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AIM: Creation of an overlapped anastomosis using handsewn sutures for common enterotomy is very popular in robotic right colectomy (RRC) with intracorpareal anastomosis (IA). The aim of this study is to present a simple method for constructing a sutureless overlapped anastomosis using a 60 mm linear stapler with a reinforced bioabsorbable material in RRC with IA. METHOD: The distal ileum and proximal colon were put in overlapping positions. Enterotomies were created 2 cm proximal to the ileal stump and 8 cm distal to the colonic stump on the antimesenteric side. Subsequently, a 60 mm linear stapler with a reinforced bioabsorbable material was inserted into each lumen and fired. Finally, the bowel was elevated while holding the bioabsorbable material, and the common enterotomy was grasped with the robotic instrument in the middle and closed using a linear stapler with a reinforced bioabsorbable material. RESULTS: This technique was applied to 10 patients with tumours of the caecum, ascending colon, or transverse colon. The median operating time, anastomosis construction time, blood loss, and postoperative stay were 281 min (range 228-459 min), 12 min (range 11-17 min), 10 mL (range 0-110 mL), and 10 days (range 8-15 days), respectively. No adverse intraoperative events were observed. Postoperatively, one patient developed chylous ascites, but there were no other complications. CONCLUSION: The simple technique for constructing a sutureless overlapped anastomosis using a 60 mm linear stapler with a reinforced bioabsorbable material in robotic right colectomy with intracorporeal anastomosis appears to be safe and feasible.
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Implantes Absorvíveis , Anastomose Cirúrgica , Colectomia , Neoplasias do Colo , Íleo , Procedimentos Cirúrgicos Robóticos , Grampeadores Cirúrgicos , Colectomia/métodos , Colectomia/instrumentação , Humanos , Anastomose Cirúrgica/métodos , Anastomose Cirúrgica/instrumentação , Procedimentos Cirúrgicos Robóticos/métodos , Procedimentos Cirúrgicos Robóticos/instrumentação , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Neoplasias do Colo/cirurgia , Íleo/cirurgia , Procedimentos Cirúrgicos sem Sutura/métodos , Procedimentos Cirúrgicos sem Sutura/instrumentação , Duração da Cirurgia , Colo/cirurgia , Resultado do Tratamento , Grampeamento Cirúrgico/métodos , Grampeamento Cirúrgico/instrumentação , Adulto , Tempo de InternaçãoRESUMO
BACKGROUND/AIM: Transanal total mesorectal excision (TaTME) remains a challenging technique for rectal dissection. This study aimed to evaluate the clinical and oncological outcomes of TaTME, compared to those of the laparoscopic TME (LaTME) in rectal cancer. PATIENTS AND METHODS: Using propensity score-matched analyses, we analyzed retrospective data from 134 consecutive patients with rectal cancer who underwent TaTME or LaTME from January 2011 to June 2020 in our hospital. Clinical and oncological outcomes were evaluated. The primary endpoint was the 2-year local recurrence rate. RESULTS: Before data analysis, significant group-dependent differences were observed only in the tumor height (p<0.01). After analysis, preoperative patient demographics were similar between the TaTME and LaTME groups. The operative time was significantly shorter in the TaTME group (p=0.02), and the rates of hand-sewn anastomosis and protective loop ileostomy were significantly higher (p<0.01). The TaTME group showed a null conversion to open surgery compared to the LaTME group (5.9%). The postoperative complications, including anastomotic leak, were comparable between the two groups. However, the rate of Clavien-Dindo grade III tended to be lower in the TaTME group (p=0.07). There were no statistically significant differences in terms of pathological findings, and the 2-year local recurrence rate was similar between the two groups (both 5.9%). CONCLUSION: TaTME based on embryology along the fascia is feasible and seems a safe alternative to LaTME in selected patients with rectal cancer when considering the conversion rate and the operative time.
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Laparoscopia , Neoplasias Retais , Cirurgia Endoscópica Transanal , Humanos , Estudos Retrospectivos , Cirurgia Endoscópica Transanal/efeitos adversos , Cirurgia Endoscópica Transanal/métodos , Neoplasias Retais/patologia , Reto/cirurgia , Reto/patologia , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Complicações Pós-Operatórias/etiologia , Fáscia , Resultado do TratamentoRESUMO
BACKGROUND/AIM: To develop a recurrence risk score for determining the clinical indication for adjuvant chemotherapy in patients with initially unresectable advanced gastric cancer who underwent conversion surgery after chemotherapy. PATIENTS AND METHODS: A total of 65 patients with stage IV gastric cancer who underwent conversion surgery after chemotherapy were retrospectively enrolled. We established a risk score based on clinicopathological factors related to recurrence after conversion surgery. RESULTS: Out of 65 patients, 40 (62%) had recurrence after conversion surgery. The 5-year overall survival rates in patients with and without recurrence were 14.4% and 87.1%, respectively (p<0.01). Multivariate logistic regression analysis identified the depth of tumor invasion (pT2-4) and histological tumor response (grade 0-1a) as an independent risk factor for disease recurrence (p=0.033 and p=0.048, respectively). A scoring system determined by these two factors was created; total score ranged from 0 to 2 points, and patients were categorized into three groups (scores of 0 vs. 1 vs. 2 points). This scoring system showed that 12 (18%), 15 (23%), and 38 (58%) patients had recurrence risk scores of 0, 1, and 2 points, respectively. There was a close relationship between a high score and the presence of tumor recurrence (p<0.01). Moreover, our model system had a high sensitivity for the prediction of recurrence, compared with the pathological stage. CONCLUSION: Recurrence risk score is a promising tool for assessing the need for adjuvant chemotherapy in patients with initially unresectable advanced gastric cancer after conversion surgery.
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Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Estadiamento de Neoplasias , Estudos Retrospectivos , Relevância Clínica , Recidiva Local de Neoplasia/patologia , Fatores de Risco , Gastrectomia/efeitos adversos , PrognósticoRESUMO
BACKGROUND: We performed pull-through hand-sewn coloanal anastomosis immediately after sphincter-preserving ultralow anterior resection (ULAR) [pull-through ultra (PTU)] to avoid permanent stoma and reduce postoperative complications of lower rectal tumors. This study aimed to compare the clinical outcomes of PTU versus non-PTU (stapled or hand-sewn coloanal anastomosis with diverting stoma) after sphincter-preserving ULAR for lower rectal tumors. METHODS: This retrospective cohort study analyzed prospectively maintained data from 100 consecutive patients who underwent PTU (n = 29) or non-PTU (n = 71) after sphincter-preserving ULAR for rectal tumors between January 2011 and March 2023. In PTU, hand-sewn coloanal anastomosis was immediately performed using 16 stitches of 4-0 monofilament suture during primary surgery. The clinical outcomes were assessed. The primary outcomes were rates of permanent stomas and overall postoperative complications. RESULTS: The PTU group was significantly less likely to require a permanent stoma than the non-PTU group (P < 0.01). None of the patients in the PTU group required permanent stoma and the rate of overall complications was significantly lower in the PTU group (P = 0.01). The median operative time was comparable between the two groups (P = 0.33) but the median operative time during the second stage was significantly shorter in the PTU group (P < 0.01). The rates of anastomotic leakage and complications of Clavien-Dindo grade III were comparable between the two groups. Diverting ileostomy was performed in two patients with an anastomotic leak in the PTU group. The PTU group was significantly less likely to require a diverting ileostomy than those in the non-PTU group (P < 0.01). The composite length of hospital stay was significantly shorter in the PTU group (P < 0.01). CONCLUSIONS: PTU via immediate coloanal anastomosis for lower rectal tumors is a safe alternative to the current sphincter-preserving ULAR with diverting ileostomy for patients who wish to avoid a stoma.
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Canal Anal , Neoplasias Retais , Humanos , Estudos Retrospectivos , Canal Anal/cirurgia , Canal Anal/patologia , Neoplasias Retais/patologia , Anastomose Cirúrgica/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Fístula Anastomótica/epidemiologia , Fístula Anastomótica/etiologia , Fístula Anastomótica/prevenção & controleRESUMO
AIM: Total proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the standard surgical treatment modality for familial adenomatous polyposis (FAP). It is challenging to perform proctectomy and preserve anal sphincter function. In this video, precise mucosectomy of the anal canal via transanal minimally invasive surgery (MAC-TAMIS) is reported. METHODS: An asymptomatic 35-year-old man was found to have a positive faecal occult blood test in routine screening examination and was diagnosed with FAP on colonoscopic examination. The patient was scheduled for total proctocolectomy with IPAA using the TAMIS approach combined with transanal total mesorectal excision. MAC-TAMIS was performed to preserve the internal anal sphincter during laparoscopy. RESULTS: The total duration of surgery was 543 min, blood loss was minimal, and the postoperative course was uneventful. The postoperative hospital stay was 12 days. The pathological findings demonstrated no evidence of malignancy. Gastrographic imaging from the ileostomy showed sufficient size of the J pouch and good tonus of the anus at 6 months after surgery. The Wexner scores at 1, 3 and 6 months after ileostomy closure were 5, 3 and 0, respectively. CONCLUSION: The MAC-TAMIS technique is safe and feasible during total proctocolectomy with IPAA in patients with FAP. This technique allows us to precisely preserve the internal anal sphincter using a laparoscopic approach.
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Polipose Adenomatosa do Colo , Bolsas Cólicas , Proctocolectomia Restauradora , Neoplasias Retais , Cirurgia Endoscópica Transanal , Masculino , Humanos , Adulto , Canal Anal/cirurgia , Anastomose Cirúrgica/métodos , Proctocolectomia Restauradora/métodos , Polipose Adenomatosa do Colo/cirurgia , Neoplasias Retais/cirurgia , Resultado do Tratamento , Complicações Pós-Operatórias/cirurgiaRESUMO
PURPOSE: This study aims to investigate changes in the tumor immune environment of patients who underwent therapy with a vascular endothelial growth factor (VEGF) inhibitor for advanced colorectal cancer. METHODS: Patients (n = 135) with T3 or T4 colorectal cancer were included in this retrospective study. They were classified as follows: patients who had not received preoperative treatment (UPFRONT group, n = 54), who had received FOLFOX as preoperative chemotherapy (FOLFOX group, n = 55), and who had undergone resection after combination FOLFOX and bevacizumab as unresectable colorectal cancer (B-MAB group, n = 26). The number of cytotoxic T lymphocytes (CTLs), FOXP3+ lymphocytes (including regulatory T cells (Tregs)), CD163+ monocytes (including M2-type tumor-associated macrophages (TAM-M2 type)), and programmed cell death 1 (PD-1)+ lymphocytes was evaluated immunohistochemically in the cancer cell area (CC) and stromal cell area (ST) of surgical specimens, and compared among the three groups. RESULTS: The CTL population did not differ among the three groups in both areas. In the B-MAB group, the numbers of PD-1+ cells in the ST, FOXP3+ lymphocytes in both areas, and CD163+monocytes in the ST was lower than that in the other two groups, and a correlation with the histological therapeutic effect was observed. CONCLUSIONS: In advanced colorectal cancer, VEGF inhibitors may decrease the number of PD-1+ cells and inhibit the infiltration of FOXP3+ lymphocytes and CD163+monocytes into the tumor environment.
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Neoplasias Colorretais , Fator A de Crescimento do Endotélio Vascular , Humanos , Fator A de Crescimento do Endotélio Vascular/farmacologia , Microambiente Tumoral , Receptor de Morte Celular Programada 1 , Estudos Retrospectivos , Neoplasias Colorretais/tratamento farmacológico , Terapia de Imunossupressão , Fatores de Transcrição Forkhead/farmacologiaRESUMO
We recently determined the RNA sequencing-based microRNA (miRNA) expression signature of colorectal cancer (CRC). Analysis of the signature showed that the expression of both strands of pre-miR-139 (miR-139-5p, the guide strand, and miR-139-3p, the passenger strand) was significantly reduced in CRC tissues. Transient transfection assays revealed that expression of miR-139-3p blocked cancer cell malignant transformation (e.g., cell proliferation, migration, and invasion). Notably, expression of miR-139-3p markedly blocked RAC-alpha serine/threonine-protein kinase (AKT) phosphorylation in CRC cells. A combination of in silico database and gene expression analyses of miR-139-3p-transfected cells revealed 29 putative targets regulated by miR-139-3p in CRC cells. RNA immunoprecipitation analysis using an Argonaute2 (AGO2) antibody revealed that KRT80 was efficiently incorporated into the RNA-induced silencing complex. Aberrant expression of Keratin 80 (KRT80) was detected in CRC clinical specimens by immunostaining. A knockdown assay using small interfering RNA (siRNA) targeting KRT80 showed that reducing KRT80 expression suppressed the malignant transformation (cancer cell migration and invasion) of CRC cells. Importantly, inhibiting KRT80 expression reduced AKT phosphorylation in CRC cells. Moreover, hexokinase-2 (HK2) expression was reduced in cells transfected with the KRT80 siRNAs or miR-139-3p. The involvement of miRNA passenger strands (e.g., miR-139-3p) in CRC cells is a new concept in miRNA studies. Our tumor-suppressive miRNA-based approach helps elucidate the molecular pathogenesis of CRC.
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Neoplasias Colorretais , MicroRNAs , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Transformação Celular Neoplásica/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Regulação Neoplásica da Expressão Gênica , Hexoquinase/metabolismo , Humanos , Queratinas/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Interferente Pequeno , Complexo de Inativação Induzido por RNA/genética , Serina/metabolismo , Treonina/metabolismoRESUMO
BACKGROUND/AIM: Our recent miRNA analyses revealed that miR-30a-5p has tumor-suppressive activity in pancreatic ductal adenocarcinoma (PDAC). Herein, we sought to identify tumor-suppressive genes controlled by miR-30a-5p, emphasizing on genes that are closely involved in the molecular pathogenesis of PDAC. We uncovered several novel findings regarding the pathogenesis of this disease. MATERIALS AND METHODS: In silico analyses were used to identify the putative target genes of miR-30a-5p and assess their expression levels. Direct regulation of RRM2 by miR-30a-5p and its oncogenic functions were evaluated in PDAC cell lines. Overexpression of RRM2 was demonstrated in clinical samples. RESULTS: A total of 24 putative targets were identified by in silico database analysis. High expression of 4 genes (CBFB, RRM2, AHNAK, and DCBLD1) was significantly associated with shorter survival of patients with PDAC. Functional assays demonstrated that knockdown of RRM2 attenuated the malignant phenotype of PDAC cells. CONCLUSION: The miR-30a-5p/RRM2 axis facilitated the malignant transformation of PDAC cells.
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Carcinoma Ductal Pancreático/patologia , Genes Supressores de Tumor/fisiologia , Neoplasias Pancreáticas/patologia , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/mortalidade , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Transformação Celular Neoplásica/genética , Subunidade beta de Fator de Ligação ao Core/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Proteínas de Membrana/genética , MicroRNAs/genética , MicroRNAs/fisiologia , Proteínas de Neoplasias/genética , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/mortalidade , Ribonucleosídeo Difosfato Redutase/genética , Ribonucleosídeo Difosfato Redutase/metabolismo , Análise de SobrevidaRESUMO
To elucidate novel aspects of the molecular pathogenesis of colorectal cancer (CRC), we have created a new microRNA (miRNA) expression signature based on RNA-sequencing. Analysis of the signature showed that 84 miRNAs were upregulated, and 70 were downregulated in CRC tissues. Interestingly, our signature indicated that both guide and passenger strands of some miRNAs were significantly dysregulated in CRC tissues. These findings support our earlier data demonstrating the involvement of miRNA passenger strands in cancer pathogenesis. Our study focused on downregulated miR-490-3p and investigated its tumor-suppressive function in CRC cells. We successfully identified a total of 38 putative oncogenic targets regulated by miR-490-3p in CRC cells. Among these targets, the expression of three genes (IRAK1: p = 0.0427, FUT1: p = 0.0468, and GPRIN2: p = 0.0080) significantly predicted 5-year overall survival of CRC patients. Moreover, we analyzed the direct regulation of IRAK1 by miR-490-3p, and its resultant oncogenic function in CRC cells. Thus, we have clarified a part of the molecular pathway of CRC based on the action of tumor-suppressive miR-490-3p. This new miRNA expression signature of CRC will be a useful tool for elucidating new molecular pathogenesis in this disease.
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Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Quinases Associadas a Receptores de Interleucina-1/genética , MicroRNAs/genética , Idoso , Idoso de 80 Anos ou mais , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Masculino , RNA-Seq , Transcriptoma/genéticaRESUMO
Oral microbiota is reportedly associated with gut microbiota and influences colorectal cancer (CRC) progression; however, the details remain unclear. This study aimed to evaluate the role of oral microbiota in CRC progression. Fifty-two patients with CRC and 51 healthy controls were included. Saliva and stool samples were collected, and microbiota were evaluated using 16S rRNA analysis and next-generation sequencing. Comparative analysis was performed on both groups. Linear discriminant analysis effect size (LEfSe) revealed the presence of indigenous oral bacteria, such as Peptostreptococcus, Streptococcus, and Solobacterium spp., at a significantly higher relative abundance in saliva and stool samples of CRC patients compared with controls. Next, CRC patients were divided into early stage (Stage I, II; n = 26; 50%) and advanced stage (Stage III, IV; n = 26; 50%) disease. LEfSe revealed that S. moorei was present at a significantly higher relative abundance in the advanced-stage group compared with the early-stage group, again consistent for both saliva and stool samples. Among bacterial species with significantly higher relative abundance in CRC patients, P. stomatis, S. anginosus, S. koreensis, and S. moorei originated from the oral cavity, suggesting indigenous oral bacteria may have promoted initiation of CRC carcinogenesis. Furthermore, S. moorei may influence CRC progression.
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The aggressive nature of intrahepatic cholangiocarcinoma (ICC) renders it a particularly lethal solid tumor. Searching for therapeutic targets for ICC is an essential challenge in the development of an effective treatment strategy. Our previous studies showed that the miR-29-3p-family members (miR-29a-3p, miR-29b-3p and miR-29c-3p) are key tumor-suppressive microRNAs that control many oncogenic genes/pathways in several cancers. In this study, we searched for therapeutic targets for ICC using the miR-29-3p-family as a starting point. Our functional studies of cell proliferation, migration and invasion confirmed that the miR-29-3p-family act as tumor-suppressors in ICC cells. Moreover, in silico analysis revealed that "focal adhesion", "ECM-receptor", "endocytosis", "PI3K-Akt signaling" and "Hippo signaling" were involved in oncogenic pathways in ICC cells. Our analysis focused on the genes for integrin-α6 (ITGA6) and integrin-ß1 (ITGB1), which are involved in multiple pathways. Overexpression of ITGA6 and ITGB1 enhanced malignant transformation of ICC cells. Both ITGA6 and ITGB1 were directly regulated by the miR-29-3p-family in ICC cells. Interestingly, expression of ITGA6/ITGB1 was positively controlled by the transcription factor SP1, and SP1 was negatively controlled by the miR-29-3p-family. Downregulation of the miR-29-3p-family enhanced SP1-mediated ITGA6/ITGB1 expression in ICC cells. MicroRNA-based exploration is an attractive strategy for identifying therapeutic targets for ICC.
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Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive types of cancer, and its prognosis is abysmal; only 25% of patients survive one year, and 5% live for five years. MicroRNA (miRNA) signature analysis of PDAC revealed that both strands of pre-miR-30c (miR-30c-5p, guide strand; miR-30c-2-3p, passenger strand) were significantly downregulated, suggesting they function as tumor-suppressors in PDAC cells. Ectopic expression assays demonstrated that these miRNAs attenuated the aggressiveness of PDAC cells, e.g., cell proliferation, migration, and invasiveness. Through a combination of in silico analyses and gene expression data, we identified 216 genes as putative oncogenic targets of miR-30c-5p and miR-30c-2-3p regulation in PDAC cells. Among these, the expression of 18 genes significantly predicted the 5-year survival rates of PDAC patients (p < 0.01). Importantly, the expression levels of 10 genes (YWHAZ, F3, TMOD3, NFE2L3, ENDOD1, ITGA3, RRAS, PRSS23, TOP2A, and LRRFIP1) were found to be independent prognostic factors for patient survival (p < 0.01). We focused on TOP2A (DNA Topoisomerase II Alpha) and investigated its potential as a therapeutic target for PDAC. The overexpression of TOP2A and its transcriptional activators (SP1 and HMGB2) was detected in PDAC clinical specimens. Moreover, the knockdown of TOP2A enhanced the sensitivity of PDAC cells to anticancer drugs. Our analyses of the PDAC miRNA signature and tumor-suppressive miRNAs provide important insights into the molecular pathogenesis of PDAC.
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Our recent studies have implicated some passenger strands of miRNAs in the molecular pathogenesis of human cancers. Analysis of the microRNA (miRNA) expression signature in pancreatic ductal adenocarcinoma (PDAC) has shown that levels of miR-30a-3p, the passenger strand derived from pre-mir-30a, are significantly downregulated in PDAC tissues. This study aimed to identify the oncogenes closely involved in PDAC molecular pathogenesis under the regulation of miR-30a-3p. Ectopic expression assays showed that miR-30a-3p expression inhibited the aggressiveness of the PDAC cells, suggesting that miR-30a-3p acts as a tumor-suppressive miRNA in PDAC cells. We further identified 102 putative targets of miR-30a-3p regulation in PDAC cells by combining in silico analysis with gene expression data. Of these, ten genes (EPS8, HMGA2, ENDOD1, SLC39A10, TGM2, MGLL, SERPINE1, ITGA2, DTL, and UACA) were independent prognostic factors in multivariate analysis of survival of patients with PDAC (p < 0.01). We also investigated the oncogenic function of the integrin ITGA2 in PDAC cell lines. The integrin family comprises cell adhesion molecules expressed as heterodimeric, transmembrane proteins on the surface of various cells. Overexpression of ITGA2/ITGB1 (an ITGA2 binding partner) was detected in the PDAC clinical specimens. The knockdown of ITGA2 expression attenuated the malignant phenotypes of the PDAC cells. Together, results from these microRNA-based approaches can accelerate our understanding of PDAC molecular pathogenesis.
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Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patologia , MicroRNAs/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adulto , Carcinogênese/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Feminino , Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Masculino , MicroRNAs/fisiologia , Pessoa de Meia-Idade , Oncogenes , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Transdução de Sinais/genética , Transcriptoma/genética , Neoplasias PancreáticasRESUMO
Aberrantly expressed microRNAs (miRNAs) disrupt intracellular RNA networks and contribute to malignant transformation of cancer cells. Utilizing the latest RNA sequencing technology, we newly created the miRNA expression signature of esophageal squamous cell carcinoma (ESCC). A total of 47 miRNAs were downregulated in ESCC tissues, and these miRNAs were candidates for antitumor miRNAs in ESCC cells. Analysis of the signature revealed that several passenger strands of miRNAs were significantly downregulated in ESCC, e.g., miR-28-3p, miR-30a-3p, miR-30c-3p, miR-133a-3p, miR-139-3p, miR-143-5p, and miR-145-3p. Recent studies indicate that some passenger strands of miRNAs closely involved in cancer pathogenesis. In this study, we focused on both strands of pre-miR-143, and investigated their antitumor roles and target oncogenes in ESCC. Ectopic expression of miR-143-5p and miR-143-3p significantly attenuated malignant phenotypes (e.g., proliferation, migration, and invasive abilities) in ESCC cell lines. We revealed that six genes (HN1, HMGA2, NETO2, STMN1, TCF3, and MET) were putative targets of miR-143-5p regulation, and one gene (KRT80) was a putative target of miR-143-3p regulation in ESCC cells. Our ESCC miRNA signature and analysis strategy provided important insights into the molecular pathogenesis of ESCC.
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Carcinoma de Células Escamosas do Esôfago/genética , MicroRNAs/genética , Transcriptoma/genética , Idoso , Idoso de 80 Anos ou mais , Antagomirs/genética , Antagomirs/uso terapêutico , Biomarcadores Tumorais/genética , Movimento Celular/genética , Proliferação de Células/genética , Transformação Celular Neoplásica/genética , Carcinoma de Células Escamosas do Esôfago/patologia , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/genéticaRESUMO
A 78-year-old woman underwent left total mastectomy for breast cancer at 65 years of age.Thirteen years after the primary surgery, CT showed a single 46mm tumor located in liver segment 4.The tumor was difficult to distinguish between cholangiocellular carcinoma and liver metastasis of the breast cancer.We did not perform biopsy, considering dissemination, and performed left hemihepatectomy and left caudate lobectomy.Pathological findings revealed liver metastasis of breast cancer.Hepatic resection is a useful option in cases of single liver metastasis from breast cancer that are difficult to distinguish from cholangiocellular carcinoma.
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Neoplasias dos Ductos Biliares , Neoplasias da Mama , Colangiocarcinoma , Neoplasias Hepáticas , Idoso , Neoplasias da Mama/cirurgia , Diagnóstico Diferencial , Feminino , Humanos , Neoplasias Hepáticas/secundário , MastectomiaRESUMO
RNA-sequencing-based microRNA (miRNA) expression signatures have revealed that miR-148a-5p (the passenger strand of the miR-148a-duplex) is downregulated in various kinds of cancer tissues. Analysis of The Cancer Genome Atlas (TCGA) database showed that low expression of miR-148a-5p was predictive of a lower survival rate (p = 0.041) in patients with gastric cancer (GC). Downregulation of miR-148a-5p was confirmed in GC clinical specimens, and its ectopic expression attenuated GC cell proliferation. Our search for miRNA target genes identified a total of 18 oncogenic targets of miR-148a-5p in GC cells. Among these targets, high expression levels of six genes (THBS2, P4HA3, SERPINH1, CDH11, BCAT1, and KCNG3) were closely associated with a poor prognosis (10-year survival rates) in GC patients (p < 0.05) according to TCGA database analyses. Furthermore, we focused on SERPINH1 as a chaperone protein involved in collagen folding in humans. Aberrant expression of SERPINH1 (mRNA and protein levels) was confirmed in GC clinical specimens. Knockdown assays of SERPINH1 using siRNAs resulted in inhibition of the aggressive phenotype of GC cells. Exploring the molecular networks controlled by miRNAs (including miRNA passenger strands) will broaden our understanding of the molecular pathogenesis of GC.
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Regulação Neoplásica da Expressão Gênica/genética , Proteínas de Choque Térmico HSP47/metabolismo , MicroRNAs/metabolismo , Neoplasias Gástricas/metabolismo , Caderinas/genética , Caderinas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Bases de Dados Genéticas , Regulação para Baixo , Perfilação da Expressão Gênica , Técnicas de Silenciamento de Genes , Proteínas de Choque Térmico HSP47/genética , Humanos , MicroRNAs/genética , Canais de Potássio de Abertura Dependente da Tensão da Membrana/genética , Canais de Potássio de Abertura Dependente da Tensão da Membrana/metabolismo , Pró-Colágeno-Prolina Dioxigenase/genética , Pró-Colágeno-Prolina Dioxigenase/metabolismo , Prognóstico , RNA Interferente Pequeno , Complexo de Inativação Induzido por RNA/genética , Complexo de Inativação Induzido por RNA/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Taxa de Sobrevida , Trombospondinas/genética , Trombospondinas/metabolismo , Transaminases/genética , Transaminases/metabolismoRESUMO
INTRODUCTION: In closure of a stoma, the small working space and adhesions hinder a precise surgical procedure, compared with conventional approaches to digestive surgery. The aim of this prospective study was to introduce a new technique of laparoscopic stoma closure (LASC). MATERIALS AND SURGICAL TECHNIQUES: After starting with three trocars, it is a priority to dissect around the arising ileum; a linear stapler is precisely inserted in both orifices of the loop stoma and applied two times, extracorporeally. Ultimately, both the oral and anal sides of the loop ileum are cut and closed using a linear cutter stapler in a delta-shaped manner just under the abdominal wall, intracorporeally. Eventually, the arising stoma is removed using an intra-abdominal and cutaneous approach. DISCUSSION: LASC for patients with a temporary loop ileostomy is safe and feasible. More data and experience will be required to verify the benefits of this new technique.
Assuntos
Laparoscopia , Humanos , Ileostomia , Íleo/cirurgia , Estudos Prospectivos , Estomas CirúrgicosRESUMO
Previously, we established a microRNA (miRNA) expression signature in pancreatic ductal adenocarcinoma (PDAC) tissues using RNA sequencing and found significantly reduced expression of miR-204-5p. Here, we aimed to investigate the functional significance of miR-204-5p and to identify miR-204-5p target genes involved in PDAC pathogenesis. Cancer cell migration and invasion were significantly inhibited by ectopic expression of miR-204-5p in PDAC cells. Comprehensive gene expression analyses and in silico database searches revealed 25 putative targets regulated by miR-204-5p in PDAC cells. Among these target genes, high expression levels of RACGAP1, DHRS9, AP1S3, FOXC1, PRP11, RHBDL2 and MUC4 were significant predictors of a poor prognosis of patients with PDAC. In this study, we focused on RACGAP1 (Rac guanosine triphosphatase-activating protein 1) because its expression was most significantly predictive of PDAC pathogenesis (overall survival rate: p = 0.0000548; disease-free survival rate: p = 0.0014). Overexpression of RACGAP1 was detected in PDAC clinical specimens, and its expression enhanced the migration and invasion of PDAC cells. Moreover, downstream genes affected by RACGAP1 (e.g., MMP28, CEP55, CDK1, ANLN and S100A14) are involved in PDAC pathogenesis. Our strategy to identify antitumor miRNAs and their target genes will help elucidate the molecular pathogenesis of PDAC.
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BACKGROUND: Perforated diverticulitis with purulent peritonitis (Hinchey III diverticulitis) has traditionally been treated with a Hartmann's procedure in order to avoid the considerable postoperative morbidity and mortality associated with one-stage resection and primary anastomosis. Although there have been reports regarding laparoscopic lavage as the initial treatment of perforated Hinchey III diverticulitis, a formal treatment strategy has not been established yet. We performed a three-stage surgery, including laparoscopic lavage and drainage with diverting ileostomy (first stage), laparoscopic sigmoidectomy (second stage), and ileostomy closure (third stage) in a morbidly obese patient with Hinchey III diverticulitis. CASE PRESENTATION: A 31-year-old man who presented with abdominal pain was diagnosed with perforated diverticulitis and sent to our hospital for evaluation. He had morbid obesity (body mass index (BMI) 50 kg/m2), acute renal failure, and uncontrolled diabetes. We performed an emergency operation including laparoscopic lavage and drainage with a diverting ileostomy for this case of Hinchey III diverticulitis. Fifteen months after the first-stage surgery, we performed laparoscopic sigmoidectomy as the second stage. Finally, 5 months later, we performed ileostomy closure. The patient recovered without significant complications. CONCLUSION: Three-stage surgery including early laparoscopic lavage and proximal diversion for morbidly obese, comorbid patients with Hinchey III diverticulitis may be indicated in the acute phase to avoid perioperative complications and permanent colostomy creation.
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INTRODUCTION: Laparoscopic cholecystectomy is the standard surgical treatment for patients with benign gallbladder disease. However, bile duct injury continues to be reported as a surgical complication. Intraoperative cholangiography is recommended to reduce the risk of bile duct injury during laparoscopic cholecystectomy. Intraoperative cholangiography using indocyanine green, which is excreted into bile and shows fluorescence under infrared light, has recently been reported as useful in preventing bile duct injury during laparoscopic cholecystectomy. We report here a case of laparoscopic cholecystectomy with an aberrant bile duct detected by intraoperative fluorescent cholangiography concomitant with angiography. PRESENTATION OF CASE: An 82-year-old woman was diagnosed with cholecystolithiasis and underwent laparoscopic cholecystectomy. An aberrant bile duct branching from the right side of the common hepatic duct was detected by intraoperative indocyanine green fluorescent cholangiography. Furthermore, we were able to confirm the cystic artery by reinjecting indocyanine green during the procedure. Laparoscopic cholecystectomy was performed safely without injuring the aberrant bile duct, despite no recognition of the abnormality on preoperative computed tomography or magnetic resonance imaging. DISCUSSION AND CONCLUSIONS: Aberrant bile ducts are rare anatomical variation and clinically important because of the susceptibility to injury during cholecystectomy. Our case reported for the first time that fluorescence cholangiography concomitant with angiography was useful for identifying an aberrant bile duct and the cystic artery during laparoscopic cholecystectomy.