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.

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.

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.

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 ).

Integrated gut microbiome and metabolome analyses identified fecal biomarkers for bowel movement regulation by Bifidobacterium longum BB536 supplementation: A RCT.

Background: Bifidobacterium longum BB536 supplementation can be used to regulate bowel movements in various people, including healthy subjects and patients with irritable bowel syndrome (IBS); however, individuals vary in their responses to B. longum BB536 treatment. One putative factor is the gut microbiota; recent studies have reported that the gut microbiota mediates the effects of diet or drugs on the host. Here, we investigated intestinal features, such as the microbiome and metabolome, related to B. longum BB536 effectiveness in increasing bowel movement frequency. Results: A randomized, double-blind controlled crossover trial was conducted with 24 adults who mainly tended to be constipated. The subjects received a two-week dietary intervention consisting of B. longum BB536 in acid-resistant seamless capsules or similarly encapsulated starch powder as the placebo control. Bowel movement frequency was recorded daily, and fecal samples were collected at several time points, and analyzed by metabologenomic approach that consists of an integrated analysis of metabolome data obtained using mass spectrometry and microbiome data obtained using high-throughput sequencing. There were differences among subjects in B. longum intake-induced bowel movement frequency. The responders were predicted by machine learning based on the microbiome and metabolome features of the fecal samples collected before B. longum intake. The abundances of eight bacterial genera were significantly different between responders and nonresponders. Conclusions: Intestinal microbiome and metabolome profiles might be utilized as potential markers of improved bowel movement after B. longum BB536 supplementation. These findings have implications for the development of personalized probiotic treatments.

Digital workflows for pathological assessment of rat estrous cycle stage using images of uterine horn and vaginal tissue.

Assessment of the estrous cycle of mature female mammals is an important component of verifying the efficacy and safety of drug candidates. The common pathological approach of relying on expert observation has several drawbacks, including laborious work and inter-viewer variability. The recent advent of image recognition technologies using deep learning is expected to bring substantial benefits to such pathological assessments. We herein propose 2 distinct deep learning-based workflows to classify the estrous cycle stage from tissue images of the uterine horn and vagina, respectively. These constructed models were able to classify the estrous cycle stages with accuracy comparable with that of expert pathologists. Our digital workflows allow efficient pathological assessments of the estrous cycle stage in rats and are thus expected to accelerate drug research and development.

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.

Association of nutritional risk and systemic inflammation with survival in patients with colorectal cancer who underwent curative surgery.

BACKGROUND & AIMS: Malnutrition and inflammation adversely affect the prognosis of patients with cancer. The Geriatric Nutritional Risk Index (GNRI) and systemic inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), lymphocyte-to-C reactive protein ratio (LCR), and C-reactive protein-to-albumin ratio (CAR), predict survival in colorectal cancer (CRC) patients. The present study aimed to examine the association of these two factors with CRC survival. METHODS: Subjects were 433 consecutive CRC patients who underwent curative surgery between 2013 and 2018. Patients were stratified by nutritional status, and relationships between overall survival (OS) and systemic inflammation were evaluated. The prognostic impact of combinations of the GNRI and inflammatory markers was assessed. Multivariable analyses were also performed. RESULTS: All assessed biomarkers predicted OS in univariable analysis (GNRI:P < 0.001, NLR:P = 0.048, LMR:P = 0.001, LCR:P = 0.010, CAR: P = 0.039). Stratified analysis showed that each inflammatory marker had a prognostic impact on OS in the low GNRI group (NLR:P = 0.028, LMR:P = 0.003, LCR:P = 0.05, CAR:P = 0.009). In contrast, inflammatory markers had no prognostic impact on OS in the high GNRI group. The combination of malnutrition and systemic inflammation had a high prognostic value (all P < 0.016). The multivariable analysis revealed that a low GNRI (hazard ratio: 2.58-2.89) was independently associated with reduced survival, whereas none of the inflammatory markers independently predicted poor prognosis. CONCLUSIONS: The GNRI is a useful prognostic biomarker for CRC patients, whereas systemic inflammatory markers can only serve as prognostic factors when patient nutritional status is taken into account. The combination of malnutrition and systemic inflammation may enhance the accuracy of prognostic prediction.

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.

Linagliptin Inhibits Interleukin-6 Production Through Toll-Like Receptor 4 Complex and Lipopolysaccharide-Binding Protein Independent Pathway in vitro Model.

PURPOSE: Lipopolysaccharides (LPS) induce inflammation by binding to the Toll-like receptor (TLR) 4 complex, including LPS-binding protein (LBP). The anti-inflammatory effects of linagliptin in LPS-induced inflammation in the TLR4-independent pathway have not been examined before. We examined the anti-inflammatory effects of linagliptin in the TLR4- and the LBP-independent pathway. METHODS: U937 cells were cultured in the medium supplemented with 10% fetal bovine serum (FBS) and treated with 100 nM phorbol myristate acetate for 48 h. Cells were then left untreated or were treated with 10 µg/mL anti-TLR4 antibodies alone or in combination with linagliptin for 1 h in media supplemented with or without 10% FBS. The cells were divided into 5 groups: a) control cells (untreated) b) cells treated with LPS c) cells treated with 10 µg/mL anti-TLR4 antibodies d) cells treated with LPS and 10 µg/mL anti-TLR4 antibodies and e) cells treated with LPS, 10 µg/mL anti-TLR4 antibodies, and linagliptin. The LPS concentrations used were 50 pg/mL or 100 pg/mL for cells treated in the presence of 10% FBS and 100 pg/mL or 1 µg/mL for cells treated in the absence of FBS. Linagliptin concentrations of 1 nM, 10 nM, and 100 nM were used for treatment. The supernatants were analyzed for interleukin (IL)-6 production after 24 h of various treatments. RESULTS: LPS increased IL-6 production compared to the untreated control cells, and anti-TLR4 antibody suppressed LPS-induced increased IL-6 levels. Linagliptin suppressed LPS-induced IL-6 production in a concentration-dependent manner in the presence of FBS. However, only 100 nM linagliptin could suppress LPS-induced IL-6 production in the absence of FBS. CONCLUSION: Concentration-dependent and -independent inflammatory suppression was observed following linagliptin treatment after LPS induction in an experimental model of TLR4 inhibition by anti-TLR4 antibodies. Our results showed that linagliptin may inhibit inflammation through multiple mechanisms centered around the TLR-4-mediated pathway.

Advanced synchronous rectal and prostate cancers diagnosed by lateral lymph node dissection: A case report.

INTRODUCTION: Rectal and prostate cancers are common cancers occurring globally, and both can metastasize to the pelvic lateral lymph nodes (LLNs). PRESENTATION OF CASE: A 69-year-old man, presenting with blood in stool, was diagnosed with rectal cancer. Computed tomography revealed a 7-mm LLN in the right internal iliac artery region, leading to the suspicion of metastasis. The patient underwent laparoscopic low anterior resection and LLN dissection. Histopathological findings of the metastatic tissue in the LLN were different than that of rectal cancer, and endocrine tumor was suspected. Immunostaining performed based on high serum prostate-specific antigen (PSA) level revealed positivity for PSA and α-methylacyl-CoA racemase in the dissected LLN. Thus, he was diagnosed with synchronous rectal and prostate cancers and received hormonal therapy for stage IV prostate cancer, which led to a dramatic reduction in PSA level after three months. He was followed regularly and did not relapse or experienced disease progression for either cancer for approximately four years after the initial diagnosis. DISCUSSION: Few studies reported synchronous rectal and prostate cancers, both of which can metastasize to pelvic LLNs. However, preoperative diagnosis of the primary cancer metastasizing to the LLNs is challenging. Treatment of synchronous rectal and prostate cancers requires a strategy to diagnose each tumor stage and corresponding degree of progression because lymph node metastases affect staging in both cancers. CONCLUSION: Lymph node dissection may be useful in determining progression and treatment plan in cases of concurrent rectal and prostate cancers with suspected LLN metastasis.

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.

Comparison of model fit and discriminatory ability of M category as defined by the 7th and 8th editions of the tumor-node-metastasis classification of colorectal cancer and the 9th edition of the Japanese classification.

BACKGROUND: In transitioning from the 7th edition of the tumor-node-metastasis classification (TNM-7) to the 8th edition (TNM-8), colorectal cancer with peritoneal metastasis was newly categorized as M1c. In the 9th edition of the Japanese Classification of colorectal, appendiceal, and anal carcinoma (JPC-9), M1c is further subdivided into M1c1 (without other organ involvement) and M1c2 (with other organ involvement). This study aimed to compare the model fit and discriminatory ability of the M category of these three classification systems, as no study to date has made this comparison. METHODS: The study population consisted of stage IV colorectal cancer patients who were referred to the National Cancer Center Hospital from 2000 to 2017. The Akaike information criterion (AIC), Harrell's concordance index (C-index), and time-dependent receiver operating characteristic (ROC) curves were used to compare the three classification systems. Subgroup analyses, stratified by initial treatment year, were also performed. RESULTS: According to TNM-8, 670 (55%) patients had M1a, 273 (22%) had M1b, and 279 (23%) had M1c (87 M1c1 and 192 M1c2 using JPC-9) tumors. Among the three classification systems, JPC-9 had the lowest AIC value (JPC-9: 10546.3; TNM-7: 10555.9; TNM-8: 10585.5), highest C-index (JPC-9: 0.608; TNM-7: 0.598; TNM-8: 0.599), and superior time-dependent ROC curves throughout the observation period. Subgroup analyses were consistent with these results. CONCLUSIONS: While the revised M category definition did not improve model fit and discriminatory ability from TNM-7 to TNM-8, further subdivision of M1c in JPC-9 improved these parameters. These results support further revisions to M1 subcategories in future editions of the TNM classification system.

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.

The Nutritional Efficacy of Chlorella Supplementation Depends on the Individual Gut Environment: A Randomised Control Study.

Recent studies have accumulated evidence that the intestinal environment is strongly correlated with host diet, which influences host health. A number of dietary products whose mechanisms of influence operate via the gut microbiota have been revealed, but they are still limited. Here, we investigated the dietary influence of Chlorella, a green alga commercially available as a dietary supplement. A randomised, double-blind, placebo-controlled crossover trial including 40 Japanese participants with constipation was performed. In this study, the primary outcome and secondary outcome were set as defecation frequency and blood folate level, respectively. In both outcomes, no significant differences were detected compared to the control intake. Therefore, we analysed the gut microbiome, gut metabolome, and blood parameters in an integrated manner as an exploratory analysis. We revealed that the consumption of Chlorella increased the level of several dicarboxylic acids in faeces. Furthermore, the analysis showed that individuals with low concentrations of faecal propionate showed an increase in propionate concentration upon Chlorella intake. In addition, increasing blood folate levels were negatively correlated with defecation frequency at baseline. Our study suggested that the effect of Chlorella consumption varies among individuals depending on their intestinal environment, which illustrates the importance of stratified dietary management based on the intestinal environment in individuals.

CT findings in a patient with Coronavirus Disease-19-associated acute pericarditis.

Coronavirus Disease-19 (COVID-19)-associated acute pericarditis is a rare complication. Several cases have been reported, but those reports have not discussed any imaging findings. Here, we report a case of a 76-year-old female diagnosed with COVID-19-associated pericarditis without pneumonia, and present image findings of the patient's contrast-enhanced CT.

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.

Survey of actual conditions of erythema marginatum as a prodromal symptom in Japanese patients with hereditary angioedema.

BACKGROUND: Hereditary angioedema (HAE) is a rare but life-threatening condition. HAE types I and II (HAE-1/2) result from C1-inhibitor (C1-INH) deficiency. However, recent genetic analysis has established a new type of HAE with normal C1-INH (HAEnC1-INH). The mutations of factor XII, plasminogen, angiopoietin 1, and kininogen 1 genes may be the cause of HAEnC1-INH. Nevertheless, other causative molecules (HAE-unknown) may be involved. The Japanese therapeutic environment for HAE has been improving owing to the self-subcutaneous injection of icatibant, which was approved for the treatment of acute attack and enables early therapy. Erythema marginatum (EM) is a visible prodromal symptom which occasionally occurs prior to an angioedema attack; hence, recognizing the risk of an acute attack is important for early treatment. However, the detailed characteristics of EM remain unclear. In this study, we first investigated the clinical manifestations of EM in Japanese patients with HAE. METHODS: A 20-point survey was developed and distributed to 40 physicians to gather clinical data on EM from patients with HAE. RESULTS: Data on 68 patients with HAE (58 patients with HAE-1/2 and 10 patients with HAE-unknown) were collected. Of the patients with HAE-1/2, 53.4% experienced EM, whereas 43.1% did not. The forearm was the most frequent area of EM (64.5%), followed by the abdomen (29.0%) and upper arm and precordium (19.3%). Of the HAE-1/2 patients with EM, 41.9% always had angioedema following EM, while 29.0% always had colocalization of EM with angioedema. Moreover, 3.2% showed a correlation between the awareness of EM and severity of an angioedema attack. In 60.9% of HAE-1/2 patients with EM, the interval between the awareness of EM and appearance of angioedema was <3 h. Of the patients with HAE-unknown, 30.0% also experienced EM. CONCLUSION: We confirmed that more than one-half of Japanese patients with HAE-1/2 and one-third of those with HAE-unknown develop EM as the prodromal symptom of an angioedema attack. Physicians should communicate the significance of EM to patients with HAE to prepare them for possible imminent attacks.