The BAFF/NF B axis is crucial to interactions between sorafenib-resistant HCC cells and cancer-associated fibroblasts.

The tumor microenvironment affects malignancy in hepatocellular carcinoma (HCC) cells, and cancer-associated fibroblasts (CAFs) play an important role in the microenvironment. As recent studies indicated a difference between CAFs isolated from chemoresistant and non-resistant cancer tissues, therefore we investigated the intracellular mechanism in resistant HCC co-cultured CAFs and interactions between these CAFs with cancer cells. We established a sorafenib-resistant (SR) Huh7 (human HCC) cell line, and characterized it with cytokine assays, then developed CAFs by co-culturing human hepatic stellate cells with resistant or parental Huh7 cells. The 2 types of CAFs were co-cultured with parental Huh7 cells, thereafter the cell viability of these Huh7 cells was checked under sorafenib treatment. The SR Huh7 (Huh7 ) cells expressed increased B-cell activating factor (BAFF), which promoted high expression of CAF-specific markers in Huh7 -co-cultured CAFs, showed activated BAFF, BAFF-R, and downstream of the NF B-Nrf2 pathway, and aggravated invasion, migration, and drug resistance in co-cultured Huh7 cells. When we knocked down BAFF expression in Huh7 cells, the previously increased malignancy and BAFF/NF B axis in Huh7 -co-cultured CAFs reversed, and enhanced chemoresistance in co-cultured Huh7 cells returned as well. In conclusion, the BAFF/NF B pathway was activated in CAFs co-cultured with cell-culture medium from resistant Huh7, which promoted chemoresistance, and increased the malignancy in co-cultured non-resistant Huh7 cells. This suggests that the BAFF/NF B axis in CAFs might be a potential therapeutic target in chemoresistance of HCC.


Cancerssociated fibroblastnduced M2olarized macrophages promote hepatocellular carcinoma progression via the plasminogen activator inhibitor 1 pathway.

Targeting the tumor stroma is an important strategy in cancer treatment. Cancerssociated fibroblasts (CAFs) and tumorssociated macrophages (TAMs) are two main components in the tumor microenvironment (TME) in hepatocellular carcinoma (HCC), which can promote tumor progression. Plasminogen activator inhibitor 1 (PAI 1) upregulation in HCC is predictive of unfavorable tumor behavior and prognosis. However, the crosstalk between cancer cells, TAMs and CAFs, and the functions of PAI 1 in HCC remain to be fully investigated. In the present study, macrophage polarization and key paracrine factors were assessed during their interactions with CAFs and cancer cells. Cell proliferation, wound healing and Transwell and Matrigel assays were used to investigate the malignant behavior of HCC cells . It was found that cancer cells and CAFs induced the M2 polarization of TAMs by upregulating the mRNA expression levels of CD163 and CD206, and downregulating IL 6 mRNA expression and secretion in the macrophages. Both TAMs derived from cancer cells and CAFs promoted HCC cell proliferation and invasion. Furthermore, PAI 1 expression was upregulated in TAMs after being stimulated with CAFonditioned medium and promoted the malignant behavior of the HCC cells by mediating epithelialesenchymal transition. CAFs were the main producer of C motif chemokine ligand 12 (CXCL12) in the TME and CXCL12 contributed to the induction of PAI 1 secretion in TAMs. In conclusion, the results of the present study suggested that CAFs promoted the M2 polarization of macrophages and induced PAI 1 secretion via CXCL12. Furthermore, it was found that PAI 1 produced by the TAMs enhanced the malignant behavior of the HCC cells. Therefore, these factors may be targets for inhibiting the crosstalk between tumor cells, CAFs and TAMs.


Utility of cone unit liver resection for small hepatocellular carcinoma: a propensity score matched analysis.

Anatomical resection (AR) is performed widely for hepatocellular carcinoma (HCC). However, it is controversial whether typical AR, which removes the whole feeding territory of the tumor-bearing portal branch bordered by the landmark veins, is necessary. The aim of this study was to investigate the utility of small AR, so-called cone unit resection, for small HCC. Between 2007 and 2019, 372 hepatectomies were performed for HCC. Among them, 91 initial resections for small (<5 cm) solitary HCC were performed by typical AR (n = 44) or cone unit AR (n = 47). Propensity score matching was performed and clinicopathological features including prognosis were compared. At baseline, platelet count was higher, and liver function (serum albumin level) and indocyanine green retention at 15 min were better in the typical AR than cone unit AR group. There was no significant difference between the typical AR and cone unit AR group for tumor characteristics, short- and long-term outcomes. Even after propensity score matching (n = 29), the short- and long-term outcomes were also equivalent in between the two groups. There was no difference in prognosis of typical and cone unit AR. Therefore, cone unit AR is a feasible procedure for small HCC.


Intestinal hypoperfusion in patients with Crohn's disease revealed by intraoperative indocyanine green fluorescence imaging.

Anastomotic leakage has been reported as an independent risk factor for surgical recurrence at the anastomotic site in patients with Crohn's disease. An inadequate blood supply may contribute to this leakage. Real-time indocyanine green angiography has been useful for confirming vascular perfusion of the intestines. The aim of this study was to evaluate the use of intraoperative indocyanine green angiography to detect vascular perfusion of the intestines during ileocaecal resection in patients with Crohn's disease and colon cancer. We retrospectively evaluated the medical records of 26 consecutive patients with colon cancer arising in the caecum or ascending colon and 3 consecutive patients with Crohn's disease without a history of disease-related surgery. The patients in the 2 cohorts had undergone ileocaecal resection at Tokushima University Hospital between January 2018 and January 2021. After ileocaecal resection, blood flow was evaluated in ileal (oral) and colon (anal) stapled stumps by indocyanine green fluorescence angiography. The fluorescence time was defined as the time from indocyanine green injection and flush of the injection route to the point when the stump showed the strongest fluorescent signal in the monitor. The fluorescence time for the ileal and colon stumps in patients with Crohn's disease was 43.3 8.8 s each and was significantly longer than the fluorescence time in the patients with colon cancer (29.4 6.5 s and 29.6 6.8 s, respectively) (P < 0.05). Intraoperative indocyanine green fluorescence imaging is safe and reproducible for assessing intestinal perfusion prior to anastomosis in patients with colon cancer and Crohn's disease.


Preoperative lymphocyte/C-reactive protein ratio and its correlation with CD8 tumor-infiltrating lymphocytes as a predictor of prognosis after resection of intrahepatic cholangiocarcinoma.

To clarify whether the preoperative lymphocyte/C-reactive protein (CRP) ratio (LCR) is a prognostic factor for patients with intrahepatic cholangiocarcinoma (IHCC), and investigate its mechanism via tumor-infiltrating lymphocytes. The subjects of this retrospective study were 42 patients who had undergone hepatectomy for IHCC. We divided the patients into low LCR and high LCR groups (cutoff value: 8780) and analyzed their overall survival (OS) and disease-free survival (DFS) with respect to LCR and other clinicopathological factors. We also investigated the levels of stromal tumor-infiltrating lymphocytes (TILs) and CD8 TILs in surgical specimens, and the relationship between LCR and TILs. A low LCR was identified in 21 patients and was significantly correlated with older age, a high CRP-albumin ratio, and advanced disease stage, and was a prognostic factor for OS and DFS. Multivariate analysis revealed that a low LCR was an independent prognostic factor for worse OS (HR 10.40, P = 0.0077). Although the LCR and levels of stromal TILs were not significantly related, LCR and levels of CD8 TILs were significantly related (P = 0.0297). The preoperative LCR may predict the postsurgical prognosis of patients with IHCC and reflect the CD8 TILs.


A Liquid Biopsy Assay for Noninvasive Identification of Lymph Node Metastases in T1 Colorectal Cancer.

We recently reported use of tissue-based transcriptomic biomarkers (microRNA [miRNA] or messenger RNA [mRNA]) for identification of lymph node metastasis (LNM) in patients with invasive submucosal colorectal cancers (T1 CRC). In this study, we translated our tissue-based biomarkers into a blood-based liquid biopsy assay for noninvasive detection of LNM in patients with high-risk T1 CRC. We analyzed 330 specimens from patients with high-risk T1 CRC, which included 188 serum samples from 2 clinical cohorts-a training cohort (N = 46) and a validation cohort (N = 142)-and matched formalin-fixed paraffin-embedded samples (N = 142). We performed quantitative reverse-transcription polymerase chain reaction, followed by logistic regression analysis, to develop an integrated transcriptomic panel and establish a risk-stratification model combined with clinical risk factors. We used comprehensive expression profiling of a training cohort of LNM-positive and LMN-negative serum specimens to identify an optimized transcriptomic panel of 4 miRNAs (miR-181b, miR-193b, miR-195, and miR-411) and 5 mRNAs (AMT, forkhead box A1 [FOXA1], polymeric immunoglobulin receptor [PIGR], matrix metalloproteinase 1 [MMP1], and matrix metalloproteinase 9 [MMP9]), which robustly identified patients with LNM (area under the curve [AUC], 0.86; 95% confidence interval [CI], 0.72-0.94). We validated panel performance in an independent validation cohort (AUC, 0.82; 95% CI, 0.74-0.88). Our risk-stratification model was more accurate than the panel and an independent predictor for identification of LNM (AUC, 0.90; univariate: odds ratio [OR], 37.17; 95% CI, 4.48-308.35; P < .001; multivariate: OR, 17.28; 95% CI, 1.82-164.07; P = .013). The model limited potential overtreatment to only 18% of all patients, which is dramatically superior to pathologic features that are currently used (92%). A novel risk-stratification model for noninvasive identification of T1 CRC has the potential to avoid unnecessary operations for patients classified as high-risk by conventional risk-classification criteria.


A multicenter phase II trial of preoperative chemoradiotherapy with S-1 plus oxaliplatin and bevacizumab for locally advanced rectal cancer.

We clarified the safety and efficacy of preoperative chemoradiotherapy for locally advanced rectal cancer using a multidrug regimen (S-1 +xaliplatin +evacizumab). This multicenter phase II trial involved 47 patients with locally advanced rectal cancer. All patients received S-1 orally (80 mg/m/day on days 1-5, 8-12, 15-19, and 22-26) and infusions of oxaliplatin (50 mg/m on days 1, 8, 15, and 22) and bevacizumab (5 mg/kg on days 1 and 15). The total radiation dose was 40 Gy delivered in daily fractions of 2 Gy via the four-field technique. The primary endpoint was the pathological complete response rate. The secondary endpoints were safety (incidence of adverse events) and clinical response, relapse-free survival, overall survival, local recurrence, R0 resection, downstaging, and treatment completion rates. All 47 patients received chemoradiotherapy, and 44 patients underwent curative resection. Two patients refused surgery and selected a watch-and-wait strategy. The pathological complete response rate was 18.2% in patients who underwent curative resection. The clinical response rate was 91.3% in 46 patients. Concerning hematotoxicity, there was one grade 4 adverse event (2.1%) and seven grade 3 events (14.9%). Diarrhea was the most frequent non-hematotoxic event, and the grade 3 event rate was 25.5%. Although preoperative chemoradiotherapy for patients with locally advanced rectal cancer using the S-1 +xaliplatin +evacizumab regimen did not achieve the expected pathological complete response rate, this regimen led to an improved clinical response rate.

International Journal of Clinical Oncology


Regeneration of caudate lobe after living donor liver transplantation : Comparison with a surrogate model of left lobe graft.

Background : The aim of this study is to clarify the regeneration of the CL (caudate lobe) without any reconstructions of short hepatic veins (SHVr) after LDLT (living donor liver transplantation) and compare the regeneration of the CL after right hepatectomy (Rt. Hx), as the surrogate model of extended left lobe graft (Ex LLG) with complete SHVr. Methods : Eleven Ex LLGs with CL were included in this study. SHVr was not performed in all cases. The volumetry was performed before, one month and six months after LDLT. Seven patients who underwent Rt. Hx were also included in this study as the surrogate model. Results : In Ex LLGs with CL, the regeneration rate of the large CL (> 30 ml) was worse than that of small CL (< 30 ml). In the surrogate model, the regeneration rate of the CL was not worse than other segments. However, the regeneration rate of the large CL was also worse than that of small CL even in the presence of complete SHVr. Conclusions : The regeneration of the large CL was worse than that of the small CL regardless of the presence or absence of SHVr, indicating that SHVr in Ex LLG with CL might not be necessary. J. Med. Invest. 68 : 330-333, August, 2021.

The Journal of Medical Investigation : JMI


Value of the CRP-albumin ratio in patients with resectable pancreatic cancer.

Background : The C-reactive protein (CRP)-albumin ratio (CAR) was reported as a prognostic factor of resectable hepatocellular carcinoma. The aim of this study was to analyse the significance of CAR in resectable pancreatic cancer. Patients and Methods : 163 patients with curative resection for pancreatic cancer were enrolled in this retrospective study. Cases of non-curative resection were excluded. The CAR was calculated with the preoperative plasma CRP and albumin values, with a cut-off value of 0.06, as calculated in a previous report. Results : Patients in the low CAR group had significantly better overall survival (OS) and disease-free survival (DFS) compared with the high CAR group (P < 0.05). On multivariate analysis, for high CAR, CA19-9 > 300 U /l and receipt of adjuvant chemotherapy were independent risk factors for OS and DFS. High CAR was significantly associated with advanced T stage. Conclusion : The CAR might be a prognostic factor for patients with resectable pancreatic cancer. J. Med. Invest. 68 : 244-248, August, 2021.


Effective in vitro differentiation of adipose-derived stem cells into Schwann-like cells with folic acid supplementation.

Peripheral nerve injury (PNI) after pelvic surgery is a common issue with a significant impact on patients. Autologous nerve grafting is the gold standard treatment for PNI, but this technique cannot be applied to fine nerve fibers in the pelvis. Schwann-like cell (SLC) differentiation is a novel therapeutic strategy for this clinical condition. However, the efficiency of SLC differentiation remains unsatisfactory. We modified an SLC differentiation protocol using adipose-derived stem cells (ADSCs) and folic acid. Morphology, gene expression and secretion of neurotrophic factors were examined to assess the differentiation quality and phenotypic characteristics. Our new modified protocol effectively induced a Schwann cell (SC) phenotype in ADSCs as assessed by morphology and expression of SC markers [S100 calcium-binding protein B (S100B), P < 0.01 ; p75 neurotrophic receptor (p75NTR), P < 0.05]. SLCs produced by the new protocol displayed a repair phenotype with decreased expression of ERBB2 and early growth response protein 2 (EGR2) /ROX20 (P < 0.01). Furthermore, our new protocol enhanced both mRNA expression and secretion of nerve growth factors by SLCs (P < 0.01). This protocol enhanced the SC characteristics and functions of ADSC-derived SLCs. This promising protocol requires further research and may contribute to SC-based nerve regeneration. J. Med. Invest. 68 : 347-353, August, 2021.


Daikenchuto accelerates the recovery from prolonged postoperative ileus after open abdominal surgery: a subgroup analysis of three randomized controlled trials.

Prolonged postoperative ileus (POI) is a common complication after open abdominal surgery (OAS). Daikenchuto (DKT), a traditional Japanese medicine that peripherally stimulates the neurogenic pathway, is used to treat prolonged POI in Japan. To analyze whether DKT accelerates the recovery from prolonged POI after OAS, we conducted a secondary analysis of three multicenter randomized controlled trials (RCTs). A secondary analysis of the three RCTs supported by the Japanese Foundation for Multidisciplinary Treatment of Cancer (project numbers 39-0902, 40-1001, 42-1002) assessing the effect of DKT on prolonged POI in patients who had undergone OAS for colon, liver, or gastric cancer was performed. The subgroup included 410 patients with no bowel movement (BM) before the first diet, a DKT group (n = 214), and a placebo group (n = 196). Patients received either 5 g DKT or a placebo orally, three times a day. The primary endpoint was defined as the time from the end of surgery to the first bowel movement (FBM). A sensitivity analysis was also performed on the age, body mass index and dosage as subgroup analyses. The primary endpoint was significantly accelerated in the DKT group compared with the placebo group (p = 0.004; hazard ratio 1.337). The median time to the FBM was 113.8 h in the placebo group and 99.1 h in the DKT treatment group. The subgroup analysis showed that DKT significantly accelerated the recovery from prolonged POI following OAS. UMIN000026292.


The protective effect of epigallocatechin 3-gallate on mouse pancreatic islets via the Nrf2 pathway.

Epigallocatechin 3-gallate (EGCG), a green tea polyphenol, has been shown to have anti-oxidant and anti-inflammatory effects in vitro and in vivo. The aim of this study was to investigate the effects and mechanism of EGCG on isolated pancreatic islets as pre-conditioning for pancreatic islet transplantation. The pancreatic islets were divided into two groups: an islet culture medium group (control) and an islet culture medium with EGCG (100 M) group. We investigated the islet viability, Nrf2 expression, reactive oxygen species (ROS) production, and heme oxygenase-1 (HO-1) mRNA. Five hundred islet equivalents after 12 h of culture for the EGCG 100 M and control group were transplanted under the kidney capsule of streptozotocin-induced diabetic ICR mice. The cell viability and insulin secretion ability in the EGCG group were preserved, and the nuclear translocation of Nrf2 was increased in the EGCG group (p < 0.01). While the HO-1 mRNA levels were also higher in the EGCG group than in the control group (p < 0.05), the ROS production was lower (p < 0.01). An in vivo functional assessment showed that the blood glucose level had decreased in the EGCG group after transplantation (p < 0.01). EGCG protects the viability and function of islets by suppressing ROS production via the Nrf2 pathway.


A new formula to calculate the resection limit in hepatectomy based on Gd-EOB-DTPA-enhanced magnetic resonance imaging.

Dynamic magnetic resonance imaging with gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (EOB-MRI) can be used not only to detect liver tumors but also to estimate liver function. The aim of this study was to establish a new EOB-MRI-based formula to determine the resection limit in patients undergoing hepatectomy. Twenty-eight patients with a normal liver (NL group) and five with an unresectable cirrhotic liver (UL group) who underwent EOB-MRI were included. Standardized liver function (SLF) was calculated based on the signal intensity (SI), the volume of each subsegment (S1-S8), and body surface area. A formula defining the resection limit was devised based on the difference in the SLF values of patients in the NL and UL groups. The formula was validated in 50 patients who underwent EOB-MRI and hepatectomy. The average SLF value in the NL and UL groups was 2038 and 962 FV/m2, respectively. The difference (1076 FV/m2) was consistent with a 70% in resection volume. Thus, the resection limit for hepatectomy was calculated as a proportion of 70%: 70 (SLF-962)/1076 (%). The one patient who underwent hepatectomy over the resection limit died due to liver failure. In other 49 patients, in whom the resection volume was less than the resection limit, procedures were safely performed. Our formula for resection limit based on EOB-MRI can improve the safety of hepatectomy.


Usefulness of blood flow evaluation by indocyanine green fluorescence system in laparoscopic anterior resection.

One of the major cause of anastomotic leakage (AL) in anterior resection of the rectum is insufficient blood flow of the remnant colon. The indocyanine green fluorescence system (ICG-FS) can visualize the blood flow of organs intra-operatively. The aim of this study is to investigate the usefulness of ICG-FS for evaluating the blood flow of the remnant colon in laparoscopic anterior resection. Rectal cancer patients (n=24) who underwent laparoscopic anterior resection were included in this study. After resection of the rectum, 7.5mg of ICG was administered intravenously, and the blood flow of the oral stump was evaluated by the ICG-FS. The relationship between the fluorescence time (FT) of the oral stump and AL was investigated retrospectively. Two of twenty-four patients (8.3%) suffered AL. The FT of these two cases were over 60 seconds. In the case with the FT was over 80 seconds, we performed additional resection of the late fluorescence portion of the remnant colon and could avoid AL. In patients whose FT was under 60 seconds, no patients suffered AL. ICG-FS may be useful for evaluating the blood flow of the remnant colon to avoid AL in laparoscopic anterior resection. J. Med. Invest. 66 : 65-69, February, 2019.


Changes of liver metabolites following hepatectomy with ischemia reperfusion towards liver regeneration.

Metabolome analysis is one of the omics which investigates the final product of a central dogma. Changes of liver metabolites during liver regeneration following hepatectomy (Hx) continue to remain unclear. The aim of the present study was to investigate the changes of liver metabolites following Hx with ischemia reperfusion (I/R) towards liver regeneration. Twenty-three patients who underwent Hx were enrolled in this study. Non-tumor tissues were sampled immediately before and after Hx and a comparison was made between the liver samples taken before and after Hx using capillary electrophoresis (CE)-time-of-flight mass spectrometry (TOFMS) as metabolome analysis. The metabolic pathway showed that there was a significant increase in "lactate" following Hx. There was a significant decrease in metabolites only in the first half of the tricarboxylic acid cycle (TCA) cycle, and adenosine triphosphate (ATP) by anaerobiotic glycolysis did not occur in time for energy consumption of the Hx. Principal component analysis revealed remarkably different component profiles between the samples taken before and after Hx. One hundred and three metabolites were selected as critical metabolites for separating components. Valine and tryptophan increased significantly after Hx and they were regulated by resected liver volume, ischemic time and liver function. The liver metabolites changed remarkably between before and after Hx. Especially, liver valine and tryptophan were increased.


Blue light-emitting diodes induce autophagy in colon cancer cells by Opsin 3.

Light emitting-diodes (LED) have various effects on living organisms and recent studies have shown the efficacy of visible light irradiation from LED for anticancer therapies. However, the mechanism of LED's effects on cancer cells remains unclear. The aim of the present study was to investigate the effects of LED on colon cancer cell lines and the role of photoreceptor Opsin 3 (Opn3) on LED irradiation in vitro. Human colon cancer cells (HT-29 or HCT-116) were seeded onto laboratory dishes and irradiated with 465-nm LED at 30 mW/cm for 30 minutes. Cell Counting Kit-8 was used to measure cell viability, and apoptosis and caspase 3/8 expression were evaluated by AnnexinV/PI and reverse transcription-polymerase chain reaction (RT-PCR), respectively. Autophagy and expression of LC-3 and beclin-1 were also evaluated by autophagy assays, RT-PCR and Western blotting. We further tested Opn3 knockdown by Opn3 siRNA and the G G-protein inhibitor NF023 in these assays. Viability of HT-29 and HCT-116 cells was lower in 465-nm LED-irradiated cultures than in control cultures. LC-3 and beclin-1 expressions were significantly higher in LED-irradiated cultures, and autophagosomes were detected in irradiated cells. The reductive effect of cancer cell viability following blue LED irradiation was reversed by Opn3 knockdown or NF023 treatment. Furthermore, increased LC-3 and beclin-1 expression that resulted from blue LED irradiation was suppressed by Opn3 knockdown or NF023 treatment. Blue LED irradiation suppressed the growth of colon cancer cells and Opn3 may play an important role as a photoreceptor.


High STAT4 Expression Indicates Better Disease-free Survival in Patients with Gastric Cancer.

The aim of this study was to investigate the significance of signal transducer and activator of transcription 4 (STAT4) expression and the correlation between STAT4 and interferon gamma (IFN- ) in patients with gastric cancer. Sixty-two patients who underwent gastrectomy for gastric cancer were enrolled in the study. STAT4 and IFNG mRNA expression was evaluated by quantitative real-time polymerase chain reaction (PCR). Immunohistochemistry was performed to examine CD8 T-cells, and STAT4 and IFN- expression. STAT4 mRNA expression was significantly correlated with IFNG mRNA expression (p<0.05). Regarding disease-free survival, there was a significant difference between the groups with high and low STAT4 expression (5-year disease-free survival: 77.8% and 56.4%, p<0.05). Univariate analysis revealed that tumor differentiation and STAT4 expression were significant factors for tumor recurrence. High expression of STAT4 in gastric cancer predicted a better clinical outcome. STAT4 might be a useful biomarker to identify patients at high risk of recurrence after gastrectomy.


Maximum Diameter and Number of Tumors as a New Prognostic Indicator of Colorectal Liver Metastases.

Surgical resection is currently considered the only potentially curative option as a treatment strategy of colorectal liver metastases (CRLM). However, the criteria for selection of resectable CRLM are not clear. The aim of this study was to confirm a new prognostic indicator of CRLM after hepatic resection. One hundred thirty nine patients who underwent initial surgical resection from 1994 to 2015 were investigated retrospectively. Prognostic factors of overall survival including the product of maximum diameter and number of metastases (MDN) were analyzed. Primary tumor differentiation, vessel invasion, lymph node (LN) metastasis, non-optimally resectable metastases, H score, grade of liver metastases, resection with non-curative intent and MDN were found to be prognostic factors of overall survival (OS). In multivariate analyses of clinicopathological features associated with OS, MDN and non-curative intent were independent prognostic factors. Patients with MDN ·30 had shown significantly poorer prognosis than patients with MDN <30 in OS and relapse-free survival (RFS). MDN ·30 is an independent prognostic factor of survival in patients with CRLM and optimal surgical criterion of hepatectomy for CRLM.


Elevated Preoperative Serum CEA Level Is Associated with Poor Prognosis in Patients with Hepatocellular Carcinoma Through the Epithelial-Mesenchymal Transition.

Serum carcinoembryonic antigen (CEA) is used as an indicator of tumor progression in a variety of carcinomas. A subset of patients with hepatocellular carcinoma (HCC) exhibit increased serum CEA level, but the significance of this is unclear. In this study, we investigated the prognosis of patients with HCC with increased serum CEA, and explored the correlations with expression of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) and epithelial-mesenchymal transition (EMT) and tumor angiogenesis. One hundred and twenty-three patients with HCC who underwent radical resection were divided into two groups according to a cut-off value of 5.0 ng/ml for serum CEA: high (n=24) and normal (n=99) groups. We compared the clinicopathological factors with serum CEA levels and its correlations with CEACAM1 expression, EMT-related factors and microvessel density (MVD) of tumor tissues by immunohistochemistry. In the high CEA group, the disease-free survival (DFS) rate was significantly worse than in the normal CEA group. Multivariate analysis revealed that a high CEA level was an independent factor predictive of recurrence. Furthermore, increased serum CEA levels were positively correlated with CEACAM1 expression. Moreover, CEACAM1 expression was positively correlated with expression of EMT-related factors and MVD of tumor tissues. Increased serum CEA level reflected CEACAM1 expression and was an independent factor predictive of recurrence in HCC through EMT and tumor angiogenesis.


Impact of intra-abdominal absorbable sutures on surgical site infection in gastrointestinal and hepato-biliary-pancreatic surgery: results of a multicenter, randomized, prospective, phase II clinical trial.

The use of absorbable sutures in wound closure has been shown to reduce the incidence of surgical site infection (SSI); however, there is no evidence that the intra-abdominal use of absorbable rather than silk sutures reduces the incidence of SSI after gastrointestinal surgery. We report the findings of a phase II trial, designed to evaluate the impact of the intra-abdominal use of absorbable sutures on the incidence of SSI. At 19 Japanese hospitals, 1147 patients undergoing elective gastrectomy, colorectal surgery, hepatectomy, or pancreaticoduodenectomy (PD) were randomly assigned to absorbable or silk intra-abdominal suture groups. The primary efficacy endpoint was the incidence of SSI. The secondary efficacy endpoints were the locations of SSI, time to resolution of SSI, length of hospital stay, and the incidence of bile leakage in hepatectomy and pancreatic fistula. The incidence of SSI was 11.3%, 15.5%, 11.3%, and 36.9% after gastrectomy, colorectal surgery, hepatectomy, and PD, respectively. The incidence of SSI was higher in the absorbable suture group than in the silk suture group for all the surgical procedures, but the difference was not significant. The intra-abdominal use of absorbable sutures did not have enough of an effect on the reduction of SSI in this phase II trial to justify the planning of a large-scale phase III trial.


Role of CD151 expression in gallbladder carcinoma.

CD151 is a member of the tetraspanin family, which interacts with laminin-binding integrins and other tetraspanins. CD151 is involved in several pathologic activities associated with tumor progression, including metastasis and angiogenesis. The aim of this study was to clarify the clinical use of CD151 expression in gallbladder cancer (GBC). Forty-five patients with GBC who had undergone operative treatment were enrolled in this study. Expressions of CD151 in the resected GBC specimens were evaluated with anti-CD151 antibody. The patients were divided into positive and negative groups according to CD151 expression: CD151-positive group (n = 26) and CD151-negative group (n = 19). Clinicopathologic factors, including Ki-67 and matrix metallopeptidase 9, also were compared between the two groups. CD151-positive expression was 58% and correlated with poorer prognosis; 5-year survival of CD151-positive and CD151-negative groups was 29% and 78%, respectively (P = .006). CD151 expression also correlated with lymphatic invasion and curability. Multivariate analysis revealed that CD151-positive expression was an independent prognostic factor (hazard ratio 2.97, P = .02). In addition, CD151 expression correlated with matrix metallopeptidase 9 expression (P < .05) but not with Ki67 expression. Those findings suggested that CD151-positive expression might be a potential prognostic indicator and one of the target molecules for the regulation of tumor metastasis for patients with GBC.