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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.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.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.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.

Purpose The impact of malnutrition on colorectal cancer (CRC) recurrence and cause of death remains poorly understood. The present study aimed to examine how malnutrition, as reflected by the Geriatric Nutritional Risk Index (GNRI), is associated with CRC recurrence and cause of death.Methods Subjects were 601 consecutive stage I-III CRC patients who underwent curative surgery between 2011 and 2017. We divided patients into two groups using GNRI 98 as the cut-off and evaluated the relationship of GNRI with overall survival (OS) and recurrence-free survival (RFS). Competing risk analysis was performed to determine prognostic factors of non-CRC-related death. Hazard functions were then used to examine changes in the risk of recurrence and death in each GNRI group over time.Results The low GNRI group predicted significantly worse OS and RFS in multivariable analyses. Moreover, Fine-Gray model regression revealed that the low GNRI group was a significant predictor of non-CRC-related death. Hazard rate of recurrence and death in the low GNRI was approximately double that observed in the high GNRI group over 5 years; meanwhile, the hazard rate for recurrence in the low GNRI group was similar to that in the high GNRI group after 3 years. Meanwhile, the low GNRI group had a higher risk of non-CRC-related death over the course of 5 years.Conclusions While preoperative malnutrition has a strong prognostic impact, its effect over time differs when endpoints are considered separately. These findings provide valuable information regarding healthcare prioritization during CRC survivorship.

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.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.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.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.

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.To identify prognostic factors of bone metastases from colorectal cancer.Retrospective cohort study using data from a prospectively collected database.A single tertiary care cancer center in Japan.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 targeted.Overall survival after diagnosis of bone metastases from colorectal cancer.Ninety-four patients developed bone metastases, accounting for 2.0% of all patients with colorectal cancer who started treatment 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: age ≥70 years at diagnosis of bone metastases (hazard ratio 2.48, 95% CI 1.24-4.95, p0.01), curative surgery not performed as initial treatment (hazard ratio 2.54, 95% confidence interval 1.24-5.19, p = 0.01), multiple bone metastases (hazard ratio 2.44, 95% CI 1.30-4.57, p0.01), albumin level3.7 g/dL (hazard ratio 3.80, 95% CI 1.95-7.39, p0.01), carcinoembryonic antigen ≥30 ng/mL (hazard ratio 1.94, 95% confidence interval 1.09-3.46, p = 0.02), and3 chemotherapy options remaining at diagnosis of bone metastases (hazard ratio 2.83, 95% CI 1.51-5.30, p0.01). 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.Single-center, retrospective design.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.

This paper investigates the coplanar and circular three-body problem in the parametrized post-Newtonian (PPN) formalism, for which we focus on a class of fully conservative theories characterized by the Eddington-Robertson parameters $\beta$ and $\gamma$. It is shown that there can still exist a collinear equilibrium configuration and a triangular one, each of which is a generalization of the post-Newtonian equilibrium configuration in general relativity. The collinear configuration can exist for arbitrary mass ratio, $\beta$, and $\gamma$. On the other hand, the PPN triangular configuration depends on the nonlinearity parameter $\beta$ but not on $\gamma$. For any value of $\beta$, the equilateral configuration is possible, if and only if three finite masses are equal or two test masses orbit around one finite mass. For general mass cases, the PPN triangle is not equilateral as in the post-Newtonian case. It is shown also that the PPN displacements from the Lagrange points in the Newtonian gravity $L_1$, $L_2$ and $L_3$ depend on $\beta$ and $\gamma$, whereas those to $L_4$ and $L_5$ rely only on $\beta$., Comment: 8 pages, 2 figures, typos corrected, version matched with publication in PRD

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., In transitioning from the TNM 7th edition to the TNM 8th edition, colorectal cancer with peritoneal metastasis was newly categorized as M1c, and in the Japanese Classification (9th edition), M1c is further subdivided into M1c1 (without other organ involvement) and M1c2 (with other organ involvement). To date, no study has compared the model fit and discriminatory ability of the M category of these three classification systems. In this study, with 1222 consecutive stage IV colorectal cancer patients, we clearly demonstrated that, by comparing AIC, Harrell's c‐index, and time‐dependent ROC curves between the three classification systems, while the revised M category definition did not improve model fit and discriminatory ability from TNM 7th edition to the TNM 8th edition, further subdivision of M1c in the Japanese Classification improved these parameters.

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.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.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).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.

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.

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 (

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 (

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

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 inflamacion sistemica contribuye en la progresion de neoplasias malignas. Recientemente se ha demostrado que la proporcion preoperatoria de linfocitos -proteina C reactiva predice la supervivencia de los pacientes con cancer colorrectal que se sometieron a cirugia, pero su valor pronostico sigue sin estar claro en pacientes con cancer colorrectal metastasico irresecable.OBJETIVO:Evaluar el valor pronostico de los scores inflamtorios centrandose en linfocito- proteina c reactiva en pacientes con cancer colorrectal metastasico.DISENO:Estudio retrospective evaluando una base de datos.AJUSTE:Este estudio se llevo a cabo en un centro oncologico terciario multidisciplinario de gran volumen en Japon.PACIENTES:Se incluyeron 756 pacientes consecutivos todos con cancer colorrectal metastasico irresecable que recibieron quimioterapia sistemica de 2000 a 2015. El valor pronostico de la proteina C reactiva se evaluo mediante analisis univariables y multivariables. Se realizo analisis de la curva de caracteristicas operativas del receptor dependiente del tiempo para comparar el impacto pronostico de la proteina linfocito-C-reactiva con el de la proporcion de neutrofilos a linfocitos, la proporcion de plaquetas a linfocitos, la proporcion de linfocitos a monocitos o la proporcion de puntuacion pronostica segun escala de Glasgow modificada.PRINCIPALES MEDIDAS DE RESULTADO:Correlacion de las puntuaciones pronosticas con la supervivencia global.RESULTADOS:La mediana de supervivencia de los pacientes con niveles altos, intermedios y bajos de proteina C reactiva de linfocitos fue de 29,4, 19,3 y 13,1 meses, respectivamente (p

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., Highlights • Lateral lymph node (LLN) metastasis is rarely reported in synchronous rectal and prostate cancer. • LLN metastasis impacts staging in synchronous rectal and prostate cancer. • Preoperative identification of the origin of LLN metastasis is difficult in such cases. • LLN dissection may be useful to assess progression and treatment of synchronous cancers.

A 55-year-old-man underwent laparoscopic sigmoidectomy for sigmoid colon cancer. Preoperative barium enema showed a slightly medial displacement of the descending colon, and the sigmoid colon was quite long. The operative findings showed that the descending colon was not fused with the retroperitoneum and shifted to the midline and the left colon adhered to the small mesentery and right pelvic wall. Thus, a diagnosis of persistent descending mesocolon (PDM) was made. The left colon, sigmoid colon, and superior rectal arteries often branch radially from the inferior mesenteric artery. The sigmoid mesentery shortens, and the inferior mesenteric vein is often close to the marginal vessels. By understanding the anatomical feature of PDM and devising surgical techniques, laparoscopic sigmoidectomy for sigmoid colon cancer with PDM could be performed without compromising its curative effect and safety.

Signs of anisotropy of the ultra-high-energy cosmic ray (UHECR) arrival direction have been reported by The Telescope Array and The Pierre Auger Observatory. Then, it is expected that source of UHECRs will be clarified. However, because of the quite low flux of UHECR, it is inevitable to extend observatory to much larger than existing ones. Cosmic Ray Fluorescence Fresnel lens Telescope (CRAFFT) project has been developed a low cost fluorescence detector to realize the huge observatory for UHECR observation. CRAFFT project reduced the cost to 1/10 against fluorescence detectors now in use, and succeeded to observe UHECR air showers by the prototype of CRAFFT telescope. In this presentation, we report the progress of CRAFFT project such as the result of the test observation and data analysis and discuss the future prospect.

Hiroshi Saito,1 Yuya Nakamura,2,3 Masahiro Inagaki,2,4 Shiho Yamadera,5 Hideo Misawa,2,3 Naoki Sato,2,6 Tatsunori Oguchi,2 Takae Inagaki,7 Yuya Tsuji,2 Mayumi Tsuji,2 Isao Ohsawa,3 Hiromichi Gotoh,3 Yuji Kiuchi2 1JA Hiroshima Genneral Hospital, Hatsukaichi City, Hiroshima, Japan; 2Department of Pharmacology, Showa University School of Medicine, Shinagawa-ku, Tokyo, Japan; 3Saiyu Soka Hospital, Soka City, Saitama, Japan; 4Faculty of Arts and Sciences at Fujiyoshida, Showa University, Fujiyoshida City, Yamanashi, Japan; 5Department of Hospital Pharmaceutics, Showa University School of Pharmacy, Shinagawa-ku, Tokyo, Japan; 6Department of Research Center, Tanabe Pharmacy Inc., Chuo-ku, Tokyo, Japan; 7Graduate School of Nursing and Rehabilitation Science, Yokohama City, Kanagawa, JapanCorrespondence: Yuya Nakamura Email y.nakamura@med.showa-u.ac.jpPurpose: 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.Keywords: lipopolysaccharide, U937 cells, fetal bovine serum, anti- toll-like receptor 4 antibody, interleukin-6

Background Preoperative and early postoperative serum carcinoembryonic antigen (CEA) levels are known prognostic factors in rectal cancer. Recently, a large‐scale study on colon cancer revealed that “preoperatively elevated and postoperatively normalized CEA levels” is not an indicator of poor prognosis. However, whether this hold true in rectal cancer patients is unknown. This study aimed to investigate the prognostic significance of preoperatively elevated and postoperatively normalized CEA levels in rectal cancer patients undergoing curative resection. Methods Subjects were consecutive stage I‐III rectal cancer patients who underwent curative resection without preoperative treatment at National Cancer Center Hospital between 2000 and 2015. Overall survival (OS) and the hazard function of recurrence or death were analyzed according to the CEA levels, as follows: normal preoperative CEA (normal group), preoperatively elevated but postoperatively normalized CEA (normalized group), and preoperatively and postoperatively elevated CEA (elevated group). Results The normalized group (n =235) had worse OS (HR 1.49, 95% CI 1.08‐2.04; P = .0142) compared to the normal group (n = 1208), and better OS compared to the elevated group (n = 47) (HR 0.53, 95% CI 0.31‐0.91; P = .0208). The elevated group had the highest and earliest peak in hazard function, followed by the normalized group and the normal group, with median times to recurrence of 8.8, 15.5, and 18.5 months, respectively (P = .0223). Conclusions Prognosis after resection of rectal cancer was worse in patients with preoperatively elevated and postoperatively normalized CEA compared to those with normal preoperative CEA. Patients with elevated preoperative CEA might require intensive follow‐up even if levels normalize after resection, especially in earlier periods, for early detection of recurrence., Recently, a large‐scale study on colon cancer revealed that “preoperatively elevated and postoperatively normalized CEA levels” is not an indicator of poor prognosis. In this study, we demonstrated that, in rectal cancer, “preoperatively elevated and postoperatively normalized CEA levels” is a definitive indicator of poor prognosis.

Ceftriaxone-associated biliary pseudolithiasis is common among children; however, there are only a few reports of pseudolithiasis in adult patients on HD. This retrospective cohort study included 278 adult patients on ceftriaxone therapy from 1 February 2016 to 1 September 2018. Pseudolithiasis was defined as a new development of sludge or stones in the gallbladder within 60 days of ceftriaxone therapy. After excluding patients with preexisting gallstones and a history of cholecystectomy, 113 patients on maintenance HD, and another 98 patients were enrolled as the HD and control group, respectively. Thirteen patients developed pseudolithiasis. Its incidence was significantly higher in the HD group than that in the control group. Multivariate logistic regression analyses showed that development of pseudolithiasis was significantly associated with HD and ceftriaxone dose. Therefore, HD in patients receiving ceftriaxone therapy appears to be associated with a risk of pseudolithiasis. These findings highlight the need for careful follow-up.