RESUMO
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.
Assuntos
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
Precise spatiotemporal control of gene expression in the developing brain is critical for neural circuit formation, and comprehensive expression mapping in the developing primate brain is crucial to understand brain function in health and disease. Here, we developed an unbiased, automated, large-scale, cellular-resolution in situ hybridization (ISH)-based gene expression profiling system (GePS) and companion analysis to reveal gene expression patterns in the neonatal New World marmoset cortex, thalamus, and striatum that are distinct from those in mice. Gene-ontology analysis of marmoset-specific genes revealed associations with catalytic activity in the visual cortex and neuropsychiatric disorders in the thalamus. Cortically expressed genes with clear area boundaries were used in a three-dimensional cortical surface mapping algorithm to delineate higher-order cortical areas not evident in two-dimensional ISH data. GePS provides a powerful platform to elucidate the molecular mechanisms underlying primate neurobiology and developmental psychiatric and neurological disorders.
Assuntos
Encéfalo/metabolismo , Callithrix/genética , Transcriptoma/genética , Animais , Animais Recém-Nascidos/genética , Animais Recém-Nascidos/crescimento & desenvolvimento , Encéfalo/crescimento & desenvolvimento , Callithrix/crescimento & desenvolvimento , Corpo Estriado/crescimento & desenvolvimento , Corpo Estriado/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/genética , Humanos , Hibridização In Situ , Camundongos , Especificidade da Espécie , Córtex Visual/crescimento & desenvolvimento , Córtex Visual/metabolismoRESUMO
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.
Assuntos
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
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.
Assuntos
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
The standard treatment of locally advanced rectal cancer is preoperative chemoradiotherapy(CRT)in Europe and the United States, while that is surgical excision and lateral pelvic lymph node dissection followed by adjuvant chemotherapy in Japan. Recently, total neoadjuvant therapy(TNT), which combines neoadjuvant chemotherapy and preoperative CRT, have been popular. We performed curative excision for initially locally advanced rectal cancer with liver metastasis after TNT. A 61- year-old woman was diagnosed as having rectal cancer with liver metastasis and invasion of the uterus, vagina, bladder, and left ureter. The patient underwent 8 courses of FOLFOX plus bevacizumab, followed by radiotherapy, and totally pelvic excision for the primary tumor. Because of liver metastasis progression, hepatectomy was performed after 6 courses of FOLFIRI plus panitumumab. The patient has been cancer free for 20 months to date. TNT is considered to be an effective strategy for the treatment of large locally advanced rectal cancer.
Assuntos
Neoplasias Hepáticas , Neoplasias Retais , Feminino , Humanos , Pessoa de Meia-Idade , Resultado do Tratamento , Estadiamento de Neoplasias , Reto/patologia , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/cirurgia , Quimiorradioterapia , Terapia Neoadjuvante , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
AIM: Totally laparoscopic colectomy with intracorporeal anastomosis (IA) is associated with less surgical trauma and wound related complications compared to laparoscopy-assisted colectomy with extracorporeal anastomosis. Delta shaped anastomosis is a widely popular IA technique. In this study, we discuss a construction technique for an overlapped delta-shaped anastomosis using a linear stapler with a reinforced bioabsorbable material. METHODS: We excised the bowel at a point 10 cm from the tumour on either sides and laid them in an overlapped fashion. The entry hole was created at a point 3 cm proximal to the right stump and 7 cm distal to the left stump on the antimesenteric side. Then, a 60-mm linear stapler with reinforced bioabsorbable material was inserted inside each lumen and fired. Finally, the common entry hole was fixed with a suture in the middle, the bowel was elevated holding the bioabsorbable material, and closed using the linear stapler in a delta-shaped manner. RESULTS: The technique was applied in five patients with tumours in the ascending, transverse, and descending colon. The median surgery time, anastomosis construction time and postoperative stay was 329 min (range 285-682 min), 19 min (range 14-29 min), and 12 days (range 9-15 days), respectively. There were no perioperative complications and only one postoperative complication. CONCLUSION: The overlapped delta-shaped anastomosis technique using linear staplers with reinforced bioabsorbable material appears to be both safe and feasible.
Assuntos
Implantes Absorvíveis , Laparoscopia , Humanos , Laparoscopia/métodos , Tempo de Internação , Resultado do Tratamento , Colectomia/métodos , Anastomose Cirúrgica/métodos , Estudos RetrospectivosRESUMO
PURPOSE: To investigate the clinical indications and prognostic significance of surgical interventions after chemotherapy using trastuzumab-containing regimens for patients with human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer (AGC). METHODS: A total of 146 patients with AGC who underwent chemotherapy were enrolled in this retrospective study. Tumors with an immunohistochemistry (IHC) score of 3 + or an IHC score of 2 + plus fluorescence in situ hybridization positivity were defined as HER2-positive AGC. We devised a scoring system for predicting prognosis associated with conversion surgery. RESULTS: Thirty-three patients received trastuzumab-based chemotherapy for HER2-positive tumors. Multivariate analyses identified advanced age, peritoneal dissemination, histologically undifferentiated tumors, and tumor response of progressive disease as independent prognostic factors for a worse prognosis. Twelve patients with HER2-positive AGC underwent conversion surgery. The conversion surgery group of patients with HER2-positive AGC had a better prognosis than the chemotherapy-alone group. A prognostic scoring system based on age, peritoneal dissemination, and histological type was significantly correlated with the presence or absence of conversion surgery and the prognosis of patients with HER2-positive AGC. CONCLUSIONS: Our scoring system has the clinical potential to predict prognosis associated with conversion surgery after trastuzumab-containing chemotherapy for patients with HER2-positive AGC.
Assuntos
Neoplasias Gástricas , Humanos , Trastuzumab , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Prognóstico , Hibridização in Situ Fluorescente , Estudos Retrospectivos , Receptor ErbB-2/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
PURPOSE: Minimally invasive esophagectomy (MIE) has been widely accepted as a treatment for esophageal cancer. This retrospective study compared the short-term outcomes and surgical invasiveness between thoracoscopic esophagectomy (TE) and mediastinoscopic esophagectomy with pneumomediastinum (pneumatic mediastinoscopic esophagectomy [PME]). METHODS: A total of 72 patients who underwent TE or PME were included and assessed for their surgical findings, postoperative complications, and inflammatory responses on postoperative day (POD) 1, 3, 5, and 7. RESULTS: The PME group exhibited a significantly shorter operative time and fewer lymph nodes retrieved than the TE group. Furthermore, the PME group tended to have greater incidences of recurrent laryngeal nerve palsy and lower incidences of atelectasis than the TE group. The PME group had significantly lower white blood cell counts on POD 5, serum C-reactive protein (CRP) levels on POD 3 than the TE group. CONCLUSION: PME seems to be less invasive than TE and can be considered the preferred option for patients with lower-stage esophageal cancer expected to have severe pleural adhesion or who cannot tolerate TE.
Assuntos
Neoplasias Esofágicas , Esofagectomia , Humanos , Estudos Retrospectivos , Neoplasias Esofágicas/cirurgia , Neoplasias Esofágicas/patologia , Mediastinoscopia , Excisão de Linfonodo , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/cirurgia , Resultado do Tratamento , ToracoscopiaRESUMO
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.
Assuntos
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
PURPOSE: To investigate the drainage patterns of the inferior mesenteric vein (IMV) and measure the distance from the root of the inferior mesenteric artery (IMA) to the IMV using preoperative three-dimensional computed tomography (3D-CT) angiography in patients undergoing surgery for left-sided colorectal cancer. METHODS: In this retrospective study, we analyzed data collected prospectively on 167 consecutive patients who underwent laparoscopic left-sided colorectal cancer surgery between July, 2014 and August, 2019. The drainage pattern of the IMV and the distance from the root of the IMA to the IMV were evaluated using 3D-CT angiography. We also assessed intraoperative adverse events and postoperative outcomes. RESULTS: The IMV drained into the superior mesenteric vein (SMV) in 44 patients, into the confluence point of the SMV and splenic vein (SV) in 38 patients, into the SV in 83 patients, and into the middle colic vein in the remaining three patients. The median length from the root of the IMA to the IMV was 22.1 mm (1.3-84.9). IMV injury occurred in only one patient during surgery, but resulted in colonic ischemia. CONCLUSION: 3D-CT angiography is useful for the preoperative assessment of vascular anatomical variations of the IMV and IMA for safe intraoperative navigation and prevention of complications during laparoscopy-assisted left-sided colorectal surgery.
Assuntos
Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/cirurgia , Angiografia por Tomografia Computadorizada/métodos , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Imageamento Tridimensional/métodos , Laparoscopia/métodos , Veias Mesentéricas/anatomia & histologia , Veias Mesentéricas/diagnóstico por imagem , Complicações Pós-Operatórias/prevenção & controle , Cirurgia Assistida por Computador/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Feminino , Humanos , Laparoscopia/efeitos adversos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Estudos RetrospectivosRESUMO
PURPOSE: To assess the clinical indications for, and prognostic impact of surgery after, chemotherapy for type 4 gastric cancer. METHODS: The subjects of this retrospective study were 67 patients who received chemotherapy for type 4 gastric cancer. The patients were grouped into those with progressive disease (PD group) and those without PD (non-PD group), according to the tumor response to chemotherapy. RESULTS: Distant metastases developed in 58 patients. With regard to tumor response, there were 16 patients in the PD group and 51 patients in the non-PD group. The prognosis of the PD group patients was significantly poorer than that of the non-PD group patients (p < 0.0001). R0 resection was performed for 21 of 23 patients who underwent surgery after chemotherapy. Multivariate analysis revealed tumor response and surgery as independent prognostic factors (p = 0.0001 and p = 0.0009, respectively). Moreover, multivariate analysis of the surgery group revealed that metastatic nodal status (N0-1 vs. N2-3) and residual tumor status (R0 vs. R1-2) were significant independent prognostic factors (p = 0.0258 and p = 0.0458, respectively). CONCLUSION: The findings of this study suggest that surgery after chemotherapy for type 4 gastric cancer may improve the prognosis of responders with N0-1 status, who undergo curative R0 resection.
Assuntos
Antineoplásicos/uso terapêutico , Gastrectomia/métodos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/classificação , Neoplasias Gástricas/patologiaRESUMO
PURPOSE: Using a circular stapler to create an anastomosis for esophagogastrostomy after esophagectomy is well accepted; however, it remains uncertain if the greater curvature (GC) or lesser curvature (LC) of the gastric conduit is better for the anastomosis. We conducted this prospective study to compare the integrity of esophagogastrostomy between the esophagus and the GC or LC side of the gastric conduit. METHODS: The subjects of this study were 70 patients who underwent esophagectomy and were randomized to a "GC" group and an "LC" group (n = 35 each). The primary and secondary end points were anastomotic leakage (AL) and anastomotic stricture (AS), respectively. RESULTS: The overall AL rate was 22.1%, without a significant difference between the groups. Stump leakage developed in eight of nine patients in the GC group, whereas leakage developed at the esophagogastric anastomosis in five of six patients in the LC group. The rate of stump leakage was significantly higher than that of esophagogastric AL in the GC group. The overall AS rate was 4.4%, with a significant difference between the groups (0% in the GC group vs. 9.1% in the LC group). CONCLUSIONS: AL rates were comparable in the two groups, but the sites of leakage were significantly different.
Assuntos
Neoplasias Esofágicas/cirurgia , Esofagectomia/métodos , Esôfago/cirurgia , Gastrostomia/métodos , Grampeadores Cirúrgicos , Grampeamento Cirúrgico/instrumentação , Anastomose Cirúrgica/instrumentação , Anastomose Cirúrgica/métodos , Fístula Anastomótica/epidemiologia , Fístula Anastomótica/etiologia , Feminino , Humanos , Masculino , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Grampeadores Cirúrgicos/efeitos adversos , Grampeamento Cirúrgico/efeitos adversos , Grampeamento Cirúrgico/métodos , Resultado do TratamentoRESUMO
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.
Assuntos
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
Although the effectiveness of trifluridine/tipiracil(TFTD)with bevacizumab for unresectable colorectal cancer that was refractory to previous standard chemotherapy was reported, its effectiveness as a first-line treatment, especially for elderly frail patients, is unclear. An 85-year-old woman complaining of anorexia was diagnosed with unresectable sigmoid colon cancer with multiple metastases. Her general status was very poor, and her performance status(PS)was 4. We first performed laparoscopic transverse colostomy. As her general status gradually improved, we administered TFTD with bevacizumab as a first-line treatment based on the patient's strong request for chemotherapy. The patient underwent this regimen in the outpatient clinic for 9 months(9 courses). Although the size of the liver metastases increased, lung metastases and abdominal disseminations were under control and her PS became 0. She has been taking mFOLFOX6 with bevacizumab (80%)as a second-line treatment. TFTD with bevacizumab treatment was safe and efficacious as a first-line treatment for a frail elderly patient with unresectable colorectal cancer.
Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Feminino , Idoso Fragilizado , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Pirrolidinas , Timina , Trifluridina/uso terapêuticoRESUMO
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.
Assuntos
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
OBJECTIVE: Nivolumab is recommended as a third-line treatment in patients with unresectable advanced or recurrent gastric cancer. Although recent studies have demonstrated the prognostic impact of salvage chemotherapy after immune checkpoint inhibitors in several malignancies, its clinical significance remains unclear in patients with gastric cancer. This study aimed to investigate tumor response to subsequent chemotherapy after nivolumab in patients with advanced gastric cancer and assess the prognostic effect of salvage chemotherapy. METHODS: We retrospectively enrolled 31 patients with unresectable advanced or recurrent gastric cancer receiving nivolumab. RESULTS: Twenty-two and nine patients received nivolumab as third-line and fourth- to sixth-line treatments, respectively. The objective response rate (ORR) and disease control rate (DCR) to nivolumab were 20.0% (4/20) and 55.0% (11/20), respectively. Eleven patients received salvage chemotherapy after nivolumab. The ORR and DCR to salvage chemotherapy were 37.5% (3/8) and 75.0% (6/8), respectively. The median progression-free survival and overall survival following salvage chemotherapy were 285 and 360 days, respectively. CONCLUSION: Our preliminary study indicates that nivolumab exposure may enhance subsequent chemosensitivity in patients with advanced gastric cancer.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Nivolumabe/administração & dosagem , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/administração & dosagem , Feminino , Humanos , Irinotecano/administração & dosagem , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Prognóstico , Intervalo Livre de Progressão , Pirrolidinas/administração & dosagem , Estudos Retrospectivos , Terapia de Salvação/métodos , Neoplasias Gástricas/diagnóstico por imagem , Timina/administração & dosagemRESUMO
OBJECTIVE: Although chemotherapy has been clinically recommended as the initial treatment for patients with peritoneal dissemination of gastric cancer, poor prognosis has been noted among the same patients. However, the prognostic significance of conversion surgery after chemotherapy remains unclear. The present study therefore aimed to assess the clinical impact of conversion surgery among patients with peritoneal dissemination of gastric cancer. METHODS: A total of 93 patients with peritoneal dissemination of gastric cancer undergoing chemotherapy between February 2002 and October 2019 were retrospectively enrolled and subsequently divided into progressive disease (PD) and non-PD groups based on tumor response to chemotherapy. RESULTS: Among the included patients, 17 developed distant metastases at another site besides peritoneal dissemination. Based on tumor response, 24 and 69 patients were determined to have PD and non-PD, respectively, with the former having significantly poorer prognosis than the latter (p < 0.0001). A total of 19 patients underwent conversion surgery after chemotherapy, with the presence or absence of conversion surgery being significantly correlated with age, first-line chemotherapy regimen, and tumor response (p = 0.0134, p = 0.0337, and p = 0.0024, respectively). Patients in the non-PD group who underwent conversion surgery or chemotherapy alone had 3-year overall survival rates of 55.6 and 6.6%, respectively. Multivariate analysis identified conversion surgery alone as an independent prognostic factor in the non-PD group (p < 0.0001). CONCLUSION: Our retrospective study demonstrated that conversion surgery for gastric cancer with peritoneal dissemination might improve the prognosis of responders who developed no peritoneal dissemination after chemotherapy.
Assuntos
Neoplasias Peritoneais/patologia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Gastrectomia , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Neoplasias Peritoneais/tratamento farmacológico , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/tratamento farmacológicoRESUMO
OBJECTIVE: Chemotherapy is generally recommended as the first-line standard treatment in patients with liver metastasis from gastric cancer. However, the clinical impact of surgical treatment remains unclear in responders after chemotherapy. The present study aimed to investigate the tumor response and prognosis after chemotherapy and to assess the clinical indication of conversion surgery in responders. METHODS: The study retrospectively reviewed the clinical data of 44 patients with liver metastasis from gastric cancer who were treated with chemotherapy between February 2002 and January 2019. These patients were classified into progressive disease (PD) and non-PD groups according to tumor response. RESULTS: Among the 44 patients, 7 and 26 had peritoneal dissemination and ≥5 had metastatic liver nodules. Additionally, 15 and 29 patients had PD and non-PD, respectively. Surgical treatment was significantly correlated with tumor response (p < 0.0321). Prognostic differences between the PD and non-PD groups were significant (p < 0.0001). Moreover, gastrectomy and hepatectomy were significantly correlated with the number of liver metastases (≥5 vs. <5, respectively) in the non-PD group (p = 0.0025 and p = 0.0169, respectively). The 3-year survival rates among patients with non-PD undergoing both gastrectomy and hepatectomy (n = 6), gastrectomy alone (n = 7), and nonsurgical treatments (n = 16) were 100, 66.7, and 0%, respectively (p = 0.0026). Multivariate analysis identified peritoneal dissemination as an independent prognostic factor (p = 0.0225). CONCLUSION: Our preliminary results suggest that conversion surgery for gastric cancer with liver metastasis might be clinically indicated in chemotherapy responders with <5 metastatic liver nodules and without peritoneal dissemination.
Assuntos
Neoplasias Hepáticas/patologia , Neoplasias Gástricas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Feminino , Gastrectomia/métodos , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/mortalidade , Taxa de SobrevidaRESUMO
BACKGROUND: Patients with stage IV gastric cancer have a poor prognosis despite the recent development of multidisciplinary treatments that include chemotherapy. However, conversion surgery has emerged as a promising strategy to improve the prognosis in responders with unresectable gastric cancer after chemotherapy. Moreover, nivolumab is currently recommended as a third-line treatment in patients with unresectable advanced gastric cancer. However, there are few reports of conversion surgery after nivolumab in patients with stage IV gastric cancer. CASE PRESENTATION: A 68-year-old woman complaining of nausea was diagnosed with stage I gastric cancer (T2N0M0). Although we planned gastrectomy with lymphadenectomy, multiple liver metastases were detected during the surgery. After staging laparoscopy, we diagnosed this patient as having stage IV unresectable gastric cancer, and we administered chemotherapy and immunotherapy for 39 months (first-line regimen: 6 courses of S-1 plus oxaliplatin; second-line regimen: 6 courses of ramucirumab plus paclitaxel; and third-line regimen: 20 courses of nivolumab). Although the liver metastases completely disappeared after the second-line chemotherapy, lung metastases and a rapid enlargement of the primary tumor were confirmed. Consequently, the patient received nivolumab at a dose of 3 mg/kg intravenously every 2 weeks, then a dose of 240 mg/kg intravenously every 2 weeks from September 2018. After 20 courses of nivolumab, the primary tumor dramatically shrank and the lung metastases disappeared. The patient had a partial primary tumor response to nivolumab. Therefore, the patient underwent laparoscopic distal gastrectomy with D2 lymph node dissection. The macroscopic examination of the resected specimen showed an ulcer scar in the primary tumor site. The pathological examination demonstrated no residual tumors and no lymph node metastases, and the histological response of the primary tumor was categorized as grade 3. The postoperative course was uneventful, and the patient is receiving nivolumab to control potential liver and lung metastases. CONCLUSIONS: Conversion surgery might help control tumor progression in responders after chemotherapy and immunotherapy.
Assuntos
Neoplasias Gástricas , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Gastrectomia , Humanos , Nivolumabe/uso terapêutico , Prognóstico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgiaRESUMO
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.