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1.
Cancer Sci ; 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-32077199

RESUMO

RAS is a well-known oncogene that plays important roles in cancer proliferation, cell survival, and cell invasion. RAS exists as three major isoforms, KRAS, HRAS, and NRAS. Mutations of these genes account for approximately 30% of all cancers. Among them, KRAS mutations are the most common, responsible for 85% and are followed by NRAS (12%) and HRAS (3%). Although the development of RAS inhibitors has been explored for a long time, so far, no effective inhibitor has been found. MicroRNAs (miRNAs) are a class of small non-coding RNAs that control the gene expression of pleural target genes at the post-transcriptional level. MiRNAs play critical roles in the physiological and pathological processes at work in cancers, such as cell proliferation, cell death, cell invasion, and metastasis. MicroRNA-143 (MIR143) is known to function as a tumor suppressor in a variety of cancers. One of its known mechanisms is suppression of RAS expression and its effector signaling pathways, such as PI3K/AKT and MAPK/ERK. Recently, we developed a potent chemically-modified MIR143-3p that enabled us to elucidate the details of the KRAS signaling networks at play in colon cancer cells and others. In this review, we will discuss the role of MIR143-3p in those RAS signaling networks that are related to various biological processes of cancer cells. Also, we will discuss the possibility of the use of MIR143 as a therapeutic drug for targeting RAS signaling networks.

2.
Anticancer Res ; 40(1): 299-304, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892580

RESUMO

BACKGROUND/AIM: To clarify whether renal dysfunction affects the incidence of adverse events associated with oxaliplatin, the present study was designed to investigate the relationship between creatinine clearance (Ccr) and the incidence of oxaliplatin-related adverse events. PATIENTS AND METHODS: A total of 287 CRC patients who received the first cycle of oxaliplatin-based chemotherapy were eligible. Adverse events, including nausea, vomiting, neutropenia and thrombocytopenia, were graded, and the relationship between Ccr and the incidence of adverse events was examined using multivariable logistic regression analysis. RESULTS: A multivariable analysis indicated that the incidence of grade ≥2 nausea increased, while the incidence of other adverse events tended to be higher, as the Ccr decreased. Particularly, renal dysfunction (Ccr <60 ml/min) was a significant risk factor for grade ≥2 nausea (p=0.042). CONCLUSION: Care should be taken to avoid adverse events associated with oxaliplatin in patients with renal dysfunction.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Rim/fisiopatologia , Oxaliplatina/efeitos adversos , Oxaliplatina/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Creatinina/metabolismo , Feminino , Humanos , Incidência , Rim/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Fatores de Risco , Adulto Jovem
3.
Gastric Cancer ; 2020 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-31982964

RESUMO

BACKGROUND: There are currently two treatment options for gastric outlet obstruction (GOO) due to gastric cancer, endoscopic stenting and surgical gastrojejunostomy. However, their therapeutic effects have not yet been established. Therefore, the present study was undertaken to examine these effects. METHODS: The Japanese Gastric Cancer Association invited its delegates to participate in a retrospective multicenter cohort study on patients with GOO due to gastric cancer who underwent stent therapy or gastrojejunostomy in 2015. RESULTS: We obtained data from 85 patients undergoing stent therapy and 94 undergoing gastrojejunostomy from 42 hospitals. Baseline data revealed that stent patients had lower food intake, poorer performance status, and worse prognostic indices than gastrojejunostomy patients. Postoperative food intake and survival times were worse in stent patients than in gastrojejunostomy patients. We performed propensity score matching to select pairs of patients with similar baseline characteristics in the two treatment groups. After matching, the frequency of postoperative complications was significantly less in stent patients (3%, 1/33) than in gastrojejunostomy patients (21%, 7/34; p = 0.03). A low residue or full diet was achieved by 97% of stent patients (32/33) and 97% of gastrojejunostomy patients (33/34) (p = 0.98). Median survival times were 7.8 months in stent patients and 4.0 months in gastrojejunostomy patients (p = 0.38). CONCLUSIONS: Propensity score matching demonstrated that endoscopic stent placement resulted in less postoperative morbidity than and a similar food intake and equivalent survival times to gastrojejunostomy. These results suggest the utility of stent therapy.

4.
Odontology ; 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31807949

RESUMO

Soft denture liners and tissue conditioners are widely used for the denture patients to cushion masticatory force and condition abused tissues, respectively. This study assessed methods for the evaluation of the viscoelasticity and glass transition temperature (Tg) of the silicone permanent soft liner, acrylic permanent soft liner, and tissue conditioner. Three rheological parameters of storage modulus (E'), loss modulus (E''), and loss tangent ([Formula: see text]), Tg, and hardness were determined using dynamic mechanical analysis (DMA), differential scanning calorimetry (DSC), and the Shore A0 hardness test. Five specimens were measured for each material. The time-temperature superposition principle was applied to produce master curves of E', E'', and [Formula: see text] for the tested materials at a reference temperature of 37 °C. The acrylic permanent soft liner and tissue conditioner exhibited viscoelastic behavior and sensitivity to frequency, especially at lower frequencies. The silicone permanent soft liner showed elastic behavior and was frequency-independent. Tg for the acrylic permanent soft liner was higher than that for the tissue conditioner, which in turn was higher than that for the silicone permanent soft liner for both DMA and DSC. In DMA, a higher frequency led to higher Tg values. A positive linear relationship was found between Shore A0 hardness and E' values, but not E'' and [Formula: see text] values. Shore hardness reflects elasticity, but not viscosity. The results of the present study can be used to improve methods for evaluating the viscoelasticity and Tg of soft denture liners and tissue conditioners.

5.
Int J Clin Oncol ; 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31807967

RESUMO

BACKGROUND: Regorafenib is a multiple tyrosine kinase inhibitor, and the use of this drug is approved for the treatment of cancers that are resistant to chemotherapy, which include advanced colorectal cancer, gastrointestinal stromal tumor, and hepatocellular carcinoma. However, the drug causes adverse events, including skin toxicities that require dose modification in approximately 75% of cases. At present, the blood concentration of regorafenib is not assessed in clinical settings; thus, we recently developed a method that can assess the blood concentration of the drug using high-performance liquid chromatography. METHODS: We measured the trough blood concentrations (Ctrough) of regorafenib and its metabolites (M2 and M5) in 14 and 4 patients with advanced colorectal cancer and gastrointestinal stromal tumor, respectively, using high-performance liquid chromatography. Then, the correlation between the Ctrough and therapeutic outcomes of regorafenib was analyzed. RESULTS: In patients who were receiving regorafenib 40-160 mg/day, the Ctrough values of regorafenib, M2, and M5 were 318-9467, 34-3594, and 38-3796 ng/mL, respectively. The difference in the values was significant. Although the specific factors influencing this difference were not elucidated, the Ctrough of regorafenib was extremely lower in some patients, even though the drug was administered at a standard dose, which may explain the lower response rate. Moreover, the Ctrough value of M5 was significantly correlated to the incidence of skin toxicities, which is the most frequent cause of dose modification. CONCLUSIONS: The use of regorafenib may not be suitable in patients with a low Ctrough value. To prevent skin toxicities, the Ctrough value of M5 should be monitored.

6.
World J Surg Oncol ; 17(1): 197, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31771590

RESUMO

BACKGROUND: In Japan, the majority of gastrointestinal tract neuroendocrine tumors (NETs) have been reported to originate from the rectum, and appendiceal NETs are relatively rare. Preoperative diagnosis is very difficult and it is diagnosed after appendectomy. Pediatric appendiceal NET is a disease with a good prognosis. However, in rare cases, lymph node metastasis could occur and additional resection is required. CASE PRESENTATION: A 10-year-old boy complained of right lower quadrant abdominal pain and underwent an appendectomy under a diagnosis of acute appendicitis in previous hospital. The final diagnosis was appendiceal NET, so he was referred to our department for additional resection. The tumor was found in the base of the appendix and invasively reached the subserosal layer with obvious vascular invasion. His Ki-67 index was 1 to 2%, so we classified it as appendiceal NET G1 according to the WHO 2015 classification. We considered the possibility of a tumor remnant or lymph node metastasis, so we performed single-incision laparoscopy with D3 lymph node dissection. The pathological diagnosis revealed no tumor remnant but metastasis to one lymph node. He was discharged on the 9th postoperative day. There has been no recurrence at 3 years and 7 months after surgery. CONCLUSION: When the tumor size is 10-20 mm, the frequency of lymph node metastasis in some reports is variable, and there is no consensus yet on the indications for additional resection. However, there are definitely a certain number of cases with lymph node metastasis that require additional resection. In the present patient, long-term survival can be obtained by additional resection. At present, factors such as the presence of vascular or lymph node invasion and the malignancy grade and tumor's location must be considered on a case-by-case basis. Although the incidence rate of appendiceal NET is rare, the diagnosis can be made only during postoperative pathological examination; thus, reliable histopathological examination is required.

7.
Oncologist ; 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31748337

RESUMO

OBJECTIVE: TAS-102 is effective for treating patients with metastatic colorectal cancer (mCRC). This study determined whether combining bevacizumab (Bmab) with TAS-102 improves clinical outcomes in refractory mCRC. PATIENTS AND METHODS: We retrospectively analyzed data from Japanese patients with refractory mCRC who received TAS-102 (35 mg/m2, twice a day) with (T-B group) or without Bmab (TAS-102 monotherapy; T group) between July 2014 and December 2018. The primary endpoint was median overall survival (OS), and secondary endpoints were median time to treatment failure, overall response rate, and the incidence of adverse events. Clinical outcomes were compared using propensity score matched analysis. RESULTS: Data from 57 patients were analyzed (T-B group: 21 patients, T group: 36 patients). Median OS was significantly longer in the T-B group than the T group (14.4 months vs. 4.5 months, p < .001). Cox proportional hazard analysis showed that combination therapy with Bmab was significantly correlated with OS. Propensity score matched analysis confirmed that the median OS was significantly longer in the T-B group than the T group (14.4 months vs. 6.1 months, p = .006) and that there was a significant correlation between Bmab and OS. The incidence of hypertension (grade ≥2) as an adverse event was significantly higher in the T-B group than the T group (23.8% vs. 0.0%, p = .005), whereas other adverse events were comparable between the two groups. CONCLUSION: Treatment with Bmab in combination with TAS-102 is significantly associated with improved clinical outcomes in patients with mCRC refractory to standard therapies. IMPLICATIONS FOR PRACTICE: Combining bevacizumab (Bmab) with TAS-102 significantly improved overall survival and several prognostic indicators in patients with metastatic colorectal cancer (mCRC) refractory to standard therapies, with manageable toxicities. Treatment with Bmab in combination with TAS-102 is significantly associated with improved clinical outcomes in patients with mCRC.

8.
World J Surg Oncol ; 17(1): 178, 2019 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-31677643

RESUMO

BACKGROUND: In recent years, laparoscopic surgery has been widely used for rectal cancer. In laparoscopic rectal surgery, a double-stapling technique (DST) anastomosis using a stapling device is considered a relatively difficult procedure. Postoperative anastomotic leakage (AL) is a major complication related to patients' quality of life and prognosis. METHODS: This study was a retrospective, single-institution study of 101 rectal cancer patients who underwent laparoscopic low anterior resection (LAR) with DST anastomosis (excluding simultaneous resection of other organs and construction of protective diverting stoma) between February 2008 and November 2017 at the Gifu University Graduate School of Medicine. This study aimed to identify risk and early predictive factors of AL. RESULTS: Among 101 patients, symptomatic AL occurred in 13 patients (12.9%), of whom 10 were male and 3 were female. Their median BMI was 22.7 kg/m2 (range, 17.9-26.4 kg/m2). Among the pre- and intraoperative factors, AL was significantly associated with tumor location (lower rectum), distance from the anal verge (< 6 cm), intraoperative blood loss (≥ 50 ml), and the number of linear staples (≥ 2) in univariate analysis. In multivariate analysis, only intraoperative blood loss (≥ 50 ml, odds ratio [OR] 4.59; 95% confidence interval [CI] 1.04-19.52; p = 0.045) was identified as an independent risk factor for AL. Among the postoperative factors, AL was significantly associated with tachycardia-POD1 (≥ 100 bpm), CRP-POD3 (≥ 15 mg/dl), fever on postoperative day (fever-POD) 3 (≥ 38 °C), and first defecation day after surgery (< POD3) in univariate analysis. In multivariate analysis, fever-POD3 (≥ 38 °C, OR 30.97; 95% CI 4.68-311.22; p = 0.0003) and first defecation day after surgery (< POD3, OR 5.82; 95% CI 1.34-31.30; p = 0.019) were identified as early predictive factors for AL. CONCLUSION: In this study, intraoperative blood loss was an indicator of difficulty in a transection and anastomosing procedure, and fever-POD3 and early first defecation day after surgery were independent early predictive factors for AL. Careful surgery using an appropriate technique and standardized procedures with minimal bleeding and careful postoperative management paying attention to fever and defecation may prevent the onset and severity of AL.

9.
J Org Chem ; 84(21): 14291-14296, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31591888

RESUMO

The potential of using chiral bicyclic NHC ligands that exhibit modularity was investigated in the Cu-catalyzed asymmetric borylation reaction of α,ß-unsaturated esters. After screening for ligands and optimization of the reaction conditions, the corresponding products were afforded with good enantioselectivities (up to 85% ee).

10.
Dent Mater J ; 38(6): 994-1001, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31511472

RESUMO

We evaluated the influence of the composition and powder/water (P/W) ratio of powder-type denture adhesives (DA) based on sodium carboxymethyl cellulose (CMC-Na) and poly(methyl vinyl ether-maleic anhydride) (PVM-MA) on the strength of adhesion to acrylic resin and initial viscosity. Twenty types of DA were prepared by mixing CMC-Na and PVM-MA at various weight ratios with distilled water in P/W ratios ranging from 0.125 to 0.500. Adhesion strength and viscosity were measured using a universal testing machine and a controlled-stress rheometer, respectively. A higher percentage of CMC-Na and higher P/W ratios resulted in higher adhesion strength and viscosity. The effect of the CMC-Na/PVM-MA weight ratio on adhesion strength and viscosity was larger than that of the P/W ratio. DA with higher viscosity had higher adhesion strength. These results suggest that the adhesion strength and initial viscosity of powder-type DA can be controlled via the P/W ratio and the CMC-Na/PVM-MA weight ratio.


Assuntos
Cimentos Dentários , Água , Adesivos , Dentaduras , Sódio , Viscosidade
11.
Ann Gastroenterol Surg ; 3(5): 544-551, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31549014

RESUMO

Aim: Gastric cancer is the second leading cause of cancer death worldwide. Surgery is the mainstay treatment for gastric cancer. There are no prediction models that examine the severity of postoperative morbidity. Herein, we constructed prediction models that analyze the risk for postoperative morbidity based on severity. Methods: Perioperative data were retrieved from the National Clinical Database in patients who underwent elective gastric cancer resection between 2011 and 2012 in Japan. Severity of postoperative complications was determined by Clavien-Dindo classification. Patients were randomly divided into two groups, the development set and the validation set. Logistic regression analysis was used to build prediction models. Calibration powers of the models were assessed by a calibration plot in which linearity between the observed and predicted event rates in 10 risk bands was assessed by the Pearson R 2 statistic. Results: We obtained 154 278 patients for the analysis. Prediction models were constructed for grade ≥2, grade ≥3, grade ≥4, and grade 5 in the development set (n = 77 423). Calibration plots of these models showed significant linearity in the validation set (n = 76 855): R 2 = 0.995 for grade ≥2, R 2 = 0.997 for grade ≥3, R 2 = 0.998 for grade ≥4, and R 2 = 0.997 for grade 5 (all: P < 0.001). Conclusion: Prediction models for postoperative morbidity based on grade will provide a comprehensive risk of surgery. These models may be useful for informed consent and surgical decision-making.

12.
Mol Clin Oncol ; 11(4): 390-396, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31475067

RESUMO

The combination regimen of TAS-102, a novel oral nucleoside antitumor agent containing trifluridine and tipiracil hydrochloride, with bevacizumab (C-TASK FORCE), a selective monoclonal antibody inhibitor of vascular endothelial growth factor-A, as salvage-line therapy for metastatic colorectal cancer (mCRC) was established based on its high clinical effectiveness. The aim of the present study was to evaluate the prognostic accuracy of the modified Glasgow Prognostic Score (mGPS) in patients receiving TAS-102 plus bevacizumab. The study included 17 patients (12 men and 5 women, mean age 60.4±13.4 years) with unresectable mCRC who were confirmed to have wild-type or mutant RAS genes. The patients received salvage-line treatment with TAS-102 plus bevacizumab at the Surgical Oncology Department of Gifu University School of Medicine between March 2016 and August 2018. The study population was heavily pretreated; the majority of the patients (71%) had received ≥4 prior regimens and, in addition to fluoropyrimidine, irinotecan and oxaliplatin, all had received bevacizumab (100%) and either cetuximab or panitumumab (47%). The RAS status was wild-type in 9 (53%) and mutant in 8 (47%) patients. The primary tumor locations included the right-sided colon in 5 patients (29%; cecum in 2 and transverse colon in 3 cases) and left-sided colorectum in 12 patients [71%; sigmoid colon in 4, rectosigmoid (Rs) in 4, and rectum above/below the peritoneal reflection (Ra/b) in 4 cases]. Metastatic sites included the liver in 15 (88%), lung in 13 (76%), lymph nodes in 7 (41%), and peritoneal dissemination in 5 (24%) patients. The number of metastatic sites was 1 in 3 (18%) and >2 in 14 (82%) patients. Their first staging imaging scans (after 2 cycles of therapy) were available for review in all 17 patients. At first evaluation, 5 (29%) patients had progressive disease (PD), 12 (71%) had stable disease, and none had a partial response to TAS-102 plus bevacizumab. The median overall survival (OS) of 14.1 months and progression-free survival (PFS) of 6.8 months were comparable to the 11.2 and 5.6 months, respectively, in the C-TASK FORCE study. Upon considering three groups, namely mGPS 0, mGPS 1 and mGPS 2, the median PFS times were significantly different (mGPS 0 vs. mGPS 2, P=0.02; and mGPS 1 vs. mGPS 2, P=0.06). The median PFS times in the mGPS 0, 1 and 2 groups were 12.1, 4.8 and 2.3 months, respectively. Median OS was also significantly different (mGPS 0 vs. mGPS 2, P=0.01; and mGPS 1 vs. mGPS 2, P=0.04). The median OS times in the mGPS 0, 1 and 2 groups were 14.0, not reached, and 2 months, respectively. The present study demonstrated the efficacy and safety of the TAS-102 plus bevacizumab combination as salvage-line treatment. This combination therapy (the TAS-102 plus bevacizumab) has obtained valid results with PFS OS as well as C-TASK.FORCE study. The results of the present study also confirmed the prognostic accuracy of mGPS in salvage-line treatment of patients with mCRC.

13.
J Prosthodont Res ; 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31501069

RESUMO

PURPOSE: The purpose of this study was to investigate the effect of denture adhesives on oral moisture in a 10-center parallel randomized clinical trial. METHODS: Two hundred edentulous subjects wearing complete dentures were allocated into three groups: cream-type adhesive, powder-type adhesive and control groups. The adhesives (and saline solution in the control group) were applied to the mucosal surface of the dentures for 4 days, and baseline data and data after the intervention for eight meals over 4 days were obtained. For the main outcome, oral moisture was measured with a moisture checking device. Secondary outcomes were denture satisfaction, masticatory performance, denture retention, and occlusal force. In addition to between-group and within-group comparisons of oral moisture, investigations for secondary outcomes were undertaken in subgroups classified according to the degree of oral moisture at baseline (normal subgroup and dry mouth subgroup). Intention-to-treat analysis was also performed. RESULTS: Between-group and within-group comparisons of oral moisture showed no significant differences. The cream-type and powder-type denture adhesives were significantly effective in the dry mouth group for denture satisfaction ratings of ability to masticate, stability, retention, and comfort of mandibular dentures (p<0.05). The masticatory performance and retentive force of the dry mouth denture adhesive using groups were significantly improved after intervention (p<0.05). CONCLUSIONS: The oral moisture of complete denture wearers was not influenced by the use of denture adhesives. Our findings showed that denture adhesives improved subjective denture satisfaction, masticatory performance, and retention for complete denture patients with oral dryness.

14.
Ann Surg ; 2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31404008

RESUMO

MINI: A prospective nationwide multicenter study revealed that total gastrectomy and para-aortic nodal dissection were not needed for esophagogastric junction tumors. Subtotal esophagectomy with dissection of upper mediastinal station 106recR should be selected if esophageal involvement exceeds 4.0 cm. Lower mediastinal station 110 should be dissected if esophageal involvement exceeds 2.0 cm. OBJECTIVE: The aim of the study was to determine the optimal extent of lymph node dissection for the 2 histological types of esophagogastric junction (EGJ) tumors based on the incidence of metastasis in a prospective nationwide multicenter study. BACKGROUND: Because most previous studies were retrospective, the optimal surgical procedure for EGJ tumors has not been standardized. METHODS: Patients with cT2-T4 adenocarcinoma or squamous cell carcinoma located within 2.0 cm of the EGJ were enrolled before surgery. Surgeons dissected all lymph nodes prespecified in the protocol, using either the abdominal transhiatal or right transthoracic approach. The primary endpoint was the metastasis rate of each lymph node. Lymph nodes were classified according to metastasis rate, as follows: category-1 (strongly recommended for dissection), rate more than 10%; category-2 (weakly recommended for dissection), rate from 5% to 10%; and category-3 (not recommended for dissection), rate less than 5%. RESULTS: Between 2014 and 2017, 1065 patients with EGJ tumor were screened, and 371 were enrolled. Among 358 patients who underwent surgical resection, category-1 nodes included abdominal stations 1, 2, 3, 7, 9, and 11p, whereas category-2 nodes included abdominal stations 8a, 19, and lower mediastinal station 110. If esophageal involvement exceeded 2.0 cm, station 110 was assigned to category-1. Among 98 patients who had either adenocarcinoma with esophageal involvement over 3.0 cm or squamous cell carcinoma, there were no category-1 nodes in the upper/middle mediastinal field, whereas category-2 nodes included upper mediastinal station 106recR and middle mediastinal station 108. When esophageal involvement exceeded 4.0 cm, station 106recR was assigned to category-1. CONCLUSION: The study accurately identified the distribution of lymph node metastases from EGJ tumors and the optimal extent of subsequent lymph node dissection.

15.
J Clin Med ; 8(9)2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31443371

RESUMO

Cancer cells can survive and grow via angiogenesis. An alternative but controversial theory is cancer cells may grow via vasculogenic mimicry (VM), in which the cancer cells themselves construct vessel-like channels that are considered a leading cause of drug resistance. The dynamic functions of the glycocalyx (GCX), a meshwork composed of proteoglycans and glycoproteins that surrounds cell membranes, have been observed in endothelial cells within tumors. However, the actual structural shape formed by the GCX in human patients remains unclear. Here, we visualized the three-dimensional (3D) network structure constructed by bulky GCX in human colorectal cancer (CRC) patients using scanning electron microscopy with lanthanum nitrate staining. The network structure extended throughout the cancer cell nest, opening into capillaries, with a tunnel channel that exhibited a net- and spongy-like ultrastructure. The expression of endothelial and cancer-specific GCX-binding lectins was dramatically increased in the interstitial spaces between cancer cells. Even accounting for the presence of artifacts resulting from sample preparation methods, the intercellular tunnels appeared to be coated with the bulky GCX. Further, this 3D network structure was also observed in the tumors of ApcMin/+ mice. In conclusion, the bulky GCX modifies the network structure of CRCs in human and mice.

16.
JAMA Netw Open ; 2(8): e198243, 2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31373648

RESUMO

Importance: Ramucirumab, a human IgG 1 antibody against vascular endothelial growth factor receptor 2, has been shown to improve progression-free survival and overall survival in patients with advanced gastric cancer in the second-line setting. Objective: To compare progression-free survival for S-1 and oxaliplatin plus ramucirumab with that for S-1 and oxaliplatin plus placebo in patients with advanced gastric cancer. Design, Setting, and Participants: This phase 2, double-blind randomized clinical trial (RAINSTORM [First-line S-1 Plus Oxaliplatin With or Without Ramucirumab Followed by Paclitaxel Plus Ramucirumab in Patients With Advanced Gastric Cancer]) was conducted from October 12, 2015, to April 11, 2018, at 36 sites in Japan, South Korea, and Taiwan. Participants were chemotherapy-naive patients (n = 189) with metastatic gastric or gastroesophageal adenocarcinoma. Analyses of the full analysis set and safety population were conducted between November 27, 2017, and June 4, 2018. Interventions: Patients randomized to the ramucirumab plus S-1 and oxaliplatin arm received S-1, 80 to 120 mg/d twice daily, on days 1 to 14 and oxaliplatin, 100 mg/m2, on day 1 with ramucirumab, 8 mg/kg, on days 1 and 8 in part A (21-day cycle). Patients randomized to the placebo plus S-1 and oxaliplatin arm received the same S-1 and oxaliplatin dosage as well as placebo on days 1 and 8 in part A. Eligible patients received second-line paclitaxel, 80 mg/m2, on days 1, 8, and 15 and ramucirumab, 8 mg/kg, on days 1 and 15 in part B (28-day cycle). Main Outcomes and Measures: The primary end point was progression-free survival, analyzed using the stratified log-rank test; the hazard ratio (HR) was estimated using the stratified Cox proportional hazards regression model. Secondary end points included overall survival and adverse events. Results: In total, 189 patients were randomized and received treatment: 96 to the ramucirumab plus S-1 and oxaliplatin arm and 93 to the placebo plus S-1 and oxaliplatin arm. Among the 189 patients, 121 (64.0%) were male, and the median (range) age was 62.0 (26-84) years. Median progression-free survival was not prolonged in the ramucirumab plus S-1 and oxaliplatin arm compared with the placebo plus S-1 and oxaliplatin arm (6.34 [80% CI, 5.65-6.93] vs 6.74 [80% CI, 5.75-7.13] months; HR, 1.07; 80% CI, 0.86-1.33; P = .70). Median overall survival was 14.65 (80% CI, 12.39-15.67) months in the ramucirumab plus S-1 and oxaliplatin arm and 14.26 (80% CI, 13.83-17.31) months in the placebo plus S-1 and oxaliplatin arm (HR, 1.11; 80% CI, 0.89-1.40; P = .55). The most commonly reported grade 3 or higher treatment-emergent adverse events in the ramucirumab plus S-1 and oxaliplatin arm in part A were decreased neutrophil count (14 patients [14.6%]), hypertension (10 patients [10.4%]), and anemia (10 patients [10.4%]). Conclusions and Relevance: In this randomized clinical trial, the addition of ramucirumab to first-line S-1 and oxaliplatin treatment did not prolong progression-free survival or overall survival compared with S-1 and oxaliplatin alone among East Asian patients with advanced gastric cancer; no new safety signals for ramucirumab were identified. Trial Registration: ClinicalTrials.gov identifier: NCT02539225.

17.
Anticancer Res ; 39(8): 4441-4448, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366542

RESUMO

BACKGROUND/AIM: Oral mucositis (OM) is one of the frequent adverse events experienced by patients receiving chemotherapy. Most diagnoses of OM are based on complaints from patients. The aim of this study was to develop a tool to diagnose OM accurately. MATERIALS AND METHODS: A central review system (CRS) was created to allow judgment when the patient background is completely unknown. The primary endpoint was the rate of grade 2 or higher OM, and the secondary endpoint was the difference in grade between each institution's clinician judgement and that of the CRS. RESULTS: In total, 53 patients were registered from four institutions. CRS successfully detected grade 2 or higher OM in 16 (30.2%) of the 53 patients. The detection rate of all grades of OM was 41.5% (22 of 53 patients) by each institution's clinician judgement and 84.9% (45 of 53 patients) by CRS judgement (p<0.0001). CONCLUSION: OM during chemotherapy may be underestimated.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/epidemiologia , Estomatite/epidemiologia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Estudos de Coortes , Neoplasias Esofágicas/complicações , Neoplasias Esofágicas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Estomatite/induzido quimicamente , Estomatite/patologia
18.
Int J Surg Case Rep ; 61: 169-173, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31376737

RESUMO

BACKGROUND: The principle treatment for retroperitoneal liposarcoma is surgical resection, however there are many cases of recurrence. In addition to local recurrence, retroperitoneal liposarcoma, particularly dedifferentiated liposarcoma is known to occasionally cause lung metastases. CASE REPORT: A 72-year-old woman with a diagnosis of retroperitoneal liposarcoma and probable right upper lobe early pulmonary adenocarcinoma underwent sequential local tumor resection and right upper lobectomy. Twenty months after liposarcoma resection, a computed tomography (CT) scan of the chest revealed a nodule located in the left lower lobe. A CT-guided biopsy was performed and she was subsequently diagnosed with pulmonary metastasis from retroperitoneal liposarcoma. The nodule enlarged chronologically, however a left lower lobectomy could not be performed because respiratory function after the right upper lobectomy was not sufficient. Therefore, in order to preserve the left superior segment (S6), the basal segments (S8+S9+S10) were resected. Seven months after the surgery, she is living a self-reliant life without recurrence of liposarcoma. CONCLUSION: Here we have reported a case of pulmonary metastasis from retroperitoneal liposarcoma following limited surgery. In cases where respiratory function is limited, lower lobe segmentectomy can be an effective treatment. For the treatment of a single pulmonary metastasis from retroperitoneal liposarcoma, metastasectomy was considered to be effective as long as no local recurrence was seen after initial primary tumor resection.

19.
Ann Gastroenterol Surg ; 3(4): 426-450, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31346582

RESUMO

Background: The Japanese National Clinical Database (NCD) is a large-scale, nationwide, web-based data entry system that is linked to the surgical board certification system and covers almost all surgical cases carried out in Japan. Aim: To evaluate outcomes according to the gastroenterological section of the NCD. Methods: The 115 surgical procedures stipulated by the "Training Curriculum for Board-Certified Surgeons in Gastroenterology" were registered from 2011 to 2017. The number of surgeries, preoperative comorbidities, and short-term outcomes were compared between registration periods. Results: In total, 3 818 414 cases have been registered. More than 70% of all surgeries were carried out at certified institutions. The annual number of cases has been increasing year after year, and the aged population has also been increasing. Although the rates of preoperative comorbidities and postoperative complications have been increasing, the postoperative mortality rate has remained relatively low; in 2017, the 30-day mortality rate was 1.0% among those who underwent esophagectomy, 0.7% among those who underwent distal gastrectomy, 1.1% among those who underwent total gastrectomy, 1.3% among those who underwent right hemicolectomy, 0.5% among those who underwent low anterior resection, 1.3% among those who underwent hepatectomy, and 1.3% among those who underwent pancreaticoduodenectomy. The annual rate of endoscopic surgery dramatically increased over 7 years between 2011 and 2017, especially for low anterior resection (29.5%-62.6%) and esophagectomy (31.0%-56.1%). Conclusion: This database is expected to ensure the quality of the board-certification system and surgical outcomes in gastroenterological surgery.

20.
Clin Trials ; 16(5): 512-522, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31331195

RESUMO

BACKGROUND/AIMS: A risk-based approach to clinical research may include a central statistical assessment of data quality. We investigated the operating characteristics of unsupervised statistical monitoring aimed at detecting atypical data in multicenter experiments. The approach is premised on the assumption that, save for random fluctuations and natural variations, data coming from all centers should be comparable and statistically consistent. Unsupervised statistical monitoring consists of performing as many statistical tests as possible on all trial data, in order to detect centers whose data are inconsistent with data from other centers. METHODS: We conducted simulations using data from a large multicenter trial conducted in Japan for patients with advanced gastric cancer. The actual trial data were contaminated in computer simulations for varying percentages of centers, percentages of patients modified within each center and numbers and types of modified variables. The unsupervised statistical monitoring software was run by a blinded team on the contaminated data sets, with the purpose of detecting the centers with contaminated data. The operating characteristics (sensitivity, specificity and Youden's J-index) were calculated for three detection methods: one using the p-values of individual statistical tests after adjustment for multiplicity, one using a summary of all p-values for a given center, called the Data Inconsistency Score, and one using both of these methods. RESULTS: The operating characteristics of the three methods were satisfactory in situations of data contamination likely to occur in practice, specifically when a single or a few centers were contaminated. As expected, the sensitivity increased for increasing proportions of patients and increasing numbers of variables contaminated. The three methods showed a specificity better than 93% in all scenarios of contamination. The method based on the Data Inconsistency Score and individual p-values adjusted for multiplicity generally had slightly higher sensitivity at the expense of a slightly lower specificity. CONCLUSIONS: The use of brute force (a computer-intensive approach that generates large numbers of statistical tests) is an effective way to check data quality in multicenter clinical trials. It can provide a cost-effective complement to other data-management and monitoring techniques.

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