[A Case of UFT/LV-Induced Acute Liver Failure after Surgery for Sigmoid Colon Cancer].

Oral uracil and tegafur plus Leucovorin(UFT/LV)therapy is one of the standard adjuvant chemotherapies for colorectal cancer, and is widely used without any serious adverse events. Herein, we describe a case of UFT/LV-induced acute liver failure in a 75-year-old woman who underwent laparoscopic sigmoidectomy for sigmoid colon cancer. She was diagnosed with advanced colon cancer and lymph node metastasis by postoperative histopathological analysis, and adjuvant chemotherapy was initiated. After 30 days of commencing the therapy, the patient visited our hospital with complaints of severe diarrhea and difficulty in food intake. The apparent cause of these symptoms was unclear on computed tomography(CT), and mild liver damage was revealed in blood test results. The hepatic disorder gradually progressed after the hospitalization, and the condition was diagnosed as acute hepatic insufficiency. Additionally, obvious atrophy of the liver parenchyma and significant ascites were confirmed on CT. Two months later, the platelet count decreased markedly, but fortunately, no bleeding occurred. There has been no recurrence since 2 years after the surgery without any additional adjuvant therapy.

Postoperative Complications Associated With Intra- Versus Extracorporeal Anastomosis for Laparoscopic Right Colectomy.

OBJECTIVE: To compare the postoperative complications of intracorporeal anastomosis (ICA) and extracorporeal anastomosis (ECA) in patients undergoing laparoscopic right colectomy (LRC). BACKGROUND: Although several studies have compared postoperative complications of ICA and ECA after LRC, most were retrospective studies. METHODS: We performed a comprehensive electronic search of the literature to identify studies that compared postoperative complications between ICA and ECA in patients who underwent LRC. We performed meta-analysis using random-effects models to calculate the risk ratio (RR) and 95% confidence interval (CI) of experiencing complications, and we analyzed heterogeneity using I2 statistics. RESULTS: Fifteen studies consist of randomized controlled trials, case-control studies, and propensity score matching studies involving a total of 3219 patients who underwent LRC were included. Among 1377 patients who received ICA, 255 (18.5%) had postoperative complications, whereas among 1652 patients who received ECA, 373 (22.6%) had such complications. The results of the meta-analysis revealed that ICA was associated with a significantly reduced risk of postoperative complications (RR, .73; 95% CI: .57-.95; P = .02; I2 = 57%) compared with ECA. Although there was no significant difference between the 2 groups in risk of anastomotic leakage (RR, .67; 95% CI: .39-1.17; P = .16; I2 = 8%), there was a significant difference between them in risk of surgical site infection (RR, .50; 95% CI: .34-.71; P = .0002; I2 = 0%). CONCLUSIONS: Intracorporeal anastomosis is associated with a reduced risk of postoperative complications compared with ECA in patients undergoing LRC.

Omentectomy Does Not Affect the Postoperative Outcome of Patients With Locally Advanced Gastric Cancer: A Systematic Review and Meta-Analysis.

OBJECTIVE: To explore the influence of omentectomy on postoperative outcomes in patients with locally advanced gastric cancer (LAGC). BACKGROUND: Although several meta-analyses have investigated the influence of bursectomy on postoperative outcomes in patients with LAGC, no meta-analyses have explored the influence of omentectomy on postoperative outcomes in such patients. METHODS: We performed a comprehensive electronic search of the literature up to December 2020 to identify studies that compared postoperative outcomes between patients with LAGC who did and did not undergo omentectomy. A meta-analysis was performed using random-effects models to calculate the risk ratio (RR) and 95% confidence interval (CI), and heterogeneity was analyzed using I2 statistics. RESULTS: Eight retrospective studies involving a total of 2658 patients with LAGC who underwent surgery were included in this meta-analysis. Among them, 3 propensity score matching (PSM) studies demonstrated that the 5-y recurrence-free survival (RFS) rate was 72.9% (314/431) in patients with LAGC who did not undergo omentectomy, whereas it was 70.3% (303/431) in those who did. The results revealed no significant difference in 5-y RFS between groups (RR, 0.91; 95% CI, 0.74-1.13; P = 0.41; I2 = 0%). Two PSM studies also revealed no significant difference in 5-y overall survival (OS) between groups (RR, 0.77; 95% CI, 0.52-1.13; P = 0.18; I2 = 47%). CONCLUSIONS: The results of these meta-analyses show that omentectomy had no significant influence on 5-y OS, especially 5-y RFS, in patients with LAGC.

Impact of anastomotic leakage on postoperative survival of patients with colorectal cancer: A meta-analysis using propensity score matching studies.

OBJECTIVE: To explore the influence of anastomotic leakage (AL) on postoperative survival in patients with colorectal cancer (CRC). BACKGROUND: Although several studies have compared the postoperative survival of patients with CRC with and without AL, the background characteristics of the two groups were not aligned in most studies. METHODS: We performed a comprehensive electronic search of the literature up to March 2020 to identify propensity score matching (PSM) studies that compared postoperative survival between CRC patients with and without AL. A meta-analysis was performed using random-effects models to calculate the risk ratio (RR) and 95% confidence interval (CI), and heterogeneity was analyzed using I (Akiyoshi et al., 2011) [2] statistics. RESULTS: Four PSM studies involving a total of 1676 patients with CRC undergoing surgery were included in this meta-analysis. Among 234 patients who had AL, 163 (69.7%) survived at 5 years after surgery, whereas among 1422 patients who did not have AL, 1156 (81.3%) survived at 5 years after surgery. Background characteristics of the two groups were adjusted with PSM in all 4 studies. The result of the meta-analysis revealed a significant difference between the two groups (RR, 1.63; 95% CI, 1.09-2.45; P = 0.02; I2 = 66%) in 5-year overall survival (OS). CONCLUSIONS: The results of this meta-analysis demonstrate a significantly decreased 5-year OS in patients with CRC who had AL compared with patients with CRC who did not have AL.

Appendectomy Does Not Increase the Risk of Future Emergence of Parkinson's Disease: A Meta-analysis.

OBJECTIVE: To explore the impact of appendectomy history on emergence of Parkinson's disease (PD). BACKGROUND: Although there are several studies to investigate the relationship between appendectomy history and emergence of PD, the results are still controversial. METHODS: We performed a comprehensive electronic search of the literature (the Cochrane Library, PubMed, and the Web of Science) up to April 2020 to identify studies that had employed databases allowing comparison of emergence of PD between patients with and those without appendectomy history. To integrate the impact of appendectomy history on emergence of PD, a meta-analysis was performed using random-effects models to calculate the risk ratio (RR) and 95% confidence interval (CI) for the selected studies, and heterogeneity was analyzed using I2 statistics. RESULTS: Four studies involving a total of 6 080 710 patients were included in this meta-analysis. Among 1 470 613 patients with appendectomy history, 1845 (.13%) had emergences of PD during the observation period, whereas among 4 610 097 patients without appendectomy history, 6743 (.15%) had emergences of PD during the observation period. These results revealed that patients with appendectomy history and without appendectomy had almost the same emergence of PD (RR, 1.02; 95% CI, .87-1.20; P = .83; I2 = 87%). CONCLUSION: This meta-analysis has demonstrated that there was no significant difference in emergence of PD between patients with and those without appendectomy history.

Is left-sided involvement of hepatocellular carcinoma an important preoperative predictive factor of poor outcome?

BACKGROUND: The tumor location is the most simple clinical factor and important in liver surgery to make surgical procedure. However, no previous study has investigated the prognostic differences and clinical features of hepatocellular carcinoma showing specific laterality. This study is the first report to focus on the laterality and aimed to lead to more simple and useful predictive factor rather than recent complicated predictive models. METHODS: Patients who underwent liver resection for the first time for single tumors located within each lobe between 2000 and 2018 were enrolled. We divided them into two groups based on tumor location: a right-sided group and a left-sided group. Univariable and multivariable analyses were performed to assess survival differences in relation to several other factors. RESULTS: There were 595 eligible patients; the 5-year survival rates and disease-free survival rates were 49.5% and 19.1% in the left-sided group and 55.6% and 24.5% in the right-sided group, respectively (p = 0.026). Statistical analyses revealed that the following preoperative prognostic factors were independently significant (p < 0.05) in the left-sided group: indocyanine green retention rate at 15 min, alpha fetoprotein, protein induced by vitamin K absence or antagonists-II level, and larger tumor size. CONCLUSION: The left-sided group had a poorer prognosis than the right-sided group. A left-sided tumor location is a significant preoperative factor predictive of poor outcome in patients with hepatocellular carcinoma.

Effects of branched-chain amino acids on postoperative tumor recurrence in patients undergoing curative resection for hepatocellular carcinoma: A randomized clinical trial.

BACKGROUND/PURPOSE: No effective postoperative adjuvant therapies have been established for patients with hepatocellular carcinoma (HCC). The aim of this study was to investigate the effect of oral administration of branched-chain amino acids (BCAA) on the recurrence-free survival (RFS) after hepatic resection in HCC patients. METHODS: In this randomized clinical trial, HCC patients undergoing curative resections were randomly assigned in a 1:1 ratio to the BCAA group or surgery-alone group. The BCAA group received BCAA (Livact® ) for up to 4 years. The primary endpoint was RFS. The secondary endpoint was overall survival (OS). Multivariate analysis was performed to detect the clinical characteristics significantly associated with RFS. RESULTS: Between January 2010 and October 2014, 156 patients (75 in BCAA group and 81 in surgery-alone group) were enrolled in the study. Of these, two patients were excluded from the efficacy analysis. Comparison of the survival curves by the log rank test demonstrated no significant difference in the RFS (P = .579) or OS (P = .268) between the BCAA and the control group. Multivariate analysis revealed that the RFS was significantly associated with age and number of tumors. A beneficial effect of BCAA on the RFS was found in patients younger than 72 years old with a HbA1c level of < 6.4%. CONCLUSIONS: Oral BCAA supplementation could not reduce the risk of recurrence after hepatic resection in HCC patients; however, the results suggested that BCAA supplementation may be beneficial for selected patients who were younger and had mildly impaired glucose tolerance.

The ABO Blood Group Impacts the Survival of Patients Undergoing Pancreatoduodenectomy for Biliary Tract Cancer.

BACKGROUND/AIM: Although ABO blood group has been reported to be associated with the outcome of patients with pancreatic cancer, little is known about its impact on patients with biliary tract cancer (BTC). We evaluated the prognostic relevance of ABO blood group in patients who had undergone resection of BTC. PATIENTS AND METHODS: A total of 154 patients with BTC undergoing pancreatoduodenectomy were retrospectively reviewed. Associations between ABO blood group and patient survival were evaluated by univariate and multivariate analysis. RESULTS: The 5-year overall survival rate was higher in group O patients (n=46) than in other blood group patients (n=108) (65.8% vs. 47%, p=0.005). Multivariate analysis revealed that a non-O blood group was an independent risk factor for poor survival (p=0.021). CONCLUSION: ABO blood group is associated with the prognosis of patients with resected BTC; group O patients have a better outcome.

Features of Hepatocellular Carcinoma With Micro Hepatic Vein Invasion and their Correlation With Hepatitis B and C Virus.

BACKGROUND/AIM: Few studies have studied micro hepatic vein invasion in hepatocellular carcinoma (HCC). We explored the correlation between hepatic vein invasion and hepatitis B/C virus infection. PATIENTS AND METHODS: Between April 2000 and February 2018, 869 patients underwent liver resection for HCC at a single center. The patients were divided into two groups: those with micro hepatic vein invasion (VV+) and those without (VV-). The clinical data, overall survival (OS) and correlations with the presence of hepatitis B and C viruses were investigated. RESULTS: There were 817 VV- patients and 43 VV+ patients. OS was 66.2 months for VV- patients and 9.9 months for VV+ patients (p=0.0010). VV+ patients had significantly higher levels of serum HBV DNA (p=0.016). CONCLUSION: HCC patients with micro hepatic vein invasion showed significantly shorter OS. A higher level of HBV DNA appears to be a risk factor for micro hepatic vein invasion.

Clinical Significance of Neoadjuvant Chemotherapy With Gemcitabine Plus S-1 for Resectable Pancreatic Ductal Adenocarcinoma.

BACKGROUND/AIM: Little is known about the efficacy of neoadjuvant chemotherapy (NAC) with gemcitabine plus S-1 (GS) for patients with resectable pancreatic ductal adenocarcinoma (R-PDAC). The aim of this study was to investigate differences in the long-term outcome of patients with R-PDAC undergoing pancreatectomy with and without NAC-GS to clarify the clinical significance of NAC-GS. PATIENTS AND METHODS: A total of 77 patients with R-PDAC who were scheduled for pancreatectomy between January 2012 and December 2017 were enrolled. Of these patients, 39 received NAC-GS (GS group) and 38 had upfront surgery (UFS group). RESULTS: Among the 77 patients, one patient in each group did not undergo pancreatectomy due to intraoperative non-curative factors. Median tumor size and the number of lymph nodes with metastasis were significantly lower in the GS group than in the UFS group (p=0.002 and p=0.017). However, the 5-year overall survival rate was similar in the two groups (26.1% versus 21.5%, p=0.930). CONCLUSION: NAC-GS may not be recommended for patients with R-PDAC since it does not seem to offer any survival benefits.

Microsatellite Analysis of Recurrent Lesions Confirms Merit of Anatomical Liver Resection for Hepatocellular Carcinoma.

BACKGROUND/AIM: This study aimed to obtain accurate differential diagnosis (DDx) of multicentric carcinogenesis (MC) and intrahepatic metastasis (IM) in recurrent lesions of hepatocellular carcinoma. MATERIALS AND METHODS: A total of 79 patients who underwent re-hepatectomy (2000-2013) were examined. PCR was used to analyze 13 chromosomal microsatellite loci by PCR. On the basis of this genetic analysis, the recurrent lesions were diagnosed as IM, MC or not determined (ND). Subsequently, DDx was compared with types of resection and outcome. RESULTS: The recurrent lesions were diagnosed as IM in 33 patients, MC in 44, and ND in 2. The anatomical resection group included 14 IM lesions (28%) and 36 MC lesions (72%), while the non-anatomical resection group included 19 IM lesions (70%) and 8 MC lesions (30%) (p<0.001). CONCLUSION: Anatomical resection at initial hepatectomy may reduce the likelihood of IM recurrence, leading to a better outcome for patients with HCC.

Prognostic Factors after Curative Resection for Single-Lesion Hepatocellular Carcinoma in Patients with Normal Liver Function: A Historical Cohort Study.

BACKGROUND: Hepatic resection for hepatocellular carcinoma (HCC) is now established as the treatment most likely to yield the best outcome. We aimed to clarify the risk factors for HCC recurrence after curative resection of single HCC in patients with normal liver function (NLF). METHODS: The clinical records of 105 patients with NFL and a single HCC less than 5 cm in diameter who had undergone curative liver resection between April 2000 and January 2013 were investigated. We analyzed risk factors for recurrence of HCC. RESULTS: Forty of the 105 patients suffered recurrence of HCC, and median recurrence-free survival (RFS) was 22.0 (5.1-148.5) months after surgery, and the liver was the most frequent site of recurrence. Univariate analysis showed that limited resection (LR; p = 0.002), the indocyanine green retention rate at 15 min (p = 0.023), C-reactive protein value (p = 0.001), bilirubin value (p = 0.042), neutrophil to lymphocyte ratio (p = 0.042), operation time (p = 0.018), and amount of bleeding (p = 0.011) were associated with RFS. Multivariate analysis showed that LR (p = 0.007) was a significant risk factor associated with RFS. CONCLUSION: LR is a risk factor for HCC recurrence in patients with single-lesion HCC and NLF.

Receptor for advanced glycation endproducts signaling cascades are activated in pancreatic fibroblasts, but not in the INS1E insulinoma cell line: Are mesenchymal cells major players in chronic inflammation?

The receptor for advanced glycation endproducts (RAGE) is a pattern recognition receptor that plays an important role in natural immunity. It is suggested that mesenchymal cells are the major players during inflammation. Previously, we reported that advanced glycation end products (AGE), known to be one of the ligands of RAGE, inhibited glucose-induced insulin secretion from ex vivo pancreatic islets, although the mechanism responsible remains largely unknown. In the present study, we examined the cascades operating downstream from RAGE using the insulinoma cell line INS1E and primary-cultured pancreatic fibroblasts as in vitro models for parenchymal (ß) cells and mesenchymal cells, respectively. Phosphorylation of c-jun N-terminal kinase, inhibitor of nuclear factor κB kinase, and nuclear factor κB was stimulated by AGE or high mobility group binding 1 (HMGB1) in pancreatic fibroblasts, whereas no such effect was observed in INS1E cells. Expression of the Ccl5, Il-6, and Il-1b genes was increased by AGE/HMGB1 in fibroblasts, but not in INS1E cells. On the other hand, AGE inhibited the secretion of insulin from ex vivo pancreatic islets, and this effect was ameliorated by MK615, a Japanese apricot extract used as an anti-inflammatory agent. Glucose-induced insulin secretion from INS1E cells was not affected by direct administration of AGE/HMGB1, but was inhibited by fibroblast-conditioned medium. These results suggest that AGE suppresses glucose-induced insulin secretion from pancreatic islets through indirect mesenchymal RAGE signaling.

Risk Factors for Early Recurrence of Single Lesion Hepatocellular Carcinoma After Curative Resection.

BACKGROUND AND OBJECTIVES: Hepatic resection is established as the treatment for HCC. However, patients sometimes experience early recurrence of HCC (ER HCC) after curative resection. METHODS: A retrospective analysis was conducted for 193 patients with single HCC who underwent curative liver resection in our medical center between April 2000 and March 2013. We divided the cohort into two groups; early recurrence group (ER G) which experienced recurrence within 6 months after resection, and non-early recurrence group (NER G). Risk factors for ER HCC were analyzed. RESULTS: Thirty-nine out of 193 (20.2 %) patients had ER HCC. Univariate analysis showed Glasgow prognostic score (GPS, p = 0.036), neutrophil to lymphocyte ratio (NLR, p = 0.001), level of PIVKA-II (p = 0.0001), level of AFP (p = 0.0001), amounts of blood loss (p = 0.001), operating time (p = 0.002), tumor size (p = 0.0001), stage III and IV (p = 0.0001), and microvascular invasions (portal vein: p = 0.0001 and hepatic vein: p = 0.001) to be associated with ER HCC. By multivariate analysis, there were significant differences in high NLR (p = 0.029) and high AFP (p = 0.0001) in patients with ER HCC. CONCLUSIONS: Preoperative high AFP (more than 250 ng/ml) and high NLR (more than 1.829) were independent risk factors for ER HCC.

Successful Right Hemihepatectomy for a Patient with Right-Sided Round Ligament.

Right-sided round ligament (RSRL) is a rare congenital anomaly that is strongly associated with a number of intrahepatic vascular anomalies. Here, we report a 77-year-old male case of hepatolithiasis associated with RSRL for which resection was performed using right hemi-hepatectomy (RHH). Intraoperative ultrasonography revealed that the portal branch of segment 4 ramified from the right anterior portal branch, and the patient was diagnosed as having RSRL. To decide the resection line, the portal branch of segment 4 was punctured and stained with indigo carmine under ultrasonographic guidance, clearly demonstrating the demarcation line between the right and left hemiliver. RHH was then carried out successfully without injuring the portal branch of segment 4.

Administration of adjuvant oral tegafur/uracil chemotherapy post hepatocellular carcinoma resection: A randomized controlled trial.

BACKGROUND: Recurrence of hepatocellular carcinoma (HCC) after surgery is frequent, and is an important factor adversely influencing the long-term survival of patients. This prospective study evaluated whether adjuvant chemotherapy with oral tegafur/uracil (UFT) reduces the recurrence rate of HCC. In addition, expression of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) were investigated in resected tumors and nontumorous tissues, and the relationship between their expression and the effectiveness of UFT was examined. METHODS: A total of 117 patients who underwent curative hepatic resection for HCC were randomly allocated to UFT 400 mg/d (n = 24, UFT group) or surgery alone (n = 56, control group). The primary endpoint was the recurrence-free survival rate, and the secondary endpoint was the overall survival rate. Expression of the DPD and TS genes were quantified with TaqMan reverse transcription-polymerase chain reaction assay using ß-actin as an internal standard. The cut-off value was set at the mean value of TS and DPD expression. RESULTS: Among the 61 patients in the UFT group, 37 patients (60.6%) discontinued UFT within 1 month. Recurrence-free survival (p = 0.16) and overall survival (p = 0.29) were similar in the two groups. In the UFT group, recurrence-free survival did not differ significantly between high-TS (TS > 3.6) and high-DPD (DPD > 8.9; n = 10), and low-TS (TS ≤ 3.6) and low-DPD (DPD ≤ 8.9; n = 9) groups. However, there was a significant difference between the two groups in overall survival (p = 0.04). CONCLUSION: Peroral UFT administration fails to prolong the recurrence-free rates and overall survival rates, in comparison with surgery alone. However, oral administration of UFT may improve the survival of HCC patients when the levels of TS and DPD mRNA are low in the tumor tissue.

Clinical significance of an inflammation-based prognostic system for gastric cancer patients with a preoperative normal serum level of carcinoembryonic antigen.

AIM: To investigate the significance of the Glasgow Prognostic Score (GPS) for predicting the postoperative survival of gastric cancer (GC) patients with a normal preoperative serum level of carcinoembryonic antigen (CEA). Because CEA is a useful marker for prognostication of several types of cancer, some patients with GC have a normal CEA level. On the other hand, the GPS has been established as a valuable inflammation-based prognostic system for cancer patients. PATIENTS AND METHODS: Among 650 patients who had undergone elective surgery for GC, 425 with a normal preoperative serum CEA level (≤5.0 ng/ml) were enrolled. Uni- and multivariate analyses were performed to evaluate the relationship of the GPS to overall survival. The Kaplan-Meier analysis and log rank test were used to compare the survival curves among patients with GPS 0, 1 and 2. RESULTS: Multivariate analysis using clinical characteristics selected from univariate analyses revealed that the GPS (0, 1/2) was associated with overall survival (hazard ratio=2.048; 95% C.I. (confidence interval)=1.002-4.185; p=0.049) along with age (≤70/>70) (years), sex, tumor type (3, 4, 5/0, 1, 2), lymph node metastasis (presence/absence) and platelet count (≤35/>35) (×10(4)/mm(3)). The Kaplan-Meier analysis and log rank test demonstrated that there were significant differences in overall survival among patients with GPS 0, 1 and 2 (p<0.001). CONCLUSION: Even if GC patients have a normal serum level of CEA, the GPS is able to predict their postoperative survival and classify such patients into three independent groups before surgery.

Prognostic nutritional index is associated with survival after total gastrectomy for patients with gastric cancer.

AIM: To investigate the influence of clinical characteristics including nutritional markers on postoperative survival in patients undergoing total gastrectomy (TG) for gastric cancer (GC). PATIENTS AND METHODS: One hundred fifty-four patients were enrolled. Uni- and multivariate analyses using the Cox proportional hazard model were performed to explore the most valuable clinical characteristic that was associated with postoperative survival. RESULTS: Multivariate analysis using twelve clinical characteristics selected from univariate analyses revealed that age (≤ 72/>72), carcinoembryonic antigen (≤ 20/>20) (ng/ml), white blood cell count (≤ 9.5/>9.5) (× 10(3)/mm(3)), prognostic nutritional index (PNI) (≤ 45/>45) and lymph node metastasis (negative/positive) were associated with postoperative survival. Kaplan-Meier analysis and log-rank test showed that patients with higher PNI (>45) had a higher postoperative survival rate than those with lower PNI (≤ 45) (p<0.001). CONCLUSION: PNI is associated with postoperative survival of patients undergoing TG for GC and is able to divide such patients into two independent groups before surgery.

Impact of prothrombin time-International Normalized Ratio on outcome of patients with septic shock receiving polymyxin B cartridge hemoperfusion.

BACKGROUND: Although most patients with septic shock have a poor outcome, some may survive after blood purification treatment such as polymyxin B cartridge hemoperfusion (PMX). OBJECTIVE: To explore the most significant characteristic associated with 28-day mortality in patients with septic shock receiving PMX. METHODS: Between April 2006 and March 2008, 116 patients with septic shock who had received PMX in a prospectively collected multicenter collaborative study were enrolled. Uni- and multivariate analyses using the Cox proportional hazard model were performed to assess the most significant clinical characteristic that was associated with 28-day mortality. RESULTS: Among 33 clinicolaboratory characteristics, receiver operating characteristic (ROC) curve analyses selected 12 characteristics with recommended cutoff values such as HCO(3)(-) (≤19.8/>19.8; mEq/L), base excess (≤-5.35/>-5.35; mEq/L), diastolic blood pressure (≤48/>48 mmHg), mean arterial pressure (≤73/>73 mmHg), pH (≤7.29/>7.29), interleukin-6 (≤19,150/>19,150 pg/dL), prothrombin time-International Normalized Ratio (PT-INR; ≤2.05/>2.05), predictive value of Acute Physiology and Chronic Health Evaluation II (APACHE II; ≤0.4/>0.4), pyruvate (≤1.82/>1.82 mg/dL), APACHE II score (≤21/>21), acetate/pyruvate ratio (≤19/>19), and acetate (≤44.8/>44.8 mg/dL) on the basis of large area under the ROC curves for 28-day mortality. The results of uni- and multivariate analyses using these selected characteristics revealed that only PT-INR (≤2.05/>2.05; hazard ratio, 2.823; 95% CI, 1.243-6.412; P = .013) was associated with 28-day mortality. Survival curve analysis demonstrated a significant difference in 28-day mortality between patients with lower (≤2.05) and higher (>2.05) PT-INR (P < .001). CONCLUSION: Prolonged PT-INR is an independent risk factor for 28-day mortality in patients receiving PMX for septic shock.