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1.
Surg Endosc ; 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35020058

RESUMO

BACKGROUND: Vertical tumor margin-negative T1 colorectal carcinoma (CRC) is an absolute curative condition following complete endoscopic resection (ER). However, the influence on prognosis in relation to vertical tumor margin is unclear. Therefore, we evaluated the influence of the distance from vertical tumor margin to resected specimen edge (vertical margin distance) of ER for T1b (submucosal invasion depth > 1000 µm) CRC on the prognosis of patients undergoing additional surgery after ER. METHODS: In total, 215 consecutive patients with T1b CRC who underwent additional surgery after ER at Hiroshima University Hospital between February 1992 and June 2019 were enrolled. We assessed 191 patients without lymph node metastases at the additional surgery. The specimens resected by ER were classified into three groups based on the vertical margin distance: patients with a vertical margin distance of ≥ 500 µm (Group A); patients with a vertical margin distance of < 500 µm (Group B); and patients with a positive vertical tumor margin (Group C). Subsequently, we evaluated the prognosis of the patients in relation to the clinicopathological characteristics among the three groups. RESULTS: There were no significant differences in clinicopathological characteristics among the three groups. Group A had a significantly higher recurrence-free 5-year survival rate than Groups B and C (100%, 84.5%, and 81.8%, respectively). Similarly, Group A had a significantly higher disease-specific 5-year survival rate than Group C (100% vs. 95.5%). CONCLUSIONS: Complete en bloc resection with sufficient submucosal layer from the invasive front (vertical margin distance > 500 µm) by ER for T1 CRC reduces the risk of metastatic recurrence after additional surgery.

2.
Int J Oncol ; 60(2)2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34981812

RESUMO

miR­1291 exerts an anti­tumor effect in a subset of human carcinomas, including pancreatic cancer. However, its role in colorectal cancer (CRC) is largely unknown. In the present study, the expression and effect of miR­1291 in CRC cells was investigated. It was identified that miR­1291 significantly suppressed the proliferation, invasion, cell mobility and colony formation of CRC cells. Additionally, miR­1291 induced cell apoptosis. A luciferase reporter assay revealed that miR­1291 directly bound the 3'­untranslated region sequence of doublecortin­like kinase 1 (DCLK1). miR­1291 also suppressed DCLK1 mRNA and protein expression in HCT116 cells that expressed DCLK1. Furthermore, miR­1291 suppressed cancer stem cell markers BMI1 and CD133, and inhibited sphere formation. The inhibitory effects on sphere formation, invasion and mobility in HCT116 cells were also explored and verified using DCLK1 siRNAs. Furthermore, miR­1291 induced CDK inhibitors p21WAF1/CIP1 and p27KIP1 in three CRC cell lines, and the overexpression of DCLK1 in HCT116 cells led to a decrease of p21WAF1/CIP1 and p27KIP1. Intravenous administration of miR­1291 loaded on the super carbonate apatite delivery system significantly inhibited tumor growth in the DLD­1 xenograft mouse model. Additionally, the resultant tumors exhibited significant upregulation of the p21WAF1/CIP1 and p27KIP1 protein with treatment of miR­1291. Taken together, the results indicated that miR­1291 served an anti­tumor effect by modulating multiple functions, including cancer stemness and cell cycle regulation. The current data suggested that miR­1291 may be a promising nucleic acid medicine against CRC.

3.
Annu Int Conf IEEE Eng Med Biol Soc ; 2021: 7551-7555, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34892838

RESUMO

Techniques for 3D endoscopic systems have been widely studied for various reasons. Among them, active stereo based systems, in which structured-light patterns are projected to surfaces and endoscopic images of the pattern are analyzed to produce 3D depth images, are promising, because of robustness and simple system configurations. For those systems, finding correspondences between a projected pattern and an original pattern is an open problem. Recently, correspondence estimation by graph neural networks (GCN) using graph-based representation of the patterns were proposed for 3D endoscopic systems. One severe problem of the approach is that the graph matching by GCN is largely affected by the stability of the graph construction process using the detected patterns of a captured image. If the detected pattern is fragmented into small pieces, graph matching may fail and 3D shapes cannot be retrieved. In this paper, we propose a solution for those problems by applying deep-layered GCN and extended graph representations of the patterns, where proximity information is added. Experiments show that the proposed method outperformed the previous method in accuracies for correspondence matching for 3D reconstruction.

4.
Gastroenterol Res Pract ; 2021: 3216193, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34956361

RESUMO

With the increasing use of capsule endoscopy (CE), screening tests for the small bowel can be performed with minimal invasiveness. However, occasionally, the entire small bowel cannot be observed because of decreased peristalsis of the stomach. For such cases, we perform delivery of CE by an endoscope. We retrospectively examined the usefulness of the endoscopic delivery method using a retrieval net for patients with CE stagnation in the stomach. From 2,270 patients who underwent small-bowel CE at Hiroshima University Hospital from January 2013 to January 2020, 29 consecutive patients (1.3% of the total number) in whom the small bowel could not be observed due to CE stagnation in the stomach at the time of the initial CE underwent the endoscopic delivery method using a retrieval net for secondary small-bowel CE. This study included 16 male (55%) and 13 female (45%) patients with a mean age of 69.2 ± 13.2 years. 11 patients (38%) had a history of gastrointestinal surgical resection. The entire small bowel could be observed in 19 patients (66%), and CE reached the terminal ileum in the remaining patients. A history of gastrointestinal surgical resection was significantly more frequent in the group where the entire small bowel could not be observed. The rate of small-bowel lesion detection was 55% (16/29). There were no adverse events associated with our endoscopic delivery method. Thus, the endoscopic delivery method using a retrieval net for patients with initial CE stagnation in the stomach may be safe and useful for the detection of small-bowel lesions.

5.
Gastroenterol Res Pract ; 2021: 9415387, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34956362

RESUMO

The Japan Gastroenterological Endoscopy Society (JGES) guidelines recommend continued warfarin treatment during gastroenterological endoscopic procedures with a high risk of bleeding as an alternative to heparin replacement in patients on warfarin therapy. However, there is insufficient evidence to support the use of warfarin in colorectal endoscopic resection (ER). The present study is aimed at verifying the risk of bleeding after ER for colorectal neoplasia (CRN) in patients with continued warfarin use. This was a single-center retrospective cohort study using clinical records. We assessed 126 consecutive patients with 159 CRNs who underwent ER (endoscopic mucosal resection, 146 cases; endoscopic submucosal dissection, 13 cases) at Hiroshima University Hospital between January 2014 and December 2019. Patients were divided into two groups: the heparin replacement group (79 patients with 79 CRNs) and the continued warfarin group (47 patients with 80 CRNs). One-to-one propensity score matching was performed to compare the bleeding rate after ER between the groups. The rate of bleeding after ER was significantly higher in the heparin replacement group than in the continued warfarin group for both before (10.1% vs. 1.3%, respectively; P = 0.0178) and after (11.9% vs. 0%, respectively; P = 0.0211) propensity score matching. None of the patients experienced thromboembolic events during the perioperative period. The risk of bleeding after colorectal ER was significantly lower in patients with continued warfarin use than in those with heparin replacement. Our data supports the recommendations of the latest JGES guidelines for patients receiving warfarin therapy.

6.
Antibiotics (Basel) ; 10(12)2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34943651

RESUMO

Copper (Cu) and its alloys have bactericidal activity known as "contact killing" with degradation of nucleic acids inside the bacteria, which is beneficial to inhibit horizontal gene transfer (HGF). In order to understand the nucleic acid degradability of Cu and its alloy surfaces, we developed a new in vitro method to quantitatively evaluate it by a swab method under a "dry" condition and compared it with that of commercially available antibacterial materials such as antibacterial stainless steel, pure silver, and antibacterial resins. As a result, only Cu and its alloys showed continuous degradation of nucleic acids for up to 6 h of contact time. The nucleic acid degradability levels of the Cu alloys and other antibacterial materials correlate to their antibacterial activities evaluated by a film method referring to JIS Z 2801:2012 for Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria. Nucleic acid degradation by copper (I) and (II) chlorides was confirmed at the ranges over 10 mM and 1-20 mM, respectively, suggesting that the copper ion release may be responsible for the degradation of the nucleic acids on Cu and its alloy surfaces. In conclusion, the higher Cu content in the alloys gave higher nucleic acid degradability and higher antibacterial activities.

7.
J Infect ; 2021 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-34953905

RESUMO

OBJECTIVES: The preS1 region plays an essential role in hepatitis B virus (HBV) infection. We construct an antibody that binds to preS1 and a measurement system for serum preS1 in chronic HBV-infected patients. METHODS: Hybridoma clones that produce anti-preS1 antibodies were obtained by the iliac lymph node method. Epitope mapping was conducted, and an enzyme-linked immunosorbent assay (ELISA)-based method was developed. Using this ELISA system, serum preS1 levels were measured in 200 chronic HBV-infected patients. RESULTS: Eight types of hybridomas were obtained, of which antibody 3-55 using amino acids 38-47 as the epitope showed high binding affinity to preS1. Serum preS1 levels measured by ELISA using 3-55 antibody were correlated with HBsAg, HBcrAg and HBV DNA levels. Among HBeAg-negative patients without antiviral therapeutic objective (HBV DNA <3.3 log IU/mL or alanine aminotransferase ≤30 U/L), preS1 was significantly higher in subjects who had progressed to the point of requiring antiviral therapy compared to subjects who had maintained their status for the preceding three years (p<0.01). CONCLUSIONS: We constructed an antibody against preS1 and an ELISA system capable of measuring serum preS1 levels. PreS1 may serve as a novel tool to predict the need for antiviral therapy in HBeAg-negative HBV-infected patients.

8.
Radiother Oncol ; 166: 65-70, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34838886

RESUMO

BACKGROUND AND PURPOSE: Radiotherapy (RT) has recently received increasing attention as an additional treatment for organ preservation after non-curative endoscopic submucosal dissection (ESD) in patients with superficial esophageal cancer. Esophageal stenosis is an adverse event related to RT after ESD that is not widely studied. The aim of this study was to investigate esophageal stenosis related to salvage RT in superficial esophageal cancer after non-curative ESD. MATERIALS AND METHODS: Fifty patients who received salvage RT after non-curative ESD at a single institution between 2011 and 2018 were included in this study. The Common Terminology Criteria for Adverse Events, version 5.0, was used to assess esophageal stenosis. Data were compared using Fisher's exact test. Statistical significance was set at P < 0.05. RESULTS: Median follow-up time was 48 months (range, 12-95 months). Grade 2 and 3 esophageal stenosis were observed in 17 (34%), and 3 patients (6%), respectively. The frequency of grade 2 or worse esophageal stenosis decreased over time (before RT, 6 months, 1 year, and 2 years after RT: 16 (32%), 13 (26%), 10 (20%), and 6 (12%) patients, respectively). Only one patient required endoscopic balloon dilation (EBD) 1 year after RT. All grade 3 esophageal stenosis improved grade 2 or less by EBD. In univariate analysis, only tumor location was a significant risk factor for grade 3 esophageal stenosis. CONCLUSIONS: Esophageal stenosis, after salvage RT in patients with esophageal cancer who received non-curative ESD, improved naturally or after EBD; only a few cases required long-term EBD.

10.
J Gastroenterol ; 56(12): 1062-1079, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34611740

RESUMO

BACKGROUND: The mortality and risk factors of severe disease and death due to arterial and venous thromboembolism (ATE and VTE, respectively) in patients with inflammatory bowel disease (IBD) remain unclear, especially in Asia. AIMS: This study aimed to reveal the mortality and risk factors of TE in IBD patients in Japan. METHODS: In the primary surveillance, responses to questionnaires regarding the number of cases of severe TE and TE-associated death in IBD patients in a span of over the past 10 years were obtained from 32 institutions in Japan. In the secondary surveillance, detailed data about IBD patients with TE were collected. The characteristics, laboratory data, therapy status, and situation at the time of TE development were retrospectively collected, and the data were compared between the patients with and without severe TE and TE-associated death. RESULTS: The incidence of TE was 1.89% among 31,940 IBD patients. The frequencies of severe TE and TE-associated mortality were 10.7% and 1.0% among the total IBD and TE with IBD patients, respectively. The only risk factor for severe ATE and ATE-associated death was ischemic heart disease. The independent risk factors for severe VTE and VTE-associated death were age (≤ 45 years old), the site of VTE, and disease severity, with anti-TNF therapy as a potential negative risk factor. Patients with severe VTE had a high risk of developing persistent VTE and sequelae. CONCLUSION: Unlike ATE, the incidence of VTE was comparable in Asian and Western countries. Therapeutic and prophylactic strategies for managing IBD-associated TE in Asia are urgently needed.

11.
Sci Rep ; 11(1): 20163, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34635790

RESUMO

Systemic sclerosis (SSc) is characterized by fibrosis of the skin and various internal organs. However, there is limited knowledge concerning small-bowel lesions. We evaluated the clinical state of patients with SSc according to the capsule endoscopy (CE) findings. Sixty-five consecutive patients with SSc (61 females; mean age, 64.3 years) underwent CE at Hiroshima University Hospital between April 2012 and December 2019. SSc was subclassified into diffuse and limited cutaneous SSc. Among the 65 patients, 55 (51 females; mean age, 64.5 years; diffuse cutaneous SSc, 27 patients) were evaluated for the presence of fibrosis in the gastrointestinal tract by biopsy. Small-bowel lesions were detected in 27 (42%) patients with SSc. Type 1b angioectasia (Yano-Yamamoto classification) was more frequent in limited cutaneous SSc patients (p = 0.0071). The average capsule transit time of the esophagus was significantly longer in diffuse cutaneous SSc patients (p = 0.0418). There were more cases of Type 1a angioectasia in SSc patients without fibrosis. The average capsule transit time of the esophagus was significantly longer in SSc patients with fibrosis. Thus, this study revealed that the frequency of small-bowel angioectasia and gastrointestinal motility in patients with SSc differed depending on SSc subclassification and the presence of fibrosis.

12.
Gastric Cancer ; 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34581902

RESUMO

BACKGROUND: This postmarketing surveillance study evaluated the real-world safety and effectiveness of nivolumab as salvage (after ≥ 2 lines) therapy in Japanese patients with unresectable advanced or recurrent gastric/gastroesophageal junction (G/GEJ) cancer. METHODS: This multicenter, observational study was conducted at 158 centers in Japan. Patients with unresectable advanced or recurrent G/GEJ cancer were registered between Nov 1, 2017, and Oct 31, 2018, and observed for 6 months after treatment initiation with nivolumab. Correlation of background characteristics with treatment-related adverse events (TRAEs) and tumor response was explored. RESULTS: Overall, 654 patients were registered (safety analysis set, n = 650; effectiveness analysis set, n = 636; response evaluation set, n = 516). The incidences of all TRAEs and grade ≥ 3 TRAEs were 31.5 and 11.2%, respectively. TRAEs significantly correlated with the absence of peritoneal metastasis; C-reactive protein level < 1; prior G/GEJ cancer surgery; and past or concomitant pulmonary, thyroid, or renal disease (each p < 0.05). The incidence of TRAEs was significantly lower in patients with higher Glasgow prognostic scores (p < 0.05). No new safety signals were observed. Complete response, partial response, stable disease, and progressive disease were observed in 1.2, 10.1, 27.1, and 58.3% of the response evaluation set, respectively. Patients aged ≥ 65 years (13.9 vs 5.3%, p = 0.0083) and ≥ 75 years (18.8 vs 9.2%, p = 0.0036) showed a higher response rate than their younger counterparts. CONCLUSIONS: The real-world safety and effectiveness of nivolumab as salvage (after ≥ 2 lines) therapy in Japanese patients with unresectable advanced or recurrent G/GEJ cancer were consistent with those observed in the phase 3 ATTRACTION-2 study.

13.
Cancer Sci ; 112(11): 4641-4654, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34510663

RESUMO

Screening custom-made libraries of inhibitors may reveal novel drugs for treating pancreatic cancer. In this manner, we identified ispinesib as a candidate and attempted to determine its clinical efficacy and the biological significance of its functional target Eg5 in pancreatic cancer. One hundred compounds in our library were screened for candidate drugs using cell cytotoxicity assays. Ispinesib was found to mediate effective antitumor effects in pancreatic cancer. The clinical significance of the expression of the ispinesib target Eg5 was investigated in 165 pancreatic cancer patients by immunohistochemical staining and in Eg5-positive pancreatic cancer patient-derived xenograft (PDX) mouse models. Patients with Eg5-positive tumors experienced significantly poorer clinical outcomes than those not expressing Eg5 (overall survival; P < .01, recurrence-free survival; P < .01). Ispinesib or Eg5 inhibition with specific siRNA significantly suppressed cell proliferation and induced apoptosis in pancreatic cancer cell lines. Mechanistically, ispinesib acted by inducing incomplete mitosis with nuclear disruption, resulting in multinucleated monoastral spindle cells. In the PDX mouse model, ispinesib dramatically reduced tumor growth relative to vehicle control (652.2 mm3 vs 18.1 mm3 in mean tumor volume, P < .01 by ANOVA; 545 mg vs 28 mg in tumor weight, P < .01, by ANOVA). Ispinesib, identified by inhibitor library screening, could be a promising novel therapeutic agent for pancreatic cancer. The expression of its target Eg5 is associated with poorer postoperative prognosis and is important for the clinical efficacy of ispinesib in pancreatic cancer.


Assuntos
Antineoplásicos/farmacologia , Benzamidas/farmacologia , Neoplasias Pancreáticas/tratamento farmacológico , Quinazolinas/farmacologia , Análise de Variância , Animais , Apoptose , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Intervalo Livre de Doença , Descoberta de Drogas , Feminino , Inativação Gênica , Humanos , /metabolismo , Bibliotecas Especializadas , Metáfase/efeitos dos fármacos , Camundongos , Camundongos Nus , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/metabolismo , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Eur J Cancer ; 157: 373-382, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34563992

RESUMO

BACKGROUND: Transarterial chemoembolisation (TACE) is a treatment option for hepatocellular carcinoma (HCC), but the optimum agent for TACE remains unclear. We compared the efficacy of TACE with cisplatin versus with epirubicin in patients with unresectable HCC. METHODS: This multicentre, randomised, phase 2/3 trial was performed at 21 hospitals in Japan. Patients with liver-confined HCC, performance status 0-2, and Child-Pugh class A/B were randomised to receive TACE with cisplatin or epirubicin. Patients were stratified in accordance with the institution, Child-Pugh class, tumour size, tumour thrombosis, α-fetoprotein and prior treatment. The primary end-point was overall survival in the intention-to-treat population. Tumour response was evaluated in accordance with the Response evaluation criteria in solid tumours criteria. FINDINGS: Between 2008 and 2012, 455 patients were randomly assigned to undergo TACE with cisplatin (n = 228) or epirubicin (n = 227). Eleven patients were ineligible, and 444 patients were included in the full analysis. Twelve patients not receiving TACE were excluded, and 432 patients were included in the safety analysis set. In phase 2, disease control rates in cisplatin (91·7%) and epirubicin (91·8%) groups exceeded the predefined threshold of 70%, and the study proceeded to phase 3. After a median follow-up of 32·7 months (IQR = 15·3-49·3), median overall survival periods were 2·93 years (95% CI 2·60-3·79) and 2·74 years (95%CI 2·26-3·21), respectively (hazard ratio 0·90 [95% CI 0·71-1·15], p = 0·22). Median times to treatment failure were 1·38 and 1·46 years (hazard ratio 1·09 [95% CI 0·88-1·35], p = 0·88), response rates were 65·3% and 60·6% (p = 0·31), and serious adverse event rates were 49·8% and 48·3% (p = 0·56), respectively. No treatment-related deaths occurred in either group. INTERPRETATION: In our phase 2/3 randomised trial, cisplatin is not significantly superior to epirubicin in TACE for patients with HCC.

15.
Nephron ; : 1-5, 2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34515167

RESUMO

The interaction between the nervous system and the immune system has recently been well-recognized. Vagus nerve stimulation (VNS) presents potential as an anti-inflammatory therapy through activation of neuroimmune pathways. Detailed understanding of the neuroimmune pathways VNS evokes is critical in order to successfully use it in the clinic for the treatment of acute kidney injury, in which inflammation plays an important role. In this review, we describe recent findings regarding VNS-induced neuroimmune pathways responsible for anti-inflammation and tissue protection.

16.
J Surg Case Rep ; 2021(8): rjab368, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34476078

RESUMO

In some patients with metastatic renal cell carcinoma to the pancreas, gastrointestinal hemorrhages occur, but because of the rarity of this condition, treatment strategies have not been established. A 71-year-old man who had undergone a nephrectomy for renal cell carcinoma (RCC) went to a hospital in a state of shock. Computed tomography revealed a hypervascularized tumor in the head of the pancreas, suggesting metastatic RCC. Upper endoscopy revealed bleeding in the duodenum due to tumor invasion. An emergency angiogram showed that the tumor received its blood supply mainly from the gastroduodenal artery. Transarterial embolization (TAE) of the gastroduodenal artery was performed and bleeding was controlled. Two months after TAE, elective pancreaticoduodenectomy was performed. The patient currently continues to undergo outpatient follow-up 2 years later without recurrence. TAE was very effective in controlling the acute phase of severe gastrointestinal hemorrhage from pancreatic metastasis of RCC.

17.
Artigo em Inglês | MEDLINE | ID: mdl-34478167

RESUMO

BACKGROUND AND AIM: Diagnostic support using artificial intelligence may contribute to the equalization of endoscopic diagnosis of colorectal lesions. We developed computer-aided diagnosis (CADx) support system for diagnosing colorectal lesions using the NBI International Colorectal Endoscopic (NICE) classification and the Japan NBI Expert Team (JNET) classification. METHODS: Using Residual Network as the classifier and NBI images as training images, we developed a CADx based on the NICE classification (CADx-N) and a CADx based on the JNET classification (CADx-J). For validation, 480 non-magnifying and magnifying NBI images were used for the CADx-N and 320 magnifying NBI images were used for the CADx-J. The diagnostic performance of the CADx-N was evaluated using the magnification rate. RESULTS: The accuracy of the CADx-N for Types 1, 2, and 3 was 97.5%, 91.2%, and 93.8%, respectively. The diagnostic performance for each magnification level was good (no statistically significant difference). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the CADx-J were 100%, 96.3%, 82.8%, 100%, and 96.9% for Type 1; 80.3%, 93.7%, 94.1%, 79.2%, and 86.3% for Type 2A; 80.4%, 84.7%, 46.8%, 96.3%, and 84.1% for Type 2B; and 62.5%, 99.6%, 96.8%, 93.8%, and 94.1% for Type 3, respectively. CONCLUSIONS: The multi-class CADx systems had good diagnostic performance with both the NICE and JNET classifications and may aid in educating non-expert endoscopists and assist in diagnosing colorectal lesions.

18.
Ann Gastroenterol Surg ; 5(5): 692-700, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34585054

RESUMO

Background: Little research is available regarding the treatments combining surgical resection with systemic chemotherapy for advanced pancreatic neuroendocrine neoplasm patients. We retrospectively elucidated whether sunitinib administration before surgery in advanced pancreatic neuroendocrine neoplasm (Pan-NEN) patients increases survival. Methods: This study included 106 of 326 Pan-NEN patients with distant metastases and/or unresectable locally advanced tumors who visited our department to receive sunitinib for more than 1 mo during April 2002 to December 2019. Risk factors for overall survival (OS) and disease-free survival (DFS) were analyzed. Results: The median duration of preoperative sunitinib administration and observation time after sunitinib were 6 and 26.5 mo, respectively. Of 106 patients, 31 (29.2%) underwent surgery following sunitinib administration. Hepatectomy, synchronous hepatopancreatectomy, pancreatectomy, and lymphadenectomy were performed for 13, 12, 5, and 1 patient, respectively. The 5-y OS rates in the resected and nonresected groups were 88.9% and 14.1%, respectively (P < .001). In the multivariate analysis, the absence of surgical resection following sunitinib (hazard ratio [HR], 13.1; P = .001), poor differentiation (HR, 5.5; P = .007), and bilateral liver metastases (HR, 3.7; P = .048) were independent risk factors for OS, although large liver tumor volumes were more evident in the nonresected group, as patient characteristics. The median DFS was 16.1 mo in 22 patients who underwent R0/1 resections, and risk factors for postoperative recurrence were Ki-67 index >7.8% (HR, 7.4; P = .02) and R1 resection (HR, 4.4; P = .04). Conclusion: Surgical resection after sunitinib administration improved OS in advanced Pan-NENs.

19.
Circ Rep ; 3(8): 449-456, 2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34414334

RESUMO

Background: There are few reports on the current awareness and status of venous ultrasonography, including the number of specialists who perform this procedure, in a specific regional area in Japan. Methods and Results: This cross-sectional survey study was conducted in Kumamoto Prefecture from October 2018 to March 2019. Of the 366 medical institutions providing cardiology services in Kumamoto Prefecture, 259 (101 general hospitals, 158 small clinics) responded to our questionnaire. In 2017, 21,773 venous ultrasound tests were performed, 21,101 (97%) of which were performed in hospitals and only 672 (3%) were performed in clinics. Both the number of institutions performing venous ultrasounds and the number of tests performed increased over time. Although 317 medical staff in Kumamoto Prefecture were performing transthoracic echocardiography (TTE) when the questionnaires were collected, only 210 performed venous ultrasounds. Although 91% (61/67) of medical institutions could perform TTE within 30 min, only 77% (53/69) performed venous ultrasounds within 30 min. The number of venous ultrasounds per population×100 was largest in the Kumamoto and Kamimashiki areas (1.67) and smallest in the Kamoto area (0.05). Conclusions: This is the first report to reveal the current awareness and status of venous ultrasonography in a specific region in Japan. There are several problems to be overcome, such as a lack of venous ultrasound specialists and the regional disparity in venous ultrasounds in Kumamoto Prefecture.

20.
Gastric Cancer ; 2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34387762

RESUMO

BACKGROUND: There is a need for a model of diffuse-type gastric cancer that captures the features of the disease, facilitates the study of its mechanisms, and aids the development of potential therapies. One such model may be Cdh1 and Trp53 double conditional knockout (DCKO) mice, which have histopathological features similar to those of human diffuse-type gastric cancer. However, a genomic profile of this mouse model has yet to be completed. METHODS: Whole-genome sequences of tumors from eight DCKO mice were analyzed and their molecular features were compared with those of human gastric adenocarcinoma. RESULTS: DCKO mice gastric cancers harbored single nucleotide variations and indel patterns comparable to those of human genomically stable gastric cancers, whereas their copy number variation fraction and ploidy were more similar to human chromosomal instability gastric cancers (perhaps due to Trp53 knockout). Copy number variations dominated changes in cancer-related genes in DCKO mice, with typical high-level amplifications observed for oncogenic drivers, e.g., Myc, Ccnd1, and Cdks, as well as gastrointestinal transcription factors, e.g., Gata4, Foxa1, and Sox9. Interestingly, frequent alterations in gastrointestinal transcription factors in DCKO mice indicated their potential role in tumorigenesis. Furthermore, mouse gastric cancer had a reproducible but smaller number of mutational signatures than human gastric cancer, including the potentially acid-related signature 17, indicating shared tumorigenic etiologies in humans and mice. CONCLUSIONS: Cdh1/Trp53 DCKO mice have similar genomic features to those found in human gastric cancer; hence, this is a suitable model for further studies of diffuse-type gastric cancer mechanisms and therapies.

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