A genome-wide association study identified PTPN2 as a population-specific susceptibility gene locus for primary biliary cholangitis.

BACKGROUND AND AIMS: Previous genome-wide association studies (GWAS) have indicated the involvement of shared (population-nonspecific) and nonshared (population-specific) susceptibility genes in the pathogenesis of primary biliary cholangitis (PBC) among European and East-Asian populations. Although a meta-analysis of these distinct populations has recently identified more than 20 novel PBC susceptibility loci, analyses of population-specific genetic architecture are still needed for a more comprehensive search for genetic factors in PBC. APPROACH AND RESULTS: Protein tyrosine phosphatase nonreceptor type 2 ( PTPN2) was identified as a novel PBC susceptibility gene locus through GWAS and subsequent genome-wide meta-analysis involving 2181 cases and 2699 controls from the Japanese population (GWAS-lead variant: rs8098858, p = 2.6 × 10 -8 ). In silico and in vitro functional analyses indicated that the risk allele of rs2292758, which is a primary functional variant, decreases PTPN2 expression by disrupting Sp1 binding to the PTPN2 promoter in T follicular helper cells and plasmacytoid dendritic cells. Infiltration of PTPN2-positive T-cells and plasmacytoid dendritic cells was confirmed in the portal area of the PBC liver by immunohistochemistry. Furthermore, transcriptomic analysis of PBC-liver samples indicated the presence of a compromised negative feedback loop in vivo between PTPN2 and IFNG in patients carrying the risk allele of rs2292758. CONCLUSIONS: PTPN2 , a novel susceptibility gene for PBC in the Japanese population, may be involved in the pathogenesis of PBC through an insufficient negative feedback loop caused by the risk allele of rs2292758 in IFN-γ signaling. This suggests that PTPN2 could be a potential molecular target for PBC treatment.

Incidence and causative agent distribution of viral-induced paediatric asthma exacerbations under strict infection control measures: a single-centre retrospective study in Japan.

BACKGROUND: The prevalence of respiratory viruses in children changed under strict infection control measures during the coronavirus disease 2019 (COVID-19) outbreak. In this study, we investigated the frequency of viral detection in the nasopharynx of paediatric patients with asthma exacerbations requiring hospitalization during the COVID-19 pandemic, as well as the distribution of causative viruses. METHODS: We included paediatric patients admitted for asthma exacerbations between November 2020 and December 2022 at a single centre in Kobe, Japan. Demographic, clinical, and laboratory data were collected from their medical records and using additional questionnaires. All patients enrolled in this study met the diagnostic criteria for asthma exacerbations outlined in the Japanese Pediatric Guideline for the Treatment and Management of Bronchial Asthma 2020. Statistical differences were calculated using univariate analyses (chi-square or Mann‒Whitney U test). RESULTS: We enrolled 203 children hospitalized for asthma attacks and collected nasopharyngeal samples from 189 patients. The median patient age was 3.0 years. Asthma severity was classified as mild (4.0%), moderate (82.3%), or severe (13.8%). The proportion of viral respiratory infections was 95.2% (180/189). The rate of patients with multiple viral infections was 20.6% (39/189). The most frequently detected pathogens were rhinovirus and enterovirus (RV/EV) at 69.3% (131/189), allowing for duplicate detection, followed by respiratory syncytial virus (RSV) at 28.6% (54/189). We also detected RV/EV almost every month compared to RSV and other viruses. In addition, RV/EV-positive patients were significantly older (p = 0.033), exhibited higher WBC counts (p < 0.001) and higher Eos counts (p < 0.001), had elevated total IgE levels (p < 0.001) and house dust mite-specific IgE levels (p = 0.019), had a shorter duration of hospitalization (p < 0.001), and had a shorter duration of oxygen therapy (p < 0.001). In patients positive for RV/EV, the use of ICSs significantly reduced the severity of the condition (p < 0.001). CONCLUSION: Even under strict infection control measures, respiratory viruses were detected in the nasopharynx of almost all paediatric patients who had asthma exacerbations requiring hospitalization.

[Short Term and Long Term Outcomes of Robotic Surgery in Sphincter Function Preserving Surgery for Lower Rectal Cancer].

BACKGROUND: Surgical and oncological outcomes of lower rectal cancer remain unsatisfactory. We investigated the short term and long term outcomes of robotic surgery for sphincter function-preserving surgery(SPS)for lower rectal cancer. METHOD: 433 lower rectal cancer patients who underwent SPS at our institution from January 2000 to July 2021 were included, excluding Stage Ⅳ cases and patients with multiple cancers. There were 288 cases of laparotomy, 81 cases of laparoscopic surgery, and 64 cases of robotic surgery; we abbreviated the group names as: OP, LAP, and R, respectively. We retrospectively reviewed the anastomotic leakage rate and prognosis of these groups. RESULTS: The anastomotic leakage rate was 23.6% in the OP group, 17.3% in the LAP group, and 6.3% in the R group, with a significant difference between the OP group and the R group. The 3-year recurrence free survival rate was 86.7% in the LAP group and 95.6% in the R group. Although there was no significant difference, the prognosis tended to be better in the R group. Local recurrence was observed in 3 patients in the LAP group and 1 patient in the R group. CONCLUSION: In SPS for advanced lower rectal cancer, robotic surgery may contribute to a reduction in anastomotic leakage.

Prognosis of patients with liver cirrhosis: A multi-center retrospective observational study.

AIM: Despite advances in the management of liver diseases and changes in the etiology of cirrhosis, few studies have updated the prognosis of cirrhosis. This study aimed to clarify the recent prognosis of cirrhosis and identify risk factors for death. METHODS: In this retrospective observational study by the Hepatic Disease Network of the National Hospital Organization in Japan, chart reviews were performed to follow patients with cirrhosis beginning in 2011. We conducted Kaplan-Meier survival time analyses stratified by Child-Pugh classification and albumin-bilirubin grade. Cox regression analysis was used to identify risk factors for death. RESULTS: We identified 444 eligible patients from 25 hospitals, including 303 (68%), 110 (25%), and 31 (7%) patients with Child-Pugh classes A, B, and C, respectively. Hepatitis C virus infection was the cause of cirrhosis for 63% of the patients. The 1-year and 5-year cumulative survival rates of patients with Child-Pugh classes A, B, and C were 90% and 61%, 78% and 42%, and 65% and 25%, respectively. The 1-year and 5-year cumulative survival rates of patients with albumin-bilirubin grades 1, 2, and 3 were 98% and 80%, 91% and 56%, and 58% and 23%, respectively. Cirrhosis classification (Child-Pugh and albumin-bilirubin), age, liver cancer, and untreated esophageal varices were associated with increased hazard of death. CONCLUSIONS: Little improvement was observed in the prognosis of cirrhosis compared with previous reports, and the prognosis of Child-Pugh class C cirrhosis remained poor. Untreated esophageal varices were identified as a risk factor for death.

[NEED FOR SUBCUTANEOUS IMMUNOTHERAPY IN PEDIATRIC PATIENTS WITH ALLERGIC RHINITIS AFTER THE EXPANDED INDICATION FOR SUBLINGUAL IMMUNOTHERAPY].

BACKGROUND: Although the indication for sublingual immunotherapy (SLIT) was expanded in pediatric patients with allergic rhinitis in recent years, some patients choose subcutaneous immunotherapy (SCIT). OBJECTIVE: The objective of this study was to investigate the reason why they chose SCIT in spite of injection pain and high risk of systemic reaction. METHODS: The subjects were 58 patients who diagnosed with allergic rhinitis and introduced SCIT at our hospital between June 2018 and January 2021. The reasons why they chose SCIT were collected from medical records. RESULT: The median age at the start of treatment was 9 years 0 months. The most common reason why they chose SCIT was "difficult to maintain adherence of SLIT" in 28 cases (48%). Other reasons were as follows: "side effects of SLIT", "expectation for the effect of SCIT", "young age (under 5 years old)" and "motivation for allergic disease treatment". CONCLUSION: Two-thirds of the reasons why they chose SCIT were because it was difficult to continue SLIT for some reasons.

Disaster preparation: Survey of patients with food allergies in Kobe, Japan.

BACKGROUND: Securing food for patients with food allergies may be more difficult during disasters, but reports on the status of household allergen-free food reserves in preparation for disasters are limited. This study investigated the household stock status of allergen-free foods in preparation for disasters in Kobe City after the Great Hanshin-Awaji Earthquake. METHODS: The survey targets were 172 parents of patients with a food allergy who underwent in-hospital oral food challenge test for allergies at four hospitals from October 2016 to March 2017. Of these, 158 patients with allergies to eggs, milk and wheat were included in the analysis. The first survey was performed to investigate patient characteristics and stockpiling status of allergen-free foods in parallel with oral food challenge tests. The second survey was performed on the follow-up visit to investigate any changes in behavior. RESULTS: Median patient age was 3 years, with boys comprising 68.4% of the patients. Eggs were the most eliminated food, and the median number of foods avoided was 2. A total of 82.3% of parents had experienced disasters. The proportion of households that stockpiled allergy-free meals was 42.4%, and the median amount was 3 days. The stockpiling situation did not differ according to the parents' disaster experience. In the second survey, 45.3% had modified their stockpiling practice. CONCLUSIONS: Even in this area where the Great Hanshin-Awaji Earthquake occurred, household stockpiles of allergen-free foods are inadequate; therefore, all medical staff should educate families about the necessity of stocking allergen-free food for disasters.

[Laparoscopic Gastrectomy for Early Gastric Cancer in a Patient with an Adachi Type â ¥ Arterial Variant-A Case Study].

We report successfull aparoscopic distalgastrectomy in a patient with early gastric cancer and an Adachi type Ⅵ arterial variant. The case is a male in his 50's who was detected a type 0-Ⅱc lesion on the antrum of the stomach and diagnosed as tub2. Laparoscopic distalgastrectomy was performed, with the pathologic diagnosis of cT1bN0M0, cStage Ⅰ. MD-CT showed absence of the common hepatic artery ventralto the portalvein, consistent with an Adachi type Ⅵ arterialvariant. The interface between pancreatic and fatty tissue was separated in suprapancreatic dissection, and was extended between the hepatoduodenal ligament and splenic artery, with exposure of the surface of the portal vein. Thus, safe dissection of No. 8a area was achieved. Discussion: Adachi classified the celiac artery branches into 6 types and 28 groups. Type Ⅵ, a variant of the common hepatic artery located on the dorsalaspect of the portalvein, has a reported frequency of 2%. Because it is a variant of the hepatic artery, a landmark of suprapancreatic dissection, careful observation is required to determine the anatomy. Although tactile sensation is limited in laparoscopic surgery, arterial pulsation is clearly visible. To ensure a safe procedure, it is important to identify vesselanatomy both pre- and intraoperatively.

[DIFFERENCE BETWEEN STANDARDIZED MITE ANTIGEN AND HOUSE DUST EXTRACT IN RUSH SUBCUTANEOUS IMMUNOTHERAPY FOR CHILDREN].

RATIONALE: Standardized allergen extracts are recommended for allergen immunotherapy. Since 2015, for patients with house dust mite allergies, we used a standardized house dust mite extract for subcutaneous immunotherapy, rather than non-standardized house dust extract. This study hypothesizes that standardized house dust mite extract (HDM group) was superior to non-standardized house dust extract (HD group) for subcutaneous immunotherapy. METHODS: In this noninterventional, retrospective study, we enrolled patients with allergic rhinitis and sensitization to house dust mites. The HDM group (27 patients) received subcutaneous standardized extract immunotherapy since 2015, and the HD group (37 patients) received non-standardized extracts before 2015. We assessed the safety and efficacy between the two groups; the safety was assessed by the systemic reaction (SR) rate. The efficacy was assessed by reductions in the allergic rhinitis symptom-medication score, and the asthma treatment score, over a year. RESULTS: The SR rate of the HDM group (44%) was significantly higher than that (14%) of the HD group. The HDM group displayed a 57% reduction in the allergic rhinitis symptom-medication score, which was markedly higher than the 40% reduction observed in the HD group. In the standardized group, there was a 66% reduction occurred in the asthma medication score, markedly higher than the 36% reduction observed among patients in the HD group. CONCLUSIONS: Standardized house dust mite extract was more effective than non-standardized house dust extract for subcutaneous immunotherapy; however, the establishment of safer methods is warranted.

Calcifying nested stromal epithelial tumor of the liver in a patient with Klinefelter syndrome: a case report and review of the literature.

BACKGROUND: Calcifying nested stromal epithelial tumor (CNSET) is a primary neoplasm of the liver, characterized by well-demarcated nests consisting of spindle and epithelioid cells with calcification and bone formation. An association of Cushing syndrome with CNSET has drawn attention, but the origin of CNSET has not been clarified. CASE PRESENTATION: We report here the case of a 20-year-old male with Klinefelter syndrome who underwent liver resection for an increasing liver tumor that was pathologically diagnosed with CNSET. He was postoperatively followed up and received several examinations, and recurrences and extrahepatic lymph node metastases were detected on the 64th day after surgery. Chemoembolization and chemotherapy were not effective, leading to tumor progression with development of progressive liver failure, and the patient finally died 164 days after hepatectomy. CONCLUSIONS: This case suggests that an imbalance of hormones affects the genesis and progression of CNSET, and indicates the importance of closely following patients with CNSET by imaging with attention to hepatic recurrence and extrahepatic metastases.

[A Case of Pancreatic Acinar Cell Carcinoma in a Young Woman without Recurrence after Systemic Chemotherapy Using S-1].

A 26-year-old woman underwent laparoscopic-assisted distal pancreatectomy and splenectomy for a tumor in the tail of the pancreas. Although the preoperative diagnosis was a solid pseudopapillary tumor, pathological tissue examination revealed that the tumor was a pancreatic acinar cell carcinoma. She was treated with S-1 chemotherapy for 6 months without severe side effects, and no recurrence was detected on several imaging inspections. Acinar cell carcinoma of the pancreas is a rare tumor in young patients, and there are few reports of treatment with postoperative chemotherapy.

[A Case of Myocardial Metastasis of Esophageal Squamous Cell Carcinoma].

Myocardial metastasis for esophageal squamous cell carcinoma(ESCC)is relatively rare and it is diagnosed as a part of widespread metastasis in the terminal stage. We experienced a case of myocardial metastasis of ESCC treated effectively with chemoradiotherapy. A 56-year-old man was diagnosed ESCC(clinical T3N2M0, Stage III). He received neoadjuvant chemotherapy of 5-fluorouracil plus cisplatin followed by subtotal esophagectomy with dissection of the 3 regional lymph nodes. The pathological diagnosis was moderate differentiated squamous cell carcinoma, CT-pT3(T3), pN1, sM0, fStage III. Four months after surgery, he had no clinical symptom, however myocardial metastasis located in the apex was detected on the follow up positron emission tomography(PET). Chemoradiotherapy was performed for the myocardial metastasis. Myocardial metastasis treated effectively with chemoradiotherapy almost disappeared on the PET and computed tomography taken 3 months after chemoradiotherapy. He died, however, of multiple liver and bone metastases 15 months after the initial surgery.

[Outcomes of Total Mesorectal Excision and Lateral Lymph Node Dissection following Neoadjuvant Chemotherapy for Lower Rectal Cancer with Lateral Lymph Node Metastasis].

INTRODUCTION: Progressive lower rectal cancer with metastasis to the lateral lymph nodes has poor prognosis, requiring systemic chemotherapy. In addition, because laparoscopic lateral lymph node dissection(LLND)in positive cases of metastasis to the lateral lymph nodes is difficult, it has not been commonly used. Here, we report the treatment results of neoadjuvant chemotherapy(NAC)and subsequent laparoscopic total mesorectal excision(TME)plus LLND in cases of lower rectal cancer with metastasis to the lateral lymph nodes. SUBJECTS AND METHODS: The subjects were 4 patients with metastasis to the lateral lymph nodes who underwent LLND after NAC. The surgical outcomes were investigated retrospectively. RESULTS: The mean surgical time was 398 minutes, and the mean bleeding amount was 150 g. In total, 33.5 lymph nodes were dissected, including 15.3 lateral lymph nodes. There was no switch to laparotomy, and no postoperative complications of Grade Ⅲ or higher according to the Clavien-Dindo classification were observed. CONCLUSION: Laparoscopic TME plus LLND after NAC is considered safe and useful as radical surgery for positive cases of metastasis to the lymph nodes.

[A Case of Laparoscopic Resection for Locally Advanced Primary Rectal Cancer after Neoadjuvant Chemotherapy].

We treateda 70-year-oldfemale patient with locally advancedrectal cancer accompaniedby metastases to other organs. Three courses of S-1 plus oxaliplatin(SOX)therapy were administered as neoadjuvant chemotherapy(NAC), andthe cancer was subsequently treatedwith laparoscopic rectal resection. She hadvisiteda physician with a chief complaint of melena. A type 2 tumor located in the rectum Rb was found during the lower gastrointestinal endoscopy, which was diagnosed as an adenocarcinoma by biopsy. Vaginal invasion andlymph node metastasis were observedon CT andMRI. After 3 courses of SOX therapy(NAC), her condition was categorized as SD. Laparoscopic rectal amputation(D3)combinedwith resection of the ovary, uterus, and vagina was performed. On histopathological examination, the tumor was an adenocarcinoma, muc> tub2, ypT4b(AI, vaginal wall), int, INF b, ly1, v2, EX(-), PN1a, grade 1, pPM0, pDM0, pRM0 and pStage Ⅲa. The histological analysis demonstrated that the therapeutic effect of chemotherapy was grade 1a. Laparoscopic surgery, which is a relatively safe procedure, may be useful after NAC for an R0 resection.

[The Impact of Neutrophil-Lymphocyte Ratio on the Prognosis in Patients Who Underwent Esophagectomy for Esophageal Cancer].

BACKGROUND: Thene utrophil-lymphocyteratio (NLR)reflects a patient's systemic inflammatory response. Several studies have revealed that the NLR is associated with a poor prognosis in several types of malignant tumors such as colorectal and lung cancer. The aim of this study was to evaluate the impact of preoperative NLR on the prognosis of patients with esophageal cancer. METHODS: The NLR was calculated for 93 consecutive patients with clinical Stage II or III esophageal cancer, who underwent curative esophagectomy following neoadjuvant chemotherapy between 2011 and 2013. The impact of preoperativeNLR on overall survival(OS)after esophagectomy was evaluated. The NLR cut off value was set to 2. RESULTS: The 3-year OS of patients with NLR≥2 was significantly shorter than patients with NLR<2(40.5% vs 67.9%, p=0.005). In a multivariateCox model, NLR≥2(HR: 2.342, 95%CI: 1.095-5.007, p=0.028), pathological depth of tumor(HR: 3.207, 95%CI: 1.114- 9.233, p=0.031), and an ageove r 60(HR: 2.342, 95%CI: 1.117-6.501, p=0.027)were identified as independent prognostic factors for OS after esophagectomy. CONCLUSIONS: The preoperative NLR was significantly associated with a poor prognosis in esophageal cancer patients who underwent curative esophagectomy following neoadjuvant chemotherapy.

[A Case of Disseminated Peritoneal Leiomyomatosis with Several Recurrences].

A 60's woman had undergone abdominal total hysterectomy due to uterine leiomyoma 17 years previously. She underwent resection of multiple intra-abdominal tumors 9 years previously, and was diagnosed with disseminated peritoneal leiomyomatosis. Because of several recurrences, she was referred to our hospital and treated with GnRH agonist therapy. However, the tumors enlarged gradually and she underwent further resection for multiple intra-abdominal tumors. After surgery, we performed several operations. This is an extremely rare disease and we present this case with a discussion of the literature.

[SAFETY AND EFFICACY OF ONE-YEAR RUSH SUBCUTANEOUS IMMUNOTHERAPY IN JAPANESE CHILDREN, USING HOUSE DUST EXTRACT].

BACKGROUND: In recent years there have been few reports on the effects of immunotherapy on bronchial asthma (BA) and allergic rhinitis (AR) in Japanese children. OBJECTIVE: To investigate the safety and efficacy of house dust extract immunotherapy for one year. METHODS: Thirty-five children with AR and BA were subjected to rush immunotherapy with house dust extract. Systemic reactions were counted to evaluate safety. BA medication score and AR symptom-medication score were recorded. RESULTS: Three patients (8.3% of all patients) experienced 6 systemic reactions (0.15% of doses). BA medication score decreased from 567 to 325 (a reduction rate of 43%). AR symptom-medication score improved from 5.1 to 2.9 (a reduction rate of 43%). CONCLUSIONS: Rush immunotherapy with house dust extract is safe and effective for Japanese children.

Branched-chain amino acids prevent hepatocarcinogenesis and prolong survival of patients with cirrhosis.

BACKGROUND & AIMS: Although a low plasma level of branched-chain amino acids (BCAAs) is a marker of cirrhosis, it is not clear whether BCAA supplements affect disease progression. We performed a multicenter study to evaluate the effects of BCAA supplementation on hepatocarcinogenesis and survival in patients with cirrhosis. METHODS: We enrolled 299 patients from 14 medical institutions in Japan in a prospective, multicenter study in 2009; 267 patients were followed through 2011. Patients were given BCAA supplements (5.5-12.0 g/day) for more than 2 years (n = 85) or no BCAAs (controls, n = 182). The primary end points were onset of hepatocellular carcinoma (HCC) and death. Factors associated with these events were analyzed by competing risk analysis. RESULTS: During the study period, 41 of 182 controls and 11 of 85 patients given BCAAs developed HCC. On the basis of the Cox and the Fine and Gray models of regression analyses, level of α-fetoprotein, ratio of BCAA:tyrosine, and BCAA supplementation were associated with development of HCC (relative risk for BCAAs, 0.45; 95% confidence interval, 0.24-0.88; P = .019). Sixteen controls and 2 patients given BCAAs died. Factors significantly associated with death were Child-Pugh score, blood level of urea nitrogen, platelet count, male sex, and BCAA supplementation (relative risk of death for BCAAs, 0.009; 95% confidence interval, 0.0002-0.365; P = .015) in both regression models. CONCLUSIONS: On the basis of a prospective study, amino acid imbalance is a significant risk factor for the onset of HCC in patients with cirrhosis. BCAA supplementation reduces the risk for HCC and prolongs survival of patients with cirrhosis.

Molecular Autopsy With Banked Cord Blood Reveals Brugada Syndrome in Past Sudden Death Case.

Molecular autopsy has recently been gaining attention as a means of postmortem diagnosis; however, it is usually performed using the victim's blood sample at the time of death. Here, we report the first case of a deceased infant with Brugada syndrome whose diagnosis was made with banked cord blood. A seemingly healthy 1-year-old male infant collapsed while having a fever; this collapse was witnessed by his mother. Despite cardiopulmonary resuscitation, he died of ventricular fibrillation. No abnormalities of cardiac structure were identified on autopsy. Genomic samples were not stored at the time because of a lack of suspicion for familial arrhythmia. Five years later, his sister showed Brugada electrocardiogram pattern while febrile from Kawasaki disease. Their father showed a spontaneous type 1 Brugada electrocardiogram pattern. A heterozygous SCN5A p.R893C variant was found by genetic testing in the proband's father and sister. Furthermore, the proband's genetic testing was performed using his banked cord blood, which identified the same variant. Family history of Brugada syndrome with an SCN5A-R893C variant and clinical evidence led to a postmortem diagnosis of Brugada syndrome in the proband. Identification of this variant in this case later contributed to verifying SCN5A-R893C as a pathogenic variant through data accumulation. Banked cord blood may prove useful for conducting molecular autopsies in previously undiagnosed cases of sudden death in which genomic samples were not stored.

Dosimetry of Occupational Eye Lens Dose Using a Novel Direct Eye Dosimeter, DOSIRIS, during Interventional Radiology Procedures.

In response to the recommendation by the International Commission on Radiological Protection to lower the equivalent eye dose limit, the Japanese Government in April 2021 lowered the equivalent dose limit for the eye lens for occupational exposure. A considerable number of interventional radiology operators are exposed to levels above the new limit. For this reason, a need exists to more accurately evaluate eye lens dose in interventional radiology operators by using a novel direct eye dosimeter, the DOSIRIS™(IRSN, France), which is capable of measuring a 3-mm dose equivalent under protective glasses. The DOSIRIS is a thermoluminescent dosimeter that exhibits good energy dependence and better directional properties than other dosimeters. Dosimetry using DOSIRIS might be accurate and compatible with the latest regulations.

The expression of both peroxisome proliferator-activated receptor delta and cyclooxygenase-2 in tissues is associated with poor prognosis in colorectal cancer patients.

BACKGROUND: The role of peroxisome proliferator-activated receptor delta (PPAR δ) in the development and progression of colorectal cancer (CRC) remains controversial. AIMS: We investigated the impact of PPAR δ expression in tissues on liver metastasis of CRC. METHODS: We analyzed samples of primary CRC and matched normal adjacent tissues from 52 patients for the expression of PPAR δ, cyclooxygenase (COX)-2, vascular endothelial growth factor (VEGF)-A, and CXC chemokine receptor 4 (CXCR4). Correlations of the molecules expressions with clinical characteristics and prognosis of patients were studied. RESULTS: The number of patients positive for PPAR δ, COX-2, CXCR4, and VEGF-A was 25, 33, 18, and 19, respectively. Among the PPAR δ (+)/COX-2 (+), PPAR δ (-)/COX-2 (+), PPAR δ (+)/COX-2 (-), and PPAR δ (-)/COX-2 (-) patient groups, PPAR δ (+)/COX-2 (+) patients had the highest incidence of liver metastasis (p<0.01). PPAR δ (+)/COX-2 (+) expression was a significant independent prognostic factor (HR=7.108, 95% CI 1.231-41.029, p=0.0283) by Cox proportional analysis. PPAR δ (+)/COX-2 (+) patients had the highest positivity for CXCR4 or VEGF-A in tissues (p<0.01). Among the patients in the CXCR4 (+)/VEGF-A (+), CXCR4 (+)/VEGF-A (-), CXCR4 (-)/VEGF-A (+), and CXCR4 (-)/VEGF-A (-) groups, CXCR4 (+)/VEGF-A (+) patients had the highest incidence of liver metastasis (p<0.01). CONCLUSIONS: The expression of both PPAR δ and COX-2 in tissues may lead to liver metastasis and consequent poor prognosis in CRC patients.