 0.040). The median overall survival was better in the liver resection group than in the non-liver resection group (44 months vs. 19.9 months, p = 0.012). The disease-free interval was also significantly longer in the liver resection group than in the non-liver resection group [22 months (range; 4-34 months) vs. 3 months (2-11), p < 0.001]. CONCLUSION: Potentially, metachronous solitary liver metastasis from bile duct cancer is an indication for liver resection when the patient has had a long disease-free interval. Observation for 3 months from first detection of metastasis may optimize the selection for this surgery.


Subject(s)
Bile Duct Neoplasms/pathology , Hepatectomy/methods , Liver Neoplasms/secondary , Liver Neoplasms/surgery , Liver/surgery , Disease-Free Survival , Female , Hepatectomy/mortality , Humans , Liver Neoplasms/mortality , Male , Neoplasm Recurrence, Local , Time Factors
20.
Hepatol Res ; 51(3): 336-342, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33381872

ABSTRACT

AIM: Hepatocellular adenoma (HCA) has a lower prevalence in Japan than in Western countries and HCA subtypes have been reported for only a few Japanese patients. We analyzed HCA subtype data 38 patients from 23 hospitals in Japan in order to examine character and difference between Western countries. METHODS: To confirm HCA and to analyze subtypes, we performed immunohistochemical examinations. RESULTS: Thirty-eight cases were found to have HCA without cirrhosis. The male/female ratio was 18/20. Ages ranged from 15 to 79 (average, 43.2) years. Male and elder patients are not rare, furthermore, most of elder patients are male. Glycogen storage disease, past history of medicament use, hepatitis B virus surface antigen-positivity, antihepatitis C virus -positivity, diabetes mellitus, obesity, lipid metabolism disorder and alcoholism were present in of 6, 8, 1, 1, 6, 6, 4, and 6 cases, respectively. As to HCA subtypes, HNF1alpha-inactivated HCA, beta-catenin activated HCA (b-HCA), inflammatory HCA (IHCA) and unclassified HCA (U-HCA) accounted for nine (23.7%), four (10.5%), 17 (44.7%) and eight (21.1%) cases, respectively. Two cases showed coexistence of HCA and hepatocellular carcinoma (HCC) at surgery, and another had HCC which had been detected 23 years after HCA diagnosis. The HCA subtype of one of the former cases was U-HCA, while the remaining two had b-HCA and U-HCA. CONCLUSIONS: In Japanese HCA cases, the proportions of U-HCA, male and elder cases were slightly higher than in Western countries, and most of elder patients were male. IHCA was however common regardless of race, and was assumed to be the predominant subtype of HCA.

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