Impact of Direct Measurement of Small Dense Low-Density Lipoprotein Cholesterol for Long-Term Secondary Prevention in Patients with Stable Coronary Artery Disease.

BACKGROUND: This study investigated whether directly measured small dense low-density lipoprotein cholesterol (D-sdLDL-C) can predict long-term coronary artery disease (CAD) events compared with low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (apoB), and estimated small dense low-density lipoprotein cholesterol (E-sdLDL-C) determined by the Sampson equation in patients with stable CAD. METHODS: D-sdLDL-C measured at Showa University between 2010 and 2022, and E-sdLDL-C were evaluated in 790 male and 244 female patients with stable CAD. CAD events, defined as sudden cardiac death, onset of acute coronary syndrome, and/or need for coronary revascularization, were monitored for 12 years. Cutoff lipid levels were determined by receiver operating characteristic curves. RESULTS: CAD events were observed in 238 male and 67 female patients. The Kaplan-Meier event-free survival curves showed that patients with D-sdLDL-C ≥32.1 mg/dL (0.83 mmol/L) had an increased risk for CAD events (P = 0.007), whereas risk in patients with E-sdLDL-C ≥36.2 mg/dL (0.94 mmol/L) was not increased. In the group with high D-sdLDL-C, the multivariable-adjusted hazard ratio (HR) was 1.47 (95% CI, 1.15-1.89), and it remained significant after adjustment for LDL-C, non-HDL-C, or apoB and in patients treated with statins. HRs for high LDL-C, non-HDL-C, or apoB were not statistically significant after adjustment for high D-sdLDL-C. Higher D-sdLDL-C was associated with enhanced risk of high LDL-C, non-HDL-C, and apoB (HR 1.73; 95% CI, 1.27-2.37). CONCLUSIONS: Higher D-sdLDL-C can predict long-term recurrence of CAD in stable CAD patients independently of apoB and non-HDL-C. D-sdLDL-C is an independent risk enhancer for secondary CAD prevention, whereas E-sdLDL-C is not.UMIN-CTR Clinical Trial Number: UMIN000027504.

Impact of malnutrition on cancer recurrence, colorectal cancer-specific death, and non-colorectal cancer-related death in patients with colorectal cancer who underwent curative surgery.

AIM: This study aimed to examine how malnutrition, as reflected by the Geriatric Nutritional Risk Index (GNRI), is associated with colorectal cancer (CRC) recurrence and cause of death. METHODS: Consecutive stage I-III CRC patients (n = 601) were divided into two groups using GNRI 98 as the cutoff. The relationship of GNRI with overall survival (OS) and recurrence-free survival (RFS) was evaluated, followed by competing risk analysis to determine prognostic factors of non-CRC-related death, and hazard function analysis to examine changes in the risk of recurrence and death. RESULTS: Median body mass index was lower in the low GNRI group than in the high GNRI group (19.8 vs. 23.5; p < 0.001). After adjusting for known prognostic factors, a low GNRI was independently associated with reduced OS/RFS, and was a significant predictor of non-CRC-related death. The risk of recurrence was higher and peaked earlier in the low GNRI group than in the high GNRI group, although after 3 years, both groups had a similar risk. Meanwhile, the low GNRI group had a higher risk of non-CRC-related death over the course of 5 years. CONCLUSION: It is important to consider preoperative nutritional status along with the cancer stage when developing strategies to improve outcomes for CRC patients.

Robotic versus open and laparoscopic pelvic exenterations for pelvic cancer: a multicenter propensity-matched analysis in Japan.

BACKGROUND: Pelvic exenteration (PE) is the last resort for achieving a complete cure for pelvic cancer; however, it is burdensome for patients. Minimally invasive surgeries, including robot-assisted surgery, have been widely used to treat malignant tumors and have also recently been used in PE. This study aimed to evaluate the safety and efficacy of robot-assisted PE (RPE) by comparing the outcomes of open PE (OPE) with those of conventional laparoscopic PE (LPE) for treating pelvic tumors. METHODS: Following the ethics committee approval, a multicenter retrospective analysis of patients who underwent pelvic exenteration between January 2012 and October 2022 was conducted. Data on patient demographics, tumor characteristics, and perioperative outcomes were collected. A 1:1 propensity score-matched analysis was performed to minimize group selection bias. RESULTS: In total, 261 patients met the study criteria, of whom 61 underwent RPE, 90 underwent OPE, and 110 underwent LPE. After propensity score matching, 50 pairs were created for RPE and OPE and 59 for RPE and LPE. RPE was associated with significantly less blood loss (RPE vs. OPE: 408 mL vs. 2385 ml, p < 0.001), lower transfusion rate (RPE vs. OPE: 32% vs. 82%, p < 0.001), and lower rate of complications over Clavien-Dindo grade II (RPE vs. OPE: 48% vs. 74%, p = 0.013; RPE vs. LPE: 48% vs. 76%, p = 0.002). CONCLUSION: This multicenter study suggests that RPE reduces blood loss and transfusion compared with OPE and has a lower rate of complications compared with OPE and LPE in patients with locally advanced and recurrent pelvic tumors.

Rapidly progressive cognitive impairment resulting in heavy psychosocial burden in a patient with Fabry disease undergoing hemodialysis: a case report.

BACKGROUND: Long-term enzyme replacement therapy (ERT) may improve prognosis in the patients with Fabry disease (FD), however, detail psychosocial burden has not been focused on long life expectancy. We experienced a male case of FD under ERT, he was placed on hemodialysis and presented rapidly progressive cognitive function. CASE PRESENTATION: A 51-year-old male patient with FD has been receiving ERT from age of 38 years. Hemodialysis was initiated at the age of 47 years. The patient experienced several attacks of cerebral infarction, and brain images demonstrated wide-spread asymptomatic ischemic lesions. His behavior became problematic at the age of 51 years. He often exhibited restlessness during hemodialysis sessions and failure to communicate effectively. The patient experienced impairment of attention and executive function, topographical disorientation, and amnesia. Consequently, it was necessary for medical staff and family members to monitor his behavior for safe extracorporeal circulation and daily life activities. Annual standardized neuropsychiatric testing revealed worsening of cognitive performance. CONCLUSIONS: Despite treating with long-term ERT, it is necessary to determine the psychosocial burden derived from the progression of cognitive impairment in patients with FD undergoing hemodialysis.

Impact of the coronavirus disease 2019 pandemic on gastric and colorectal cancer surgeries: a multicenter epidemiologic study from the Kinki region of Japan.

The coronavirus disease 2019 pandemic affected cancer surgeries and advanced cancer diagnoses; however, the trends in patient characteristics in medical institutions during this time, and the surgical approaches used are unclear. We investigated the impact of the pandemic on gastric and colorectal cancer surgeries in the Kinki region of Japan. We grouped 1688 gastric and 3493 colorectal cancer surgeries into three periods: "pre-pandemic" (April 2019-March 2020), "pandemic 1" (April 2020-March 2021), and "pandemic 2" (April 2021-September 2021), to investigate changes in the number of surgeries, patient characteristics, surgical approaches, and cancer progression after surgery. Gastric and colorectal cancer surgeries decreased from the pre-pandemic levels, by 20% and 4%, respectively, in pandemic 1, and by 31% and 19%, respectively, in pandemic 2. This decrease had not recovered to pre-pandemic levels by September, 2021. Patient characteristics, surgical approaches, and cancer progression of gastric and colorectal surgeries did not change remarkably as a result of the coronavirus disease 2019 pandemic.

Prognostic Factors of Bone Metastases From Colorectal Cancer in the Era of Targeted Therapy.

BACKGROUND: Various prognostic factors have been reported for bone metastases from different primary tumor sites. However, bone metastases from colorectal cancer are very rare, and the prognostic factors have not been investigated in detail. OBJECTIVE: This study aimed to identify prognostic factors of bone metastases from colorectal cancer. DESIGN: This is a retrospective cohort study using data from a prospectively collected database. SETTINGS: This study was conducted at a single tertiary care cancer center in Japan. PATIENTS: Patients who developed bone metastases from colorectal cancer during the study period among all patients who received initial treatment for colorectal cancer at our hospital between 2005 and 2016 (n = 4538) were included. MAIN OUTCOME MEASURES: Overall survival after diagnosis of bone metastases from colorectal cancer was the main outcome measure. RESULTS: Ninety-four patients developed bone metastases during the study period. The 5-year overall survival rate was 11.0%. Multivariable analysis identified the following independent risk factors associated with poor prognosis: ≥70 years of age at diagnosis of bone metastases (HR, 2.48; 95% CI, 1.24-4.95; p < 0.01), curative surgery not performed as initial treatment (HR, 2.54; 95% CI, 1.24-5.19; p = 0.01), multiple bone metastases (HR, 2.44; 95% CI, 1.30-4.57; p < 0.01), albumin level <3.7 g/dL (HR, 3.80; 95% CI, 1.95-7.39; p < 0.01), CEA ≥30 ng/mL (HR, 1.94; 95% CI, 1.09-3.46; p = 0.02), and less than 3 chemotherapy options remaining at diagnosis of bone metastases (HR, 2.83; 95% CI, 1.51-5.30; p < 0.01). The median survival times for patients with 0-2, 3, and 4-6 risk factors were 25.0, 8.8, and 4.3 months, respectively. LIMITATIONS: The main limitation is the single-center, retrospective design of this study. CONCLUSIONS: Our results may facilitate multidisciplinary decision-making in patients with bone metastases from colorectal cancer. See Video Abstract at http://links.lww.com/DCR/B930 . FACTORES PRONSTICOS DE LAS METSTASIS SEAS DEL CNCER COLORRECTAL EN LA ERA DE LA TERAPIA DIRIGIDA: ANTECEDENTES:Se han reportado varios factores pronósticos para las metástasis óseas de diferentes sitios de tumores primarios. Sin embargo, las metástasis óseas del cáncer colorrectal son muy raras y los factores pronósticos no se han investigado en detalle.OBJETIVO:Identificar los factores pronósticos de las metástasis óseas del cáncer colorrectal.DISEÑO:Estudio de cohorte retrospectivo utilizando datos de una base de datos recolectada prospectivamente.ENTORNO CLINICO:Un solo centro oncológico de atención terciaria en Japón.PACIENTES:Se seleccionaron pacientes que desarrollaron metástasis óseas de cáncer colorrectal durante el período de estudio entre todos los pacientes que recibieron tratamiento inicial para el cáncer colorrectal en nuestro hospital entre 2005 y 2016 (n = 4538).MEDIDA DE RESULTADO PRINCIPAL:Supervivencia general después del diagnóstico de metástasis óseas por cáncer colorrectal.RESULTADOS:Noventa y cuatro pacientes desarrollaron metástasis óseas, lo que representa el 2,0% de todos los pacientes con cáncer colorrectal que comenzaron el tratamiento durante el período de estudio. La tasa de supervivencia global a 5 años fue del 11,0 %. El análisis multivariable identificó los siguientes factores de riesgo independientes asociados con mal pronóstico: edad ≥70 años al momento del diagnóstico de metástasis óseas (hazard ratio 2,48, CI del 95 % 1,24-4,95, p < 0,01), cirugía curativa no realizada como tratamiento inicial (hazard ratio 2,54, CI 95 % 1,24-5,19, p = 0,01), metástasis óseas múltiples (hazard ratio 2,44, CI del 95 % 1,30-4,57, p < 0,01), nivel de albúmina <3,7 g/dL (hazard ratio 3,80, CI del 95 % 1,95 -7,39, p < 0,01), antígeno carcinoembrionario ≥30 ng/mL (hazard ratio 1,94, CI del 95 % 1,09-3,46, p = 0,02) y menos de 3 opciones de quimioterapia restantes al momento del diagnóstico de metástasis óseas (hazard ratio 2,83, 95 % CI 1,51-5,30, p < 0,01). La mediana de los tiempos de supervivencia para los pacientes con 0-2, 3 y 4-6 factores de riesgo fue de 25,0, 8,8 y 4,3 meses, respectivamente.LIMITACIONES:Diseño retrospectivo de un solo centro.CONCLUSIÓN:Nuestros resultados pueden facilitar la toma de decisiones multidisciplinares en pacientes con metástasis óseas de cáncer colorrectal. Consulte Video Resumen en http://links.lww.com/DCR/B930 . (Traducción- Dr. Francisco M. Abarca-Rendon ).

Level of Inferior Mesenteric Artery Ligation in Sigmoid Colon and Rectal Cancer Surgery: Analysis of Apical Lymph Node Metastasis and Recurrence.

INTRODUCTION: Whether high or low ligation of the inferior mesenteric artery (IMA) is optimal for treating sigmoid colon and rectal cancers is controversial. The present study aimed to compare outcomes of high and low ligation of the IMA and determine the adequate extent of IMA lymph node dissection. METHODS: Subjects were 455 consecutive stage I-III colorectal cancer patients who underwent curative surgery between 2011 and 2019. We assessed the association between the level of IMA ligation and overall survival and recurrence-free survival (RFS) by propensity score matching analysis. Clinicopathological features of IMA lymph node metastasis and recurrence patterns were analyzed. RESULTS: After propensity score matching, the low ligation group had a significantly worse prognosis than that of the high ligation group for RFS (p = 0.039). Positive IMA lymph nodes were associated with pathological T3 or T4 stage and N2 stage. IMA lymph node recurrences in the high ligation group occurred at the superior left side of the IMA root. In contrast, all recurrences in the low ligation group occurred at the left colic artery bifurcation. CONCLUSION: High ligation of IMA is oncologically safe. However, even with high ligation, care must be taken to ensure adequate lymph node dissection.

Evaluation of Recurrence Risk After Curative Resection for Patients With Stage I to III Colorectal Cancer Using the Hazard Function: Retrospective Analysis of a Single-institution Large Cohort.

OBJECTIVE: This study aimed to investigate transitions of recurrence hazard and peak recurrence time in patients with nonmetastatic CRC using the hazard function. SUMMARY OF BACKGROUND DATA: A postoperative surveillance period of 5 years is consistent across major guidelines for patients with nonmetastatic CRC, but surveillance intervals differ. Estimates of instantaneous conditional recurrence rate can help set appropriate intervals. METHODS: The study population consisted of 4330 patients with stage I to III CRC who underwent curative resection at the National Cancer Center Hospital between January 2000 and December 2013. Hazard rates of recurrence were calculated using the hazard function. RESULTS: Recurrence rates in patients with stage I, II, and III CRC were 4% (50/1432), 11% (136/1231), and 25% (424/1667), respectively. The hazard curve for stage I was relatively flat and hazard rates were consistently low (<0.0015) for 5 years after surgery. The hazard curve for stage II had a peak hazard rate of 0.0046 at 13.7 months, after which the curve had a long hem to the right. The hazard curve for stage III had an earlier and higher peak than that of stage II (0.0105 at 11.6 months), with a long hem to the right. CONCLUSIONS: Changes in recurrence hazard for CRC patients varied considerably by stage. Our findings suggest that short-interval surveillance might be unnecessary for stage I patients for the first 3 years after surgery, whereas short-interval surveillance for the first 3 years should be considered for stage III patients.

Impact of severe postoperative inflammatory response on recurrence after curative resection of colorectal cancer.

PURPOSE: The relationship between recurrence and systemic inflammation in the early postoperative period of colorectal cancer (CRC) is unclear, and no study has examined changes in recurrence risk resulting from postoperative inflammation. This study aimed to investigate the prognostic impact of severe postoperative inflammatory response after curative resection of CRC. METHODS: Subjects were 422 consecutive CRC patients who underwent curative surgery between 2012 and 2016, with a follow-up period of 5 years after surgery. The prognostic impacts of high and low postoperative C-reactive protein (CRP) levels were examined, and temporal changes in recurrence risk were examined using hazard function analysis. RESULTS: Patients were divided into high (n = 68) and low (n = 354) CRP groups using CRP 12.5 mg/dL as the cut-off based on receiver-operating characteristic (ROC) curve analysis. Multivariable analysis revealed that high CRP was a significant predictor of recurrence (hazard ratio: 2.21; p < 0.001). According to the hazard function of recurrence risk, the hazard rate of the low CRP group peaked at 8.4 months postoperatively (peak hazard rate: 0.0073/month) and decreased thereafter, while that of the high CRP group peaked at 5.6 months (0.0142/month) and was persistently higher than that of the low CRP group for the study duration. CONCLUSIONS: A severe inflammatory response in the early postoperative period of CRC increased the recurrence risk, and the recurrence hazard of patients with high CRP levels was earlier and persistently higher than that of patients with low CRP levels. CRC patients with high CRP levels may require more frequent follow-up.

Esophageal thermal lesions in radiofrequency ablation for atrial fibrillation: A prospective comparative study of thermal sensors.

BACKGROUND: Esophageal thermal lesion (ETL) is a complication of radiofrequency ablation for atrial fibrillation (RFAF). To prospectively compare the incidence of ETL, we used two linear, five- and three-sensor esophageal thermal monitoring catheters (ETMC5 and ETMC3). We also evaluated the predictors of ETL. METHODS: Patients receiving their first RFAF (n = 106) were randomized into two groups, ETMC5 (n = 52) and ETMC3 (n = 54). Ablation was followed by esophagogastroduodenoscopy within 3 days. RESULTS: Esophageal thermal lesion was detected in 7/106 (6.6%) patients (ETMC5: 3/52 [5.8%] vs. ETMC3: 4/54 [7.4%]; p = 1.0). The maximum temperature and number of measurements > 39.0°C did not differ between the groups (ETMC5: 40.5°C and 5.4 vs. ETMC3: 40.6°C and 4.9; p = .83 and p = .58, respectively). In ETMC5 group, the catheter had to be moved significantly less often (0.12 vs. 0.42; p = .0014) and fluoroscopy time was significantly shorter (79.2 min vs. 101.7 min; p = .0038) compared with ECMC3 group. The total number of ablations in ETMC5 group was significantly greater (50.2 vs. 37.7; p = .030) and ablation time was significantly longer (52.1 min vs. 40.1 min; p = .0039). Only body mass index (BMI) was significantly different between patients with and without ETL (21.4 ± 2.5 vs. 24.3 ± 3.4; p = .022). CONCLUSIONS: The incidence of ETL was comparable between ETMC5 and ETMC3 groups; however, fluoroscopy time, total ablation time, and total number of ablations differed significantly. Lower BMI may increase the risk of developing ETL.

Postoperative, but not preoperative, inflammation-based prognostic markers are prognostic factors in stage III colorectal cancer patients.

BACKGROUND: Recent evidence suggests that both preoperative and postoperative inflammation-based prognostic markers are useful for predicting the survival of colorectal cancer (CRC) patients. However, associations between longitudinal changes in inflammation-based prognostic markers and prognosis are controversial. METHODS: The subjects of this study were 568 patients with stage III CRC between 2008 and 2014. Preoperative and postoperative neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), C-reactive protein/albumin ratio (CAR) and lymphocyte-to-C-reactive protein ratio (LCR) were calculated to assess the inflammatory state of subjects. Subjects were stratified into three groups for each marker: preoperatively low inflammatory state (normal group), preoperatively high but postoperatively low inflammatory state (normalised group) and persistently high inflammatory state (elevated group). Multivariable analyses for overall survival (OS) and recurrence-free survival (RFS) were performed to adjust for well-established clinicopathologic factors. RESULTS: For all assessed markers, the normalised group had a significantly better prognosis than the elevated group and a similar prognosis as the normal group for both OS and RFS. CONCLUSIONS: Postoperative, but not preoperative, inflammation-based prognostic markers more accurately predict OS and RFS in patients with stage III CRC.

Laparoscopic versus Open Colectomy for Elderly Patients with Colon Cancer: A Propensity Score Analysis with the Controlling Nutritional Status (CONUT) Score.

The feasibility of laparoscopic surgery for elderly patients remains unclear, as these patients usually present with comorbidities. Recently, the controlling nutritional status (CONUT) score has drawn attention as an evaluation score of patients' general status as well as a predictor of survival. We retrospectively analyzed overall survival in 424 patients aged ≥75 years with colon cancer, who underwent curative surgery (laparoscopic (n = 167) or open surgery (n = 257)) between January 2004 and December 2013. To adjust for heterogeneity in both groups, a propensity score-matched analysis was performed, with the CONUT score as a confounding covariate. 5-year overall survival rates of patients with normal (0-1), mildly abnormal (2-4), or abnormal (≥5) CONUT score were 88.6%, 79.4%, and 41.4%, respectively (p < 0.001). T3 or less, N negative, late period (2009-2013), and normal CONUT score were associated with the tendency to undergo laparoscopic surgery (p < 0.001). The analysis of the propensity score-matched cohort (124 pairs) revealed that patients in the laparoscopic surgery group had a similar prognosis to those in the open surgery group, with a 5-year overall survival of 91.9% vs. 82.0%, respectively (p = 0.102). Laparoscopic surgery for colon cancer is an acceptable surgical approach in elderly patients.

Lymphocyte-to-C-Reactive Protein Ratio Is the Most Sensitive Inflammation-Based Prognostic Score in Patients With Unresectable Metastatic Colorectal Cancer.

BACKGROUND: Systemic inflammation contributes to the progression of malignancies. The preoperative lymphocyte-to-C-reactive protein ratio has recently been shown to predict survival of patients with colorectal cancer who undergo surgery, but its prognostic value remains unclear in patients with unresectable metastatic colorectal cancer. OBJECTIVE: This study aimed to examine the prognostic values of inflammation-based prognostic scores in patients with metastatic colorectal cancer, focusing on the lymphocyte-to-C-reactive protein ratio. DESIGN: This is a retrospective study from a prospectively collected database. SETTINGS: This study was conducted at a high-volume multidisciplinary tertiary cancer center in Japan. PATIENTS: The subjects were 756 consecutive patients with unresectable metastatic colorectal cancer who received systemic chemotherapy from 2000 to 2015. The prognostic value of the lymphocyte-to-C-reactive protein ratio was evaluated by univariable and multivariable analyses. Time-dependent receiver operating characteristics curve analysis was conducted to compare the prognostic impact of the lymphocyte-to-C-reactive protein ratio with the impact of the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, or the modified Glasgow Prognostic Score. MAIN OUTCOME MEASURES: The primary outcomes measured were the correlations of prognostic scores with overall survival. RESULTS: Median survival times of patients with high, intermediate, and low lymphocyte-to-C-reactive protein ratios were 29.4, 19.3, and 13.1 months (p < 0.001). In all subgroups according to key prognostic factors (performance status, use of targeted agents, pretreatment CEA levels, tumor sidedness, M category, and primary tumor resection), patient prognosis could be clearly stratified into 3 groups by the lymphocyte-to-C-reactive protein ratio. Multivariable analysis revealed that decreased lymphocyte-to-C-reactive protein ratio was independently associated with reduced survival (low vs high: HR 1.96, p < 0.001; intermediate vs high: HR 1.44, p < 0.001). The time-dependent receiver operating characteristics curve analysis revealed that the lymphocyte-to-C-reactive protein ratio was the most sensitive predictor of survival among all inflammation-based prognostic scores on a continuous basis. LIMITATIONS: This study was retrospective in nature. CONCLUSIONS: The lymphocyte-to-C-reactive protein ratio is a useful prognostic biomarker for unresectable metastatic colorectal cancer and could contribute to accurate prognostication and therapeutic decision making. See Video Abstract at http://links.lww.com/DCR/B600. RELACIN ENTRE LINFOCITOS Y PROTENA C ES EL SCORE PRONOSTICO INFLAMATORIO MAS SENSIBLE EN PACIENTES CON CNCER COLORRECTAL METASTSICO IRRESECABLE: ANTECEDENTES:La inflamación sistémica contribuye en la progresión de neoplasias malignas. Recientemente se ha demostrado que la proporción preoperatoria de linfocitos -proteína C reactiva predice la supervivencia de los pacientes con cáncer colorrectal que se sometieron a cirugía, pero su valor pronóstico sigue sin estar claro en pacientes con cáncer colorrectal metastásico irresecable.OBJETIVO:Evaluar el valor pronostico de los scores inflamtorios centrandose en linfocito- proteina c reactiva en pacientes con cáncer colorrectal metastásico.DISEÑO:Estudio retrospective evaluando una base de datos.AJUSTE:Este estudio se llevó a cabo en un centro oncológico terciario multidisciplinario de gran volumen en Japón.PACIENTES:Se incluyeron 756 pacientes consecutivos todos con cáncer colorrectal metastásico irresecable que recibieron quimioterapia sistémica de 2000 a 2015. El valor pronóstico de la proteína C reactiva se evaluó mediante análisis univariables y multivariables. Se realizó análisis de la curva de características operativas del receptor dependiente del tiempo para comparar el impacto pronóstico de la proteína linfocito-C-reactiva con el de la proporción de neutrófilos a linfocitos, la proporción de plaquetas a linfocitos, la proporción de linfocitos a monocitos o la proporción de puntuación pronóstica segun escala de Glasgow modificada.PRINCIPALES MEDIDAS DE RESULTADO:Correlacion de las puntuaciones pronósticas con la supervivencia global.RESULTADOS:La mediana de supervivencia de los pacientes con niveles altos, intermedios y bajos de proteína C reactiva de linfocitos fue de 29,4, 19,3 y 13,1 meses, respectivamente (p <0,001). En todos los subgrupos de acuerdo con los factores pronósticos clave (estado funcional, uso de agentes dirigidos, niveles de antígeno carcinoembrionario antes del tratamiento, lado del tumor, categoría M y resección del tumor primario), el pronóstico del paciente podría estratificarse claramente en tres grupos por linfocito a C- proteína reactiva. El análisis multivariable reveló que la disminución de linfocitos a proteína C reactiva se asoció de forma independiente con una supervivencia reducida (baja frente a alta: cociente de riesgo 1,96, p <0,001; intermedio frente a alto: cociente de riesgo 1,44, p <0,001). El análisis de la curva de características operativas del receptor dependiente del tiempo reveló que de linfocito a proteína C reactiva era el predictor de supervivencia más sensible entre todas las puntuaciones de pronóstico basadas en inflamación de forma continua.LIMITACIONES:Este estudio fue de naturaleza retrospectiva.CONCLUSIONES:La proteína C reactiva de linfocitos a C es un biomarcador pronóstico útil para el cáncer colorrectal metastásico irresecable y podría contribuir a un pronóstico preciso y a la toma de decisiones terapéuticas. Consulte Video Resumen en http://links.lww.com/DCR/B600.

Preoperative Nutritional Scores as Host-Related Prognostic Factors for Both Overall Survival and Postoperative Complications in Patients With Stage II to III Colorectal Cancer.

BACKGROUND: In the TNM eighth edition, nutritional status and inflammatory scores are newly described as host-related prognostic factors for esophageal cancer, hepatocellular carcinoma, and pancreatic cancer. However, only age and race are listed as host-related prognostic factors for colorectal cancer. OBJECTIVE: The purpose of this study was to evaluate the prognostic significance of nutritional and inflammatory scores for postoperative outcomes in patients with colorectal cancer. DESIGN: This was a retrospective study using a database that prospectively collects data. SETTINGS: The study was conducted at a high-volume multidisciplinary tertiary cancer center in Japan. PATIENTS: Study participants were 1880 consecutive patients with stage II to III colorectal cancer who underwent curative resection at the National Cancer Center Hospital between 2004 and 2012. Two nutritional scores (prognostic nutritional index and controlling nutritional status score) and 4 inflammatory scores (modified Glasgow prognostic score, neutrophil:lymphocyte ratio, platelet:lymphocyte ratio, and C-reactive protein:albumin ratio) were calculated. MAIN OUTCOME MEASURES: Correlations of nutritional scores and inflammatory scores with overall survival and postoperative complications were measured. RESULTS: After adjusting for key clinical and pathologic factors by multivariable analysis, 2 nutritional scores (prognostic nutritional index and controlling nutritional status score) and 2 inflammatory scores (neutrophil:lymphocyte ratio and C-reactive protein:albumin ratio) were independent prognostic factors for overall survival. With respect to discriminative ability, time-dependent receiver operating characteristic curves and Harrell concordance index revealed that prognostic nutritional index and controlling nutritional status score were superior to the 4 inflammatory scores for predicting overall survival. Multivariable logistic regression analyses also revealed that prognostic nutritional index, controlling nutritional status score, and C-reactive protein:albumin ratio were independent predictors for postoperative complications. LIMITATIONS: The retrospective design of the study was a limitation. CONCLUSIONS: Preoperative nutritional scores are promising host-related prognostic factors for overall survival and postoperative complications in patients with stage II and III colorectal cancer. See Video Abstract at http://links.lww.com/DCR/B587. EVALUACIN DE SCORE NUTRICIONALES PREOPERATORIOS COMO FACTORES PRONSTICOS PARA SOBREVIDA Y COMPLICACIONES POSTOPERATORIAS EN PACIENTES CON CANCER COLORECTAL ETAPA II Y III: ANTECEDENTES:En las últimas etapificaciones T-N-M, tanto el estado nutricional como inflamatorio han sido descritos como factores pronósticos en cáncer de esófago, hepático y pancreático. Sin embargo en cáncer colorectal solo la edad y la raza son enumerados como factores pronósticos.OBJETIVO:Evaluar la importancia pronóstica de los scores nutricionales e inflamatorias para los resultados posoperatorios en pacientes con cáncer colorrectal.DISEÑO:Estudio retrospectivo utilizando una base de datos.AJUSTE:Centro oncológico teciario en Japón.PACIENTES:Fueron incluidos en el estudio 1880 pacientes, consecutivos, con cancer colorectal etapa II y III sometidos a reseeción curativa en el National Cancer Center Hospital entre 2004 y 2012. Se aplicaron dos scores: nutricional (índice nutricional pronóstico y puntuación del estado nutricional) e inflamatorias (Glasgow modificada, proporción de neutrófilos a linfocitos, de plaquetas a linfocitos y de proteína C reactiva a albúmina).PRINCIPALES MEDIDAS DE RESULTADO:Evaluar scores nutricional e inflamatorio con sobrevida y complicaciones postoperatoria.RESULTADOS:Después de ajustar los factores clínicos y patológicos clave mediante análisis multivariable, dos scores nutricionales (índice nutricional pronóstico y puntuación del estado nutricional de control) y dos inflamatorias (proporción de neutrófilos a linfocitos y proporción de proteína C reactiva a albúmina) fueron pronósticos independientes factores para la sobrevida. Con respecto a la capacidad discriminativa, las curvas de características operativas del receptor, dependientes del tiempo y el índice de concordancia de Harrell, revelaron que el índice nutricional pronóstico y del estado nutricional de control eran superiores a las cuatro inflamatorias para predecir la sobrevida general. Los análisis de regresión logística multivariable también revelaron que el índice nutricional pronóstico, el estado nutricional de control y la relación proteína C reactiva / albúmina fueron predictores independientes de complicaciones postoperatorias.LIMITACIONES:Estudio de tipo retrospectivo.CONCLUSIONES:Los scores nutricionales preoperatorias son factores pronósticos prometedores relacionados con la sobrevida y las complicaciones postoperatorias en pacientes con cáncer colorrectal en estadio II y III. Consulte Video Resumen en http://links.lww.com/DCR/B587.

Comparison of model fit and discriminatory ability of the 8th edition of the tumor-node-metastasis classification and the 9th edition of the Japanese classification to identify stage III colorectal cancer.

BACKGROUND: The most widely accepted staging system for colorectal cancer (CRC) is the tumor-node-metastasis (TNM) classification. In Japan, the Japanese Classification of Colorectal, Appendiceal, and Anal Carcinoma (JCCRC) system is used. The two systems differ mainly in relation to tumor deposits (TD) and metastasis in the regional lymph nodes along the main feeding arteries and lateral pelvic lymph nodes (N3). Here, we investigated the prognostic ability of the two systems for stage III CRC. METHODS: We reviewed 696 consecutive patients who underwent curative resection of stage III CRC at the National Cancer Center Hospital between May 2007 and April 2014. We examined the clinicopathological features of CRC and predicted overall survival (OS) and relapse-free survival (RFS) according to the 8th TNM and 9th JCCRC systems. The systems were compared using Akaike's information criterion (AIC), Harrell's concordance index (C-index), and time-dependent receiver-operating characteristic (ROC) curves. RESULTS: The 9th JCCRC system was more clinically effective according to AIC (OS, 1199 vs. 1206; RFS, 2047 vs. 2057), showed better discriminatory ability according to the C-index (OS, 0.65 vs. 0.62; RFS, 0.62 vs. 0.58), and its time-dependent ROC curve was superior compared with the 8th TNM system. CONCLUSION: These results suggest that the 9th JCCRC system has superior discriminative ability to the 8th TNM system, because the 9th JCCRC accounts for the presence of TD and N3 disease, which were both significant predictors of poor prognosis. Reconsidering the clinical value of these two factors in the TNM system could improve its clinical significance.

Nutritional and inflammatory measures predict survival of patients with stage IV colorectal cancer.

BACKGROUND: This study aimed to evaluate the prognostic impact of nutritional and inflammatory measures (controlling nutritional status (CONUT) score, prognostic nutritional index (PNI), and modified Glasgow prognostic score (mGPS)) on overall survival (OS) in patients with stage IV colorectal cancer (CRC). METHODS: Subjects were 996 patients with stage IV CRC who were referred to the National Cancer Center Hospital between 2001 and 2015. We retrospectively investigated correlations between OS and CONUT score, PNI, and mGPS. Multivariate analyses were performed using Cox proportional hazards regression models. RESULTS: After adjusting for known factors (age, gender, BMI, ECOG performance status, location of primary tumor, CEA levels, histological type, M category, and prior surgical treatment), all three measures were found to be independent prognostic factors for OS in patients with stage (CONUT score, p < 0.001; PNI, p < 0.001; mGPS, p < 0.001). Significant differences in OS were found between low CONUT score (0/1) (n = 614; 61%) and intermediate CONUT score (2/3) (n = 276; 28%) (hazard ratio (HR) = 1.20, 95% confidence interval (CI): 1.02-1.42, p = 0.032), and intermediate CONUT score and high CONUT score (≥4) (n = 106; 11%) (HR = 1.30, 95% CI: 1.01-1.67, p = 0.045). Significant differences in OS were found between mGPS = 0 (n = 633; 64%) and mGPS = 1 (n = 234; 23%) (HR = 1.84, 95% CI: 1.54-2.19, p < 0.001), but not between mGPS = 1 and mGPS = 2 (n = 129; 13%) (HR = 1.12, 95% CI: 0.88-1.41, p = 0.349). Patients with low PNI (< 48.0) (n = 443; 44%) showed a significantly lower OS rate than those with high PNI (≥48.0) (n = 553; 56%) (HR = 1.39, 95% CI: 1.19-1.62, p < 0.001). CONCLUSIONS: CONUT score, PNI, and mGPS were found to be independent prognostic factors for OS in patients with stage IV CRC, suggesting that nutritional and inflammatory status is a useful host-related prognostic indicator in stage IV CRC.

MazF activation causes ACA sequence-independent and selective alterations in RNA levels in Escherichia coli.

Escherichia coli MazF is a toxin protein that cleaves RNA at ACA sequences. Its activation has been thought to cause growth inhibition, primarily through indiscriminate cleavage of RNA. To investigate responses following MazF activation, transcriptomic profiles of mazF-overexpressing and non-overexpressing E. coli K12 cells were compared. Analyses of differentially expressed genes demonstrated that the presence and the number of ACA trimers in RNA was unrelated to cellular RNA levels. Mapping differentially expressed genes onto the chromosome identified two chromosomal segments in which upregulated genes formed clusters, and these segments were absent in the chromosomes of E. coli strains other than K12. These results suggest that MazF regulates selective, rather than indiscriminate, categories of genes, and is involved in the regulation of horizontally acquired genes. We conclude that the primary role of MazF is not only cleaving RNA indiscriminately but also generating a specific cellular state.

Effective silicon production from SiCl4 source using hydrogen radicals generated and transported at atmospheric pressure.

In the Siemens method, high-purity Si is produced by reducing SiHCl3 source gas with H2 ambient under atmospheric pressure. Since the pyrolysis of SiHCl3, which produces SiCl4 as a byproduct, occurs dominantly in the practical Siemens process, the Si yield is low (~30%). In the present study, we generated hydrogen radicals (H-radicals) at pressures greater than 1 atm using tungsten filaments and transported the H-radicals into a reactor. On the basis of the absorbance at 600 nm of WO3-glass exposed to H-radicals in the reactor, we observed that H-radicals with a density of ~1.1 × 1012 cm-3 were transported approximately 30 cm under 1 atm. When SiCl4 was supplied as a source into the reactor containing H-radicals and allowed to react at 850°C or 900°C, Si was produced more efficiently than in reactions conducted under H2 ambient. Because the H-radicals can effectively reduce SiCl4, which is a byproduct in the Siemens method, their use is expected to increase the Si yield for this method.

Long-term outcomes after surgical dissection of inguinal lymph node metastasis from rectal or anal canal adenocarcinoma.

BACKGROUND: The 8th edition of the tumor-node-metastasis (TNM) classification classifies inguinal lymph nodes as regional lymph nodes for anal canal carcinoma but non-regional lymph nodes for rectal carcinoma. This difference might reflect the different prognosis of inguinal lymph node metastasis from anal canal carcinoma and rectal carcinoma. However, long-term outcomes of inguinal lymph node metastasis from rectal or anal canal adenocarcinoma are unclear, which we aimed to investigate in this study. METHODS: The study population included 31 consecutive patients with rectal or anal canal adenocarcinoma who underwent inguinal lymph node dissection with curative intent at the National Cancer Center Hospital from 1986 to 2017. Long-term outcomes were assessed and clinicopathologic variables analyzed for prognostic significance. RESULTS: Of the 31 patients, 12 patients had rectal adenocarcinoma and 19 patients had anal canal adenocarcinoma. Synchronous metastasis were observed in 14 patients and metachronous metastasis in 17 patients. After dissection of inguinal lymph node metastasis with curative intent, the 5-year overall survival rate was 55.2%, with 12 patients surviving for more than 5 years. Median survival time was 66.6 months. Multivariate analyses revealed that location of primary tumor (rectum versus anal canal) was not a prognostic factor, whereas lateral lymph node metastasis and histological findings were independent prognostic factors. CONCLUSION: Given the good prognosis, inguinal lymph node metastasis in patients with rectal or anal canal adenocarcinoma appears to be regional rather than distant. If R0 resection can be achieved, inguinal lymph node dissection may be indicated for these patients.

J-Wave Elevation in the Inferior Leads Predicts Lethal Ventricular Arrhythmia Initiated by Premature Ventricular Contractions With Right Bundle Branch Block and Superior Axis.

BACKGROUND: Lethal ventricular arrhythmia (VA) can be initiated by idiopathic premature ventricular contractions (PVCs) originating from the left ventricular (LV) inferior wall. Furthermore, J-wave elevation in the inferior leads on ECG is sometimes associated with lethal VA. However, the relationship between these PVCs and J-wave elevation in patients with lethal VA is unclear, so we investigated it in the present study.Methods and Results:We studied 32 consecutive patients who underwent radiofrequency (RF) ablation of idiopathic PVCs with right bundle branch block (RBBB) and superior axis. Thee PVCs were originating from the inferior wall of the LV. Lethal VA was defined as ventricular fibrillation (VF) or ventricular tachycardia (VT) with loss of consciousness (LOC). Among 32 patients, 3 had VF and 2 had VT with LOC. Other 27 had non-lethal VA. Baseline clinical characteristics were not significantly difference between lethal and non-lethal VA. The ratio of J-wave elevation in lethal VA was significantly higher as compared with non-lethal VA (100% vs. 11.1%, P<0.0001). Furthermore, no patients with J-wave elevation in the inferior leads had recurrence of lethal VA after RF ablation of the PVCs. CONCLUSIONS: We speculate that J-wave elevation in the inferior leads might be a predictor of lethal VA initiated by PVCs with RBBB and superior axis. RF ablation of these PVCs was a useful method of treating lethal VA.