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1.
J Gastrointest Surg ; 2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33825120

RESUMO

BACKGROUND: With aging of the population, the number of colorectal cancer patients with impairment of activities of daily living (ADLs) has increased. The Barthel index is a validated tool for assessing functional levels of ADLs. In this retrospective study, we aimed to examine associations of Barthel index scores with recurrence and mortality after curative resection of colorectal cancer. METHODS: We retrospectively analyzed data of 815 consecutive patients who had undergone curative resection of stage I-III colorectal adenocarcinoma between January 2009 and December 2017. Preoperative functional levels of ADLs were assessed prospectively using the Barthel index (range, 0 to 100; higher scores indicate greater independence). Recurrence-free survival (RFS) and overall survival (OS) were compared according to Barthel index scores. The Cox proportional hazards model was used to calculate hazard ratios (HRs), controlling for potential confounders. RESULTS: Of the 815 patients, Barthel index scores were 40 or lower in 129 (16%), 41-85 in 110 (13%), and 86 or more in 576 (71%). In multivariable analyses adjusting for potential confounders including age and disease stage, scores of 85 or lower on the Barthel index were independently associated with shorter RFS (multivariable HR: 1.74, 95% confidence interval: 1.28-2.37, P<0.001) and OS (multivariable HR: 2.10, 95% confidence interval: 1.45-3.04, P<0.001). CONCLUSIONS: Lower scores on the Barthel index are associated with shorter RFS and OS following resection of nonmetastatic colorectal cancer. Further studies are needed to establish treatment strategies for colorectal cancer patients with poor functional capacity.

2.
Surg Case Rep ; 7(1): 83, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33825980

RESUMO

BACKGROUND: Obturator hernia is a life-threatening condition, requiring emergency intervention due to strangulation, if non-invasive repair for strangulation cannot be complete. Change from emergency surgery to elective surgery using minimal non-invasive options can greatly contribute to perioperative safety and curability of the underlying disease. CASE PRESENTATION: 12 cases of strangulated obturator hernia from April 2013 to February 2020 with male:female patient ratio of 0:12. Reduction under ultrasound guidance was possible amongst 10 out of 12 cases. The average age was 85.3 years (74-97) and average BMI was 17.4 (15.0-20.1). Based on physical findings and CT examination, diagnosis of obturator hernia was made using echo guided non-invasive reduction. Prevention in the intestinal ischemia and perforation was observed in the treated cases. Upon request, elective radical surgery was performed in 7 of these patients after their condition improved and monitored other organs for any signs. CONCLUSION: Attempt to improve the strangulation of obturator hernia under an echo-guided approach could enable elective and safe surgery and is believed to be a diagnostic treatment worth attempting.

3.
Clin J Gastroenterol ; 2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33830448

RESUMO

A 72-year-old woman was referred to our hospital with the diagnosis of peritonitis due to the rupture of a huge abdominal cystic tumor, 27 cm in diameter. Abdominal computed tomography 14 years before revealed the tumor, which was 18 cm in diameter. She had undergone no examinations or treatment in the interim. She was in shock upon presentation to our hospital. She was intubated immediately and underwent an emergent laparotomy. The huge ruptured tumor with adherent small intestine was resected. The tumor weighed 6 kg and consisted of solid and cystic components filled with 4 kg of brown feces-like fluid. Bacteroides fragilis was detected in a fluid specimen. The cystic component of the tumor was filled with old blood clots, and a portion of the tumor wall was highly calcified. Old blood and fibrin with blood vessels of various sizes inside the tumor were observed during the pathologic evaluation; there were no malignant features. The final pathologic diagnosis was a chronic expanding hematoma (CEH). The patient had an uneventful recovery and was discharged 16 days post-operatively. She was involved in a traffic accident approximately 30 years before the current hospital admission; however, she did not recall if she had abdominal pain at that time. A CEH is a benign lesion, but rupture of a CEH can be life-threatening.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33797866

RESUMO

INTRODUCTION: Two novel clinical risk scores (CRS) that incorporate KRAS mutation status (modified CRS (mCRS) and GAME score) were developed. However, they have not been tested in large national and international cohorts. The aim of this study was to validate the prognostic discrimination utility and determine the clinical usefulness of the two novel CRS. METHODS: Patients undergoing hepatectomy for CRLM (2000-2018) in ten centers were included. The discriminatory abilities of mCRS, GAME, and Fong CRS were evaluated using Harrel's C-index and Akaike's Information Criterion. RESULTS: In the entire cohort, the C-index of the GAME score (0.61) was significantly higher than those of Fong score (0.57) and mCRS (0.54), while the C-Index of mCRS was significantly lower than that of Fong score. When we compared the models in the various geographical regions, the C-index of GAME score was significantly higher than that of mCRS in North America, Europe, and South America. The AIC of Fong score, mCRS, and GAME score were 14405, 14447, and 14319, respectively. CONCLUSION: In conclusion, using the largest and most heterogenous population of CRLM patients with known KRAS status, this independent, external validation demonstrated that the GAME score outperforms both the traditional Fong score and mCRS.

5.
JAMA Surg ; 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33656542

RESUMO

Importance: In distal pancreatectomy (DP), the splenic vein is isolated from the pancreatic parenchyma prior to being ligated and divided to prevent intra-abdominal hemorrhage from the splenic vein stump with pancreatic fistula (PF). Conversely, dissecting the splenic vein with the pancreatic parenchyma is easy and time-saving. Objective: To establish the safety of combined division of the splenic vein compared with separate division of the splenic vein. Design, Setting, and Participants: This study was designed as a multicenter prospective randomized phase 3 trial. All results were analyzed using the modified intent-to-treat set. Patients undergoing DP for pancreatic body and tail tumors were eligible for inclusion. Patients were randomly assigned between August 10, 2016, and July 30, 2019. Interventions: Patients were centrally randomized (1:1) to either separate division of the splenic vein or combined division of the splenic vein. Main Outcomes and Measures: The primary end point was the incidence of grade B/C PF, and the incidence of intra-abdominal hemorrhage was included as one of the secondary end points. Results: A total of 318 patients were randomly assigned, and 2 patients were excluded as ineligible. Of the 316 remaining patients, 150 (50.3%) were male. The modified intent-to-treat population constituted 159 patients (50.3%) in the separate division group and 157 patients (49.7%) in the combined division group. In the modified intent-to-treat set, the proportion of grade B/C PF in the separate division group was 27.1% (42 of 155) vs 28.6% (44 of 154) in the combined division group (adjusted odds ratio, 1.108; 95% CI, 0.847-1.225; P = .047), demonstrating noninferiority of the combined division of the splenic vein against separate division. The incidence of postoperative intra-abdominal hemorrhage in the 2 groups was identical at 1.3%. Conclusions and Relevance: This study demonstrated noninferiority of the combined division of the splenic vein compared with separate division of the splenic vein regarding safety. Thus, isolating the splenic vein from the pancreatic parenchyma is deemed unnecessary. Trial Registration: ClinicalTrials.gov Identifier: NCT02871804.

6.
Hepatology ; 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33725402

RESUMO

BACKGROUND & AIMS: Tumor recurrence is frequent even in intrahepatic cholangiocarcinoma (ICC); and improved strategies are needed to identify patients at highest risk for such recurrence. We performed genome-wide expression profile analyses to discover and validate a gene signature associated with recurrence in patients with ICC. APPROACH & RESULTS: For biomarker discovery, we analyzed genome-wide transcriptomic profiling in ICC tumors from two public datasets (TCGA, n=27 and GSE107943, n=28). We identified an 8-gene panel (BIRC5, CDC20, CDH2, CENPW, JPH1, MAD2L1, NEIL3, and POC1A), which robustly identified patients with recurrence in the discovery (area under the curve [AUC]=0.92) and in-silico validation cohorts (AUC=0.91). We next analyzed 241 specimens from patients with ICC (training cohort: n=64, validation cohort: n=177), followed by Cox proportional hazard regression analysis, to develop an integrated transcriptomic panel and establish a risk-stratification model for recurrence in ICC. We subsequently trained this transcriptomic panel in a clinical cohort (AUC=0.89, 95% confidence intervals [CI]=0.79-0.95), followed by evaluating its performance in an independent validation cohort (AUC=0.86, 95% CI=0.80-0.90). By combining our transcriptomic panel with various clinicopathologic features we established a risk-stratification model which was significantly superior for the identification of recurrence (AUC=0.89, Univariate: hazard ratio [HR]=6.08, 95% CI=3.55-10.41, P<0.01; Multivariate: HR=3.49, 95% CI=1.81-6.71, P<0.01). The risk-stratification model identified potential recurrence in 85% of high-risk patients and non-recurrence in 76% of low-risk patients, which is dramatically superior to currently used pathological features. CONCLUSIONS: We report a novel transcriptomic signature for risk-stratification and recurrence prediction that is superior to currently used clinicopathological features in patients with ICC.

7.
Talanta ; 228: 122239, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33773741

RESUMO

Cancer cell count in the blood of cancer patients is extremely low. If these cells are easily detectable, cancer diagnosis may be possible by simply using a blood test, thus reducing patient burden. This study aimed to develop a cancer detection device by combining a microfilter that can be dynamically deformed and a nucleic acid aptamer that has a specific binding ability to cancer cells for easy detection. The cancer detection device was fabricated by photolithography, electroforming, and three-dimensional printing. The cancer cell detection ability of the fabricated device was evaluated using 1 mL of blood samples spiked with different concentrations of cancer cells. The lowest concentration of cancer cells in the blood was 5 cancer cells/1 mL blood. The fabricated microfilters specifically detected cancer cells in the blood successfully at exceedingly low concentrations. Moreover, the cancer detection experiment results using human whole blood revealed that cancer detection could be performed with higher accuracy using the fabricated cancer detection device compared to pre-existing cancer detection equipment (e.g., CellSearch system, Veridex). These findings provide important insights into the use of cancer cells in the blood as a diagnostic approach for cancer.

8.
Cancer Sci ; 112(4): 1567-1578, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33548159

RESUMO

Oxaliplatin (OX) and irinotecan (IRI) are used as key drugs for the first-line treatment of metastatic colorectal cancer (mCRC). However, no biomarkers have been identified to decide which of the drugs is initially used. In this translational research (TR) of the TRICOLORE trial, the advanced colorectal cancer subtype (aCRCS) was analyzed as a potential biomarker for the selection of OX or IRI. We collected 335 (68.8%) formalin-fixed, paraffin-embedded (FFPE) primary tumor specimens from 487 patients registered in the TRICOLORE trial and performed direct sequencing and immunohistochemical staining of CRC-related genes, comprehensive gene-expression analysis, and genome-wide methylation analysis. The progression-free survival (PFS) of the IRI group was significantly better compared with the OX group in BRAF wild-type (WT), PTEN-positive, and aCRCS A1 patients. Among the molecular factors, aCRCS were only associated with the PFS of OX and IRI groups. The PFS of the IRI group was significantly better compared with the OX group in aCRCS A1 + B1 (hazard ratio [HR] = 0.58; 95% confidence interval [CI] = 0.41-0.82; P = .0023). In contrast, the OX group had better PFS compared with the IRI group in aCRCS B2, although this was not statistically significant (HR = 1.66; 95% CI = 0.94-2.96; P = .083). Nearly half of patients with mCRC (46.8%, aCRCS A1 + B1) respond well to IRI, while only about 18.5% (aCRCS B2) of patients with mCRC responded well to OX. In conclusion, the aCRCS might be a predictive factor for the clinical outcomes of OX-based and IRI-based therapies.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Irinotecano/uso terapêutico , Oxaliplatina/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/metabolismo , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Adulto Jovem
9.
Cell Rep ; 34(8): 108779, 2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33626356

RESUMO

In the tumor microenvironment, senescent non-malignant cells, including cancer-associated fibroblasts (CAFs), exhibit a secretory profile under stress conditions; this senescence-associated secretory phenotype (SASP) leads to cancer progression and chemoresistance. However, the role of senescent CAFs in metastatic lesions and the molecular mechanism of inflammation-related SASP induction are not well understood. We show that pro-inflammatory cytokine-driven EZH2 downregulation maintains the SASP by demethylating H3K27me3 marks in CAFs and enhances peritoneal tumor formation of gastric cancer (GC) through JAK/STAT3 signaling in a mouse model. A JAK/STAT3 inhibitor blocks the increase in GC cell viability induced by senescent CAFs and peritoneal tumor formation. Single-cell mass cytometry revealed that fibroblasts exist in the ascites of GC patients with peritoneal dissemination, and the fibroblast population shows p16 expression and SASP factors at high levels. These findings provide insights into the inflammation-related SASP maintenance by histone modification and the role of senescent CAFs in GC peritoneal dissemination.

10.
Surg Case Rep ; 7(1): 53, 2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33616793

RESUMO

BACKGROUND: Visceral artery aneurysms are rare, but they may cause heavy bleeding and high mortality. In addition, aneurysms originating from the superior mesenteric artery (SMA) account for only 1% of visceral artery aneurysms. We report the rare case of a ruptured transverse pancreatic artery aneurysm originating from the SMA that required urgent surgical treatment. CASE PRESENTATION: A 66-year-old woman presented with acute back pain after lunch, and she was transported by ambulance. She had upper quadrant spontaneous pain and moderate tenderness, but no guarding or rebound pain. She had rheumatoid arthritis, and was taking 10 mg of steroids per day. Contrast-enhanced computed tomography demonstrated a retroperitoneal hematoma spreading to the ventral side of the left kidney and extravasation of contrast agent from a branch of the SMA. We diagnosed rupture of aneurysm. We conferred with our IVR team on treatment strategy for the ruptured aneurysm. In addition, we finally selected operation, since the branch of the SMA to the aneurysm was too thin and complex to conduct IVR. For this reason, we performed emergency simple aneurysmectomy of the transverse pancreatic artery. The postoperative course was relatively smooth. CONCLUSION: Rupture of a transverse pancreatic artery aneurysm originating from the SMA is rare. However, when diagnosing patients with acute abdomen or back pain, we should consider rupture of a visceral artery aneurysm. Endovascular treatment may currently be common for ruptured visceral artery aneurysms, but we should flexibly treat them according to the patient's condition and facility considerations.

11.
Eur J Cancer ; 146: 125-134, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33607476

RESUMO

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies. While the extracellular matrix component plays an integral role in PDAC pathogenesis and mediating chemoresistance, its role in predicting response to chemotherapy in patients with PDAC remains unclear. METHODS: We performed a systematic biomarker discovery by analysing genome-wide transcriptomic profiling data from 423 patients (GSE71729, GSE21501 and The Cancer Genome Atlas [TCGA]) for predicting overall survival (OS). This was subsequently validated in two independent clinical cohorts of 270 patients with PDAC (training cohort, n = 121, and validation cohort, n = 149). In addition, we investigated endoscopic ultrasound-fine needle aspiration biopsy specimens from 51 patients with PDAC with an unresectable cancer for predicting therapeutic response to gemcitabine-based therapy. RESULTS: After rigorous bioinformatic analysis, we identified laminin γ2 (LAMC2) to be a significant prognostic factor in all three PDAC data sets (GSE71729: hazard ratio [HR] = 2.04, P = 0.002; GSE21501: HR = 2.17, P = 0.031; TCGA: HR = 2.57, P < 0.001). High LAMC2 expression in patients with PDAC was associated with a significantly poor OS and relapse-free survival in both the training (P < 0.001, P < 0.001) and validation cohorts (P = 0.001, P = 0.026). More importantly, LAMC2 expression robustly identified patients with PDAC and unresectable disease and those who responded to gemcitabine-based therapy (area under the curve = 0.79; 95% confidence interval [CI], 0.65-0.89). The univariate logistic regression analysis revealed that high LAMC2 expression was the only factor that predicted poor response to gemcitabine in patients with PDAC (odds ratio = 4.90; 95% CI, 1.45-16.6; P = 0.011). CONCLUSION: We conclude that LAMC2 is a novel prognostic and predictive biomarker for gemcitabine-based therapy in both the adjuvant and palliative setting; which could have significant impact on precision and individualised treatment of patients with PDAC.

12.
BMC Cancer ; 21(1): 23, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33402130

RESUMO

BACKGROUND: Preoperative chemoradiotherapy (CRT), the current standard of care for locally advanced rectal cancer (LARC), is associated with many radiotherapy (RT)-related side effects. We aimed to evaluate whether S-1 and oxaliplatin (SOX) or folinic acid, 5-FU, and oxaliplatin (mFOLFOX6) can be as effective as neoadjuvant chemotherapy (NAC) regimens for LARC without RT. METHODS: Patients with untreated resectable LARC were randomly assigned to receive SOX or mFOLFOX6. The NAC protocol period was 3 months. The primary endpoint was 3-year disease-free survival (DFS), and the secondary endpoints included pathological effects, surgical completion rate, 3-year survival, and safety. RESULTS: From September 2013 to October 2015, 56 and 54 patients were enrolled in the SOX and mFOLFOX6 arms, respectively. The 3-year DFS rates were 69.4% (95% confidence interval [CI] 54.9-83.6) and 73.4% (95% CI 58.7-83.6) in the SOX and mFOLFOX6 arms, respectively; no significant differences were found between the arms (log-rank test; P = 0.5315, hazard ratio: 0.808, 95% CI 0.414-1.578). The 3-year survival rates were 92.3 and 91.8% in the SOX and mFOLFOX6 arms, respectively. The surgical completion rate was 98.1% overall, 100% in the SOX arm, and 96.0% in the mFOLFOX6 arm. The incidences of pathological response rates ≥grade 1b were 41.5 and 43.8% in the SOX and mFOLFOX6 arms, respectively. Both treatments were manageable and tolerable. CONCLUSION: We demonstrated the effectiveness and safety of SOX and mFOLFOX6, both of which may be new neoadjuvant treatment candidates in previously untreated LARC cases. TRIAL REGISTRATION: Date of enrolment of the first participant to the trial: 3rd Oct 2013; This study was registered in the UMIN clinical trials registry on 14th Aug, 2013. (Prospectively registered, UMIN-CTR number UMIN000011486). https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&recptno=R000013441&language=J.

13.
Eur J Gastroenterol Hepatol ; Publish Ahead of Print2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33405423

RESUMO

BACKGROUND: Follow-up after pediatric liver transplantation (LTX) is challenging and needs to be refined to extend graft survival as well as general functional health and patients´ quality of life. Strategies towards individual immunosuppressive therapy seem to play a key role. Our aim was to evaluate protocol liver biopsies (PLB) as a tool in personalized follow up after pediatric LTX. PATIENTS AND METHODS: Our retrospective analysis evaluates 92 PLB in clinically asymptomatic pediatric patients after LTX between 2009 and 2019. Histological findings were characterized using the Desmet scoring system. In addition to PLB, other follow-up tools like laboratory parameters, ultrasound imaging and transient elastography were evaluated. Risk factors for development of fibrosis or inflammation were analyzed. RESULTS: PLB revealed a high prevalence of graft fibrosis (67.4%) and graft inflammation (47.8%). Graft inflammation was significantly (P = 0.0353*) more frequent within the first 5 years after transplantation compared to later time points. Besides conventional ultrasound, the measurement of liver stiffness using transient elastography correlate with stage of fibrosis (r = 0.567, P = <0.0001***). Presence of donor-specific anti-human leukocyte antigen antibodies in blood correlates with grade of inflammation in PLB (r = 0.6040, P = 0.0018 **). None of the patients who underwent PLB suffered from intervention-related complications. Histopathological results had an impact on clinical decision making in one-third of all patients after PLB. CONCLUSION: PLB are a safe and useful tool to detect silent immune-mediated allograft injuries in the context of normal liver parameters.

14.
Ann Thorac Surg ; 2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33482156

RESUMO

BACKGROUND: Immune checkpoint inhibitors targeting the PD-1/PD-L1 pathway have demonstrated antitumor effects in patients with various malignancies, including esophageal cancer. Thus, a better understanding of local immunity in esophageal cancer is crucial for improving treatment and clinical outcomes. METHODS: We evaluated PD-1 expression on TILs, as well as PD-L1 expression on cancer cells, by immunohistochemistry and immunofluorescence using a non-biased database of 433 curatively resected esophageal cancers. With the idea of application as liquid biopsy, PD-1 expression status on peripheral lymphocytes was evaluated by flow cytometry. RESULTS: The cutoff value of PD-1 expression was the median PD-1 count. Compared with cases of low PD-1 expression (n=219), cases with high levels of PD-1 expression (n=213) showed significantly worse overall survival (log rank P=0.0017). The prognostic effect of PD-1 differed according to the preoperative treatment status (P for interaction=0.040); PD-1 expression was associated with high overall mortality among patients without preoperative therapy, while no such association was present among those with preoperative treatment. A stratification based on PD-1 and PD-L1 status was also significantly associated with overall survival (log rank P=0.0005). PD-1 expression on TILs was significantly associated with that on peripheral lymphocytes (P<0.0001). CONCLUSIONS: PD-1 expression on TILs was associated with an unfavorable clinical outcome in esophageal cancer, supporting its role as a prognostic biomarker. The combination of PD-1 and PD-L1 expression enabled further classification of patients according to clinical outcome.

15.
Artigo em Inglês | MEDLINE | ID: mdl-33453135

RESUMO

BACKGROUND: Postoperative complications after pancreaticoduodenectomy (PD) is still a major concern. The aim of this study was to propose how to choose antibiotics, based on bacterial sensitivity profiling involved in postoperative complications after PD. METHODS: Two hundred and thirty patients underwent PD between 2008 and 2018 at Kumamoto University Hospital. We enrolled 121 patients who had both intraoperative bile culture and drain culture on postoperative day (POD) 3. The clinical impact of the bacterial profile on postoperative outcome was retrospectively analyzed. RESULTS: Multivariate regression analysis revealed that intraperitoneal contamination on POD3 was independently associated with postoperative complications (odds ratio 2.62, P = .02). The bacteria in intraperitoneal drain on POD3 showed 94.9% similarity with those in bile collected during surgery. The major species were Enterococcus (44.6%) and Enterobacter (38.5%). Enterobacter species caused a higher rate of postoperative complications than others (83% vs 54%, P = .04). Three out of five Enterococcus faecium were resistant to carbapenems that were active against all Gram-negative rods. CONCLUSIONS: Intraperitoneal contamination on POD3, which had similar bacterial species as bile collected during surgery, was correlated with postoperative complications. The bacterial antibiotic sensitivity profile may help selecting optimal antibiotics against infectious postoperative complications in PD.

16.
Ann Surg Oncol ; 2021 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-33393038

RESUMO

BACKGROUND: Pancreatic cancer has an extremely poor prognosis, even after curative resection. Treatment options for pancreatic cancer remain limited, therefore new therapeutic targets are urgently needed. We searched for genes predictive of poor prognosis in pancreatic cancer using a public database and validated the survival impact of the selected gene in a patient cohort. METHODS: We used a public database to search for genes associated with early pancreatic cancer recurrence. As a validation cohort, 201 patients who underwent radical resection in our institution were enrolled. Expression of the target gene was evaluated using immunohistochemistry (IHC). We evaluated growth and invasiveness using small interfering RNAs, then performed pathway analysis using gene set enrichment analysis. RESULTS: We extracted ARHGEF2 from GSE21501 as a gene with a high hazard ratio (HR) for early recurrence within 1 year. The high ARHGEF2 expression group had significantly poorer recurrence-free survival (RFS) and poorer overall survival (OS) than the low ARHGEF2 expression group. Multivariate analysis demonstrated that high ARHGEF2 expression was an independent poor prognostic factor for RFS (HR 1.92) and OS (HR 1.63). In vitro, ARHGEF2 suppression resulted in reduced cell growth and invasiveness. Bioinformatic analysis revealed that ARHGEF2 expression was associated with MYC, G2M, E2F, and CDC25A expression, suggesting that c-Myc and cell cycle genes are associated with high ARHGEF2 expression. IHC revealed a positive correlation between ARHGEF2 and c-Myc expression. CONCLUSIONS: High ARHGEF2 expression is associated with cell cycle progression, and predicts early recurrence and poor survival in patients with pancreatic cancer.

17.
World J Surg ; 45(4): 1159-1167, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33386452

RESUMO

BACKGROUNDS AND AIMS: Postoperative early recurrence after hepatic resection for hepatocellular carcinoma (HCC) poses a challenge to surgeons, and the effect of a surgical margin is still controversial. This study aimed to identify an ideal margin to prevent early recurrence. METHODS: A total of 226 consecutive patients who underwent primary curative hepatic resection for solitary and primary HCC were enrolled. The definition of early recurrence was determined using the minimum P value approach. Logistic regression analysis was used to identify the risk factors of early recurrence. The receiver-operating characteristic (ROC) curve was used to identify the optimal cut-off of the surgical margin and early recurrence. RESULTS: Recurrence within 8 months induced the poorest overall survival (P = 2×10-15). ROC analysis showed that the optimal cut-off value of the surgical margin was 7 mm. The risk factors of early recurrence (≤ 8-month recurrence) were preoperative alpha-fetoprotein levels ≥ 100 ng/ml (Odds ratio [OR] 4.92 [2.28-10.77], P < 0.0001) and a surgical margin < 7 mm (OR 3.09 [1.26-8.85], P = 0.01) by multivariable analysis. The probability of early recurrence ranged from 5.0% in the absence of any factors to 43.5% in the presence of both factors. Among patients with alpha-fetoprotein levels ≥ 100 ng/ml, non-capsule formation, or microvascular invasion, there was a significant difference in 5-year overall survival between surgical margins of < 7 mm and ≥ 7 mm. CONCLUSIONS: A > 7-mm margin is important to prevent early recurrence. Patients with HCC and alpha-fetoprotein levels > 100 ng/ml, non-capsule formation, or microvascular invasion may have a survival benefit from a ≥ 7-mm margin.

18.
Int J Clin Oncol ; 2021 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-33507434

RESUMO

BACKGROUND: The number of frail patients with colorectal cancer (CRC) has increased. Despite evidence-based treatment guidelines, a large proportion of patients with resected CRC do not receive adjuvant chemotherapy in daily practice. This retrospective study aimed to examine the effect of adjuvant chemotherapy for CRC according to frailty. METHODS: We retrospectively analyzed data from 507 consecutive patients with curatively resected high-risk stage II or stage III CRC between 2009 and 2016. Frailty was assessed using the Clinical Frailty Scale (CFS): 1 (very fit) to 9 (terminally ill), and frailty was defined as CFS ≥ 4. Recurrence-free survival (RFS) and overall survival (OS) were compared between surgery alone and adjuvant chemotherapy in frail and non-frail patients. A cox proportional hazards model was used to calculate hazard ratios (HRs), controlling for potential confounders. RESULTS: Of the 507 patients, 194 (38%) were frail. There were no significant interactions between frailty and adjuvant chemotherapy regarding RFS (Pinteraction = 0.59) and OS (Pinteraction = 0.81). In multivariable analyses, associations of adjuvant chemotherapy with longer RFS and OS in frail patients (RFS, HR: 0.33, 95% CI 0.15-0.63; OS, HR: 0.23, 95% CI 0.08-0.54) were comparable to non-frail patients (RFS, HR: 0.36, 95% CI 0.22-0.58; OS, HR: 0.34, 95% CI 0.15-0.69). Frail patients receiving adjuvant chemotherapy were younger and had better nutritional status than those undergoing surgery alone (all P < 0.005). CONCLUSION: Selected frail patients with CRC may experience a similar survival benefit from adjuvant chemotherapy as non-frail patients. Clinical trials are needed to establish adjuvant chemotherapy for CRC in frail patients.

19.
Anticancer Res ; 41(2): 1069-1076, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33517317

RESUMO

BACKGROUND/AIM: Emergency surgery for colorectal cancer (CRC) is a high-risk procedure with high morbidity and mortality rates, especially for older patients. The relationship between patient age status and long-term outcomes is unclear. We hypothesize that patient age might be associated with long-term outcomes in patients with CRC who undergo emergency surgery. PATIENTS AND METHODS: Utilizing a database of CRC patients who received emergency surgery, we examined the prognostic association of patient age. RESULTS: The ≥80-years group was significantly associated with American Society of Anesthesiologists (ASA) physical status, bowel obstruction, N stage, shorter operating time, and less adjuvant chemotherapy (all p<0.03); and also, with shorter recurrence-free survival [multivariable hazard ratio, 2.79; 95% confidence interval, 1.13-7.21; p=0.026]. ASA status and adjuvant chemotherapy were significantly associated with recurrence-free survival (all p<0.03). CONCLUSION: Advanced age is associated with shorter recurrence-free survival in CRC patients who undergo emergency surgery.


Assuntos
Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/cirurgia , Tratamento de Emergência/métodos , Obstrução Intestinal/etiologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante , Neoplasias Colorretais/tratamento farmacológico , Bases de Dados Factuais , Tratamento de Emergência/efeitos adversos , Feminino , Humanos , Obstrução Intestinal/epidemiologia , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Complicações Pós-Operatórias/epidemiologia , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida
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