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1.
Cancer Sci ; 115(6): 1989-2001, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38531808

RESUMEN

Considering the cost and invasiveness of monitoring postoperative minimal residual disease (MRD) of colorectal cancer (CRC) after adjuvant chemoradiotherapy (ACT), we developed a favorable approach based on methylated circulating tumor DNA to detect MRD after radical resection. Analyzing the public database, we identified the methylated promoter regions of the genes FGD5, GPC6, and MSC. Using digital polymerase chain reaction (dPCR), we termed the "amplicon of methylated sites using a specific enzyme" assay as "AMUSE." We examined 180 and 114 pre- and postoperative serial plasma samples from 28 recurrent and 19 recurrence-free pathological stage III CRC patients, respectively. The results showed 22 AMUSE-positive of 28 recurrent patients (sensitivity, 78.6%) and 17 AMUSE-negative of 19 recurrence-free patients (specificity, 89.5%). AMUSE predicted recurrence 208 days before conventional diagnosis using radiological imaging. Regarding ACT evaluation by the reactive response, 19 AMUSE-positive patients during their second or third blood samples showed a significantly poorer prognosis than the other patients (p = 9E-04). The AMUSE assay stratified four groups by the altered patterns of tumor burden postoperatively. Interestingly, only 34.8% of cases tested AMUSE-negative during ACT treatment, indicating eligibility for ACT. The AMUSE assay addresses the clinical need for accurate MRD monitoring with universal applicability, minimal invasiveness, and cost-effectiveness, thereby enabling the timely detection of recurrences. This assay can effectively evaluate the efficacy of ACT in patients with stage III CRC following curative resection. Our study strongly recommends reevaluating the clinical application of ACT using the AMUSE assay.


Asunto(s)
Neoplasias Colorrectales , Recurrencia Local de Neoplasia , Neoplasia Residual , Humanos , Neoplasias Colorrectales/terapia , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/genética , Masculino , Femenino , Persona de Mediana Edad , Anciano , Metilación de ADN , ADN Tumoral Circulante/sangre , ADN Tumoral Circulante/genética , Pronóstico , Quimioradioterapia Adyuvante/métodos , Regiones Promotoras Genéticas , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/genética , Adulto , Estadificación de Neoplasias , Anciano de 80 o más Años , Reacción en Cadena de la Polimerasa/métodos
2.
Cancer Sci ; 115(6): 1866-1880, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38494600

RESUMEN

Bromodomain and extraterminal domain (BET) family proteins are epigenetic master regulators of gene expression via recognition of acetylated histones and recruitment of transcription factors and co-activators to chromatin. Hence, BET family proteins have emerged as promising therapeutic targets in cancer. In this study, we examined the functional role of bromodomain containing 3 (BRD3), a BET family protein, in colorectal cancer (CRC). In vitro and vivo analyses using BRD3-knockdown or BRD3-overexpressing CRC cells showed that BRD3 suppressed tumor growth and cell cycle G1/S transition and induced p21 expression. Clinical analysis of CRC datasets from our hospital or The Cancer Genome Atlas revealed that BET family genes, including BRD3, were overexpressed in tumor tissues. In immunohistochemical analyses, BRD3 was observed mainly in the nucleus of CRC cells. According to single-cell RNA sequencing in untreated CRC tissues, BRD3 was highly expressed in malignant epithelial cells, and cell cycle checkpoint-related pathways were enriched in the epithelial cells with high BRD3 expression. Spatial transcriptomic and single-cell RNA sequencing analyses of CRC tissues showed that BRD3 expression was positively associated with high p21 expression. Furthermore, overexpression of BRD3 combined with knockdown of, a driver gene in the BRD family, showed strong inhibition of CRC cells in vitro. In conclusion, we demonstrated a novel tumor suppressive role of BRD3 that inhibits tumor growth by cell cycle inhibition in part via induction of p21 expression. BRD3 activation might be a novel therapeutic approach for CRC.


Asunto(s)
Neoplasias Colorrectales , Epigénesis Genética , Regulación Neoplásica de la Expresión Génica , Factores de Transcripción , Humanos , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Animales , Ratones , Línea Celular Tumoral , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Proliferación Celular/genética , Femenino , Masculino , Proteínas que Contienen Bromodominio
3.
Br J Cancer ; 129(7): 1105-1118, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37596408

RESUMEN

BACKGROUND: Intratumor heterogeneity (ITH) in microsatellite instability-high (MSI-H) colorectal cancer (CRC) has been poorly studied. We aimed to clarify how the ITH of MSI-H CRCs is generated in cancer evolution and how immune selective pressure affects ITH. METHODS: We reanalyzed public whole-exome sequencing data on 246 MSI-H CRCs. In addition, we performed a multi-region analysis from 6 MSI-H CRCs. To verify the process of subclonal immune escape accumulation, a novel computational model of cancer evolution under immune pressure was developed. RESULTS: Our analysis presented the enrichment of functional genomic alterations in antigen-presentation machinery (APM). Associative analysis of neoantigens indicated the generation of immune escape mechanisms via HLA alterations. Multiregion analysis revealed the clonal acquisition of driver mutations and subclonal accumulation of APM defects in MSI-H CRCs. Examination of variant allele frequencies demonstrated that subclonal mutations tend to be subjected to selective sweep. Computational simulations of tumour progression with the interaction of immune cells successfully verified the subclonal accumulation of immune escape mutations and suggested the efficacy of early initiation of an immune checkpoint inhibitor (ICI) -based treatment. CONCLUSIONS: Our results demonstrate the heterogeneous acquisition of immune escape mechanisms in MSI-H CRCs by Darwinian selection, providing novel insights into ICI-based treatment strategies.


Asunto(s)
Neoplasias del Colon , Neoplasias Colorrectales , Humanos , Inestabilidad de Microsatélites , Neoplasias Colorrectales/patología , Neoplasias del Colon/genética , Mutación , Presentación de Antígeno , Repeticiones de Microsatélite/genética
4.
Cancer Sci ; 113(1): 156-169, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34704338

RESUMEN

Colorectal cancer (CRC) is one of the most common types of cancer and a significant cause of cancer mortality worldwide. Further improvements of CRC therapeutic approaches are needed. BCL2-associated athanogene 6 (BAG6), a multifunctional scaffold protein, plays an important role in tumor progression. However, regulation of BAG6 in malignancies remains unclear. This study showed that guided entry of tail-anchored proteins factor 4 (GET4), a component of the BAG6 complex, regulates the intercellular localization of BAG6 in CRC. Furthermore, GET4 was identified as a candidate driver gene on the short arm of chromosome 7, which is often amplified in CRC, by our bioinformatics approach using the CRC dataset from The Cancer Genome Atlas. Clinicopathologic and prognostic analyses using CRC datasets showed that GET4 was overexpressed in tumor cells due to an increased DNA copy number. High GET4 expression was an independent poor prognostic factor in CRC, whereas BAG6 was mainly overexpressed in the cytoplasm of tumor cells without gene alteration. The biological significance of GET4 was examined using GET4 KO CRC cells generated with CRISPR-Cas9 technology or transfected CRC cells. In vitro and in vivo analyses showed that GET4 promoted tumor growth. It appears to facilitate cell cycle progression by cytoplasmic enrichment of BAG6-mediated p53 acetylation followed by reduced p21 expression. In conclusion, we showed that GET4 is a novel driver gene and a prognostic biomarker that promotes CRC progression by inducing the cytoplasmic transport of BAG6. GET4 could be a promising therapeutic molecular target in CRC.


Asunto(s)
Neoplasias Colorrectales/patología , Chaperonas Moleculares/genética , Regulación hacia Arriba , Acetilación , Animales , Línea Celular Tumoral , Proliferación Celular , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica , Células Hep G2 , Humanos , Masculino , Ratones , Estadificación de Neoplasias , Trasplante de Neoplasias , Pronóstico , Proteína p53 Supresora de Tumor/metabolismo
5.
Surg Case Rep ; 10(1): 30, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38300348

RESUMEN

BACKGROUND: Nodular regenerative hyperplasia (NRH) is a rare disease that presents pathologically as diffuse hepatic nodules without fibrous septa. It is believed to be caused by vasculopathy against a background of various systemic diseases, such as hematologic, autoimmune, and drug-induced diseases, with various symptoms. In spite of the recent imaging advances, various atypical cases of nodular lesions are observed in daily clinical practice. Cases that do not completely meet these criteria are referred to as -like or -similar lesions in clinical situations, making it difficult to understand their pathogenesis. We present a case in which two hepatic nodular lesions were noted and difficult to differentiate from malignancy preoperatively. The lesions were laparoscopically resected and a pathological diagnosis with non-neoplastic liver regenerative nodules resembling NRH was made. CASE PRESENTATION: A 49-year-old man with no alcohol or drug intake and no past medical history was identified as having liver tumors on screening examination without any symptoms. Contrast-enhanced computed tomography (CT) showed two hepatic tumors; approximately 2-cm tumors at S7 and S8. Gadolinium-ethoxybenzyl-diethylenetriamine-pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) revealed fat inclusions in their contents. Ethoxybenzyl (EOB) uptake was also observed during the hepatobiliary phase. Based on preoperative examinations, we suspected well-differentiated hepatocellular carcinoma (HCC) and performed laparoscopic S7/8 partial resection for these lesions. Macroscopically, the resected specimens showed a non-cirrhotic yellowish-cut surface containing brownish, ill-defined lesions with irregular borders. Microscopically, these lesions showed zonal necrosis, congestion, and aggregation of hemosiderin-laden macrophages around the central vein. In these areas, the fatty deposition of hepatocytes was lower than that in the surrounding background hepatocytes. Histopathologically, neither neoplastic nor hyperplastic lesions were observed, and he was diagnosed as regenerative hepatic change with centrilobular necrosis. CONCLUSIONS: Considering the pathological results, these lesions were thought to be a type of NRH-like lesion with possible hepatic vessel disorder. However, the lesion's cause and classification was difficult to determine. The accumulation of these regenerative changes accompanying fatty liver is needed to clarify the mechanism and its clinical significance.

6.
Int J Oncol ; 65(6)2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39450547

RESUMEN

Colorectal cancer (CRC) is widely prevalent and represents a significant contributor to global cancer­related mortality. There remains a pressing demand for advancements in CRC treatment modalities. The E3 ubiquitin ligase is a critical enzyme involved in modulating protein expression levels via posttranslational ubiquitin­mediated proteolysis, and it is reportedly involved in the progression of various cancers, making it a target of recent interest in anticancer therapy. In the present study, using comprehensive expression analysis involving spatial transcriptomic analysis with single­cell RNA sequencing in clinical CRC datasets, the ubiquitin­associated protein Shank­associated RH domain interactor (SHARPIN) was identified, located on amplified chromosome 8q, which could promote CRC progression. SHARPIN was found to be upregulated in tumor cells, with elevated expression observed in tumor tissues. This heightened expression of SHARPIN was positively associated with lymphatic invasion and served as an independent predictor of a poor prognosis in patients with CRC. In vitro and in vivo analyses using SHARPIN­overexpressing or ­knockout CRC cells revealed that SHARPIN overexpression upregulated MDM2, resulting in the downregulation of p53, while SHARPIN silencing or knockout downregulated MDM2, leading to p53 upregulation, which affects cell cycle progression, tumor cell apoptosis and tumor growth in CRC. Furthermore, SHARPIN was found to be overexpressed in several cancer types, exerting significant effects on survival outcomes. In conclusion, SHARPIN represents a newly identified novel gene with the potential to promote tumor growth following apoptosis inhibition and cell cycle progression in part by inhibiting p53 expression via MDM2 upregulation; therefore, SHARPIN represents a potential therapeutic target for CRC.


Asunto(s)
Neoplasias Colorrectales , Regulación Neoplásica de la Expresión Génica , Proteína p53 Supresora de Tumor , Humanos , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/metabolismo , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Masculino , Ratones , Femenino , Animales , Proliferación Celular/genética , Proteínas Proto-Oncogénicas c-mdm2/genética , Proteínas Proto-Oncogénicas c-mdm2/metabolismo , Línea Celular Tumoral , Pronóstico , Persona de Mediana Edad , Apoptosis/genética , Regulación hacia Arriba , Ubiquitinas
7.
EBioMedicine ; 103: 105102, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38614865

RESUMEN

BACKGROUND: Cell-cell interaction factors that facilitate the progression of adenoma to sporadic colorectal cancer (CRC) remain unclear, thereby hindering patient survival. METHODS: We performed spatial transcriptomics on five early CRC cases, which included adenoma and carcinoma, and one advanced CRC. To elucidate cell-cell interactions within the tumour microenvironment (TME), we investigated the colocalisation network at single-cell resolution using a deep generative model for colocalisation analysis, combined with a single-cell transcriptome, and assessed the clinical significance in CRC patients. FINDINGS: CRC cells colocalised with regulatory T cells (Tregs) at the adenoma-carcinoma interface. At early-stage carcinogenesis, cell-cell interaction inference between colocalised adenoma and cancer epithelial cells and Tregs based on the spatial distribution of single cells highlighted midkine (MDK) as a prominent signalling molecule sent from tumour epithelial cells to Tregs. Interaction between MDK-high CRC cells and SPP1+ macrophages and stromal cells proved to be the mechanism underlying immunosuppression in the TME. Additionally, we identified syndecan4 (SDC4) as a receptor for MDK associated with Treg colocalisation. Finally, clinical analysis using CRC datasets indicated that increased MDK/SDC4 levels correlated with poor overall survival in CRC patients. INTERPRETATION: MDK is involved in the immune tolerance shown by Tregs to tumour growth. MDK-mediated formation of the TME could be a potential target for early diagnosis and treatment of CRC. FUNDING: Japan Society for the Promotion of Science (JSPS) Grant-in-Aid for Science Research; OITA Cancer Research Foundation; AMED under Grant Number; Japan Science and Technology Agency (JST); Takeda Science Foundation; The Princess Takamatsu Cancer Research Fund.


Asunto(s)
Neoplasias Colorrectales , Midkina , Análisis de la Célula Individual , Linfocitos T Reguladores , Microambiente Tumoral , Femenino , Humanos , Masculino , Carcinogénesis/genética , Carcinogénesis/inmunología , Comunicación Celular/inmunología , Neoplasias Colorrectales/inmunología , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/mortalidad , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Tolerancia Inmunológica , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/metabolismo , Transcriptoma , Microambiente Tumoral/inmunología , Midkina/inmunología , Midkina/metabolismo
8.
Fukuoka Igaku Zasshi ; 104(12): 599-602, 2013 Dec.
Artículo en Japonés | MEDLINE | ID: mdl-24693692

RESUMEN

Incarcerated diaphragmatic hernia after laparoscopic right hepatectomy is very rare. An 81-year-old man underwent laparoscopic right hepatectomy for giant hepatic hemangioma. Twenty months after the surgery, he began to complain of nausea and abdominal pain and was brought to our hospital. Chest X-ray showed an abdominal gas shadow above the right diaphragm and computed tomography showed herniation of the colon into the right thoracic cavity. We diagnosed ileus due to incarcerated diaphragmatic hernia and performed emergency operation under laparoscopic surgery. After successfully reducing the prolapsed colon back to the abdominal cavity, the diaphragmatic hernia orifice was repaired. Incarcerated diaphragmatic hernia sometimes causes the fatal state. Clinicians must therefore consider such findings a late complication of laparoscopic hepatectomy.


Asunto(s)
Hemangioma/cirugía , Hepatectomía , Hernia Diafragmática/cirugía , Herniorrafia , Laparoscopía , Neoplasias Hepáticas/cirugía , Complicaciones Posoperatorias/cirugía , Anciano de 80 o más Años , Urgencias Médicas , Hernia Diafragmática/complicaciones , Hernia Diafragmática/diagnóstico , Humanos , Ileus/etiología , Ileus/cirugía , Masculino , Complicaciones Posoperatorias/diagnóstico , Factores de Tiempo , Tomografía Computarizada por Rayos X , Resultado del Tratamiento
9.
Ann Gastroenterol Surg ; 7(1): 63-70, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36643367

RESUMEN

Aim: Gastric mucosal changes associated with chronic gastritis are known to be precancerous lesions of gastric cancer. We aimed to identify individuals with a high risk of gastric cancer by detection of microRNAs (miRNA) in the blood as biomarkers. Methods: Of 1206 individuals screened, 144 who were positive for Helicobacter pylori (H. pylori) by the serum antibody test and who underwent endoscopy were the subjects of this study. For the gross assessment of mucosal inflammation, we applied the Kimura-Takemoto classification, in which normal mucosa was defined as grade 0, and atrophy was categorized as grade 1 (C-1 and C-2), grade 2 (C-3 and O-1), and grade 3 (O-2 and O-3). Serum samples were divided into two phases and used for miRNA microarray profiling. We compared the expression of miRNAs in grade 3 mucosa and other grades. Expression in gastric cancer was confirmed with TCGA data. Results: miR-196b-3p was significantly upregulated, and miR-92a-2-5p was downregulated (P < .05 and q < 0.2). TCGA data showed a high expression of miR-196b-3p in gastric cancer cases (P < .001). Comparing grade 3 and the others, the area under the receiver operating characteristic curve using the detected miRNAs was as high as about 0.7. Furthermore, the combination of miRNAs resulted in higher accuracy. In terms of the significance of the combinatory mRNAs, the combination of three miRNAs (miR-196b-3p, miR-92a-2-5p, and miR-6791-3p) revealed high sensitivity and specificity, with the area under the curve exceeding 0.8. Conclusion: The identified combinatory miRNAs may represent promising biomarkers of precancerous lesions in gastric cancer.

10.
Int Cancer Conf J ; 12(4): 274-278, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37577350

RESUMEN

Atezolizumab plus bevacizumab is the first-line regimen in Japan for hepatocellular carcinoma following the results of the IMbrave 150 trial. However, the safety and efficiency of atezolizumab plus bevacizumab in older patients, especially in the oldest-old patients aged over 80 years, have not been thoroughly studied and is still controversial. Eighteen months ago, a 90-year-old woman underwent a laparoscopic hepatectomy (S6) for her primary hepatocellular carcinoma (S6, 2 cm). Nine months after the first surgery, she received transcatheter arterial chemoembolization treatment for solitary hepatocellular carcinoma recurrence (S8, 2 cm). The subsequent recurrence (S3, 1 cm; S5, 2 cm; S8, 1 cm) was uncovered by radiological assessment 1 year after transcatheter arterial chemoembolization treatment. We then initiated chemotherapy treatment with lenvatinib at 8 mg daily. Despite reducing the lenvatinib dosage, the adverse event of severe fatigue and asitia did not resolve; therefore, the regimen of atezolizumab + bevacizumab combination therapy was changed to be started. After the first 2 months, tumor regression was observed on computed tomography; the patient tolerated the atezolizumab + bevacizumab combination regimen over 8 months for 10 cycles without any adverse effects. She finally showed a complete response; no recurrence developed 1 year after the complete response. Therefore, older adult patients may benefit highly from atezolizumab plus bevacizumab with appropriate patient selection.

11.
Cell Rep ; 42(1): 111929, 2023 01 31.
Artículo en Inglés | MEDLINE | ID: mdl-36656712

RESUMEN

The cellular interactions in the tumor microenvironment of colorectal cancer (CRC) are poorly understood, hindering patient treatment. In the current study, we investigate whether events occurring at the invasion front are of particular importance for CRC treatment strategies. To this end, we analyze CRC tissues by combining spatial transcriptomics from patients with a public single-cell transcriptomic atlas to determine cell-cell interactions at the invasion front. We show that CRC cells are localized specifically at the invasion front. These cells induce human leukocyte antigen G (HLA-G) to produce secreted phosphoprotein 1 (SPP1)+ macrophages while conferring CRC cells with anti-tumor immunity, as well as proliferative and invasive properties. Taken together, these findings highlight the signaling between CRC cell populations and stromal cell populations at the cellular level.


Asunto(s)
Neoplasias Colorrectales , Antígenos HLA-G , Humanos , Antígenos HLA-G/genética , Osteopontina , Transcriptoma/genética , Neoplasias Colorrectales/patología , Macrófagos , Microambiente Tumoral
12.
Surg Today ; 42(1): 41-5, 2012 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-22075660

RESUMEN

PURPOSE: Laparoscopic colonic surgery is now widely accepted. We assessed the safety and effectiveness of using a total intracorporeal surgical strategy to perform intracorporeal functional end-to-end anastomosis with an endoscopic linear stapler to treat colon cancer. METHODS: Forty-three selected patients underwent elective laparoscopic colon resection for carcinoma. A total intracorporeal colon resection was performed in all patients, using a functional end-to-end anastomosis with an endoscopic linear stapler. RESULTS: Good results were achieved in all 43 patients, none of whom required conversion to open surgery with extracorporeal anastomosis. There have been no intraoperative complications related to this technique and no instances of postoperative anastomotic leakage, intra-abdominal abscess, or wound infection. CONCLUSION: Intracorporeal functional end-to-end anastomosis using a linear stapler can be performed safely and easily for the resection of any part of the colon. We consider it an effective modality for totally laparoscopic colon resection. Favorable results have been achieved by this method, particularly for small tumors, since natural-orifice transluminal endoscopic surgery remains a challenging method to perform.


Asunto(s)
Colectomía/métodos , Neoplasias del Colon/cirugía , Laparoscopía/métodos , Adulto , Anciano , Anciano de 80 o más Años , Anastomosis Quirúrgica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Engrapadoras Quirúrgicas , Resultado del Tratamiento
13.
Anticancer Res ; 42(10): 4701-4706, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36192001

RESUMEN

BACKGROUND/AIM: Alternative splicing plays a vital role in cancer development and progression. The splicing C complex is involved in alternative splicing. However, the role of PRKR-interacting protein 1 (PRKRIP1), a component of the splicing C complex, in colorectal cancer (CRC) remains unclear. This study aimed to determine the clinicopathological, biological and prognostic significance of PRKRIP1 expression in CRC. MATERIALS AND METHODS: We used a bioinformatics approach to screen for oncogenes using The Cancer Genome Atlas (TCGA) and Cancer Cell Line Encyclopedia (CCLE) datasets and identified PRKRIP1 as a driver gene on chromosome 7q. The mRNA expression of PRKRIP1 was measured using reverse transcription-quantitative PCR in 165 surgically resected CRC samples in our hospital, and its localization was determined using immunohistochemical staining. Gene Set Enrichment Analysis (GSEA) was performed using TCGA dataset. RESULTS: High PRKRIP1 expression was significantly associated with poor prognosis in both the samples and TCGA dataset. A positive correlation was observed between copy number variation and PRKRIP1 expression in TCGA and CCLE datasets, and the frequency of PRKRIP1 mutations was less than 5%. Immunohistochemistry revealed that PRKRIP1 was located in the cytoplasm of tumor cells. GSEA revealed that PRKRIP1 expression was correlated with apoptosis-related gene sets. CONCLUSION: PRKRIP1 overexpression may be a poor prognostic biomarker for CRC. Although it is known that PRKRIP1, a spliceosome factor, is essential for splicing, we now revealed the way by which its expression accelerates CRC progression.


Asunto(s)
Neoplasias Colorrectales , Proteínas de Unión al ARN , Biomarcadores , Neoplasias Colorrectales/patología , Variaciones en el Número de Copia de ADN , Regulación Neoplásica de la Expresión Génica , Humanos , Pronóstico , Factores de Empalme de ARN/genética , ARN Mensajero , Proteínas de Unión al ARN/genética
14.
PLoS One ; 17(10): e0273566, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36264865

RESUMEN

BACKGROUND: Colorectal cancer (CRC) can be classified into four consensus molecular subtypes (CMS) according to genomic aberrations and gene expression profiles. CMS is expected to be useful in predicting prognosis and selecting chemotherapy regimens. However, there are still no reports on the relationship between the morphology and CMS. METHODS: This retrospective study included 55 subjects with T2 CRC undergoing surgical resection, of whom 30 had the depressed type and 25 the protruded type. In the classification of the CMS, we first defined cases with deficient mismatch repair as CMS1. And then, CMS2/3 and CMS4 were classified using an online classifier developed by Trinh et al. The staining intensity of CDX2, HTR2B, FRMD6, ZEB1, and KER and the percentage contents of CDX2, FRMD6, and KER are input into the classifier to obtain automatic output classifying the specimen as CMS2/3 or CMS4. RESULTS: According to the results yielded by the online classifier, of the 30 depressed-type cases, 15 (50%) were classified as CMS2/3 and 15 (50%) as CMS4. Of the 25 protruded-type cases, 3 (12%) were classified as CMS1 and 22 (88%) as CMS2/3. All of the T2 CRCs classified as CMS4 were depressed CRCs. More malignant pathological findings such as lymphatic invasion were associated with the depressed rather than protruded T2 CRC cases. CONCLUSIONS: Depressed-type T2 CRC had a significant association with CMS4, showing more malignant pathological findings such as lymphatic invasion than the protruded-type, which could explain the reported association between CMS4 CRC and poor prognosis.


Asunto(s)
Neoplasias Colorrectales , Humanos , Biomarcadores de Tumor/genética , Neoplasias Colorrectales/patología , Pronóstico , Estudios Retrospectivos , Transcriptoma
15.
Surg Today ; 41(5): 637-42, 2011 May.
Artículo en Inglés | MEDLINE | ID: mdl-21533934

RESUMEN

PURPOSE: To evaluate the technical feasibility and safety of overtube-guided covered metallic stent placement as palliative treatment for patients with inoperable malignant gastric outlet obstructions. METHODS: To relieve the symptoms of severe nausea and recurrent vomiting in five patients with inoperable gastric cancer, we used an overtube (Long overtube; Sumitomo Bakelite, Tokyo, Japan) to place large-diameter, self-expandable, covered esophageal Ultraflex stents (inner diameter 22-28 mm, length 10 or 12 cm; Boston Scientific, Watertown, MA, USA). Success was defined both technically and clinically. RESULTS: The stent placement was technically successful in all patients and resulted in improvement of symptoms in all five patients, four of whom were thereafter able to ingest solid food. The remaining patient, a 94-year-old man, was unable to ingest food because of dysmasesis. During the mean follow-up of 17 weeks, there was no stent reocclusion and no life-threatening complications developed. CONCLUSIONS: The placement of a large diameter, self-expandable, covered esophageal stent using an overtube appears to be effective for the palliative treatment of malignant gastric outlet obstruction.


Asunto(s)
Obstrucción Duodenal/terapia , Cuidados Paliativos , Stents , Anciano , Anciano de 80 o más Años , Materiales Biocompatibles Revestidos , Femenino , Obstrucción de la Salida Gástrica/terapia , Gastroscopía , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Gástricas/complicaciones
16.
Surg Today ; 41(5): 667-73, 2011 May.
Artículo en Inglés | MEDLINE | ID: mdl-21533939

RESUMEN

PURPOSE: The goals of this report are to present the characteristics of biliary complications associated with laparoscopic cholecystectomies (LC) performed at a single center, and to evaluate the efficacy of intraoperative cholangiography (IOC) using an endoscopic nasobiliary tube (ENBT) during an LC in order to prevent biliary complications. METHODS: A retrospective audit was conducted on a total of 657 patients who underwent either LC or open cholecystectomies (OC). There were 19 patients who developed bile duct injury (BDI; n = 9) or bile leakage (BL; n = 10) during an LC and were actively treated. After May of 1999, the patients with a higher risk of developing biliary complications were selected for preoperative placement of an ENBT, and IOC was performed. RESULTS: Intraoperative cholangiography using ENBT was performed on 93 (27.1%) out of 343 patients who underwent either LC or OC after May of 1999. An LC was performed in 335 cases (97.7%), and a conversion from an LC to OC was necessary in only three cases. Even though BDI never occurred, BL from the cystic duct and gallbladder bed were recognized in five cases. CONCLUSIONS: The selective use of IOC using ENBT may help to prevent BDI during LC, thereby expanding the indications for LC, while also reducing the rate of conversion to open procedures.


Asunto(s)
Colangiografía , Colecistectomía Laparoscópica , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Conductos Biliares/lesiones , Colecistectomía , Colecistectomía Laparoscópica/efectos adversos , Drenaje/instrumentación , Femenino , Humanos , Periodo Intraoperatorio , Masculino , Persona de Mediana Edad , Adulto Joven
17.
Surg Today ; 41(12): 1592-8, 2011 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-21969190

RESUMEN

PURPOSE: Although laparoscopic liver resection has been widely adopted, performing a pure laparoscopic right hepatectomy remains a challenging procedure. The aim of this report is to evaluate the efficiency of a pure laparoscopic right hepatectomy (PLRH) in the semi-prone position using the intrahepatic Glissonian approach and a modified hanging maneuver. METHODS: Pure laparoscopic right hepatectomy was performed in the semi-prone position with the use of an intrahepatic Glissonian approach and modified hanging maneuver for patients with primary liver cancer (n = 3) and metastatic liver cancer (n = 1). RESULTS: The intraoperative total blood loss was only 95-140 g (mean: 126.2 g). None of the patients required a blood transfusion, and no serious complications were encountered. The durations of the surgeries ranged from were 308 to 445 min (mean: 394.8 min). The postoperative hospital stay was 8-11 days (mean 9.5 days). CONCLUSION: Pure laparoscopic right hepatectomy in the semi-prone position using the intrahepatic Glissonian approach and a modified hanging maneuver is thus considered to be a safe modality, which minimizes intraoperative bleeding.


Asunto(s)
Pérdida de Sangre Quirúrgica/prevención & control , Hepatectomía/métodos , Laparoscopía , Neoplasias Hepáticas/cirugía , Posición Prona , Anciano , Carcinoma Hepatocelular/cirugía , Femenino , Hemostasis Quirúrgica/métodos , Humanos , Masculino , Persona de Mediana Edad
18.
Surg Case Rep ; 7(1): 165, 2021 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-34264431

RESUMEN

BACKGROUND: A congenital prepubic sinus (CPS) is a rare congenital anomaly in which a duct remnant extends from the skin opening near the pubic symphysis to various parts and the lesions are mostly located in the preperitoneal space. The totally extraperitoneal (TEP) approach is an operational method that provides a good field of view for the preperitoneal space. We report the CPS through the pubic symphysis in which complete resection was achieved by a TEP approach. TEP approach was minimally invasive and achieved satisfactory cosmetic outcome. CASE PRESENTATION: We herein report the case of a 13-year-old boy with a fistula opening near the dorsal penis. He was admitted to our hospital due to fever and lower abdominal pain. Abdominal ultrasonography and computed tomography revealed an abscess inside a fistula lumen on the posterior surface of the rectus abdominis muscles in the midline of the lower abdomen. Under a diagnosis of CPS, which was located in the preperitoneal space, endoscopic resection was performed by a totally extraperitoneal approach. After making an umbilical incision, the rectus abdominis muscle was excised outward to expose the preperitoneal space. A single-port system was placed in the preperitoneal space. Three 5-mm-port trocars were inserted. As the preperitoneal cavity was expanded, a sinus connecting to the pubic symphysis was confirmed. The pubic symphysis did not connect with the bladder. Because the fistula was penetrated with the pubic symphysis, the remaining caudal fistula was removed from the body surface with a small spindle-shaped incision around the fistula opening. Finally, the sinus was completely resected, with confirmation from both the cranial side and dorsal side of the pubic symphysis. We were able to perform complete resection of the CPS with good visibility and without any peritoneal damage. There were no intraoperative complications. His postoperative course was uneventful during the 1-year follow-up. CONCLUSIONS: The TEP approach may be feasible for the resection of a CPS and may allow safe and secure resection due to good visibility, even in pediatric patients.

19.
Interv Radiol (Higashimatsuyama) ; 6(2): 44-50, 2021 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-35909910

RESUMEN

A 73-year-old woman with portal vein stenosis caused by tumor recurrence after pancreatoduodenectomy was treated with stent placement without embolization of the jejunal varix. Anticoagulation therapy using heparin followed by rivaroxaban was administered after the procedure. She continued to receive systemic chemotherapy as an outpatient. Neither restenosis nor stent thrombosis was observed after 7 months. Based on the presented case and literature review, portal vein stenting is an effective treatment option for jejunal variceal bleeding caused by malignant portal venous stricture after pancreaticoduodenectomy. Antithrombotic therapy following portal venous stenting is required to prevent stent thrombosis in the majority of cases, although it has a risk of inducing recurrent variceal bleeding. Adjunctive jejunal variceal embolization can possibly be omitted in selected cases to obtain sufficient portal-SMV flow reconstruction.

20.
Surg Today ; 40(4): 373-5, 2010 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-20339994

RESUMEN

Internal hernias are relatively rare viscous protrusions through a defect in the peritoneal cavity. Paracecal hernia is one of the least common types, and only a few cases have been reported to date. We herein present the case of a 43-year-old woman, who was preoperatively diagnosed to have a small bowel obstruction caused by a paracecal hernia resulting from intestinal protrusion and invagination into a paracecal pouch. Laparoscopic surgery was performed for definitive diagnosis and treatment. The surgery achieved a good outcome and the patient experienced an uneventful perioperative course.


Asunto(s)
Hernia/diagnóstico , Herniorrafia , Laparoscopía , Adulto , Ciego , Femenino , Humanos , Obstrucción Intestinal/etiología
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