Neutrophil to Lymphocyte Ratio is a Predictive Factor of Malignant Potential for Intraductal Papillary Mucinous Neoplasms of the pancreas.

Intraductal papillary mucinous neoplasms (IPMNs) are cystic neoplasms with the potential for progression to pancreatic cancer. Accurate prediction of the malignant potential is challenging and a proper treatment strategy has not been well established. Preoperative neutrophil-to-lymphocyte ratio (NLR) is a biomarker of the malignant potential in patients with several types of malignancy. We explored malignant potential in patients with IPMN. The present study included 56 patients aged of 73 ± 9 years (mean ± standard deviation) who underwent curative resection for IPMN from 1996 to 2017. We analyzed the relationship between the characteristics including NLR and malignant component for predicting pathological results. The nonmalignant IPMN group (N = 21) included patients with low-grade dysplasia (LGD) and intermediate-grade dysplasia (IGD), and the malignant IPMN group (N = 35) included patients with high-grade dysplasia (HGD) and invasive carcinoma. In a univariate analysis, NLR ⩾ 2.2 (P = .001), prognostic nutritional index (PNI) < 45 (P = .016), CA 19-9 > 37 U/mL (P = .039), and cystic diameter ⩾ 30 mm (P = .010), and mural nodule (P = .010) were significantly different between the malignant IPMN and the nonmalignant IPMN groups. Multivariate analysis showed that high NLR (⩾2.2) (odds ratio 9.79; 95% confidence interval: 2.06-45.6), cystic diameter ⩾ 30 mm (4.65; 1.14-18.9), and mural nodule (4.91; 1.20-20.1) were independently predictive of malignant IPMN. These results suggest that preoperative NLR is a useful predictive biomarker for evaluating malignant potential in patients with IPMN.1.

Clinical role of Foxp3+ regulatory T cell in Living donor related liver transplantation for prediction of life-threatening complications.

PURPOSES: It is no doubt that regulatory T cells (Foxp3(+)CD4(+)CD25(+)T cells: Treg) play important roles in transplant immunity. We investigated the significance of Treg expression in acute stage of living donorrelated liver transplantation (LDLT) for the possibility of the sensitive marker for immunological state and homeostatic stress after liver transplantation. METHODS: Peripheral blood was drawn from 5 recipients of LDLT preoperatively and on post operative 1, 4, 7, and 14 days. The peripheral blood mononuclear cells (PBMCs) were stained with CD4, CD25, Foxp3, and were analyzed with FACScan. This data was compared with clinical output of LDLT. RESULT: The populations of Treg were significantly decreased in all patients on day 1 after LDLT and significantly increased in patients who had early postoperative complications compared with patients who had no complications. CONCLUSIONS: The population of Treg in peripheral blood may reflect the surgical stress such as life-threatening complications after LDLT.

Effective use of a vessel-sealing system for laparoscopic unroofing of liver cysts.

INTRODUCTION: Liver cysts that present with symptoms such as jaundice, abdominal pain, and intra-cystic infection require treatment. In laparoscopic unroofing of liver cysts, appropriate treatment is needed in cases where the cystic walls contain vessels or bile ducts. A vessel-sealing system can seal not only vessels, but also bile ducts. We experienced four cases in which laparoscopic unroofing of liver cysts was performed with a vessel-sealing system. MATERIALS AND SURGICAL TECHNIQUE: Case 1 was a woman in her 70s who presented at our hospital with abdominal pressure. Abdominal CT showed liver cysts with a maximum diameter of 13 cm. Laparoscopic unroofing was performed with LigaSure Impact. Case 2 was a woman in her 50s with abdominal discomfort. CT showed a cyst 15 cm in diameter situated in the right lobe. We performed SILS using a LigaSure Blunt Tip to unroof the cyst. Case 3 was a man in his 80s with abdominal pain. CT showed a huge cyst 25 cm in diameter in the right lobe. We performed hybrid SILS with a LigaSure Blunt Tip to unroof the cysts. Case 4 was a woman in her 70s with upper abdominal pain. CT showed multiple cysts with a maximum diameter of 15 cm in the bilateral lobes. We performed hybrid SILS to successfully unroof her cysts. None of the cases experienced postoperative complications, such as bleeding or bile leakage, and none experienced recurrence of cysts. DISCUSSION: A laparoscopic unroofing using a vessel-sealing system can be a minimally invasive and safe treatment for liver cysts.

Detection of Lymph Nodes Metastasis in Biliary Carcinomas: Morphological Criteria by MDCT and the Clinical Impact of DWI-MRI.

BACKGROUND/AIMS: This study was conducted to assess the usefulness of multi-slice CT (MDCT) and diffusion weighted MR images (DWI-MRI) for diagnosis of metastatic lymph nodes (LNs) in biliary carcinomas. METHODOLOGY: Eighteen patients with biliary carcinomas (total 121 LNs) underwent surgical resection were included. In MDCT, the following criteria were measured: the maximum diameter, the enhanced value and the long and short axis (L/S) ratio. In DWI-MRI, the apparent diffusion coefficients (ADCs) were measured from ADC maps. RESULTS: In ROC analysis, the maximum diameter has the highest diagnostic power with area under curves of 0.903. And when the maximum diameter 8 mm and L/S ratio is less than 2, the accuracy was improved with a sensitivity of 81%, positive predictive value (PPV) of 45%. In DWI-MRI, ADCs values of metastatic LNs significantly lower than that of non-metastatic LNs (mean: 1.65 vs. 2.11 x10 3mm2/s). When the ADC value of 1.8 x10(-3) was used as a cut-off value, the best results were obtained with sensitivity of 75%, PPV of 82%. CONCLUSIONS: Using MDCT, diagnosis of LNs metastasis should be more than 8mm diameter and less than 2 of L/S ratio. In addition, DWI-MRI is more useful modality for diagnosis of LNs metastasis.

Clinical role of Notch signaling pathway in intraductal papillary mucinous neoplasm of the pancreas.

BACKGROUND AND AIM: This study was performed to elucidate the expression of the Notch signaling pathway and its correlations to clinicopathological factors of intraductal papillary mucinous neoplasms (IPMNs). It is incontrovertible that regulatory T cells (Tregs) play an important role in tumor immunity. However, the whole mechanism of control of peripheral Tregs remains unclear. It is also known that the Notch signaling pathway is involved in Treg suppressor function. Moreover, IPMNs have a high malignant potential. METHODS: Peripheral blood samples and resected specimens from 18 patients with IPMN were evaluated. All patients were pathologically diagnosed with IPMN. Resected specimens were immunohistochemically evaluated (anti-Notch1, anti-Notch2, and anti-Notch2-intracellular domain antibody staining) and compared in terms of clinicopathological factors. Peripheral Treg populations were analyzed with an automated flow cytometer. RESULTS: Disease-free survival was significantly worse in the Notch1 high-expression group (P = 0.023). Notch2 family expressions were higher in intraductal papillary mucinous carcinoma (IPMC) than in intraductal papillary mucinous adenoma (IPMA) (Notch2, P = 0.012; Notch2-intracellular domain, P = 0.036). Jagged1 expression was significantly higher in IPMC than in IPMA (P < 0.05) and was significantly related to recurrence. The Treg population in peripheral blood was higher in patients with IPMC than in those with IPMA (P < 0.01). CONCLUSIONS: Notch signaling, especially Jagged1 expression, reflects IPMN aggressiveness. Our data may suggest that the Notch signaling pathway is a key pathway that determines IPMN pathological aggressiveness and reflects the peripheral Treg population.

Homing effect of adipose-derived stem cells to the injured liver: the shift of stromal cell-derived factor 1 expressions.

BACKGROUND: Whether systemically transplanted human adipose-derived stem cells (ADSCs) homed to the injured liver in nude mice under stress with subsequent hepatectomy (Hx) and ischemia-reperfusion (I/R) was investigated in the present study. The types of cells in the liver that were involved in the homing of ADSCs were clarified, with focus on the stromal-derived factor-1 (SDF-1)/C-X-C chemokine receptor type 4 (CXCR-4) axis. METHODS: Adipose-derived stem cells were transplanted intravenously immediately after 70% Hx and I/R. ADSCs were traced by in vivo imaging for 24 h after transplantation and ADSCs were histologically detected in the liver. SDF-1 and CXCR-4 expressions in the liver were evaluated by real time RT-PCR. The immunohistochemical analysis of SDF-1 was also performed to identify SDF-1 expressing cells in the liver. RESULTS: Adipose-derived stem cells were found in various organs immediately following transplantation and almost accumulated in remnant liver or spleen at 6 h after transplantation. ADSCs were also histologically revealed in the harvested liver. Hx and I/R injury significantly enhanced SDF-1 expressions regardless of ADSCs transplantation, and only ADSC transplantation increased CXCR-4 expressions. The predominant SDF-1 positive cells in the liver were equally identified in parenchymal and non-parenchymal cells at 6 h, but shifted to non-parenchymal cells at 24 h after transplantation. CONCLUSIONS: Systemically transplanted ADSCs homed to the injured liver after transplantation, possibly based on the mechanisms of SDF-1/CXCR-4 axis. Therefore, systemic transplantation might be an effective and practical route for the transplantation of ADSCs.

Effect of Twist and Bmi1 on intraductal papillary mucinous neoplasm of the pancreas.

BACKGROUND: Intraductal papillary mucinous neoplasm (IPMN) is a well-established entity among pancreatic neoplasms that ranges from low-grade dysplasia to invasive carcinoma. Epithelial-mesenchymal transition (EMT) contributes to tumor progression in various cancers. Moreover, Notch signaling is one of the important upstream effectors of EMT promotion. Currently, it is unclear whether EMT causes pathological progression of IPMN. AIM: We evaluated the expression of EMT-promoting transcription factors Twist and B cell-specific Moloney murine leukemia virus insertion site 1 (Bmi1) in IPMN. METHODS: Patients who underwent resections at our institute and its affiliated hospital were enrolled in this study (n = 35). Protein expression of EMT markers Twist, Bmi1, Jagged1, and E-cadherin in resected specimens was investigated by immunohistochemistry. Expression of these proteins was compared with the clinicopathological factors and patient survival. RESULTS: Positive expression of Twist and Bmi1 was observed in 40.0% and 42.9% of IPMNs, respectively. Twist and Bmi1 expression was significantly higher in IPMNs with high-grade dysplasia (P < 0.05) and invasive carcinoma (P < 0.05) than that in IPMNs with low-grade dysplasia. High expression of Twist was correlated with Jagged1 expression and inversely correlated with expression of E-cadherin (P = 0.06 and P < 0.05, respectively). In survival analyses, the recurrence rate was significantly higher in the group that showed simultaneous high expression of Twist and Bmi1 (P < 0.05). CONCLUSIONS: Expression of Twist and Bmi1 is associated with aggressiveness and poor prognoses of IPMN through EMT promotion that might be induced by Notch signaling.

High STAT4 expression is a better prognostic indicator in patients with hepatocellular carcinoma after hepatectomy.

BACKGROUND: Signal transducer and activator of transcription 4 (STAT4) mediates the intracellular effects of interleukin-12, leading to the production of interferon gamma (IFN-γ) and natural killer cells cytotoxicity. However, the clinical significance of STAT4 expression in patients with hepatocellular carcinoma (HCC) remains virtually unknown. METHODS: A total of 66 HCC patients who underwent hepatectomy were enrolled in this study. Quantitative real-time polymerase chain reaction was performed to determine STAT4 and IFNG mRNA expression levels. Tissue microarray-based immunohistochemistry was performed to examine CD8(+) T cells, STAT4, and INF-γ proteins. RESULTS: STAT4 was differentially expressed in tumor and nontumor tissues (P = 0.001) and positively correlated with IFNG expression (R (2) = 0.506, P < 0.05) and CD8(+) T cell infiltration (R (2) = 0.53, P < 0.001). Significant correlations were observed between STAT4 expression and tumor TNM stage (P = 0.043), hepatic venous invasion (P = 0.003), des-gamma-carboxy prothrombin (P = 0.011), tumor size (P = 0.036), and tumor differentiation (P = 0.034). Patients with high STAT4 expression had significantly better recurrence-free survival (P = 0.009). Low STAT4 expression (P = 0.030) and presence of portal venous invasion or hepatic venous invasion (P = 0.006) were independent risk factors for HCC recurrence. CONCLUSIONS: Downregulation of STAT4 in HCC indicated aggressive tumor behavior and predicted a worse clinical outcome. STAT4 might be a useful biomarker to identify patients at high risk of recurrence after hepatectomy.

Clinicopathological characteristics of patients with non-B non-C hepatocellular carcinoma: a special reference to metabolic syndrome.

BACKGROUND/AIMS: This study was carried out to clarify the clinicopathological features of hepatocellular carcinoma (HCC) arising in patients without viral infection and to confirm the influence of metabolic syndrome (MS) on characteristics in HCC patients. METHODOLOGY: Two hundred and thirty-three hepatectomized HCC patients were enrolled. The status of the hepatitis viral infection was defined; non-B non-C (NBNC) (n = 15), negative for HBs-Ag, HBc-Ab or HCV-Ab; HBV (n = 70); HCV (n = 148). We compared clinicopathological features and surgical outcomes among three groups. Additionally, fifty-six HCC patients who were evaluated on coexistence of MS were divided into two groups and analyzed; MS (n = 16) and non-MS (n = 40) groups. RESULTS: In NBNC-patients, preoperative platelet counts and ICGR15 were significantly better compared to HCV-patients (21.8 x 10(4)/mm3 vs. 11.3 x 10(4)/mm3, 14.0% vs. 19.2%, p <0.05). Body mass index was significantly higher in NBNC-patients (24.9 vs. 22.4, p < 0.05). Overall survival rates were significantly higher in NBNC-patients compared with HBV or HCV-patients (5 y: 87.5% vs. 48.8%, 42.9%, p < 0.05). For NBNC-patients there were significantly more patients in the MS group than in the non-MS group. CONCLUSIONS: HCC with MS included more NBNC-HCC than HBV or HCV related HCC. Aggressive hepatectomy contributed to the favorable outcome in NBNC-patients because of their better liver function.

Role of Fbxw7 expression in hepatocellular carcinoma and adjacent non-tumor liver tissue.

BACKGROUND AND AIM: Fbxw7 is a tumor suppressor gene through ubiquitination and degradation of multiple oncoproteins. Loss of Fbxw7 expression is frequently observed in various human cancers. In the present study, we examined the role of Fbxw7 expression in both non-tumor liver tissues and tumor tissues on clinicopathological significance. METHODS: Sixty-six patients with hepatocellular carcinoma (HCC), who underwent hepatectomy, were divided into two groups: high and low gene-expression group, based on the Fbxw7 expression level. We compared the clinicopathological factors between the high expression and low expression groups in both tumor and non-tumor tissues. RESULTS: Fbxw7 messenger RNA expression level in the non-tumor tissues was significantly higher than that in the tumor tissues. In the analysis of Fbxw7 expression in tumor and non-tumor tissues, disease-free survival rate in the Fbxw7 high expression group was significantly higher than that in the low expression group. In multivariable analysis, Fbxw7 low expression in both tumor and non-tumor tissue was detected as the strongest independent risk factor for HCC recurrence. CONCLUSIONS: Low Fbxw7 expression in both tumor and non-tumor tissue may be an independent prognostic factor for tumor recurrence after hepatectomy in patients with HCC.

Bevacizumab improves splenomegaly and decreases production of hyaluronic acid after L-OHP based chemotherapy.

BACKGROUND: Oxaliplatin-based chemotherapy can cause hepatic sinusoidal injury such as sinusoidal obstructive syndrome (SOS). Spleen size is correlated with sinusoidal damage, and serum hyaluronic acid is also a marker of SOS. The aim of the present study was to clarify the impact of the current chemotherapeutic regimen plus bevacizumab against oxaliplatin-associated hepatic damage with serum hyaluronic acid and spleen size. PATIENTS AND METHODS: Sixteen adult patients with colorectal cancer and liver metastasis were evaluated retrospectively. In the bevacizumab-treated group (n=9), oxaliplatin-based chemotherapy with bevacizumab prior to hepatic resection was administered, while oxaliplatin-based chemotherapy-alone was administered prior to hepatic resection in the control group (n=7). Hepatic sinusoidal injury, change in spleen size and serum value of hyaluronic acid were evaluated. RESULTS: The incidence and severity of sinusoidal dilation was lower in the bevacizumab group than in the control group (moderate or severe: 2/9 (22.2%) vs. 5/7 (71.4%), incidence of sinusoidal dialation: 5/9 (55.6%) vs. 7/7 (100%), both p<0.05). The change in spleen size and serum hyaluronic acid were significantly lower in the bevacizumab-treated group compared to the control group (change in spleen size: 110.3%±27.5% vs. 146.3%±34.2%, hyaluronic acid: 33.6±21.2 ng/ml vs. 124.5±34.0 ng/ml, both p<0.05). CONCLUSION: In the current study, bevacizumab reduced SOS in pathological findings and suppressed the elevation of hyaluronic acid, and splenomegaly. In addition, a change in spleen size and serum hyaluronic acid could serve as a biomarker for a predictive effect of bevacizumab against SOS.

Gene profile in the spleen under massive partial hepatectomy using complementary DNA microarray and pathway analysis.

BACKGROUND AND AIM: In general, the spleen is one of the abdominal organs connected by the portal system, and a splenectomy improves hepatic functions in the settings of partial hepatectomy (Hx) for portal hypertensive cases or living donor liver transplantation with excessive portal vein flow. Those precise mechanisms remain still unclear; therefore, we investigated the DNA expression profile in the spleen after 90% Hx in rats using complementary DNA microarray and pathway analysis. METHODS: Messenger RNAs (mRNAs) were prepared from three rat spleens at each time point (0, 3, and 6 h after 90% Hx). Using the gene chip, mRNA was hybridized to Affymetrix GeneChip Rat Genome 230 2.0 Array (Affymetrix®) and pathway analysis was done with Ingenuity Pathway Analysis (IPA®). RESULTS: We determined the 3-h or 6-h/0-h ratio to assess the influence of Hx, and cut-off values were set at more than 2.0-fold or less than 1/2 (0.5)-fold. Chemokine activity-related genes including Cxcl1 (GRO1) and Cxcl2 (MIP-2) related pathway were upregulated in the spleen. Also, immediate early response genes including early growth response-1 (EGR1), FBJ murine osteosarcoma (FOS) and activating transcription factor 3 (ATF3) related pathway were upregulated in the spleen. CONCLUSIONS: We concluded that in the spleen the expression of numerous inflammatory-related genes would occur after 90% Hx. The spleen could take a harmful role and provide a negative impact during post Hx phase due to the induction of chemokine and transcription factors including GRO1 and EGR1.

Loss of FBXW7 expression is associated with poor prognosis in intrahepatic cholangiocarcinoma.

AIM: FBXW7 acts as a tumor suppressor gene by targeting several oncogenic regulators of proliferation, growth and apoptosis for proteasomal degradation. However, the significance of this protein is not yet well understood in intrahepatic cholangiocarcinoma (IHCC). In this study, we aimed to investigate the correlation between FBXW7 expression and clinicopathological variables in IHCC patients. METHODS: Thirty-one patients with IHCC who underwent hepatic resection were enrolled. FBXW7 expression in tumor tissue was determined by immunohistochemistry and patients were divided into two groups, the FBXW7 high expression group (n = 11) and the FBXW7 low expression group (n = 20). We then compared clinicopathological variables including prognosis between the high and low expression groups in tumor tissue. RESULTS: FBXW7 expression was significantly correlated with staging (P = 0.006), and tended to correlate with lymph node metastasis. The FBXW7 low expression group had significantly poorer prognosis compared with the FBXW7 high expression group (P = 0.020); 3-year survival rates were 29.4% and 72.7%, respectively. Furthermore, the disease-free survival rate in the FBXW7 low expression group was significantly worse than in the FBXW7 high expression group (P = 0.022). On multivariate analysis, intrahepatic metastasis (P = 0.006) was a significant independent prognostic factor for disease-free survival, and FBXW7 low expression tended to be an independent prognostic factor for both overall (P = 0.067) and disease-free survival (P = 0.083). CONCLUSION: Our results confirmed that low expression of FBXW7 in IHCC correlates with tumor progression and poor prognosis in IHCC.

Expressions of hypoxia-inducible factor-1 and epithelial cell adhesion molecule are linked with aggressive local recurrence of hepatocellular carcinoma after radiofrequency ablation therapy.

BACKGROUND: Radiofrequency ablation (RFA) is a widely used therapy for hepatocellular carcinoma (HCC). Several reports have demonstrated the aggressive local recurrence of HCC after RFA, suggesting that induction of further malignant transformation of HCC has occurred. METHODS: Eighty-eight (88) patients with HCC who underwent hepatic resection were included in this study. Hepatectomy was indicated for local recurrence of HCC after RFA (n = 10, RFA group) and for HCC without prior RFA (n = 78, non-RFA group). Clinicopathological data and the patient's prognosis after hepatectomy were compared between the two groups. Expression levels of hypoxia-inducible factor-1 (HIF-1), epithelial cell adhesion molecule (EpCAM), CD44, and vascular endothelial growth factor messenger RNA (mRNA) in the tumor tissues were also examined. RESULTS: The RFA group showed higher frequency of portal vein invasion and less tumor differentiation compared with the non-RFA group (p < 0.05). Overall and disease-free survival rates in the RFA group were significantly worse than those in the non-RFA group (p < 0.05). HIF-1 and EpCAM mRNA expression levels in the RFA group were significantly higher than those in the non-RFA group (p < 0.05). CONCLUSIONS: These results suggest that local HCC recurrence after RFA shows an aggressive tumor phenotype and poor prognosis through the enhanced expressions of HIF-1 and EpCAM in the residual HCC tumors after insufficient or sub-lethal treatment by RFA.

Specific miRNA expression profiles of non-tumor liver tissue predict a risk for recurrence of hepatocellular carcinoma.

AIM: It is reasonable to investigate non-tumor liver tissues to predict a risk for development of hepatocellular carcinoma (HCC). A molecular analysis of chronically damaged liver tissues may identify specific miRNA expression profiles associated with a risk for multicentric (MC) HCC. METHODS: Twenty HCC patients, who underwent a curative hepatectomy were classified into two groups: a non-MC group (no MC recurrence in more than 3 years, n = 10) and an MC group (MC recurrence within 3 years after hepatectomy, n = 10). An miRNA microarray (955 probes) was used to compare the miRNA expression patterns of the non-cancerous liver tissues between the two groups. This study identified the differentially expressed miRNA related to MC recurrence in the liver remnant. RESULTS: No differences were observed between the two groups in the liver function tests and pathological variables including both tumor factors and non-tumor liver tissues. The investigation selected 20 differentially expressed miRNA related to MC recurrence. Eighteen miRNA were downregulated, while two miRNA were upregulated in the MC group. A hierarchical clustering analysis identified a cluster that may be associated with risk of the MC recurrence of HCC. The MC recurrence-related miRNA included let-7d*, miR-328 and miR18a*, which potentially regulate K-ras gene expression. A significant inverse correlation between the miR-18a* expression and the K-ras mRNA expression was confirmed by quantitative reverse transcription polymerase chain reaction. CONCLUSION: Specific miRNA expression signatures in non-cancerous liver tissue may help to predict the risk for de novo development of HCC.

Laparoscopic hepatic resection for metastatic liver tumor of colorectal cancer: comparative analysis of short- and long-term results.

BACKGROUND: With the progress of surgical techniques and devices, laparoscopic hepatectomy (Lap-Hx) became a realizable option for patients with liver tumors. However, the feasibility of Lap-Hx for metastatic liver tumor of colorectal cancer also should be guaranteed oncologically. This study evaluated the short- and long-term outcomes of Lap-Hx compared with open hepatectomy (Open-Hx) for patients with colorectal liver metastasis (CLM) by matched-pair analysis. METHODS: This study enrolled 21 patients who underwent Lap-Hx and compared them with 21 matched patients who underwent Open-Hx. The following parameters were matched between the two cohorts: tumor size, tumor location, and operative procedures. Both short- and long-term outcomes of Lap-Hx were compared with those of Open-Hx. RESULTS: No difference was observed between the two groups in terms of age, gender, tumor size, or operative procedures. With regard to short-term outcomes, the operative time for Lap-Hx (377 ± 29 min) was similar to that for Open-Hx (369 ± 31 min), whereas the blood loss for the patients who underwent a Lap-Hx (198 ± 39 ml) was significantly less than for those who underwent an Open-Hx (326 ± 50 ml). The incidence of postoperative complications among the patients who underwent Lap-Hx tended to be lower than for the patients who underwent Open-Hx, and intraabdominal abscess was observed only in the Open-Hx group. The hospital stay for Lap-Hx (average, 18.3 days) tended to be shorter than for Open-Hx (27 days). With respect to long-term outcomes, the two groups did not differ significantly in terms of 5-year overall and disease-free survival rates. CONCLUSIONS: Lap-Hx is a safe and feasible option for selected patients with CLM. The short- and long-term outcomes of Lap-Hx also are considered to be acceptable.

CXC receptor 4 and stromal cell-derived factor 1 in primary tumors and liver metastases of colorectal cancer.

BACKGROUND: It has been determined that the chemokine receptor CXC receptor 4 (CXCR4) and its ligand, stromal cell-derived factor 1 (SDF-1), regulate several key processes in a wide variety of cancers. In this study, we investigate the possible role of SDF-1 (noncancerous liver tissue) and CXCR4 in liver metastases of colorectal cancer (CRC). MATERIALS AND METHODS: Reverse transcription-polymerase chain reaction was performed to examine the expression of SDF-1 in noncancerous liver tissues of 16 CRC patients with liver metastasis and in normal liver tissues of six patients with benign liver disease. We also examined the expression of CXCR4 in cancerous tissues from primary and metastatic tumors. RESULTS: Using reverse transcription-polymerase chain reaction, CXCR4 expression in metastatic tumors tended to be higher than that in primary tumors (P = 0.16). High CXCR4 expression in a primary tumor was found to be related to an increased lymphatic invasion (P = 0.01), an advanced depth of tumor invasion (P = 0.07), and a decrease in the overall survival rate. The SDF-1 expression observed in noncancerous liver tissues of CRC with liver metastasis was significantly higher than that observed in normal liver tissues of benign liver disease (P < 0.05). CONCLUSIONS: In CRC with liver metastasis, CXCR4 expression demonstrated associations with local progression, liver metastasis, and poor overall survival.

Trophic effect of adipose tissue-derived stem cells on porcine islet cells.

BACKGROUND: Adipose tissue-derived stem cells (ADSCs), which are widely known as multipotent progenitor cells, release several cytokines that support cell survival and repair. The aim of this study was to investigate whether ADSC-secreted molecules could induce a trophic effect in pancreatic islet culture conditions in vitro. MATERIALS AND METHODS: We cocultured porcine islet cells with ADSCs using a transwell system for 48 h and evaluated the viability of islet cells. We also determined the concentration levels of cytokines and insulin in the supernatant of the culture medium. We used anti-vascular endothelial growth factor (VEGF) and anti-interleukin (IL)-6 receptor antibodies to investigate the effect of VEGF and IL-6 on islet cells. RESULTS: ADSCs improved the viability of islet cells in the absence of cell-cell contact (P < 0.05). VEGF and IL-6 levels in the culture medium increased when islet cells were cocultured with ADSCs (P < 0.05). Furthermore, inhibition of VEGF decreased the viability of islet cells (P < 0.05); however, inhibition of IL-6 did not affect islet cell viability. CONCLUSIONS: These results suggested that trophic factors, particularly VEGF, secreted by human ADSCs enhanced the survival and function of porcine islet cells.

Changes of immunological parameters with administration of Japanese Kampo medicine (Juzen-Taihoto/TJ-48) in patients with advanced pancreatic cancer.

BACKGROUND: The prognosis of pancreatic cancer is extremely poor regardless of various combination therapies. Immunoaugumentation against tumor cells was recently A focus. We reported that the population of Foxp3(+)CD25(+)CD4(+) regulatory T cells (Foxp3(+)Treg) was the new parameter for the estimation of host immunity and had correlation with tumor aggressiveness. Here we show the immunoaugumentation effects of Japanese Kampo medicine, Juzen-Taihoto/TJ-48, empirically considered as an immunoaugumentation drug, with investigation of Treg and other immunological parameters. PATIENTS AND METHOD: Peripheral Foxp3(+) Treg populations, CD4/CD8 ratio, and CD57(+) cells (NK cells) populations in advanced pancreatic cancer patients (n = 30, stage VI A and B according to TNM classification) were estimated after TJ-48 administration for 14 days before the anti-cancer therapy. RESULTS: Treg populations were significantly increased compared to healthy donors (Mann-Whitney U test, P < 0.001). Administration of Juzen-Taihoto/TJ-48 significantly decreased Treg populations (Mann-Whitney U test, P < 0.001) and increased the CD4/CD8 ratio (Mann-Whitney U test, P < 0.01), even though CD57(+) cell populations did not change significantly. CONCLUSIONS: Juzen-Taihoto/TJ-48 increased regulatory activities in T cells through decreasing Foxp3(+) Treg populations in advanced pancreatic cancer patients. This effect can lead to immunoaugumentation for various combination therapies.

The role of Aurora B expression in non-tumor liver tissues of patients with hepatocellular carcinoma.

BACKGROUND: Aurora B is a serine-threonine kinase and chromosomal passenger protein involved in the control of chromosome assembly and segregation during mitosis. Aberrant expression of Aurora B has been reported in some tumors, including lung and hepatocellular carcinoma (HCC). We investigated the role of Aurora B expression in both HCC and matched adjacent non-tumor tissue. METHODS: Sixty-three patients with HCC who underwent hepatic resection were enrolled in this study. Aurora B expression in tumor and non-tumor tissue was examined by use of quantitative reverse transcription-polymerase chain reaction. The patients were divided into high and low gene expression groups by median value, and clinicopathological data were compared between the two groups. RESULTS: Aurora B expression was significantly higher in tumor tissue than in non-cancerous tissue (P < 0.001). Disease-free survival was not significantly different between groups with high and low expression in the tumor tissues. For non-tumor tissues, disease-free survival of the low-expression group was significantly better than that of the high-expression group (P < 0.05). The gene expression level of Aurora B correlated with results from liver function tests, for example prothrombin time. CONCLUSION: Aurora B expression in non-cancerous tissues may be a prognostic factor for HCC.