RESUMO
BACKGROUND: For patients with gastric cancer, a well-balanced treatment that considers both oncological aspects and surgical risk is demanded. This study aimed to explore the optimal extent of lymph node dissection (LND) for patients with gastric cancer according to surgical risk, stratified by the risk calculator system produced by the Japan National Clinical Database (NCD). PATIENTS AND METHODS: We retrospectively evaluated 187 patients who underwent radical gastrectomy for gastric cancer. Using the median predicted anastomotic leak rate obtained by the NCD risk calculator as the cutoff value, we classified 97 and 90 patients as having high and low risks, respectively. RESULTS: In low-risk patients, although limited LND reduced the postoperative intraabdominal infectious complications (IAIC), multivariate analysis revealed standard LND as an independent prognostic factor that improved Relapse-free survival (RFS). In high-risk patients, the rates of postoperative IAIC and RFS were similar between standard and limited LND. Pancreatic fistula was not observed in the limited dissection group. CONCLUSION: Limited LND might be the optimal treatment strategy for patients with gastric cancer with high surgical risk.
Assuntos
Gastrectomia , Excisão de Linfonodo , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/mortalidade , Excisão de Linfonodo/métodos , Masculino , Feminino , Estudos Retrospectivos , Gastrectomia/métodos , Idoso , Pessoa de Meia-Idade , Medição de Risco/métodos , Japão/epidemiologia , Bases de Dados Factuais , Adulto , Idoso de 80 Anos ou mais , Complicações Pós-Operatórias/epidemiologia , Prognóstico , Resultado do TratamentoRESUMO
OBJECTIVE: The aim of this study was to clarify the risk of loss of independence (LOI) following gastrectomy in elderly patients with gastric cancer (GC). METHODS: In this prospective study, frailty was assessed preoperatively by a frailty index (FI) in 243 patients aged ≥ 65 years who underwent gastrectomy for GC between August 2016 and December 2020. Patients were assigned into two groups (high FI vs. low FI) to investigate frailty and the risk of LOI after gastrectomy for GC. RESULTS: Overall and minor (Clavien-Dindo classification [CD] 1, 2) complication rates were significantly higher in the high FI group, but the two groups had similar rates of major (CD ≥ 3) complications. The frequency of pneumonia was significantly higher in the high FI group. In univariate and multivariate analyses for LOI after surgery, high FI, older age (≥ 75 years), and major (CD ≥ 3) complications were independent risk factors. A risk score assigning 1 point for each of these variables was useful in predicting postoperative LOI (LOI: score 0, 7.4%; score 1, 18.2%; score 2, 43.9%; score 3, 100%; area under the curve [AUC] = 0.765.) CONCLUSIONS: LOI after gastrectomy was independently associated with high FI, older age (≥ 75 years), and major (CD ≥ 3) complications. A simple risk score assigning points for these factors was an accurate predictor of postoperative LOI. We propose that frailty screening should be applied for all elderly GC patients before surgery.
Assuntos
Fragilidade , Neoplasias Gástricas , Idoso , Humanos , Fragilidade/complicações , Fragilidade/cirurgia , Neoplasias Gástricas/complicações , Estudos Prospectivos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Fatores de Risco , Gastrectomia/efeitos adversos , Estudos RetrospectivosRESUMO
Since April 2018, robot-assisted rectal resection has been approved as an insurance medical treatment, and robot- assisted rectal resection is rapidly becoming widespread. Even in robot-assisted laparoscopic surgery, mesorectal division is difficult in a narrow pelvic cavity. At the beginning of the operation, Vessel Sealer ExtendTM(price 89,250 yen)was used, but as the procedure became stable, the mesorectal division was started with bipolar forceps and monopolar scissors. The purpose of this study was to investigate the mesorectal division time and postoperative complications associated with changes in the procedure. 36 patients who underwent robot-assisted anterior resection for rectal cancer by the same surgeon from January 2019 to December 2021. We compared mesorectal division time and postoperative complication. Median operation time were 267 minutes, median console time were 132 minutes. There were no complications such as intestinal obstruction or anastomotic leakage. There was no difference in mesorectal division time time between Vessel Sealer groups and Scissors groups(14 min 55 sec vs 16 min 5 sec). The mesorectal division with bipolar forceps and monopolar scissors could be performed without extending the operation time, and could be performed with cost-benefit and safely.
Assuntos
Laparoscopia , Protectomia , Neoplasias Retais , Procedimentos Cirúrgicos Robóticos , Robótica , Humanos , Neoplasias Retais/cirurgia , Laparoscopia/métodos , Complicações Pós-Operatórias , Resultado do Tratamento , Estudos RetrospectivosRESUMO
BACKGROUND: The impact of robotic gastrectomy (RG) for gastric cancer (GC) on the incidence of postoperative complication is debatable and unclear. METHODS: This study enrolled 200 patients with GC who were surgically treated and consisted of 100 RG and 100 laparoscopic gastrectomy (LG) cases using an ultrasonic scalpel. The short-term outcomes were compared between the two groups. These outcomes were compared using a 1:1 propensity score (PS)-matching analysis. RESULTS: After PS matching, 76 cases in each group were well matched. Mean surgical time was significantly longer in the RG group than in the LG group (393 vs. 342 min, p < 0.005), whereas mean blood loss during surgery was significantly lower in the RG group than in the LG group (30.1 vs. 50.1 mL, p = 0.023). The median number of surgeons who attend the main part of the surgery was significantly less in the RG group than in the LG group (2.0 vs. 3.0, p = 0.01). The rate of severe intra-abdominal infectious complication was significantly lower in the RG group than in the LG group (0% vs. 9.2%, p = 0.014). The duration from surgery to adjuvant chemotherapy was significantly shorter in the RG group than in the LG group (29.6 ± 11.0 vs. 45.2 ± 27.8 days, p = 0.046). CONCLUSIONS: RG using an ultrasonic scalpel may be a viable alternative to LG because of the improvement in the rate of postoperative intra-abdominal infectious complications after curative surgery for GC.
Assuntos
Infecções Intra-Abdominais , Laparoscopia , Procedimentos Cirúrgicos Robóticos , Neoplasias Gástricas , Gastrectomia/efeitos adversos , Humanos , Laparoscopia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Pontuação de Propensão , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Neoplasias Gástricas/complicações , Neoplasias Gástricas/cirurgia , Resultado do TratamentoRESUMO
BACKGROUND: Although the role of Lipocalin-2 (LCN2) in cancer development has been focused on recent studies, the molecular mechanisms and clinical relevance of LCN2 in gastric cancer (GC) still remain unclear. METHODS: Transcriptome analysis of GC samples from public human data was performed according to Lauren's classification and molecular classification. In vitro, Western blotting, RT-PCR, wound healing assay and invasion assay were performed to reveal the function and mechanisms of LCN2 in cell proliferation, migration and invasion using LCN2 knockdown cells. Gene set enrichment analysis (GSEA) of GC samples from public human data was analyzed according to LCN2 expression. The clinical significance of LCN2 expression was investigated in GC patients from public data and our hospital. RESULTS: LCN2 was downregulated in diffuse-type GC, as well as in Epithelial-Mesenchymal Transition (EMT) type GC. LCN2 downregulation significantly promoted proliferation, invasion and migration of GC cells. The molecular mechanisms of LCN2 downregulation contribute to Matrix Metalloproteinases-2 (MMP2) stimulation which enhances EMT signaling in GC cells. GSEA revealed that LCN2 downregulation in human samples was involved in EMT signaling. Low LCN2 protein and mRNA levels were significantly associated with poor prognosis in patients with GC. LCN2 mRNA level was an independent prognostic factor for overall survival in GC patients. CONCLUSIONS: LCN2 has a critical role in EMT signaling via MMP2 activity during GC progression. Thus, LCN2 might be a promising therapeutic target to revert EMT signaling in GC patients with poor outcomes.
Assuntos
Transição Epitelial-Mesenquimal , Lipocalina-2/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Neoplasias Gástricas , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação para Baixo , Humanos , Lipocalina-2/genética , Metaloproteinase 2 da Matriz/genética , Invasividade Neoplásica , RNA Mensageiro , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologiaRESUMO
OBJECTIVES: To clarify a characteristic of dynamic stability during gait in idiopathic normal pressure hydrocephalus (iNPH) and Parkinson's disease (PD), and to explore the association between dynamic stability and disease severity in each disease. MATERIALS AND METHODS: The 5-m gait of 36 iNPH (precerebrospinal fluid drainage), 20 PD (medicated state), and 25 healthy controls (HC) were evaluated using three-dimensional motion analysis. Ambulatory dynamic stability was defined as the ability to maintain the extrapolated center of mass within the base of support at heel contact, with the distance between the two referred to as the margin of stability (MOS). RESULTS: Anteroposterior direction (AP) MOS was significantly larger in the iNPH and PD groups than in the HC group; no significant difference was found between the iNPH and PD groups. Mediolateral direction (ML) MOS was significantly larger in the iNPH and PD groups than in the HC group and significantly larger in the iNPH group than in the PD group. In the iNPH group, the disease severity was positively correlated with only ML MOS. In the PD group, the disease severity was positively correlated with the AP MOS and ML MOS. CONCLUSIONS: Dynamic stability in iNPH increases in AP and ML, and it may be associated with not only iNPH-associated gait disturbance but also with a voluntarily cautious gait strategy. Dynamic stability in PD only increased in AP, and this may be associated with PD symptoms. These findings will help physicians understand the difference in pathological gait including dynamic stability between patients with iNPH and PD.
Assuntos
Transtornos Neurológicos da Marcha , Hidrocefalia de Pressão Normal , Doença de Parkinson , Marcha , Transtornos Neurológicos da Marcha/etiologia , Humanos , Hidrocefalia de Pressão Normal/complicações , Doença de Parkinson/complicações , Índice de Gravidade de DoençaRESUMO
The patient was an 81-year-old man who visited a clinic for fever and lower abdominal pain. He was subsequently diagnosed with prostatitis based on computed tomography (CT) findings that showed swelling of the prostate. Despite treatment with antibacterial therapy, his symptoms did not improve significantly. Since the patient also had myelodysplastic syndrome, he was transferred to our hospital and subsequently diagnosed with prostate abscess based on findings on magnetic resonance imaging (MRI). The abscess had spread widely from the dorsal side of the trigone of the bladder to anterior wall of the rectum. Transperineal drainage was performed to preserve the urethral mucosa of the prostatic urethra. Considering the shape of the abscess cavity, one pigtail catheter was placed in the prostate and another was placed transperineally on the dorsal side of the trigone of the bladder. Cystostomy was performed at the same time. Culture of the abscess revealed the presence of Staphylococcus aureus. As there was little exudate from the abscess 9 days after drainage, the pigtail catheter on the dorsal side of the trigone of the bladder was removed following an injection of minocycline into the abscess. CT showed shrinkage of the abscess 4 days later, and the remaining intraprostatic pigtail catheter was removed after an injection of minocycline. The cystostomy pigtail catheter was subsequently removed since the patient was able to urinate smoothly after clamping. MRI confirmed the disappearance of the abscess cavity 2 months later.
Assuntos
Abscesso , Doenças Prostáticas , Abscesso/diagnóstico por imagem , Abscesso/cirurgia , Idoso de 80 Anos ou mais , Drenagem/métodos , Humanos , Masculino , Minociclina , Próstata , Doenças Prostáticas/diagnóstico por imagem , Doenças Prostáticas/cirurgiaRESUMO
A 67-year-old man was introduced to examine for abnormal findings in physical examination. Upper gastrointestinal endoscopy detected the 3 lesions and diagnosed multiple gastric cancers with biopsy. Laparoscopic total gastrectomy was performed and final pathological diagnosis was pT2N1M0, pStage â ¡A with HER2 positive(3+). Adjuvant chemotherapy was not administrated. CT findings 6 months after procedure showed 2 liver metastases(S6, S7)and laparoscopic partial liver resection was performed. Pathological findings proved the metastasis of previous gastric cancer. Although adjuvant chemotherapy of S-1 was started 2 months after hepatectomy, CT findings showed second recurrences in liver and right adrenal gland. Chemotherapy was changed to S-1 plus cisplatin(SP)plus trastuzumab. AS these recurrence sites and ascites could not be detected by CT after 6 courses, therapeutic effect was judged as clinical CR(cCR)and SP plus trastuzumab was stopped due to side effect. Since then, regular follow-up CT showed preservation of status of cCR without chemotherapy and he has been alive without recurrence for 8 years and 9 months after gastrectomy. We report a case of recurrent gastric cancer of multiple organ metastasis with long-term survival due to multimodal treatment.
Assuntos
Neoplasias Hepáticas , Neoplasias Gástricas , Idoso , Humanos , Masculino , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Gastrectomia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Recidiva Local de Neoplasia/cirurgia , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Trastuzumab/uso terapêutico , RecidivaRESUMO
This study aimed to investigate the short- and long-term outcomes in patients with sarcopenia who underwent surgery for advanced gastric cancer. We included 76 patients with pStage â ¡ or â ¢ gastric cancer who underwent gastrectomy between January 2017 and June 2021. Patients with pT3N0 cancer were excluded. Using the Asian Working Group for Sarcopenia( AWGS)2019 criteria, the patients were divided into the sarcopenia group(S group)and the non-sarcopenia group (NS group). The surgical outcomes, effects on postoperative adjuvant chemotherapy, and prognosis of the 2 groups were evaluated and compared. No significant differences were observed in the operative time, blood loss, postoperative hospital stays, or incidence of postoperative complications with a grade higher than Clavien-Dindo Grade â ¡. The number of patients who received postoperative adjuvant chemotherapy was 5(26.3%)in the S group and 38(66.7%)in the NS group which was significantly lower in the S group(p=0.003). The 3-year overall survival rate was 45.7% in the S group and 71.0% in the NS group(p=0.302). There was no significant difference but survival rate was lower in the S group. The results suggest that postoperative adjuvant chemotherapy is not always available for patients with advanced gastric cancer, and that may worsen the prognosis.
Assuntos
Sarcopenia , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/complicações , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Fatores de Risco , Prognóstico , Sarcopenia/complicações , Sarcopenia/epidemiologia , Incidência , Gastrectomia/efeitos adversos , Gastrectomia/métodos , Complicações Pós-Operatórias/etiologia , Estudos RetrospectivosRESUMO
A 35-year-old women with sigmoid cancer(pT4aN1aM0, pStage â ¢b)underwent laparoscopic sigmoidectomy. She had 8 courses of CapeOX for adjuvant chemotherapy, but follow up CT scan 1 year after the operation detected intraabdominal nodules in anastomotic site and in left lower quadrant of abdomen. After 10 courses of IRIS plus bevacizumab, the both intraabdominal nodules decreased in size. Robot assisted laparoscopic lower anterior resection and laparoscopic disseminated nodule resection were performed. The patient had no postoperative complications and the postoperative course was good. She remains alive without recurrence at 6 months after the second operation.
Assuntos
Neoplasias Peritoneais , Procedimentos Cirúrgicos Robóticos , Neoplasias do Colo Sigmoide , Humanos , Feminino , Adulto , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/cirurgia , Peritônio , Bevacizumab/uso terapêutico , Neoplasias do Colo Sigmoide/tratamento farmacológico , Neoplasias do Colo Sigmoide/cirurgia , Recidiva Local de NeoplasiaRESUMO
OBJECTIVES: We evaluated the perceived and actual changes in gait and balance function immediately after cerebrospinal fluid (CSF) shunting in patients with idiopathic normal pressure hydrocephalus (iNPH), including those with mild cases. MATERIALS AND METHODS: Ninety-nine iNPH patients were assessed using the timed Up and Go (TUG) and Functional Gait Assessment (FGA) before and 1-week after CSF shunting and their perceived changes were assessed on a Global Rate of Change (GRC) scale. Minimal clinically important differences (MCIDs) were calculated using a receiver operating characteristic (ROC) curve method using GRC scores. RESULTS: In all patients (n = 99), the TUG value postoperatively was significantly faster than the preoperative value (difference; 3.1 ± 4.6 s, p < 0.001), and the postoperative FGA score was significantly better than the preoperative score (difference; 3.8 ± 3.3 points, p < 0.001). In the TUG <15 s group (n = 51), the postoperative FGA score was significantly improved (difference; 3.3 ± 2.9 points, p < 0.001), whereas the TUG value was only slightly improved (difference; 0.6 ± 1.6 s, p = 0.008). The ROC curve MCIDs of GRC ≥2 points, which is the recommended level of improvement, were 1.7 s (16.5%) for the TUG and 4 points (20.0%) for the FGA in all patients (n = 99) and the TUG <15 s group (n = 51). CONCLUSIONS: FGA can be used to confirm treatment effects, including perceived and actual changes after CSF shunting, in patients with mild iNPH. Our results can help clinicians to determine the clinical significance of improvements in gait and balance function immediately after CSF shunting in individual patients with iNPH.
Assuntos
Derivações do Líquido Cefalorraquidiano/tendências , Transtornos Neurológicos da Marcha/cirurgia , Marcha/fisiologia , Hidrocefalia de Pressão Normal/cirurgia , Percepção/fisiologia , Equilíbrio Postural/fisiologia , Idoso , Idoso de 80 Anos ou mais , Derivações do Líquido Cefalorraquidiano/métodos , Feminino , Transtornos Neurológicos da Marcha/diagnóstico , Transtornos Neurológicos da Marcha/fisiopatologia , Humanos , Hidrocefalia de Pressão Normal/diagnóstico , Hidrocefalia de Pressão Normal/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
A 70-year-old man previously underwent laparoscopic total gastrectomy for gastric cancer in 2010 and pathological diagnoses were pT4a, pN3, M0, pStage â ¢C. The postoperative adjuvant chemotherapy was interrupted due to nausea, but the patient had no apparent recurrence within 5 years after gastrectomy. In 2019, a swelling appeared from the left inguinal region to the scrotum, and MRI scan showed subcutaneous edematous changes in the same region. Biopsy showed adenocarcinoma and we diagnosed a recurrence of gastric cancer with skin metastasis. In November 2020, the patient complained of defecation disorder, and CT scan showed a circumferential wall thickening with contrast effect in the rectum. Although colonoscopy revealed rectal stenosis, biopsy specimen showed no malignant findings. We suspected rectal stenosis due to peritoneal dissemination of gastric cancer and performed a colostomy. Intraoperative findings showed that the rectal wall was remarkably thickened with serosal erythema. Adenocarcinoma cells were found from the cytology of ascites. The patient was treated with nab-paclitaxel plus ramucirumab, then treated with nivolumab after failure of first-line therapy.
Assuntos
Neoplasias Gástricas , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Constrição Patológica , Gastrectomia , Humanos , Masculino , Recidiva Local de Neoplasia , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgiaRESUMO
We examined the controlling nutritional status(CONUT)score and the long-term prognosis of colorectal cancer surgery cases. We retrospectively examined the prognosis of colorectal cancer patients who underwent surgery between January 2013 and December 2015. We targeted 449 patients who were able to calculate the CONUT score. A total of 266 patients (59.2%)had normal nutritional status(1 or less)and 183 patients(40.8%)had mildly poor or worse nutritional status (2 or more). The CONUT score was calculated through preoperative blood tests. The relationship between the CONUT score and overall survival was examined in the low and high groups. Overall survival was significantly shorter in the high group but relapse-free survival did not differ significantly between the 2 groups. There was no difference in cancer-specific survival between the 2 groups, but the survival time due to death from other diseases was significantly shorter in the high group. The CONUT score obtained from preoperative blood sampling suggested that the overall survival time was short in the malnourished group, and that it could be used as an index of prognosis due to death from other diseases.
Assuntos
Neoplasias Colorretais , Desnutrição , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/cirurgia , Humanos , Estado Nutricional , Prognóstico , Estudos RetrospectivosRESUMO
We examined 14 cases who underwent robotic rectal resection with neoadjuvant chemotherapy(NAC)or neoadjuvant chemoradiation therapy(NACRT)for local advanced rectal cancer in our hospital from 2018 June to 2020 December. Two patients underwent NACRT, 12 patients underwent NAC. Sex was 10 males and 4 females. The median age was 66. The surgical procedure was ISR 2 cases, LAR 8 cases, APR 4 cases. The median operation time was 397 minutes and the median blood loss was 73 mL. The histological response grade were Grade 3: 1 case, 2: 7 cases, 1b: 3 cases, and 1a: 3 cases. Surgical margin was negative in all cases. Postoperative complications(≥Clavien-Dindo Grade â ¢)required reoperation due to intestinal obstruction in 1 case. Urinary dysfunction was nothing in all cases. Although long-term results such as prognosis and function preservation need to be examined, short-term results of robot-assisted rectal resection after NAC or NACRT were generally good.
Assuntos
Protectomia , Neoplasias Retais , Procedimentos Cirúrgicos Robóticos , Idoso , Feminino , Humanos , Masculino , Terapia Neoadjuvante , Neoplasias Retais/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Persistent descending mesocolon(PDM)is caused by absence of fusion of the descending colon to the retroperitoneum. A 67-year-old man with bloody stools was diagnosed with rectal cancer on colonoscopy. A computed tomography showed a medial displacement of his descending colon. The preoperative clinical diagnosis was rectal cancer with PDM, and robot assisted low anterior resection was performed. We found that the left-sided colon was shifted to the midline and adhered the cecum and the mesentery of small intestine. Robot assisted surgery enables surgery with the precise adhesiotomy in a stable field. PDM is a relatively rare anatomic abnormality. Character of PDM is adhesion between the left-sided colon and other organs and radially branch from the inferior mesenteric artery. It is important to understand the anatomical characteristics of PDM and to improve on existing surgical procedures to ensure safe robot assisted surgery these patients.
Assuntos
Laparoscopia , Mesocolo , Protectomia , Robótica , Idoso , Colectomia , Humanos , Masculino , Mesocolo/cirurgiaRESUMO
Scirrhous-type gastric carcinoma (SGC), which is characterized by the rapid proliferation of cancer cells accompanied by extensive fibrosis, shows extremely poor survival. A reason for the poor prognosis of SGC is that the driver gene responsible for SGC has not been identified. To identify the characteristic driver gene of SGC, we examined the genomic landscape of six human SGC cell lines of OCUM-1, OCUM-2M, OCUM-8, OCUM-9, OCUM-12 and OCUM-14, using multiplex gene panel testing by next-generation sequencing. In this study, the non-synonymous mutations of serine threonine kinase 11/liver kinase B1 (STK11/LKB1) gene were detected in OCUM-12, OCUM-2M and OCUM-14 among the six SGC cell lines. Capillary sequencing analysis confirmed the non-sense or missense mutation of STK11/LKB1 in the three cell lines. Western blot analysis showed that LKB1 expression was decreased in OCUM-12 cells and OCUM-14 cells harboring STK11/LKB1 mutation. The mammalian target of rapamycin (mTOR) inhibitor significantly inhibited the proliferation of OCUM-12 and OCUM-14 cells. The correlations between STK11/LKB1 expression and clinicopathologic features of gastric cancer were examined using 708 primary gastric carcinomas by immunochemical study. The low STK11/LKB1 expression group was significantly associated with SGC, high invasion depth and frequent nodal involvement, in compared with the high STK11/LKB1 expression group. Collectively, our study demonstrated that STK11/LKB1 mutation might be responsible for the progression of SGC, and suggested that mTOR signaling by STK11/LKB1 mutation might be one of therapeutic targets for patients with SGC.
Assuntos
Adenocarcinoma Esquirroso/patologia , Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica , Mutação , Proteínas Serina-Treonina Quinases/genética , Neoplasias Gástricas/patologia , Quinases Proteína-Quinases Ativadas por AMP , Adenocarcinoma Esquirroso/genética , Adenocarcinoma Esquirroso/metabolismo , Idoso , Apoptose , Proliferação de Células , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Taxa de Sobrevida , Células Tumorais CultivadasRESUMO
Fibroblast growth factor receptor (FGFR) is associated with proliferation, migration, and angiogenesis of carcinomas, and FGFR signaling inhibitors are considered a key drug for the treatment of solid tumors with FGFR overexpression. Amplification of FGFR2 is reportedly identified in 3%-10% of gastric cancers (GCs). The aim of this study is to clarify whether the identification of the circulating tumor cells (CTCs) with FGFR2 overexpression is useful to detect patients with FGFR2-overexpressing GC. One hundred GC patients who underwent gastrectomy were enrolled. A total volume of 8 mL of peripheral blood was collected from each patient just before gastrectomy, and mononuclear cells were enriched by Ficol density gradient centrifugation. These cells were immunostained with PI/CD45/EpCAM/FGFR2. The number of CTCs with FGFR2 expression in each sample was enumerated by FACScan. The FGFR2 expression level of the resected primary tumor was assessed by immunohistochemistry. The number of FGFR2-positive CTCs in the GC patients' peripheral blood was significantly correlated with the FGFR2 expression level of the primary GC. The relapse-free survival of the patients with FGFR2-positive CTCs (≥5 cells/10 mL blood) was significantly poorer (P = .018, log-rank) than that of the patients without FGFR2-positive CTCs (<5 cell/10 mL blood). These findings suggested that the determination of FGFR2-positive CTCs might help identify an existing tumor with FGFR2 overexpression.
Assuntos
Células Neoplásicas Circulantes/química , Células Neoplásicas Circulantes/metabolismo , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/análise , Neoplasias Gástricas/sangue , Neoplasias Gástricas/diagnóstico , Idoso , Centrifugação com Gradiente de Concentração/métodos , Distribuição de Qui-Quadrado , Intervalo Livre de Doença , Feminino , Gastrectomia , Amplificação de Genes , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Estimativa de Kaplan-Meier , Masculino , Prognóstico , Estatísticas não Paramétricas , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/cirurgiaRESUMO
BACKGROUND: As a member of the Rho small guanosine triphosphatase family, ras-related C3 botulinum toxin substrate 1 (RAC1) interacts with various specific effectors, and p21-activated kinase 1 (PAK1), which has a role in both carcinogenesis and cellular invasion, binds to RAC1, after which activated PAK1 regulates cellular functions. There have been few reports about the simultaneous analysis of RAC1 and its downstream effector PAK1 in upper urinary tract urothelial carcinoma (UTUC). We assessed the expressions of both RAC1 and PAK1 and evaluated their association with clinicopathological parameters. METHODS: Immunohistochemical studies of RAC1 or PAK1 were performed with specimens from 104 patients with N0M0 UTUC and cancer-free surgical margins. Correlation of the positive expression of RAC1 or PAK1 or both with clinicopathological parameters was evaluated. RESULTS: A hazard model showed that the presence of mixed histologic features and moderate or strong positive expression of both RAC1 and PAK1 were independent factors for shortened disease-specific survival time (Ps = 0.041 and 0.016, respectively), and another hazard model revealed that only moderate or strong positive expression of both RAC1 and PAK1 was an independent factor for shortened recurrence-free survival time in the multivariate analysis (P = 0.036). Neither moderate or strong positive expression of RAC1 alone nor moderate or strong positive expression of PAK1 alone was an independent factor for a worse rate of disease-specific or recurrence-free survival in multivariate analysis. CONCLUSIONS: Patients with N0M0 UTUC, cancer-free surgical margins and moderate or strong positive expression of both RAC1 and PAK1 should be carefully monitored after surgery.
Assuntos
Carcinoma de Células de Transição/cirurgia , Margens de Excisão , Sistema Urinário/patologia , Neoplasias Urológicas/metabolismo , Neoplasias Urológicas/cirurgia , Quinases Ativadas por p21/metabolismo , Proteínas rac1 de Ligação ao GTP/metabolismo , Carcinoma de Células de Transição/mortalidade , Carcinoma de Células de Transição/patologia , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Neoplasias Urológicas/patologiaRESUMO
BACKGROUND: The prognosis of scirrhous gastric carcinoma (SGC), which is characterized by rapid infiltration and proliferation of cancer cells accompanied by extensive stromal fibrosis, is extremely poor. In this study, we report the establishment of a unique SGC cell line from a gastric cancer patient in whom an autopsy was performed. METHODS: A new SGC cell line, OCUM-14, was established from malignant ascites of a male patient with SGC. A postmortem autopsy was performed on the patient. Characterization of OCUM-14 cells was analyzed by microscopic examination, reverse transcription polymerase chain reaction, fluorescence in situ hybridization analysis, immunohistochemical examination, CCK-8 assay, and in vivo assay. RESULTS: OCUM-14 cells grew singly or in clusters, and were floating and round-shaped. Most OCUM-14 cells had many microvilli on their surfaces. The doubling time was 43.1 h, and the subcutaneous inoculation of 1.0 × 107 OCUM-14 cells into mice resulted in 50% tumor formation. mRNA expressions of fibroblast growth factor receptor 2 (FGFR2) and human epidermal growth factor receptor 2 (HER2) were observed in OCUM-14 cells. FGFR2, but not HER2, overexpression was found in OCUM-14 cells. The heterogeneous overexpression of FGFR2 was also found in both the primary tumor and metastatic lesions of the peritoneum, lymph node, bone marrow, and lung of the patient. The FGFR2 inhibitors AZD4547 and BGJ398 significantly decreased the growth of OCUM-14 cells, while paclitaxel and 5-fluorouracil significantly decreased the proliferation of OCUM-14 cells, but cisplatin did not. CONCLUSION: A new gastric cancer cell line, OCUM-14, was established from SGC and showed FGFR2 overexpression. OCUM-14 might be useful for elucidating the characteristic mechanisms of SGC and clarifying the effect of FGFR2 inhibitors on SGC.
Assuntos
Adenocarcinoma Esquirroso/patologia , Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/metabolismo , Neoplasias Gástricas/patologia , Adenocarcinoma Esquirroso/tratamento farmacológico , Adenocarcinoma Esquirroso/metabolismo , Animais , Técnicas de Cultura de Células , Humanos , Masculino , Camundongos Nus , Pessoa de Meia-Idade , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismo , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
OBJECTIVES: To investigate which clinical assessments are suitable for differentiating patients who fall from patients who do not fall in patients with idiopathic normal pressure hydrocephalus (iNPH). DESIGN: Prospective observational study. SETTING: Osaka Medical College Hospital. PARTICIPANTS: Patients with a cerebrospinal fluid tap test (TT) result meeting the diagnosis criteria for iNPH (N=68). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Participants were assessed before the TT based on the following: timed Up and Go (TUG), 10-meter walk test (10MWT), Functional Gait Assessment (FGA), Berg Balance Scale (BBS), isometric quadriceps strength (QS), and a history of falls within the past 6 months. RESULTS: The full area under the curve (AUC) of the receiver operating characteristic curves and 95% confidence interval were found to be 0.651 (95% confidence interval, 0.503-0.775) for the TUG, 0.692 (95% confidence interval, 0.540-0.812) for the 10MWT, 0.869 (95% confidence interval, 0.761-0.933) for the FGA, and 0.796 (95% confidence interval, 0.663-0.886) for the BBS; except for QS, they all were identified as statistically significant predictive variables. In the TUG<20 seconds group (n=47), the FGA (AUC 0.849 [95% confidence interval, 0.698-0.932]) and BBS (AUC 0.734 [95% confidence interval, 0.550-0.862]) were found to be statistically significant predictive variables; however, the other assessments were not. In the TUG<15 seconds group (n=34), the FGA was found to be the only statistically significant predictive variable (AUC 0.842 [95% confidence interval, 0.640-0.942]), whereas the other assessments were not. The AUC of the FGA was statistically significantly greater than those of the other assessments. CONCLUSIONS: Our findings indicate that patients with iNPH who fall experience falls due to dynamic balance dysfunction during gait rather than lower limb muscle strength. The FGA may be more suitable than other assessments for differentiating patients who fall from patients who do not fall in patients with mild iNPH.