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1.
Artigo em Inglês | MEDLINE | ID: mdl-34791304

RESUMO

BACKGROUND: Previous studies showed that although the risk of thyroid dysfunction (thyroid immune-related adverse events [irAEs]) induced by anti-programmed cell death-1 antibodies (PD-1-Ab) was as low as 2-7% in patients negative for anti-thyroid-antibodies (ATAs) at baseline, it was much higher (30-50%) in patients positive for ATAs. However, whether a similar increase occurs with combination therapy using PD-1-Ab plus anti-cytotoxic T-lymphocyte antigen-4 antibody (CTLA-4-Ab) is unknown. METHODS: A total of 451 patients with malignancies treated with PD-1-Ab, CTLA-4-Ab, or a combination of PD-1-Ab plus CTLA-4-Ab (PD-1/CTLA-4-Abs) were evaluated for ATAs at baseline and for thyroid function every 6 weeks for 24 weeks after treatment initiation, and then observed until the last clinical visit. RESULTS: Of the 451 patients, 51 developed thyroid-irAEs after immunotherapy [41 of 416 (9.9%) treated with PD-1-Ab, 0 of 8 (0%) with CTLA-4-Ab, and 10 of 27 (37.0%) with PD-1/CTLA-4-Abs]. The cumulative incidence of thyroid-irAEs was significantly higher in patients who were positive versus negative for ATAs at baseline after both PD-1-Ab [28/87 (32.2%) vs. 13/329 (4.0%), p < 0.001] and PD-1/CTLA-4-Abs [6/10 (60.0%) vs. 4/17 (23.5%), p < 0.05] treatments. The risk of thyroid-irAEs induced by PD-1/CTLA-4Abs, which was significantly higher than that induced by PD-1-Ab, in patients negative for ATAs at baseline was not statistically different from that induced by PD-1-Ab in patients positive for ATAs at baseline. CONCLUSIONS: This study showed that the incidence of thyroid-irAEs was high and not negligible after PD-1/CTLA-4-Abs treatment even in patients negative for ATAs at baseline.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34776358

RESUMO

Chemoradiotherapy (CRT) followed by radical surgery is one of the standard therapies for patients with locally advanced rectal cancer (LARC). Various combination therapies have been developed to improve the efficacy of preoperative therapies. One promising approach is the combination of ionizing radiation and immune checkpoint inhibitors (ICIs) because it enhances both local and distal immunogenic efficacy according to several xenograft models. To date, promising short-term efficacy results of 23% to 37.5% of the pathological complete response (pCR) rate have been reported in clinical trials investigating the combination of CRT and ICIs in patients with microsatellite stable (MSS) LARC. In patients with high-level microsatellite instability (MSI-H) LARC, CRT followed by ICI also achieved a 60% (3/5) pCR rate according to the data of the VOLTAGE study, suggesting increased efficacy of ICIs in this subgroup, albeit with a small sample size. In patients with MSS LARC, programmed cell death-ligand 1 tumor proportion score positivity, elevated CD8/effector regulatory T cell ratio, higher immune-score, consensus molecular subtype 1, and higher tumor mutational burden appear to be positive predictors of ICIs efficacy. In addition, various prospective studies combining CRT with ICI, chemotherapy, and target agents are currently being conducted. To confirm the survival benefits of these approaches, confirmatory phase III trials are needed.

3.
Ann Gastroenterol Surg ; 5(6): 804-812, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34755012

RESUMO

Background: Previously, we conducted a randomized controlled trial (JCOG0404) for stage II/III colon cancer patients and reported that the long-term survival after open surgery (OP) and laparoscopic surgery (LAP) were almost identical; however, JCOG0404 suggested that survival of patients after LAP with tumors located in the rectosigmoid colon, cT4 or cN2 tumors, and high body mass index (BMI) might be unfavorable. Aim: To identify the patient subgroups associated with poor long-term survival in the LAP arm compared with the OP arm. Methods: Patients aged 20-75, clinical T3 or deeper lesion without involvement of other organs, clinical N0-2 and M0 were included. The patients with pathological stage IV and R2 resection were excluded from the current analysis. In each subgroup, the hazard ratio for LAP (vs. OP) in overall survival (OS) from surgery was estimated using a multivariable Cox regression model adjusted for the clinical and pathological factors. Results: In total, 1025 patients (OP, 511 and LAP, 514) were included in the current analysis. Adjusted hazards ratios for OS of patients with high BMI (>25 kg/m2), pT4, and pN2 in LAP were 3.37 (95% confidence interval [CI], 1.24-9.19), 1.33 (0.73-2.41), and 1.74 (0.76-3.97), respectively. In contrast, that of rectosigmoid colon tumors was 0.98 (0.46-2.09). Conclusions: Although LAP is an acceptable optional treatment for stage II/III colon cancer, the present subgroup analysis suggests that high BMI (>25 kg/m2), pT4, and pN2 except for RS were factors associated with unfavorable long-term outcomes of LAP in patients with colon cancer who underwent curative resection. (JCOG 0404: NCT00147134/UMIN-CTR: C000000105.).

4.
Ann Gastroenterol Surg ; 5(6): 823-831, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34755014

RESUMO

Background: Institutional variation in outcomes is a key factor to ascertain the generalizability of results and reliability of the clinical trial. This study evaluated institutional variation in survival and postoperative complications using data from JCOG0404 comparing laparoscopic colectomy (LAP) with open colectomy (OP). Methods: Institutions with fewer than 10 registered patients were excluded from this analysis. Institutional variation was evaluated in terms of early postoperative complications, overall survival, and relapse-free survival and estimated using a mixed-effect model with institution as a random effect after adjusting for background factors. Results: This analysis included 1028 patients in the safety analysis and 1040 patients in the efficacy analysis from 26 institutions. In the safety analysis, there was no variation in grades 3-4 early postoperative complications (in OP, median 6.3% [range 6.3%-6.3%]; in LAP, median 2.6% [range 2.6%-2.6%]), but some variation in grades 1-4 early postoperative complications was observed (in OP, median 20.8% [range 13.2%-31.8%]; in LAP, median 11.9% [range 7.2%-28.7%]), and that in grades 2-4 was observed only in LAP (median 8.8% [range 4.7%-24.0%]; in OP, median 12.7% [range 12.7%-12.7%]). Two specific institutions showed especially high incidences of postoperative complications in LAP. In the efficacy analysis, there was no institutional variation in OP, although a certain variation was observed in LAP. Conclusions: Some institutional variations in safety and efficacy were observed, although only in LAP. We conclude that a qualification system, including training and education, is needed when new surgical techniques such as laparoscopic surgery are introduced in clinical practice.

6.
Int J Clin Oncol ; 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34632560

RESUMO

BACKGROUND: RalA is a member of the Ras superfamily of small GTPases. The Anti-RalA autoantibodies (s-RalA-Abs) act as tumor markers in various types of cancer and are negatively associated with the p53 autoantibodies (s-p53-Abs). This study aimed to evaluate the relationship between s-RalA-Abs and s-p53-Abs in various types of cancer. METHODS: A total of 1833 cancer patients (esophageal cancer, 172; hepatocellular carcinoma, 91; lung cancer, 269; gastric cancer, 317; colon cancer, 262; breast cancer, 364; and prostate cancer, 358) and 73 healthy subjects were enrolled in the study. The levels of s-RalA-Abs and s-p53-Abs were analyzed using enzyme-linked immunosorbent assay, and the positivity rates and relations between the two autoantibodies were evaluated. The cutoff values for s-RalA abs and s-p53 abs were set as mean + 2 standard deviation and the values higher than the cutoff values were defined as positive. RESULTS: The titers in all cancer types were significantly higher than those in the controls (P < 0.01). The positivity rates for s-RalA-Abs ranged between 11.7 and 21.5%, and those for s-p53-Abs ranged between 12 and 28.5%. A combined assay of the two antibodies revealed positivity rates of 20.9 and 44.2%. In Stage 0/I/II tumors, the positivity rates of the combination of the two antibodies ranged between 21.5 and 42.3%. The two autoantibodies were complementary to each other in the prostate and breast cancers, but independent in other carcinomas. CONCLUSION: The combined use of s-RalA-Abs and s-p53-Abs tended to increase the positivity rate in all cancers, including Stage 0/I/II cancers.

7.
Mol Clin Oncol ; 15(5): 237, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34650804

RESUMO

Solid cancers have a poor prognosis, and their morbidity and mortality after surgery is high. Even after radical surgery for esophageal cancer, there have been cases of early postoperative death. The present study therefore aimed to explore new tumor markers that can predict the early postoperative prognosis. To identify antibody markers, serological antigens were identified using recombinant cDNA expression cloning (SEREX). The results identified striatin 4 (STRN4) as the antigen recognized by serum IgG antibodies in patients with esophageal cancer. After performing an amplified luminescence proximity homogeneous assay-linked immunosorbent assay (AlphaLISA), it was revealed that when compared with healthy donors, serum anti-STRN4 antibody (STRN4-Ab) levels were significantly higher not only in patients with esophageal cancer but also to lesser extent, in those with gastric cancer, colorectal cancer, lung cancer and breast cancer. Compared with STRN4-Ab-negative patients with esophageal cancer, STRN4-Ab-positive patients had a poorer postoperative prognosis at early stages, suggesting that STRN4-Abs may be useful for predicting poor early-stage prognoses of patients with esophageal cancer. The positive diagnosis rates of esophageal cancer using the STRN4-Ab marker and conventional markers, including squamous cell carcinoma antigen and p53 antibody alone, were 26.4, 35.2 and 19.1% respectively; a result that increased up to 59.1% by combining all three markers. Serum STRN4-Ab may serve as a novel marker of esophageal cancer.

8.
Dis Colon Rectum ; 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34657080

RESUMO

BACKGROUND: The International Transanal Total Mesorectal Excision Registry group showed that transanal total mesorectal excision included clinical issues regarding anastomosis-related complications. OBJECTIVE: This study evaluated anastomotic complications in patients whose anastomoses were created with the stapler plus reinforced sutures procedure following transanal total mesorectal excision for low rectal cancer. DESIGN: A retrospective single-center study. SETTING: The National Cancer Center Hospital East, Japan. PATIENTS: Between June 2016 and December 2019, 150 patients underwent transanal total mesorectal excision for low rectal cancer. Stapled anastomosis was performed for 55 and coloanal handsewn anastomosis was performed for 95 patients. Blood perfusion of the colon was routinely evaluated with intraoperative indocyanine green fluorescence angiography. All patients who underwent stapled anastomosis received additional handsewn sutures on all rounds of the stapled line. Patients who underwent intersphincteric resection were excluded. MAIN OUTCOME MEASURES: The anastomosis-related complications were compared between the groups. RESULTS: Early anastomotic leakage was found in 1 (1.8%) and 8 (8.4%) patients in the stapled group and handsewn group, respectively. Overall anastomosis-related complications, pelvic abscess, and anastomotic stenosis were significantly less frequent in the stapled group (p<0.001, p<0.048, p<0.032, respectively). Incomplete donuts following the stapled anastomosis were observed in 9 patients (16.4%); however, we reinforced all around the stapled line in these patients, and this reduced the subsequent occurrence of anastomotic leakage. LIMITATIONS: First, this was a retrospective single-center study that was not randomized or controlled. Second, there were chronological differences regarding the anastomotic method between the two groups. Third, our study included a relatively small number of patients who received preoperative chemoradiotherapy. CONCLUSIONS: Stapled anastomosis with reinforced handsewn sutures resulted in fewer anastomosis-related complications than did coloanal handsewn anastomosis following transanal total mesorectal excision for low rectal cancer; thus, the former may be superior and should be the preferred method, when technically possible. See Video Abstract at http://links.lww.com/DCR/B749.

9.
Hypertens Res ; 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34616031

RESUMO

The regulation of muscle contraction is a critical function in the cardiovascular system, and abnormalities may be life-threatening or cause illness. The common basic mechanism in muscle contraction is the interaction between the protein filaments myosin and actin. Although this interaction is primarily regulated by intracellular Ca2+, the primary targets and intracellular signaling pathways differ in vascular smooth muscle and cardiac muscle. Phosphorylation of the myosin regulatory light chain (RLC) is a primary molecular switch for smooth muscle contraction. The equilibrium between phosphorylated and unphosphorylated RLC is dynamically achieved through two enzymes, myosin light chain kinase, a Ca2+-dependent enzyme, and myosin phosphatase, which modifies the Ca2+ sensitivity of contractions. In cardiac muscle, the primary target protein for Ca2+ is troponin C on thin filaments; however, RLC phosphorylation also plays a modulatory role in contraction. This review summarizes recent advances in our understanding of the regulation, physiological function, and pathophysiological involvement of RLC phosphorylation in smooth and cardiac muscles.

10.
Sci Rep ; 11(1): 20556, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34654837

RESUMO

Crb2 is a cell polarity-related type I transmembrane protein expressed in the apical membrane of podocytes. Knockdown of crb2 causes glomerular permeability defects in zebrafish, and its complete knockout causes embryonic lethality in mice. There are also reports of Crb2 mutations in patients with steroid-resistant nephrotic syndrome, although the precise mechanism is unclear. The present study demonstrated that podocyte-specific Crb2 knockout mice develop massive albuminuria and microhematuria 2-month after birth and focal segmental glomerulosclerosis and tubulointerstitial fibrosis with hemosiderin-laden macrophages at 6-month of age. Transmission and scanning electron microscopic studies demonstrated injury and foot process effacement of podocytes in 6-month aged podocyte-specific Crb2 knockout mice. The number of glomerular Wt1-positive cells and the expressions of Nphs2, Podxl, and Nphs1 were reduced in podocyte-specific Crb2 knockout mice compared to negative control mice. Human podocytes lacking CRB2 had significantly decreased F-actin positive area and were more susceptible to apoptosis than their wild-type counterparts. Overall, this study's results suggest that the specific deprivation of Crb2 in podocytes induces altered actin cytoskeleton reorganization associated with dysfunction and accelerated apoptosis of podocytes that ultimately cause focal segmental glomerulosclerosis.

11.
Dis Colon Rectum ; 64(12): 1479-1487, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34657076

RESUMO

BACKGROUND: Identifying preoperative risk factors of local recurrence and patterns of treatment failure resulting after rectal cancer management is important for planning treatment strategies and improving the results of multidisciplinary care. OBJECTIVE: The purpose of this study was to analyze the associations between the preoperative factors and local recurrence and to investigate the local recurrence areas in patients with locally advanced lower rectal cancer who underwent lateral pelvic lymph node dissection. DESIGN: The study used a retrospective cohort design. SETTINGS: It was conducted at a single institution. PATIENTS: Overall 469 patients with locally advanced lower rectal adenocarcinoma located below the peritoneal reflex who received curative resection with lateral pelvic lymph node dissection during 2010 to 2018 were included. MAIN OUTCOME MEASURES: Independent risk factors for local recurrence were assessed using multivariate Cox regression. Local recurrence was classified into 3 areas using follow-up images. RESULTS: A total of 286 patients underwent upfront surgery, 132 patients received neoadjuvant chemotherapy followed by surgery, and 51 patients received preoperative chemoradiotherapy followed by surgery. Eighty-six patients (18.3%) were extramural venous invasion positive, and 113 patients (24.1%) were circumferential resection margin positive. The median follow-up period was 46 months. Local recurrence showed significant association with extramural venous invasion positive (HR = 2.596 (95% CI, 1.321-5.102); p = 0.006) or circumferential resection margin positive (HR = 2.298 (95% CI, 1.158-4.560); p = 0.017). The incidence of local recurrence was observed in 51 patients (10.8%), with the pelvic plexus and internal iliac area being the most frequent (6.6%), followed by the central pelvis area (3.8%), and was markedly low in the obturator area (0.4%). LIMITATIONS: This was a retrospective, single-institution design. CONCLUSIONS: Extramural venous invasion status and circumferential resection margin status were associated with a high local recurrence rate in patients who underwent lateral pelvic lymph node dissection. In addition, local recurrence in the obturator area was low compared with that in other areas. See Video Abstract at http://links.lww.com/DCR/B683. FACTORES RADIOLGICOS Y REAS DE RECURRENCIA LOCAL EN EL CNCER DE RECTO INFERIOR LOCALMENTE AVANZADO DESPUS DE LA DISECCIN GANGLIONAR PLVICA LATERAL: ANTECEDENTES:El identificar los factores de riesgo preoperatorios para recurrencia local y los patrones de fracaso del tratamiento que resultan del manejo del cáncer de recto es importante para planificar las estrategias de tratamiento y mejorar los resultados de la atención multidisciplinaria.OBJETIVO:Analizar las asociaciones entre los factores preoperatorios y la recidiva local, e investigar las áreas de recidiva local en pacientes con cáncer de recto inferior localmente avanzado que se sometieron a disección de ganglios linfáticos pélvicos laterales.DISEÑO:Un diseño de cohorte retrospectivo.ENTORNO CLÍNICO:Una sola institución.PACIENTES:Un total de 469 pacientes con adenocarcinoma rectal inferior localmente avanzado ubicado debajo del reflejo peritoneal que recibieron resección curativa con disección de ganglios linfáticos pélvicos laterales durante 2010-2018.PRINCIPALES MEDIDAS DE RESULTADO:Los factores de riesgo independientes de recurrencia local se evaluaron mediante regresión de Cox multivariante. La recurrencia local se clasificó en 3 áreas utilizando imágenes de seguimiento.RESULTADOS:Doscientos ochenta y seis pacientes se sometieron a cirugía inicial, 132 pacientes recibieron quimioterapia neoadyuvante seguida de cirugía y 51 pacientes recibieron quimiorradioterapia preoperatoria seguida de cirugía. Ochenta y seis pacientes (18,3%) fueron positivos para invasión venosa extramural y 113 pacientes (24,1%) fueron positivos para el margen de resección circunferencial. La mediana del período de seguimiento fue de 46 meses. La recidiva local mostró una asociación significativa con la invasión venosa extramural positiva (cociente de riesgo: 2,596; intervalo de confianza del 95%: 1,321-5,102; p = 0,006) o el margen de resección circunferencial positivo (cociente de riesgo: 2,298; intervalo de confianza del 95%: 1,158-4,560; p = 0,017). La incidencia de recidiva local se observó en 51 pacientes (10,8%), siendo el plexo pélvico y el área ilíaca interna los más frecuentes (6,6%), seguidos del área pélvica central (3,8%), y fue marcadamente baja en el área del obtudador (0.4%).LIMITACIONES:Un diseño retrospectivo de una sola institución.CONCLUSIONES:El estado de invasión venosa extramural o el estado del margen de resección circunferencial se asociaron con una alta tasa de recurrencia local en pacientes que se sometieron a disección de ganglios linfáticos pélvicos laterales. Además, la recurrencia local en el área del obturador fue baja en comparación con la de otras áreas. Consulte Video Resumen en http://links.lww.com/DCR/B683.

12.
Sci Rep ; 11(1): 18995, 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34556757

RESUMO

Catheter ablation is an important non-pharmacological intervention for atrial fibrillation (AF), but its effect on the incidence of asymptomatic cerebral emboli and long-term effects on cognitive function remain unknown. We prospectively enrolled 101 patients who underwent AF ablation. Brain magnetic resonance imaging (MRI) (72 patients) and neuropsychological assessments (66 patients) were performed 1-3 days (baseline) and 6 months after ablation. Immediately after ablation, diffusion-weighted MRI and 3-dimensional double inversion recovery (3D-DIR) detected embolic microinfarctions in 63 patients (87.5%) and 62 patients (86.1%), respectively. After 6 months, DIR lesions disappeared in 41 patients. Microbleeds (MBs) increased by 17%, and 65% of the de novo MBs were exactly at the same location as the microinfarctions. Average Mini-Mental State Examination scores improved from 27.9 ± 2.4 to 28.5 ± 1.7 (p = 0.037), and detailed neuropsychological assessment scores showed improvement in memory, constructional, and frontal lobe functions. Ejection fraction, left atrial volume index and brain natriuretic peptide level improved from baseline to 3-6 months after ablation. Despite incidental microemboli, cognitive function was preserved 6 months after ablation.

13.
Front Oncol ; 11: 708039, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34504788

RESUMO

Background: Esophageal cancer often appears as postoperative metastasis or recurrence after radical surgery. Although we had previously reported that serum programmed cell death ligand 1 (PD-L1) level correlated with the prognosis of esophageal cancer, further novel biomarkers are required for more precise prediction of the prognosis. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is associated with the cholesterol metabolism. But there was no report of relationship between serum PCSK9 antibody and cancer. Therefore, we investigated whether anti-PCSK9 antibodies could be a novel biomarker for solid cancer. Methods: Serum levels of anti-PCSK9 antibodies and antigens in patients with solid cancer were analyzed using amplified luminescence proximity homogeneous assay-linked immunosorbent assay (AlphaLISA). The reactivity of serum antibodies against recombinant PCSK9 protein was investigated by Western blotting, and the expression of PCSK9 antigens in esophageal cancer tissues was examined by immunohistochemical staining. Results: AlphaLISA showed that serum anti-PCSK9 antibody (s-PCSK9-Ab) levels were significantly higher in patients with esophageal cancer, gastric cancer, colorectal cancer, lung cancer, and breast cancer than in healthy donors, and patients with esophageal cancer had the highest levels. The presence of serum antibody in patients was confirmed by Western blotting. There was no apparent correlation between s-PCSK9-Ab and PCSK9 antigen levels. Immunohistochemical staining demonstrated the expression of PCSK9 antigen in both the cytoplasm and nuclear compartments of esophageal squamous cell carcinoma tissue but not in normal tissue. Compared with patients with low s-PCSK9-Ab levels, those with high s-PCSK9-Ab levels had a favorable postoperative prognosis after radical surgery for esophageal cancer. In the multivariate analysis, tumor depth and s-PCSK9-Ab level were identified as independent prognostic factors. In the univariate analysis of clinicopathological features, high PCSK9 antibody levels were not associated with sex, age, location, tumor depth, lymph node status, squamous cell carcinoma antigen, or p53-Ab, whereas they correlated significantly with PD-L1 levels, which were associated with unfavorable prognosis. Correlation between s-PCSK9-Ab and PD-L1 levels was also confirmed in the logistic regression analysis; therefore, low s-PCSK9-Ab levels could discriminate another poor prognosis group other than high-PD-L1 group. Conclusions: Patients with solid cancer had higher s-PCSK9-Ab levels than healthy donors. High s-PCSK9-Ab levels indicated better prognosis for overall survival after surgery in patients with esophageal cancer.

14.
Clin Exp Metastasis ; 38(5): 459-466, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34406563

RESUMO

This study aimed to examine the risk factors for surgical site infection (SSI) and the association of that with recurrence in JCOG0212. The results for secondary endpoints showed that compared with the mesorectal excision (ME) alone group, ME with lateral lymph node dissection (LLND) group showed significantly longer operative time and significantly higher blood loss. These results suggested that LLND was a risk factor for SSI. All 701 patients registered in JCOG0212 were analyzed in this study. Wound infection was defined as incisional/deep SSI, and pelvic abscess and anastomotic leakage were defined as organ/space SSI. The risk factors for the incidence of SSI and the effect of SSI on relapse-free survival (RFS) were investigated. Multivariable odds ratio of Grade 2 or higher all SSI was 0.58 [95% Confidence interval: 0.36-0.93] for female (vs. male) and that of Grade 2 or higher incisional/deep SSI was 2.24 [1.03-4.86] for blood infusion. For RFS, patients with Grade 3 or higher all SSI showed poor prognosis (multivariable hazard ratio: 1.66 [1.03-2.68]). LLND is not significant factor for the incidence of all SSI. Male sex might be a risk factor of Grade 2 or higher SSI, and blood transfusion is a possible risk factor of Grade 2 or higher incisional/deep SSI. Grade 3 or higher all SSI might be a significant worse prognostic factor for lower rectal cancer.


Assuntos
Neoplasias Retais/cirurgia , Infecção da Ferida Cirúrgica/etiologia , Adulto , Idoso , Feminino , Humanos , Incidência , Modelos Logísticos , Excisão de Linfonodo , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Retais/mortalidade , Neoplasias Retais/patologia , Fatores de Risco , Infecção da Ferida Cirúrgica/epidemiologia
15.
JAMA Netw Open ; 4(8): e2120786, 2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34387676

RESUMO

Importance: A high level of surgical skill is essential to prevent intraoperative problems. One important aspect of surgical education is surgical skill assessment, with pertinent feedback facilitating efficient skill acquisition by novices. Objectives: To develop a 3-dimensional (3-D) convolutional neural network (CNN) model for automatic surgical skill assessment and to evaluate the performance of the model in classification tasks by using laparoscopic colorectal surgical videos. Design, Setting, and Participants: This prognostic study used surgical videos acquired prior to 2017. In total, 650 laparoscopic colorectal surgical videos were provided for study purposes by the Japan Society for Endoscopic Surgery, and 74 were randomly extracted. Every video had highly reliable scores based on the Endoscopic Surgical Skill Qualification System (ESSQS, range 1-100, with higher scores indicating greater surgical skill) established by the society. Data were analyzed June to December 2020. Main Outcomes and Measures: From the groups with scores less than the difference between the mean and 2 SDs, within the range spanning the mean and 1 SD, and greater than the sum of the mean and 2 SDs, 17, 26, and 31 videos, respectively, were randomly extracted. In total, 1480 video clips with a length of 40 seconds each were extracted for each surgical step (medial mobilization, lateral mobilization, inferior mesenteric artery transection, and mesorectal transection) and separated into 1184 training sets and 296 test sets. Automatic surgical skill classification was performed based on spatiotemporal video analysis using the fully automated 3-D CNN model, and classification accuracies and screening accuracies for the groups with scores less than the mean minus 2 SDs and greater than the mean plus 2 SDs were calculated. Results: The mean (SD) ESSQS score of all 650 intraoperative videos was 66.2 (8.6) points and for the 74 videos used in the study, 67.6 (16.1) points. The proposed 3-D CNN model automatically classified video clips into groups with scores less than the mean minus 2 SDs, within 1 SD of the mean, and greater than the mean plus 2 SDs with a mean (SD) accuracy of 75.0% (6.3%). The highest accuracy was 83.8% for the inferior mesenteric artery transection. The model also screened for the group with scores less than the mean minus 2 SDs with 94.1% sensitivity and 96.5% specificity and for group with greater than the mean plus 2 SDs with 87.1% sensitivity and 86.0% specificity. Conclusions and Relevance: The results of this prognostic study showed that the proposed 3-D CNN model classified laparoscopic colorectal surgical videos with sufficient accuracy to be used for screening groups with scores greater than the mean plus 2 SDs and less than the mean minus 2 SDs. The proposed approach was fully automatic and easy to use for various types of surgery, and no special annotations or kinetics data extraction were required, indicating that this approach warrants further development for application to automatic surgical skill assessment.

16.
Colorectal Dis ; 2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34379874

RESUMO

AIM: Recent reports have described the use and efficacy of several types of transanal tube (TAT) for preventing anastomotic leakage by reducing intraluminal pressure. The aim of this study was to evaluate the safety and efficacy of a newly developed TAT for the prevention of anastomotic leakage after low anterior resection (LAR) for rectal cancer. METHOD: A multicentre confirmatory single-arm trial was designed to evaluate the safety and efficacy of a new TAT after LAR for rectal cancer. A total of 115 patients were registered in the trial at several cancer centres and other hospitals. All patients initially received reconstruction with a stapled anastomosis, but 18 then underwent creation of a diverting stoma. Of the remaining 97 patients, the first 96 were included in the protocol-defined primary analysis set. The primary outcome was the incidence of symptomatic leakage and the secondary endpoint was the incidence of complications associated with use of the TAT. The TAT was placed during LAR without creating a covering stoma and the drain was removed 4 or 5 days postoperatively. RESULTS: The rate of symptomatic leakage was 5.2% (95% confidence interval 1.7-11.7), which was significantly lower than the predetermined threshold value of 15.8% (one-sided p-value 0.0013). Only one patient had Grade 3 rectal bleeding that might have been related to use of the TAT. CONCLUSION: This nonrandomized study shows that the TAT appears to be safe and results in lower rates of anastomotic leakage in LAR compared with previous studies.

17.
Heart Vessels ; 2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34347137

RESUMO

Cardiovascular events and death are more prevalent in hemodialysis (HD) patients than in the general population. However, a detailed prognostic risk stratification of HD patients with acute myocardial infarction (AMI) has not yet been performed in the modern interventional era. We examined 4509 AMI patients (89 AMI/HD and 4420 AMI/non-HD) from the Mie ACS registry and detailed prognostic analyses based on the Killip classification were performed (Cohort A). In addition, prognosis of Killip class1 AMI/HD was compared with those of 313 non-AMI/HD patients from the MIE-CARE HD study using propensity score-matching method (Cohort B). Primary endpoint was all-cause mortality for up to 2 years. All-cause death occurred in 13.0% of AMI/non-HD and 35.8% of AMI/HD during follow-up, and patients with Killip class 1 had lower 30-day and 2-year mortality than those with Killip class ≥ 2 in both AMI/non-HD and AMI/HD. Cox regression analyses identified that Killip class ≥ 2 was the strongest independent prognostic factor of 30-day mortality with a hazard ratio of 7.44 (p < 0.001), whereas both presence of HD and Killip class ≥ 2 were the independent prognostic factors of mortality for up to 2 years. In Cohort B, a propensity score-matching analysis revealed similar all-cause mortality rates between Killip class 1 AMI/HD and non-AMI/HD. In HD patients with Killip class 1 AMI, 30-day mortality was around 6%, and long-term mortality among 30-day survivors after AMI was comparable with the natural course of HD patients in the modern interventional era. Clinical trial registration: URL: https://www.umin.ac.jp/ctr/index-j.htm . UMIN000036020 and UMIN000008128.

18.
Mol Clin Oncol ; 15(3): 179, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34276998

RESUMO

Although serum galectin-1 antibodies (s-GAL-1-Abs) have been evaluated in a small number of patients with cancer, a large series of patients with different cancer types have not been reported. The current study evaluated 1,833 patients with esophageal cancer (n=172), gastric cancer (n=317), colorectal cancer (n=262), hepatocellular carcinoma (n=91), prostate cancer (n=358), breast cancer (n=364), lung cancer (n=269) and 72 healthy individuals. s-GAL-1-Abs levels were analyzed using an originally developed ELISA system. A cut-off optical density value was determined as the mean (0.053) + 3 standard deviations (0.105) of sera from healthy controls. The results revealed that the positive rate of s-GAL-1-Abs in patients with hepatocellular carcinoma (16.7%) and lung cancer (13.8%) were significantly higher compared with the other groups: Esophageal cancer (11.6%), colorectal cancer (11.5%), prostate cancer (7.3%), gastric cancer (6.9%), breast cancer (6.9%) and healthy controls (4.2%). Although the positive rates of s-GAL-1-Abs in different cancer types were relatively low, s-GAL-1-Abs may be useful for patients with hepatocellular carcinoma and lung cancer.

19.
Diabetologia ; 64(10): 2183-2192, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34268631

RESUMO

AIMS/HYPOTHESIS: Patients with GAD antibodies (GADAb) showing clinical features of type 2 diabetes typically exhibit progression to an insulin-dependent state in several months or years. This condition is diagnosed as slowly progressive insulin-dependent (type 1) diabetes mellitus (SPIDDM) or latent autoimmune diabetes in adults, a subtype of adult-onset autoimmune diabetes. However, some patients diagnosed with adult-onset autoimmune diabetes do not progress to an insulin-dependent state. We conducted a retrospective cohort study to identify patients with non-insulin-dependent diabetes among those diagnosed with adult-onset autoimmune diabetes using measurable indicators in routine clinical practice. METHODS: We surveyed data from the electronic medical records of all patients with GADAb from eight medical centres in Japan for selecting and analysing patients who matched the diagnostic criteria of SPIDDM. RESULTS: Overall, 345 patients were analysed; of these, 162 initiated insulin therapy (insulin therapy group), whereas 183 did not (non-insulin therapy group) during the follow-up period (median 3.0 years). Patients in the non-insulin therapy group were more likely to be male and presented a later diabetes onset, shorter duration of diabetes, higher BMI, higher blood pressure levels, lower HbA1c levels, lower GADAb levels and lesser antidiabetic agent use than those in the insulin therapy group when GADAb was first identified as positive. A Cox proportional hazards model showed that BMI, HbA1c levels and GADAb levels were independent factors for progression to insulin therapy. Kaplan-Meier analyses revealed that 86.0% of the patients with diabetes having GADAb who presented all three factors (BMI ≥ 22 kg/m2, HbA1c < 75 mmol/mol [9.0%] and GADAb <10.0 U/ml) did not require insulin therapy for 4 years. CONCLUSIONS/INTERPRETATION: Higher BMI (≥22 kg/m2), lower HbA1c (<75 mmol/mol [9.0%]) and lower GADAb levels (<10.0 U/ml) can predict a non-insulin-dependent state for at least several years in Japanese patients with diabetes having GADAb.

20.
Aquat Toxicol ; 237: 105908, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34273772

RESUMO

Tetrodotoxin (TTX), also known as pufferfish toxin, has been detected in marine edible bivalves worldwide. In this study, several bivalve species, Azumapecten farreri subsp. akazara, Patinopecten yessoensis and Mytilus galloprovincialis, collected from the Pacific side of the northern Japanese Islands, were studied for the accumulation of TTX in the presence of toxic planocerid larvae. LC-MS/MS analysis demonstrated that TTX was detected only in the midgut gland of A. farreri subsp. akazara. Toxic flatworm-specific PCR and direct sequencing of the amplicons showed that the DNA fragments of the Planocera multitentaculata COI gene were detected in the gut contents of the toxified bivalves. The planocerid larvae were also detected in the environmental seawaters. Toxification experiments in the aquarium demonstrated that the mussel M. galloprovincialis was also toxified by feeding on the toxic flatworm larvae. These results suggest that the source of TTX accumulation in edible bivalves is toxic flatworm larvae.


Assuntos
Mytilus , Platelmintos , Poluentes Químicos da Água , Animais , Cromatografia Líquida , Larva , Espectrometria de Massas em Tandem , Tetrodotoxina/toxicidade , Poluentes Químicos da Água/toxicidade
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