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BACKGROUND AIMS: With the aim of strengthening the scientific evidence of immune-cell therapy for cancer and further examining its safety, in October 2015, our hospital jointly established the Cancer Immune-Cell Therapy Evaluation Group (CITEG) with 39 medical facilities nationwide. METHODS: Medical information, such as patients' background characteristics, clinical efficacy and therapeutic cell types obtained from each facility, has been accumulated, analyzed and evaluated by CITEG. In this prospective study, we analyzed the adverse events associated with immune-cell therapy until the end of September 2022, and we presented our interim safety evaluation. RESULTS: A total of 3839 patients with malignant tumor were treated with immune-cell therapy, with a median age of 64 years (range, 13-97 years) and a male-to-female ratio of 1:1.08 (1846:1993). Most patients' performance status was 0 or 1 (86.8%) at the first visit, and 3234 cases (84.2%) were advanced or recurrent cases, which accounted for the majority. The total number of administrations reported in CITEG was 31890, of which 960 (3.0%) showed adverse events. The numbers of adverse events caused by treatment were 363 (1.8%) of 19661 administrations of αßT cell therapy, 9 of 845 administrations of γδT-cell therapy (1.1%) and 10 of 626 administrations of natural killer cell therapy (1.6%). The number of adverse events caused by dendritic cell (DC) vaccine therapy was 578 of 10748 administrations (5.4%), which was significantly larger than those for other treatments. Multivariate analysis revealed that αßT cell therapy had a significantly greater risk of adverse events at performance status 1 or higher, and patients younger than 64 years, women or adjuvant immune-cell therapy had a greater risk of adverse events in DC vaccine therapy. Injection-site reactions were the most frequently reported adverse events, with 449 events, the majority of which were associated with DC vaccine therapy. Among all other adverse events, fever (228 events), fatigue (141 events) and itching (131 events) were frequently reported. In contrast, three patients had adverse events (fever, abdominal pain and interstitial pneumonia) that required hospitalization, although they were weakly related to this therapy; rather, it was considered to be the effect of treatment for the primary disease. CONCLUSIONS: Immune-cell therapy for cancer was considered to be a safe treatment without serious adverse events.
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Neoplasias , Humanos , Masculino , Femenino , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Estudios Prospectivos , Neoplasias/terapia , Inmunoterapia Adoptiva , Resultado del TratamientoRESUMEN
BACKGROUND: We had previously reported that the administration of Gastrografin through a nasogastric tube (NGT-G) followed by long tube (LT) strategy could be a novel standard treatment for adhesive small bowel obstruction (ASBO); however, the long-term outcomes after initial improvement remain unknown. This study aimed to analyze the long-term outcomes of first-line NGT-G. METHODS: Enrolled patients with ASBO were randomly assigned to receive LT or NGT-G between July 2016 and November 2018. Thereafter, the cumulative surgery rate, cumulative recurrence rate, and overall survival (OS) rate were analyzed. In addition, subset analysis was conducted to determine the cumulative recurrence rate according to colonic contrast with Gastrografin at 24 h. RESULTS: A total of 223 patients (LT group, n = 111; NGT-G group, n = 112) were analyzed over a median follow-up duration of 550 days. The cumulative 1-year surgery rates, cumulative 1-year recurrence rates, and 1-year OS rates in the LT and NGT-G groups were 18.8% and 18.1%, 30.0% and 31.7%, and 99.1% and 96.6%, respectively; no significant differences were observed between both groups. In the NGT-G group, a negative colonic contrast at 24 h demonstrated a higher tendency for future recurrence compared with a positive colonic contrast at 24 h (1-year recurrence rate: negative contrast, 46.9% vs positive contrast, 27.6%). CONCLUSIONS: Gastrografin through a nasogastric tube followed by LT can be a promising treatment strategy for ASBO, with long-term efficacies equivalent to initial LT placement.
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Diatrizoato de Meglumina , Obstrucción Intestinal , Intubación Gastrointestinal , Medios de Contraste/administración & dosificación , Diatrizoato de Meglumina/administración & dosificación , Humanos , Obstrucción Intestinal/etiología , Obstrucción Intestinal/terapia , Intestino Delgado , Adherencias Tisulares/complicaciones , Resultado del TratamientoRESUMEN
OBJECTIVES: The oncological outcomes, especially high recurrence rate, of bridge-to-surgery (BTS) self-expandable metallic stent (SEMS) placement remain concerning, emphasizing the necessity of standardized SEMS placement. However, its impact on long-term BTS outcomes is unknown. We investigated the long-term outcomes of BTS colonic stenting using standardized SEMS placement. METHODS: This prospective, multicenter cohort study conducted at 46 hospitals in Japan (March 2012 to October 2013) included consecutive patients with stage II and III obstructive colorectal cancer managed with BTS SEMS placement. The SEMS placement technique was standardized by information dissemination among the participating hospitals. The primary outcome was overall survival (OS) after SEMS placement, and the secondary outcomes were relapse-free survival (RFS), recurrence, and short-term outcomes of SEMS placement and surgery. RESULTS: The 1-, 3-, and 5-year OS rates were 94.1%, 77.4%, and 67.4% (Kaplan-Meier), respectively, with high technical success (99.0%, 206/208) and low perforation (1.9%, 4/208) rates. The 1-, 3-, and 5-year RFS rates were 81.6%, 65.6%, and 57.9% (Kaplan-Meier), respectively, and the overall recurrence rate was 31.0% (62/200). The RFS rate was significantly poorer in patients with perforation (n = 4) than in those without perforation (n = 196) (log-rank P = 0.017); moreover, perforation was identified as an independent factor affecting RFS (hazard ratio 3.31; 95% confidence interval 1.03-10.71, multivariate Cox regression). CONCLUSION: This large, prospective, multicenter study revealed satisfactory long-term outcomes of BTS colonic stenting using a standardized SEMS insertion method, which might be specifically due to the reduced perforation rate. (UMIN000007953).
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Neoplasias del Colon , Neoplasias Colorrectales , Obstrucción Intestinal , Stents Metálicos Autoexpandibles , Estudios de Cohortes , Neoplasias del Colon/complicaciones , Neoplasias Colorrectales/complicaciones , Neoplasias Colorrectales/cirugía , Humanos , Obstrucción Intestinal/etiología , Obstrucción Intestinal/cirugía , Recurrencia Local de Neoplasia , Estudios Prospectivos , Estudios Retrospectivos , Stents , Resultado del TratamientoRESUMEN
PURPOSE: Endoscopic clipping closure after colorectal endoscopic submucosal dissection (ESD) did not reduce the incidence of post-ESD coagulation syndrome (PECS) in our recent randomized controlled trial (RCT); however, the definition of PECS is still controversial. The aim of this study is to establish optimal definition of PECS with additional analysis of RCT based on another definition. METHODS: In this multicenter, single-blind RCT, individuals were randomly assigned to colorectal ESD followed by endoscopic clipping closure or non-closure. In this post hoc analysis, the definition of PECS was modified as both localized abdominal pain on visual analogue scale and inflammatory response (fever or leukocytosis), from either localized abdominal pain or inflammatory response in the original study. All participants underwent a computed tomography after ESD, and PECS was classified into type I, conventional PECS without extra-luminal air, and type II, PECS with peri-luminal air. RESULTS: A total of 155 patients (84 in the non-closure group and 71 in the closure group) were analyzed. As a result of criteria modification, 21 type I PECS and four type II PECS cases in the original study, which included patients with clear pain and inflammatory response, were downgraded to no adverse event and simple peri-luminal air, respectively. The frequency of PECS showed no significant difference between non-closure and closure groups. CONCLUSION: Clipping closure after colorectal ESD does not reduce the incidence of PECS regardless of the diagnostic criteria. Either localized abdominal pain or inflammatory response might be optimal criteria of PECS (UMIN000027031). TRIAL REGISTRATION NUMBER: UMIN000027031 DATE OF REGISTRATION: April 18, 2017.
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Neoplasias Colorrectales , Resección Endoscópica de la Mucosa , Dolor Abdominal/etiología , Neoplasias Colorrectales/cirugía , Resección Endoscópica de la Mucosa/efectos adversos , Humanos , Instrumentos Quirúrgicos , Resultado del TratamientoRESUMEN
BACKGROUND: With the goal of discovering non-invasive biomarkers for early diagnosis of GC, we conducted a case-control study utilising urine samples from individuals with predominantly early GC vs. healthy control (HC). METHODS: Among urine samples from 372 patients, age- and sex-matched 282 patients were randomly divided into three groups: 18 patients in a discovery cohort; 176 patients in a training cohort and 88 patients in a validation cohort. RESULTS: Among urinary proteins identified in the comprehensive quantitative proteomics analysis, urinary levels of TFF1 (uTFF1) and ADAM12 (uADAM12) were significantly independent diagnostic biomarkers for GC, in addition to Helicobacter pylori status. A urinary biomarker panel combining uTFF1, uADAM12 and H. pylori significantly distinguished between HC and GC patients in both training and validation cohorts. On the analysis for sex-specific biomarkers, this combination panel demonstrated a good AUC of 0.858 for male GC, whereas another combination panel of uTFF1, uBARD1 and H. pylori also provided a good AUC of 0.893 for female GC. Notably, each panel could distinguish even stage I GC patients from HC patients (AUC = 0.850 for males; AUC = 0.845 for females). CONCLUSIONS: Novel urinary protein biomarker panels represent promising non-invasive biomarkers for GC, including early-stage disease.
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Biomarcadores de Tumor/orina , Detección Precoz del Cáncer/métodos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/orina , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sensibilidad y EspecificidadRESUMEN
BACKGROUND AND AIMS: Post endoscopic submucosal dissection coagulation syndrome (PECS) occasionally occurs after colorectal endoscopic submucosal dissection (ESD), presenting with localized abdominal pain and inflammation. We conducted a randomized controlled trial (RCT) to assess the usefulness of endoscopic clipping closure to prevent PECS and delayed perforation (DP). METHODS: This is a multicenter, single-blind RCT. Prospectively enrolled patients undergoing colorectal ESD were randomly allocated to endoscopic clipping closure and nonclosure after ESD, stratifying by institution and tumor size. All participants underwent a computed tomography scan after ESD. PECS was defined as visual analog scale (VAS) ≥30 mm, an increase in VAS ≥20 mm from baseline, body temperature ≥37.5°C or white blood cells ≥10,000/µL after colorectal ESD. DP was defined as PECS accompanied by extraluminal air. The preplanned sample size was 320 patients, and the primary endpoint was the rate of PECS/DP. RESULTS: At the planned interim analysis, this trial was terminated by recommendation of the independent data and safety monitoring committee because conditional power with superiority was lower than the preplanned futility limit. Finally, 155 patients were analyzed. The rate of PECS/DP was 16% (95% confidence interval [CI], 8%-23%) in the nonclosure group and 24% (95% CI, 14%-34%) in the closure group (P = .184). All cases of DP were within minor criteria, and all PECS/DP patients were managed conservatively without surgical treatment. Simple periluminal air without PECS was observed in 16% (95% CI, 8%-23%) in the nonclosure group and 10% (95% CI, 3%-17%) in the closure group. CONCLUSION: Endoscopic clipping closure could not reduce the high incidence of PECS/DP after colorectal ESD. (University Hospital Medical Network Clinical Trials Registry number: UMIN000027031.).
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Neoplasias Colorrectales , Resección Endoscópica de la Mucosa , Dolor Abdominal , Neoplasias Colorrectales/cirugía , Resección Endoscópica de la Mucosa/efectos adversos , Humanos , Método Simple Ciego , Instrumentos Quirúrgicos , Resultado del TratamientoRESUMEN
BACKGROUND: Colorectal cancer (CRC) with acute colorectal obstruction (ACO) is an emergency. Transanal colorectal tube (TCT) use can be a safe single-stage surgery with laparoscopy-assisted colectomy; it offers long-term outcomes equivalent to emergency surgery for stage-II/III CRC with ACO. Self-expanding metallic stent use, another alternative, may have detrimental pathological and molecular effects, whereas the pathological impact of TCT placement remains unclear. We hypothesized that TCT placement might exert little damage on primary tumor. Hence, the current study analyzed the pathological impact of TCT placement for CRC with ACO compared to emergency surgery. METHODS: Data from consecutive patients with stage-II/III distal CRC with ACO who underwent surgery between January 2007 and December 2015 were retrospectively reviewed at two Japanese affiliate hospitals. Inflammatory and malignant potential-related parameters were analyzed by a single blinded pathologist. We extracted mRNA from tumor tissues to analyze inflammatory cytokines. RESULTS: Sixty-eight patients with stage-II/III distal CRC with ACO were identified (surgery: 25 patients; TCT: 43 patients). Baseline characteristics were well balanced between the two groups. TCT showed a significantly lower frequency of abscess (surgery vs TCT, 36.0% vs 11.6%; P = 0.017) and a lower tendency of pathological perforation (surgery vs TCT, 20.0% vs 4.7%, respectively; P = 0.091), compared to the surgery group. There were no significant intergroup differences in oncological factors, including perineural invasion (surgery vs TCT, 52.0% vs 62.8%; P = 0.383), microlymphatic involvement (surgery vs TCT, 52.0% vs 58.1%; P = 0.623), and microvascular involvement (surgery vs TCT, 32.0% vs 25.6%; P = 0.570). No significant intergroup differences were found in interleukin (IL)-6, IL-8, or IL-1ß gene expression levels (P = 0.580, 0.250, 0.941). CONCLUSIONS: TCT placement had no pathologically detrimental effects on the tumor or surrounding tissues and might be an attractive non-invasive strategy for cases of curative distal CRC with ACO.
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Canal Anal/cirugía , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/cirugía , Obstrucción Intestinal/patología , Obstrucción Intestinal/cirugía , Anciano , Colectomía , Citocinas/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Inflamación/patología , Mediadores de Inflamación/metabolismo , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Stents Metálicos AutoexpandiblesRESUMEN
In Methods of Abstract, the word "2015" should be changed to "2011".
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PURPOSE: This study compared the feasibility and safety of endoscopic placement of self-expandable metallic stents (SEMSs) as a bridge to surgery (BTS) between patients with obstructive colorectal cancer (CRC) classified as ColoRectal Obstruction Scoring System (CROSS) 0 and those with CROSS 1 or 2. METHODS: We conducted a post hoc analysis of two prospective, observational, single-arm multicenter clinical trials and performed a pooled analysis of the data. In total, 336 consecutive patients with malignant colorectal obstruction underwent SEMS placement. The primary endpoint was clinical success, defined as resolution of symptoms and radiological findings within 24 h. Secondary endpoints were technical success and adverse events. RESULTS: High clinical (98.0% vs. 98.4%) and technical (96.7% vs. 97.8%) success rates were observed in both groups (CROSS 0 vs. CROSS 1 or 2). The adverse event rate was low. The mean stricture length was lower (3.8 ± 1.2 cm vs. 4.4 ± 1.8 cm) and laparoscopic surgery more common (56.7% vs 52.2%) in the CROSS 0 group than in the CROSS 1 and 2 group. CONCLUSION: This study was the first to compare the degree of stricture in different CROSS groups and demonstrated comparable results with respect to the short-term efficacy and safety of SEMS placement as a BTS for obstructive CRC in CROSS 0, 1, and 2 patients.
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Neoplasias del Colon/cirugía , Análisis de Datos , Endoscopía Gastrointestinal/métodos , Obstrucción Intestinal/cirugía , Laparoscopía/métodos , Stents Metálicos Autoexpandibles , Neoplasias del Colon/complicaciones , Estudios de Factibilidad , Humanos , Obstrucción Intestinal/etiología , Seguridad , Stents Metálicos Autoexpandibles/efectos adversos , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
BACKGROUND: Self-expandable metallic stenting (SEMS) for malignant colorectal obstruction (MCO) as a bridge to elective surgery (BTS) is a widely used procedure. The aim of this study was to assess short-term outcomes of SEMS for MCO as BTS. METHODS: This study analyzed pooled data from BTS patients who were enrolled in two multicenter prospective single-arm observational clinical studies that used different stent types. Both studies were conducted by the Japan Colonic Stent Safe Procedure Research Group (JCSSPRG). The first study evaluated the WallFlex™ colonic stent for BTS or palliative treatment (PAL) from May 2012 to October 2013 and the second evaluated the Niti-S™ colonic stent from October 2013 to May 2014. Fifty-three facilities in Japan participated in the studies. Before each study started, the procedure had been shared with the participating institutions by posting details of the standard methods of SEMS placement on the JCSSPRG website. Patients were followed until discharged after surgery. RESULTS: A total of 723 consecutive patients were enrolled in the two studies. After excluding nine patients, the remaining 714 patients were evaluated as a per-protocol cohort. SEMS placement was performed in 426 patients (312 WallFlex and 114 Niti-S) as BTS and in 288 as PAL. In the 426 BTS patients, the technical success rate was 98.1% (418/426). The clinical success rate was 93.8% (392/418). SEMS-related preoperative complications occurred in 8.5% of patients (36/426), perforations in 1.9% (8/426), and stent migration in 1.2% (5/426). Primary anastomosis was possible in 91.8% of patients (391/426), 3.8% of whom (15/393) had anastomosis leakage. The overall stoma creation rate was 10.6% (45/426). The postoperative complication rate was 16.9% (72/426) and mortality rate was 0.5% (2/426). CONCLUSIONS: SEMS placement for MCO as BTS is safe and effective with respect to peri-procedural outcomes. Further investigations are needed to confirm long-term oncological outcomes.
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Neoplasias Colorrectales/cirugía , Obstrucción Intestinal/cirugía , Stents Metálicos Autoexpandibles , Anciano , Neoplasias Colorrectales/complicaciones , Procedimientos Quirúrgicos Electivos/efectos adversos , Estudios de Factibilidad , Femenino , Humanos , Obstrucción Intestinal/etiología , Obstrucción Intestinal/mortalidad , Japón , Masculino , Persona de Mediana Edad , Cuidados Paliativos , Complicaciones Posoperatorias/epidemiología , Estudios Prospectivos , Stents Metálicos Autoexpandibles/efectos adversosRESUMEN
BACKGROUND AND AIM: Colorectal cancer patients often present with large bowel obstruction. Elective placement of a self-expandable metallic stent (SEMS) can relieve obstruction, but can be challenging. Previous studies have compared cases by outcomes only, but the present study investigated successful cases only to identify factors related to prolonged and difficult SEMS placement in patients with malignant colonic obstruction. METHODS: A post-hoc analysis of a multicenter clinical trial conducted between March 2012 and October 2013 at 46 facilities across Japan (UMIN000007953) was carried out; 511 patients who required SEMS placement for acute colorectal obstruction or symptomatic stricture secondary to malignant neoplasm were enrolled. Technical success rates and procedure times were recorded. Clinical and interventional parameters were investigated for their potential effect on procedure time by univariate and multivariate analyses. RESULTS: Technical success rate of SEMS placement was 98%. Median procedure time was 30 (range, 4-170) min. In 27% of patients, procedure time exceeded 45 min, indicating technically difficult placement. Multivariate analyses showed significant associations between technically difficult placement and a ColoRectal Obstruction Scoring System (CROSS) score of 0 before SEMS placement (odds ratio [OR], 1.6; P < 0.05), tumor site in the right colon (OR, 2.5; P < 0.0001), stricture length ≥5 cm (OR, 2.2; P < 0.001), peritoneal carcinomatosis (OR, 1.7; P < 0.05), and multiple SEMS placement (OR, 8.0; P < 0.01). CONCLUSION: Clinicians must anticipate technical challenges in cases with peritoneal carcinomatosis, a CROSS score of 0, or expansive strictures; such cases require experienced clinicians to carry out SEMS placement.
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Enfermedades del Colon/cirugía , Neoplasias Colorrectales/patología , Obstrucción Intestinal/cirugía , Stents Metálicos Autoexpandibles , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Enfermedades del Colon/etiología , Enfermedades del Colon/patología , Femenino , Humanos , Obstrucción Intestinal/etiología , Obstrucción Intestinal/patología , Japón , Masculino , Persona de Mediana Edad , Tempo Operativo , Resultado del TratamientoRESUMEN
Background Acquired resistance (AR) to an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) is a common event, and several underlying mechanisms, including T790 M, MET amplification and PTEN downregulation, have been reported for the common EGFR mutations. EGFR G719X is an uncommon mutation that has been reported to show sensitivity to EGFR-TKIs. However, no established cell lines harboring the EGFR G719X have been reported in the literature. Materials and Methods G719S-GR cells were established from malignant pleural effusion of a patient whose tumor developed AR from gefitinib treatment. G719S-GR cells were then genotyped and tested for drug sensitivities. Multiplex ligation-dependent probe amplification (MLPA) was used to compare the clinical tumor samples with G719S-GR. Results G719S-GR cells were resistant to EGFR-TKIs with an LC50 of around 10 µM. A genomic analysis showed that G719S-GR cells harbor the EGFR G719S mutation as well as the amplification of EGFR locus. The homozygous deletion of CDKN2A and the loss of PTEN and TSC1 were also detected. On comparing the copy number of tumor suppressor genes using MLPA, G719S-GR cells were found to lack one copy of PTEN, which was not observed in a tumor obtained before gefitinib treatment. Loss of PTEN may result in AKT activation. The mTORC1/2 inhibitor Torin-1 was able to inhibit the downstream signaling when combined with osimertinib. Discussion The newly established G719S-GR cell line may be useful for investigating the mechanism underlying the development of AR in the G719X mutation; the loss of PTEN may be one such mechanism.
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Resistencia a Antineoplásicos/genética , Receptores ErbB/genética , Mutación/genética , Inhibidores de Proteínas Quinasas/farmacología , Anciano , Secuencia de Bases , Línea Celular Tumoral , Resistencia a Antineoplásicos/efectos de los fármacos , Receptores ErbB/metabolismo , Humanos , MasculinoRESUMEN
BACKGROUND: Obstructive colorectal cancer (CRC) is an emergency situation with high morbidity and mortality, but long-term outcomes of stage II/III obstructive CRC remain unclear. The aim of this study was to evaluate prognostic factors, including colorectal obstruction. METHODS: Data were retrospectively reviewed from consecutive patients with stage II/III CRC who underwent curative surgery between January 2007 and December 2011 at two Japanese institutions. We analyzed overall survival (OS) and relapse-free survival (RFS), according to various prognostic factors including colorectal obstruction. RESULTS: In total, 979 patients with stage II/III CRC were identified for this study. Among these 979 patients, 94 patients showed colorectal obstruction (9.6%). In both stage II and stage III CRCs, colorectal obstruction showed significantly poorer OS and RFS compared to non-obstruction (5-year OS, obstruction vs. non-obstruction, stage II: 65.9 vs. 86.5%, P = 0.002; stage III: 55.9 vs. 73.6%, P = 0.007) (5-year RFS, obstruction vs. non-obstruction, stage II: 59.2 vs. 77.8%, P = 0.008; stage III 31.3 vs. 56.3%, P = 0.001). Multivariate analysis demonstrated colorectal obstruction as a significant independent and poor prognostic factor in terms of both OS (hazard ratio (HR) 2.469; 95% CI 1.339-4.545; P = 0.004) and RFS (HR 1.992; 95% CI 1.160-3.425; P = 0.012) for stage II CRC, as well as pT4 stage. On multivariate analysis for stage III CRC, colorectal obstruction was a significant predictor of poor RFS (HR 1.626; 95% CI 1.070-2.469; P = 0.023), but not poor OS. CONCLUSIONS: Colorectal obstruction is an independent poor prognostic factor for stage II CRC. Adjuvant chemotherapy might be feasible for stage II CRC with colorectal obstruction.
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Neoplasias Colorrectales/cirugía , Cirugía Colorrectal/efectos adversos , Obstrucción Intestinal/diagnóstico , Recurrencia Local de Neoplasia/diagnóstico , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/patología , Femenino , Humanos , Obstrucción Intestinal/etiología , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/etiología , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
In general, solitary right aortic arch carries the left-sided ductus arteriosus communicating between the left subclavian and pulmonary arteries or the right-sided ductus connecting the descending aorta to the left pulmonary artery. Serial sections of fifteen 5- to 6-week-old embryos and ten 8- to 9-week-old fetuses suggested that the pathogenesis was unrelated to inversion due to dysfunction in gene cascades that control the systemic left/right axis. With inversion, conversely, the ductus or the sixth pharyngeal arch artery should connect to the right pulmonary artery. The disappearance of the right aortic arch started before the caudal migration of the aortic attachment of the ductus. Sympathetic nerve ganglia developed immediately posterior to both aortae, with a single embryonic specimen showing a large ganglion at the midline close to the union of the aortic arches. These ganglia may interfere with blood flow through the distal left arch, resulting in the ductus ending at the descending aorta behind the oesophagus. In another fetus examined, a midline shift of the ductus course resulted in the trachea curving posteriorly. Therefore, solitary right arch is likely to accompany abnormalities of the surrounding structures. The timing and site of the obstruction should be different between types: an almost midline obstruction near the aortic union needed for the development of the left-sided ductus and a distal obstruction near the left subclavian arterial origin needed for the development of the right-sided ductus. A mass effect of the sympathetic ganglia may explain the pathogenesis of any type of anomalous ductus arteriosus shown in previous reports of the solitary right arch.
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Aorta Torácica/anomalías , Conducto Arterioso Permeable/diagnóstico , Feto , Malformaciones Vasculares/embriología , Aorta Torácica/embriología , Conducto Arterial/embriología , Conducto Arterioso Permeable/embriología , HumanosRESUMEN
BACKGROUND: Endoscopic stenting with a self-expandable metallic stent (SEMS) is a widely accepted procedure for malignant colonic obstruction. The Colonic Stent Safe Procedure Research Group conducted the present prospective feasibility study. METHODS: Our objectives were to estimate the safety and feasibility of SEMS placement as a bridge to surgery (BTS) for malignant colorectal obstruction. We conducted a prospective, observational, single-arm, multicenter clinical trial from March 2012 to October 2013. Each patient was treated with an uncovered WallFlex enteral colonic stent. Patients were followed up until discharge after surgery. RESULTS: A total of 518 consecutive patients were enrolled in this study. The cohort intended for BTS consisted of 312 patients (61 %), and the stent could be released in 305 patients. Technical and clinical success rates were 98 and 92 %, respectively. Elective surgery was performed in 297 patients, and emergency surgery was performed in eight patients for the treatment of complications. The overall preoperative complication rate was 7.2 %. Major complications, including perforation, occurred in 1.6 %, persistent colonic obstruction occurred in 1.0 %, and stent migration occurred in 1.3 % patients. The median time from SEMS to surgery was 16 days. Silent perforations were observed in 1.3 %. Open and laparoscopic surgery was performed in 121 and 184 patients, respectively. The tumor could be resected in 297 patients. The primary anastomosis rate was 92 %. The rate of anastomotic leakage was 4 %, and the overall stoma creation rate was 10 %. The median duration of hospitalization following surgery was 12 days. Overall postoperative morbidity and mortality rates were 16 and 0.7 %, respectively. CONCLUSIONS: This largest, multicenter, prospective study demonstrates the feasibility of SEMS placement as a BTS for malignant colorectal obstruction. SEMS serves as a safe and effective BTS with acceptable stoma creation and complication rates in patients with acute malignant colonic obstruction.
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Neoplasias del Colon/complicaciones , Obstrucción Intestinal/etiología , Obstrucción Intestinal/cirugía , Neoplasias del Recto/complicaciones , Stents Metálicos Autoexpandibles , Adulto , Anciano , Anciano de 80 o más Años , Procedimientos Quirúrgicos Electivos , Urgencias Médicas , Estudios de Factibilidad , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Estudios ProspectivosRESUMEN
BACKGROUND: Endoscopic self-expandable metal stent placement has been used as an alternative to surgery for malignant colorectal obstruction; however, factors affecting its clinical outcome are unclear. OBJECTIVE: To clarify the short-term safety and efficacy of endoscopic self-expandable metal stent placement for malignant colorectal obstruction and to identify factors associated with its clinical and technical failure. DESIGN: Prospective clinical cohort study. SETTING: Fourteen academic centers and 32 community hospitals. PATIENTS: A total of 513 consecutive patients with malignant colorectal obstruction. INTERVENTION: Endoscopic self-expandable metal stent placement, sharing of stent placement methods among participating facilities. MAIN OUTCOME MEASUREMENTS: The primary endpoint was clinical success, defined as symptom and radiological finding resolution within 24 hours. Secondary endpoints were technical success and adverse events. The follow-up period was 7 days. RESULTS: The clinical and technical success rates were 95.5% and 97.9%, respectively. Major adverse events included perforation (2.1%), stent migration (1.0%), and stent occlusion (0.8%). The main causes of perforation were the procedure itself (0.8%) and comorbidities (obstructive colitis and impending perforation) not apparent before stent placement (0.6%). Extrinsic tumor origin was independently associated with the clinical failure after stent placement (odds ratio 4.23; 95% confidence interval, 1.21-14.79; P = .02). Stricture marking trended toward a negative association with technical failure (P = .09). LIMITATIONS: Noncomparative study. CONCLUSION: Strict inclusion criteria and stricture marking may improve the technical and clinical success of stent placement.
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Neoplasias Colorrectales/complicaciones , Obstrucción Intestinal/terapia , Stents Metálicos Autoexpandibles , Adulto , Anciano , Estudios de Factibilidad , Femenino , Estudios de Seguimiento , Humanos , Obstrucción Intestinal/etiología , Japón , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Magnifying endoscopy with narrow-band imaging (ME-NBI) has been used to estimate the invasion depth of superficial esophageal squamous cell carcinoma (SESCC), but the real diagnostic power of ME-NBI remains unclear because of few prospective studies. OBJECTIVES: To evaluate whether ME-NBI adds additional information to white-light imaging (WLI) for the diagnosis of invasion depth of SESCC. DESIGN: Multicenter, prospective trial using real-time imaging and diagnosis. SETTING: Seven Japanese institutions. PATIENTS: Fifty-five patients with SESCC were enrolled from June 2011 to October 2013, and the results for 49 lesions were analyzed. INTERVENTIONS: Patients underwent primary WLI followed by ME-NBI, and reports of primary WLI (WLI alone) were completed before secondary ME-NBI (WLI followed by ME-NBI). To standardize diagnosis among examiners, this trial was started after achievement of a mean κ value≥.6 among 11 participating endoscopists. MAIN OUTCOME MEASUREMENTS: Diagnosis of invasion depth by each tool was divided into cancer limited to the epithelium and the lamina propria mucosa and cancer invading beyond the muscularis mucosae (≥T1a-MM) and then collated with the final pathologic diagnosis by an independent pathologist blinded to the clinical data. RESULTS: The accuracy of invasion depth in WLI alone and WLI followed by ME-NBI was 71.4% and 65.3% (P=.375), respectively. Sensitivity for ≥T1a-MM was 61.1% for both groups (P=1.000), and specificity for ≥T1a-MM was 77.4% for WLI alone and 67.7% for WLI followed by ME-NBI (P=.375). LIMITATION: Open-label trial. CONCLUSIONS: ME-NBI showed no additional benefit to WLI for diagnosis of invasion depth of SESCC. (University Hospital Network Clinical Trials Registry number: UMIN000005632.).
Asunto(s)
Carcinoma de Células Escamosas/patología , Neoplasias Esofágicas/patología , Esofagoscopía/métodos , Esófago/patología , Membrana Mucosa/patología , Anciano , Carcinoma de Células Escamosas/diagnóstico , Neoplasias Esofágicas/diagnóstico , Carcinoma de Células Escamosas de Esófago , Femenino , Humanos , Masculino , Microscopía , Persona de Mediana Edad , Imagen de Banda Estrecha , Invasividad Neoplásica , Estudios Prospectivos , Sensibilidad y EspecificidadRESUMEN
BACKGROUND AND AIM: Self-expandable metallic stents (SEMS) have been widely accepted as palliation therapy for malignant gastric outlet obstruction (GOO). However, the factors predictive of poor oral intake after SEMS placement have not been elucidated sufficiently. We aimed to clarify both the patient and stent-related predictive factors. METHODS: We retrospectively reviewed 126 consecutive patients who underwent uncovered SEMS placement for malignant GOO between April 2010 and March 2013 at a university hospital and two tertiary care referral centers. RESULTS: Technical success of SEMS placement was achieved in all 126 (100%) patients. Improved oral intake was observed in 111 (88.1%) patients. A Karnofsky performance status ≤ 40 (odds ratio [OR], 1.19; 95% confidence interval [CI], 1.02-1.28; P = 0.041), peritoneal dissemination (OR, 1.20; 95% CI, 1.01-1.26; P = 0.038), and under-expansion of the SEMS on the procedure day (OR, 1.55; 95% CI, 1.26-1.62; P < 0.001) were independent predictive factors for poor improvement on the GOO scoring system, according to multivariate analysis. CONCLUSIONS: SEMS under-expansion was a stent related, while poor performance status and peritoneal dissemination were patient related, predictive factors for poor oral intake after SEMS placement for malignant GOO.
Asunto(s)
Ingestión de Alimentos/fisiología , Obstrucción de la Salida Gástrica/terapia , Stents , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Predicción , Obstrucción de la Salida Gástrica/etiología , Neoplasias Gastrointestinales/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Cuidados Paliativos/métodos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
We give a theoretical validation for calculating fundamental frequencies of a molecule from classical molecular dynamics (MD) when its anharmonicity is small enough to be treated by perturbation theory. We specifically give concrete answers to the following questions: (1) What is the appropriate initial condition of classical MD to calculate the fundamental frequency? (2) From that condition, how accurately can we extract fundamental frequencies of a molecule? (3) What is the benefit of using ab initio MD for frequency calculations? Our analytical approaches to those questions are classical and quantum normal form theories. As numerical examples we perform two types of MD to calculate fundamental frequencies of H2O with MP2/aug-cc-pVTZ: one is based on the quartic force field and the other one is direct ab initio MD, where the potential energies and the gradients are calculated on the fly. From those calculations, we show comparisons of the frequencies from MD with the post vibrational self-consistent field calculations, second- and fourth-order perturbation theories, and experiments. We also apply direct ab initio MD to frequency calculations of C-H vibrational modes of tetracene and naphthalene. We conclude that MD can give the same accuracy in fundamental frequency calculation as second-order perturbation theory but the computational cost is lower for large molecules.
RESUMEN
A useful definition of orbital degeneracyform-degeneracyis introduced, which is distinct from the usual energy-degeneracy: Two canonical spatial orbitals are form-degenerate when the energy expectation value in the restricted Hartree-Fock (RHF) wave function is unaltered upon a two-electron excitation from one of these orbitals to the other. Form-degenerate orbitals tend to have isomorphic electron densities and occur in the highest-occupied and lowest-unoccupied molecular orbitals (HOMOs and LUMOs) of strongly correlated systems. Here, we present a mathematical proof of the existence of a triplet instability in a real or complex RHF wave function of a finite system in the space of real or complex unrestricted Hartree-Fock wave functions when HOMO and LUMO are energy- or form-degenerate. We also show that a singlet instability always exists in a real RHF wave function of a finite system in the space of complex RHF wave functions, when HOMO and LUMO are form-degenerate, but have nonidentical electron densities, or are energy-degenerate. These theorems provide Hartree-Fock-theory-based explanations of Hund's rule, a singlet instability in Jahn-Teller systems, biradicaloid electronic structures, and a triplet instability during some covalent bond breaking. They also suggest (but not guarantee) the spontaneous formation of a spin density wave (SDW) in a metallic solid. The stability theory underlying these theorems extended to a continuous orbital-energy spectrum proves the existence of an oscillating (nonspiral) SDW instability in one- and three-dimensional homogeneous electron gases, but only at low densities or for strong interactions.