Coil embolization of a celiac artery pseudoaneurysm under balloon-assisted flow control: A case report.

Coil migration can occur when coil embolization is used for treating pseudoaneurysms associated with large arteries. The double microcatheter technique is useful for preventing coil migration; the balloon catheter can reduce blood flow and active bleeding upon balloon inflation, and can also compress the bleeding point and arrest bleeding temporarily. We report a case describing the management of a pseudoaneurysm with coil embolization using double microcatheters and a balloon catheter to control blood flow and prevent coil migration. A 73-year-old male patient presented with a pseudoaneurysm of the celiac artery arising from the splenic artery stump following surgery. Coil embolization of the pseudoaneurysm using a double microcatheter embolization technique with a balloon catheter was considered. A balloon catheter was inserted into the celiac artery and active bleeding was temporarily arrested with the inflated balloon. First, a microcatheter was inserted into the balloon catheter, and another microcatheter was placed in the celiac artery. An electrical detachable coil was inserted into the proximal common hepatic artery just distal to the pseudoaneurysm. The second electrically detachable coil was inserted while the first coil remained attached. After detachment of the second coil, additional electrically detachable coils were inserted for similar embolization. The balloon was gradually deflated. Finally, the first coil was detached and we confirmed absence of the bleeding. Our case report demonstrated that a balloon catheter can control the flow vessels, and the double microcatheter embolization technique with a balloon catheter is useful for coil embolization in high-flow or large vessels.

Aberrant phosphorylation of human LRH1 at serine 510 is predictable of hepatocellular carcinoma recurrence.

We previously identified the AKT-phosphorylation sites in nuclear receptors and showed that phosphorylation of S379 in mouse retinoic acid γ and S518 in human estrogen receptor α regulate their activity independently of the ligands. Since this site is conserved at S510 in human liver receptor homolog 1 (hLRH1), we developed a monoclonal antibody (mAb) that recognized the phosphorylation form of hLRH1S510 (hLRH1pS510) and verified its clinicopathological significance in hepatocellular carcinoma (HCC). We generated the anti-hLRH1pS510 mAb and assessed its selectivity. We then evaluated the hLRH1pS510 signals in 157 cases of HCC tissues by immunohistochemistry because LRH1 contributes to the pathogenesis of diverse cancers. The developed mAb specifically recognized hLRH1pS510 and worked for immunohistochemistry of formalin-fixed paraffin-embedded tissues. hLRH1pS510 was exclusively localized in the nucleus of HCC cells, but the signal intensity and positive rates varied among the subjects. According to the semi-quantification, 45 cases (34.9%) showed hLRH1pS510-high, and the remaining 112 cases (65.1%) exhibited hLRH1pS510-low. There were significant differences in the recurrence-free survival (RFS) between the two groups, and the 5-year RFS rates in the hLRH1pS510-high and hLRH1pS510-low groups were 26.5% and 46.1%, respectively. In addition, high hLRH1pS510 was significantly correlated with portal vein invasion, hepatic vein invasion, and high levels of serum alpha-fetoprotein (AFP). Furthermore, multivariable analysis revealed that hLRH1pS510-high was an independent biomarker for HCC recurrence. We conclude that aberrant phosphorylation of hLRH1S510 is a predictor of poor prognosis for HCC. The anti-hLRH1pS510 mAb could provide a powerful tool to validate the relevance of hLRH1pS510 in pathological processes such as tumor development and progression.

Tissue-Engineered Hepatocyte Sheets Supplemented with Adipose-Derived Stem Cells.

The ability to engineer biologically viable hepatocytes and tissue matrices with long-term functional maintenance has attracted considerable interest in the fields of hepatocyte transplantation and liver tissue engineering. Here, newly developed hepatocyte sheets supplemented with adipose-derived stem cells (ADSCs) were evaluated to assess the effects of ADSCs on hepatocyte function and engraftment into the subcutaneous space. Eight-week-old male C57BL/6J mice were used as donors, and 6-week-old male C.B-17/Icr-scid/scid mice were used as recipients. Hepatocyte-ADSC composite sheets were developed using temperature-responsive culture dishes. Hepatocyte viability in the hepatocyte-ADSC composite sheets was evaluated in an in vitro assay, and the outcome of subcutaneous transplantation of the sheet was evaluated. Hepatocyte viability was sustained in the hepatocyte-ADSC composite sheets in vitro. Albumin secretion was significantly higher (p = 0.015) in the hepatocytes of the hepatocyte-ADSC composite sheets (70.5 µg/mL) than in hepatocyte-only sheets (24.0 µg/mL). Cytokine assays showed that hepatocyte growth factor and interleukin-6 were contributed by ADSCs and not hepatocytes, which were not capable of constitutively secreting them. Immunohistochemically, phosphorylated STAT3 and c-MET expression in hepatocytes in the hepatocyte-ADSC composite sheets was significantly higher than that in the hepatocyte-only sheets. Engraftment of the transplanted hepatocyte-ADSC composite sheets was significantly enhanced without pretreatment of the subcutaneous tissue to induce a vascular network. In the hepatocyte-ADSC composite sheets, the viability of the hepatocytes was significantly maintained as the co-cultured ADSCs provided cytokines, enhancing pivotal cell signaling necessary for hepatocyte activity. Impact statement Hepatocyte transplantation is a safe, less invasive bridge treatment for liver transplantation, but its effectiveness is low and transitory. Herein, we introduce newly developed hepatocyte-adipose-derived stem cell composite sheets with improved strength, easier transplantation, and increased hepatocyte viability in the subcutaneous transplantation compared with hepatocyte-only sheets.

Case report: Unusual development of hepatocellular carcinoma during immunosuppressive treatments against rheumatoid arthritis overlapping Sjögren's syndrome; cirrhotic steatohepatitis with liver inflammation and fibrosis lurks in autoimmune disorders.

The sequential progression from chronic liver disease to cirrhosis may be a risk factor for hepatocellular carcinoma (HCC) development. Although HCC originates from hepatitis B virus- or hepatitis C virus-associated liver cirrhosis, it has recently been reported in patients with non-alcoholic steatohepatitis (NASH) with advanced fibrosis. However, little is known about the pathophysiological mechanisms linking HCC to rheumatic disorders, including rheumatoid arthritis (RA). Herein, we describe the case of HCC with NASH complicated by RA and Sjögren's syndrome (SS). A fifty-two-year-old patient with RA and diabetes was referred to our hospital for further examination of a liver tumor. She received methotrexate (4 mg/week) for 3 years and adalimumab (40 mg/biweekly) for 2 years. On admission, laboratory data showed mild thrombocytopenia and hypoalbuminemia, with normal hepatitis virus markers or liver enzymes. Anti-nuclear antibodies were positive with high titers (x640), and anti-SS-A/Ro (187.0 U/ml; normal range [NR]: ≤6.9 U/mL) and anti-SS-B/La (320 U/ml; NR: ≤6.9 U/mL) antibodies were also high. Abdominal ultrasonography and computed tomography revealed liver cirrhosis and a tumor in the left lobe (S4) of the liver. She was diagnosed with HCC based on imaging findings, and elevated levels of protein induced by vitamin K absence- II (PIVKA-II) were detected. She underwent laparoscopic partial hepatectomy, and histopathological examination revealed steatohepatitis HCC with background liver cirrhosis. The patient was discharged on the 8th day post-operation without any complications. At the 30 months follow-up, no significant evidence of recurrence was observed. Our case suggests that clinical screening for HCC is needed in patients with RA who are at a high risk of NASH, as they may progress to HCC even without elevated liver enzymes.

[A Case of Pancreatic Cancer That Developed Peritoneal Recurrence after Radical Surgery following Neoadjuvant Chemoradiation Therapy(NACRT)with Pathological Complete Response(pCR)].

A 71-year-old woman was diagnosed with a tumor in the pancreatic head on CT imaging, which was performed as a close examination of an exacerbation of diabetes mellitus. The pancreatic tumor was diagnosed as resectable pancreatic cancer, and after preoperative adjuvant chemoradiotherapy, pancreatoduodenectomy was performed as a radical surgery. There were no residual tumor cells in the resected specimen histopathologically, and the patient was judged to have a pathological complete response(pCR). Six months of postoperative adjuvant chemotherapy was administered, but peritoneal recurrence was observed at 20 months postoperatively, and the patient is currently undergoing treatment for recurrence. There have been other reports of recurrence even after pCR was achieved with preoperative treatment, so it is important to follow up carefully, keeping in mind that pancreatic cancer is a latent systemic disease.

Laparoscopic Surgery for Acute Diffuse Peritonitis Due to Gastrointestinal Perforation: A Nationwide Epidemiologic Study Using the National Clinical Database.

Background: Elective laparoscopic surgery is now widely accepted in the treatment of abdominal diseases because of its minimal invasiveness and rapid postoperative recovery. It is also used in the emergency setting for the diagnosis and treatment of acute diffuse peritonitis regardless of the causative disease. However, the value of laparoscopy in acute diffuse peritonitis remains unclear. In this study we aimed to show trends in the use of laparoscopy over time and compare the real-world performance of laparoscopic surgery with that of open surgery for acute diffuse peritonitis due to gastrointestinal perforation. Methods: We extracted data from the National Clinical Database, a nationwide surgery registration system in Japan, for patients with a diagnosis of acute diffuse peritonitis due to gastroduodenal or colorectal perforation between 2016 and 2019. Trends in the use of laparoscopy over time were identified. Patient characteristics, laboratory findings, surgical findings, and postoperative complications were compared between laparoscopic surgery and open surgery. Results: Patients in poor condition and those with abnormal laboratory findings tended to undergo open surgery. Anesthesia time and operating time were longer for laparoscopic surgery in patients with gastroduodenal perforation but shorter in those with colorectal perforation. Fewer complications occurred in patients who underwent laparoscopic surgery. The number of institutions where laparoscopic surgery was performed and the proportion of the use of laparoscopy at each institution increased over time. Conclusion: The use of laparoscopy is becoming common in surgery for acute diffuse peritonitis due to gastrointestinal perforation. This approach may be a useful option for acute diffuse peritonitis.

Predicting Post-Hepatectomy Liver Failure Using Intra-Operative Measurement of Indocyanine Green Clearance in Anatomical Hepatectomy.

BACKGROUND: Prediction of post-hepatectomy liver failure (PHLF) based on remnant liver function reserve is important for successful hepatectomy. The aim of this study was to investigate whether intraoperative indocyanine green (ICG) clearance in a future remnant liver was a predictor of PHLF. METHODS: This prospective study enrolled 31 consecutive patients who underwent anatomical hepatectomy between June 2016 and August 2019. Intraoperative ICG plasma disappearance rate (ICG-PDR) and ICG retention rate at 15 min (ICG-R15) were measured after clamping the selective hepatic inflow to the liver to be resected. The discriminative performance of the ICG-associated variables for the prediction of PHLF grade B/C was evaluated by receiver operator curve (ROC) analysis. RESULTS: Of the operations performed, 87.1% were major hepatectomy. PHLF Grade B/C was observed in eight patients (25.8%) with no mortality. The concordance indices of intraoperative ICG-PDR and ICG-PDR for predicting PHLF were 0.834 (95% CI, 0.69-0.98) and 0.834 (95% CI, 0.69-0.98), respectively. A subgroup analysis of patients with preoperative biliary drainage (BD) (n = 17) showed that the concordance indices of intraoperative ICG-PDR increased to 0.923 (95% CI, 0.79-1.00). CONCLUSIONS: Intraoperative ICG clearance in the remnant liver was a promising predictor for PHLF in patients undergoing anatomical hepatectomy, especially in patients with BD.

Intratumor Abscess in a Posttraumatic Hepatic Inflammatory Pseudotumor Spreading Out of the Liver.

A 45-year-old woman with abdominal pain after minor trauma was referred to our hospital. Computed tomography (CT) showed a hypovascular tumor in the left liver lobe. A tumor biopsy revealed granuloma, although no findings indicated malignancy or infection. A follow-up imaging study showed spread of the hepatic tumor. Her abdominal pain worsened after a second minor trauma. CT revealed an intratumor abscess, and pus overflowed from the patient's umbilicus. The abscess was improved by antibiotics and drainage therapy. In this case, unusual imaging findings and an atypical disease course of a hepatic inflammatory pseudotumor were observed.

[FOLFIRINOX for Locally Advanced and Recurrent Pancreatic Cancer with UGT1A1 *6 and or UGT1A1*28 Polymorphisms-A Report of Two Cases].

Treatment containing FOLFIRINOX was planned to be administered to a 51-year-old man with locally advanced pancreatic cancer as second-line chemotherapy and to a 66-year-old woman with recurrent pancreatic cancer as third-line chemotherapy in their treatments. Since both patients were revealed to harbor UGT1A1 polymorphisms, which were highly associated with irinotecan-induced toxicity(the former: UGT1A1 *6/*28, the latter: UGT1A1*6/*6), there was no alternative hopeful treatment other than FOLFIRINOX for them. Therefore, FOLFIRINOX was administered very carefully. Although both patients showed Grade 4 neutropenia during the initial course, it was controllable with G-CSF administration and following stepwise reduction of the irinotecan dose. Severe diarrhea and other adverse events were not observed in both cases. Since the determined regimen of FOLFIRINOX for patients with high-risk UGT1A1 polymorphisms has not been developed yet, it would be critical to accumulate and review an experience of FOLFIRINOX administration for these patients.

miRNA-148a-3p Regulates Immunosuppression in DNA Mismatch Repair-Deficient Colorectal Cancer by Targeting PD-L1.

Immunotherapy against the interaction between programmed cell death 1/programmed cell death ligand 1 (PD-L1) has emerged as a promising strategy for colorectal cancer with mismatch repair deficiency (dMMR) or microsatellite instability-high (MSI-H). The study aimed to identify miRNAs that posttranscriptionally control PD-L1 expression on tumor cells and also regulate immune evasion. A comprehensive miRNA screening using The Cancer Genome Atlas (TCGA) dataset (n = 260) combined with eight different miRNA target prediction programs resulted in the identification of a tumor suppressive miRNA, miR-148a-3p, as a potential negative regulator of PD-L1 expression, particularly in dMMR/MSI-H colorectal cancer. Using multiple cohorts of colorectal cancer, including TCGA data, a microarray dataset (n = 148), and formalin-fixed, paraffin-embedded samples (n = 395), we found that the expression of miR-148a-3p was decreased in dMMR/MSI-H tumors, correlating inversely with PD-L1 levels. We demonstrate that miR-148a-3p directly binds to the 3'-untranslated region of PD-L1, thereby reducing whole-cell and cell surface PD-L1 levels in HCT116 and SW837 cell lines. Overexpression of miR-148a-3p repressed IFNγ-induced PD-L1 expression on tumor cells and consequently diminished T-cell apoptosis in a coculture model of IL2-activated T cells and IFNγ-treated tumor cells. In conclusion, our data support a regulatory mechanism of PD-L1 expression on tumor cells and immune suppression via miR-148a-3p downregulation in colorectal cancer. IMPLICATIONS: This study provides novel evidence that miR-148a-3p negatively regulates tumor cell PD-L1 expression and decreased levels of miR-148a-3p contributes to the immunosuppressive tumor microenvironment.

Prognostic impact of soluble intercellular adhesion molecule-1 in hepatocellular carcinoma.

The identification of novel biomarkers for hepatocellular carcinoma (HCC) is of great importance in improving the outcome of patients with HCC. The present study aimed to determine the prognostic significance of the soluble intercellular adhesion molecule (sICAM)-1 in patients with HCC. The present study prospectively collected clinicopathological data from 36 patients with HCC who had undergone successful hepatectomy. An analysis using a receiver operating characteristic (ROC) curve was performed to determine the cut-off value for predicting prognosis. Overall survival (OS), recurrence-free survival (RFS) and potential prognostic factors were analyzed. The ROC curve analysis revealed a sICAM-1 cut-off value of 440 ng/ml. HCC patients with sICAM-1 ≥440 ng/ml exhibited a poorer OS and RFS than those with sICAM-1 <440 ng/ml (P=0.002). sICAM-1 ≥440 ng/ml (hazard ratio=3.623; 95% confidence interval: 1.145-11.458; P=0.028) and Child B (hazard ratio=1.514; 95% confidence interval: 1.066-2.150; P=0.021) were independent prognostic factors for OS, and sICAM-1 ≥440 ng/ml was an independent prognostic factor for RFS (hazard ratio=3.625; 95% confidence interval: 1.233-10.659; P=0.019). Serum sICAM-1 may be a promising predictor for the overall and recurrence-free survival of patients with HCC.

HOXA9 methylation and blood vessel invasion in FFPE tissues for prognostic stratification of stage I lung adenocarcinoma patients.

OBJECTIVES: Surgery with curative intent is the standard treatment for stage I lung adenocarcinoma. However, disease recurrence occurs in a third of patients. Prognostic biomarkers are needed to improve postoperative management. Here, we evaluate the utility of Homeobox A9 (HOXA9) promoter methylation, alone or in combination with Blood Vessel Invasion (BVI) assessment, for prognostic stratification of stage I lung adenocarcinoma patients. MATERIALS AND METHODS: We developed a Droplet Digital PCR (ddPCR) assay to measure HOXA9 promoter methylation in formalin-fixed paraffin-embedded (FFPE) biospecimens generated during routine pathology. The prognostic value of HOXA9 promoter methylation and BVI, alone and in combination, was evaluated by Kaplan-Meier survival and Cox regression analyses in a cohort of 177 stage I lung adenocarcinoma patients from the NCI-MD study. RESULTS: The ddPCR assay showed linearity, sensitivity and specificity for measuring HOXA9 promoter methylation down to 0.1% methylated DNA input. The HOXA9 promoter was methylated de novo in FFPE tumors (P < 0.0001). High methylation was independently associated with worse cancer-specific survival (Hazard Ratio [HR], 3.37; P = 0.0002) and identified high-risk stage IA and IB patients. Addition of this molecular marker improved a risk model comprised of clinical and pathologic parameters (age, gender, race, stage, and smoking history; nested likelihood ratio test; P = 0.0004) and increased the C-index from 0.60 (95% CI 0.51-0.69) to 0.68 (0.60-0.76). High methylation tumors displayed high frequency of TP53 mutations and other molecular characteristics associated with aggressiveness. BVI was independently associated with poor outcome (HR, 2.62; P = 0.054). A score that combined BVI with HOXA9 promoter methylation further stratified high-risk patients (trend P = 0.0001 comparing 0, 1 or 2 positive markers). CONCLUSIONS: ddPCR can be used to quantify HOXA9 promoter methylation in FFPE samples. Alone or combined with BVI in a prognostic classifier, HOXA9 promoter methylation could potentially inform the clinical management of patients with early-stage lung adenocarcinoma.

Pancreatic metastasis of papillary thyroid carcinoma preoperatively diagnosed by endoscopic ultrasound-guided fine-needle aspiration biopsy: a case report with review of literatures.

Pancreatic metastatic tumors from thyroid carcinoma are extremely rare. We report a case of an 80-year-old female with a pancreatic metastatic tumor derived from papillary thyroid carcinoma which was initially resected 158 months prior to detection of the metastatic pancreatic tumor. The patient has encountered cervical lymph-node metastasis on three occasions following the initial operation. Metastatic pancreatic lesions and cervical lymph nodes were first detected using 18-fluorodeoxyglucose positron-emission tomography/computed tomography, and she was preoperatively diagnosed using endoscopic ultrasound-guided fine-needle aspiration biopsy. A coin lesion, 10 mm in size, was detected in the left lung by chest computed tomography with no abnormal uptake in 18-fluorodeoxyglucose positron-emission tomography/computed tomography. Distal pancreatectomy and cervical lymph-node dissection were performed. Adjuvant chemotherapy with weekly paclitaxel was administered because anaplastic transformation had been detected in one of the cervical lymph nodes. The patient eventually died from multiple lung metastases 11 months after removing the metastatic pancreatic lesion. We reported a rare case of a pancreatic metastatic tumor from thyroid carcinoma, and found that 18-fluorodeoxyglucose positron-emission tomography/computed tomography and endoscopic ultrasound-guided fine-needle aspiration biopsy are useful for preoperatively diagnosing tumors.

[A Case of Long-Term Survival of Metastatic and Recurrent Duodenal Gastrointestinal Stromal Tumor Treated with Multimodality Managements].

We hereby report a case of long-term survival of metastatic and recurrent duodenal gastrointestinal stromal tumor(GIST) treated with multimodality managements. A 59-year-old man was diagnosed with duodenal GIST and underwent surgical resection of a primary lesion of the duodenum. Since the pathological findings on mitotic rate indicated its high risk of recurrence, the systemic treatment by imatinib mesylate was given shortly after the surgery. Six months later, metastatic lesions being considered to be imatinib-resistant were observed in the remnant liver. Since there were no other drugs available for GISTs in clinic at that time, surgery of central bisegmentectomy with partial resection of the liver was performed to eliminate all metastatic lesions. However, recurrences had been repeatedly diagnosed afterward. In response to them, four more surgery for recurrent liver or peritoneal tumors, two transcatheter arterial chemoembolizations(TACE)and one radiofrequency ablation(RFA)were performed on the basis of its resectability. Sunitinib malate had been given since it was approved for imatinib-resistant GISTs in clinic. Eventually, as long as 99 months had passed since we observed the first evidence of the resistance to imatinib mesylate when he died from the GIST.

Clinical significance of serum transthyretin level in patients with hepatocellular carcinoma.

BACKGROUND: Although serum albumin has been reported to be useful as a prognostic biomarker for various malignancies, it is not suitable for prognosis of patients with hepatocellular carcinoma (HCC) due to impaired liver function. We aimed to determine whether serum transthyretin (TTR) level can be used as a novel prognostic biomarker. METHODS: Serum levels of TTR, as well as other nutritional and inflammatory parameters including angiogenic factors, were examined in 25 patients with HCC. RESULTS: The serum TTR levels exhibited a statistically significant inverse correlation with interleukin-6 (r = -0.412, P = 0.041), and showed statistically significant correlations with retinol-binding protein (r = 0.919, P < 0.001) and albumin (r = 0.442, P = 0.027). The patients with TTR <11.4 mg/dL (P = 0.012), those with ≥T2 (P = 0.011) and those with a retention rate of indocyanine green after 15 min ≥15.5 (P = 0.037) showed poorer prognoses than the counterparts of each parameter. The TTR level <11.4 mg/dL (hazard ratio: 4.837, 95% confidence interval: 1.118-20.926, P = 0.035) and ≥T2 (hazard ratio: 5.011, 95% confidence interval: 1.243-20.203, P = 0.023) were independent prognostic factors of HCC patients. CONCLUSION: Serum TTR measurement can be useful for predicting the prognosis of patients with HCC.

[A Case of Long-Term Survival of the Pancreatic Tail Cancer with the Concomitant Small Liver Metastasis].

We hereby report a case of long-term survival of the pancreatic tail cancer with a synchronous small liver metastasis. A 62- year-old male with pancreatic tail cancer was incidentally diagnosed with single tiny metastasis in the left medial section of the liver duringthe distal pancreatectomy. The lesion was also resected together with primary lesion. Since then, systemic chemotherapies such as gemcitabine(GEM)plus S-1 combination therapy, GEM alone therapy and S-1 alone therapy had been given to escape from recurrence. However, the recurrences were found in the liver at 21 months after surgery. Left hepatectomy was performed for metastatic lesions. Afterwards, proton radiation therapy was twice performed for the metastatic lesions in the liver which were unable to be removed by surgery alone. Partial resection of transverse colon was also needed to be performed for the bowel obstruction caused by recurrence on the surgical margin of the liver. Systemic chemotherapies includingS -1 therapy, FOLFIRINOX therapy and GEM plus nab-paclitaxel therapy have been continued throughout his entire treatment history after recurrence. He has been keepingin good physical condition with these multidisciplinary therapies, even though 51 months have passed since the first evidence of liver metastasis was diagnosed.

Upregulated solute carrier family 37 member 1 in colorectal cancer is associated with poor patient outcome and metastasis.

Solute carrier (SLC) drug transporters exchange various molecules without energy from adenosine triphosphate hydrolysis, indicating an association with anticancer drug resistance. However, the expression and role of SLC transporters in malignant tumors has not yet been fully elucidated. Therefore, in the current study, the expression of SLC37A family genes was evaluated in patients with colorectal cancer (CRC), and it was revealed that SLC family 37 member 1 (SLC37A1) expression was significantly increased in tumorous tissues compared with that in non-tumorous tissues. The cases with upregulated expression of SLC37A1 by immunohistochemical staining were significantly associated with positive venous invasion and liver metastasis. Furthermore, upregulated SLC37A1 expression was associated with poor overall survival time in the present cohort. These results indicated that SLC37A1 is involved in the hematogenous metastasis of CRC. To investigate whether SLC37A1 is associated with hematogenous metastasis and glycolipid metabolism, SLC37A1 was knocked down in colon cancer cells, and the expression of sialyl Lewis A and sialyl Lewis X was observed to be decreased. In summary, upregulation of SLC37A1 was observed in patients with CRC, and was associated with poor patient outcomes and survival. To the best of our knowledge, the present study is the first to propose a key role of SLC37A1 in CRC, and additional studies are warranted to reveal the functional role of SLC37A1 in CRC development.

Enhanced expression of KIF4A in colorectal cancer is associated with lymph node metastasis.

Kinesin family member 4A (KIF4A) is a member of the kinesin 4 subfamily of kinesin-related proteins and serves an important role in cell division. The expression levels of KIF4A have been investigated in numerous types of cancer, including cervical, lung, oral, and breast cancer, and are established to be associated with poor patient prognosis. However, the role of KIF4A, as well as its expression in colorectal cancer (CRC), remains to be elucidated. Therefore, the current study investigated KIF4A expression levels in patients with CRC and demonstrated that its levels were increased in tumor tissues compared with non-tumor tissues. To investigate the functional role of KIF4A, KIF4A was knocked down in CRC cells and cell viability was evaluated. CRC cells with KIF4A knockdown exhibited lower cell proliferation compared with control cells. In addition, KIF4A expression levels, as determined by immunohistochemistry, were compared with the expression of Ki-67, but no significant associations were observed in the patients with CRC. Therefore, KIF4A was found to be upregulated in patients with CRC and downregulation of KIF4A reduced cell proliferation in CRC cells. These results suggest that KIF4A may be a potential therapeutic target, which may improve the outcomes of patients with CRC.

Upregulated HOXA9 expression is associated with lymph node metastasis in colorectal cancer.

Homeobox A (HOXA) cluster genes, members of the HOX family, perform an important role in normal organ development. It has previously been reported that HOXA gene expression in various types of cancer is associated with poor patient outcomes. However, the role of HOXA genes, as well as their expression, in colorectal cancers (CRC) remains unknown. Therefore, the present study investigated HOXA gene expression in patients with CRC and revealed that HOXA9 expression was significantly increased in tumor tissues compared with non-tumor tissues. Additionally, the functional role of HOXA9 was assessed by knocking down the HOXA9 gene in CRC cells and by evaluating cell growth. Regarding gene expression, cases with positive HOXA9 expression (as detected by immunohistochemical staining) were significantly associated with higher TNM stage and positive lymph node metastasis, although no association was observed between increased HOXA9 levels and the rate of overall survival in the present cohort. Regarding the functional role, HOXA9 expression was demonstrated to be upregulated in patients with CRC and was associated with lymph node metastasis.

Clinical Significance of Soluble Intercellular Adhesion Molecule-1 and Interleukin-6 in Patients with Extrahepatic Cholangiocarcinoma.

Purpose/Aim: Although several prognostic factors for extrahepatic cholangiocarcinoma (EHC) have been reported, preoperative prognostic factors have yet to be established. We investigated the serum concentration of angiogenic, inflammatory, and nutritional parameters. MATERIALS AND METHODS: Twenty-five patients with EHC were enrolled before starting treatment. Preoperative prognostic factors were identified using multivariate analyses. RESULTS: The serum soluble intercellular adhesion molecule-1 (sICAM-1) levels were significantly higher in the patients with EHC (436.0 ± 43.2 ng/ml) than in the healthy volunteers (228.6 ± 22.0 ng/ml) (p <.001). In addition, the serum IL-6 levels were significantly higher in the patients (18.0 ± 5.6 pg/ml) than in the healthy volunteers (5.7 ± 0.8 pg/ml) (p <.05). The serum IL-6 and sICAM-1 showed a strong correlation (r = 0.559) in the patients with EHC (p <.01). The serum IL-6 (area under the curve = 0.764, p =.030, cut-off level = 11.6) and sICAM-1 (area under the curve = 0.818, p =.007, cutoff level = 322.6) were revealed to be useful as prognostic factors by the receiver operating characteristic curves. The high IL-6 group and the high sICAM-1 group showed poorer DSS than those of the respective low groups. In the multivariate analysis, IL-6 (hazard ratio: 1.050, 95% confidence interval: 1.002-1.100, p =.043) and sICAM-1 (hazard ratio: 1.009, 95% confidence interval: 1.002-1.015, p =.009) were independent prognostic factors for DSS. CONCLUSIONS: IL-6 and sICAM-1 were independent preoperative prognostic factors in EHC patients, causing continuous inflammation and malnutrition in collaboration with other pro-angiogenic factors.