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Using a self-expanding metal stent as a bridge to surgery (BTS) is considered a reasonable strategy for patients with acute malignant large bowel obstruction. Since postoperative complications have a negative impact on patient survival, we aim to clarify the predictors of complications in patients undergoing BTS using a self-expanding metal stent.We conducted a retrospective review of 61 patients with colorectal cancer (CRC) who underwent stenting as a BTS at our institution. We analyzed the association of postoperative complications with clinicopathologic, surgical, and patient factors, and with the prestenting or preoperative laboratory data.Both postoperative complications in general and severe complications were significantly associated with a longer stenotic-section length (p = 0.007 and p = 0.003), lower preoperative hemoglobin levels (p 0.001 and p = 0.081), and lower prestenting hemoglobin levels (p = 0.006 and p = 0.042). Multivariate logistic regression analysis showed that lower prestenting (13.0 g/dl) and preoperative (11.5 g/dl) hemoglobin levels were independent predictive factors for postoperative complications (odds ratio [OR]: 4.15; 95% confidence interval [CI]: 1.07-18.90; p = 0.040; and OR: 4.93; 95% CI: 1.35-20.28; p = 0.016). A stenotic-section length of 5.0 cm or greater was predictive of severe complications (OR: 25.67; 95% CI: 1.95-1185.00; p = 0.011).Our data suggest that lower hemoglobin levels before stenting and a longer length of the stenotic section of bowel might predict postoperative complications in patients with CRC undergoing BTS for obstruction.

At present, ≥ 20% of patients experience clinically relevant postoperative pancreatic fistula (POPF) after distal pancreatectomy (DP).We developed a new bioabsorbable pancreatic clip (BioPaC) made of polycaprolactone that does not crush the pancreatic parenchyma during occlusion of the pancreatic stump. We confirmed the efficacy of this BioPac in a porcine DP model and compared it to a linear stapling device (Reinforce®).Pigs were killed at 1 month after DP. In the BioPaC group, all swine (n = 3) survived well without POPF. In the Reinforce® group (n = 2), one pig died early at postoperative day 7 with Grade C POPF (amylase 43 700 U/l), and the other survived until 1 month at scarification with biochemical leakage of POPF (amylase 3 725 U/l). Pathologically, the main pancreatic duct and pancreatic parenchyma were well closed by BioPaC.The newly developed BioPaC is effective in a porcine DP model.

Primary carcinosarcoma of the liver is extremely rare. Here, we report an unusual case of carcinosarcoma of the liver containing combined hepatocellular carcinoma and cholangiocarcinoma. A 66-year-old man with a history of viral hepatitis B was admitted for investigation of multiple liver masses. Dynamic computed tomography revealed a mostly hypoenhancing main tumor with a peripheral ring enhancement and several satellite nodules. After transcatheter arterial chemoembolization and portal vein embolization, an extended right posterior sectionectomy was performed. The resected tumor was macroscopically a simple nodular type, 4.3 × 4.2 cm in diameter, with a dense fibrous capsule. The pathological findings showed that both carcinomatous and sarcomatous elements were present, and diagnosis of carcinosarcoma of the liver was confirmed. The carcinomatous element consisted of hepatocellular carcinoma and cholangiocarcinoma. The sarcomatous element was composed of spindle cells. Immunohistochemical studies demonstrated that cytokeratin AE1/AE3, human serum albumin, cytokeratin 7, and Arginase-1 were partially positive in tumor cells of the carcinomatous element but not in tumor cells of the sarcomatous element. Follow-up for 30 months after surgery has shown no signs of recurrence.

Inflammatory and immune cells in the tumor microenvironment are reported to be associated with tumor progression in several cancers. In total, 225 patients who underwent initial and curative hepatectomy for hepatocellular carcinoma (HCC) from 2004 to 2013 were enrolled in this study. Tumor-associated neutrophils (TANs), M2 macrophages (TAMs; tumor-associated macrophages), CD8

Pancreatic cancer has an extremely poor prognosis, even after curative resection. Treatment options for pancreatic cancer remain limited, therefore new therapeutic targets are urgently needed. We searched for genes predictive of poor prognosis in pancreatic cancer using a public database and validated the survival impact of the selected gene in a patient cohort. We used a public database to search for genes associated with early pancreatic cancer recurrence. As a validation cohort, 201 patients who underwent radical resection in our institution were enrolled. Expression of the target gene was evaluated using immunohistochemistry (IHC). We evaluated growth and invasiveness using small interfering RNAs, then performed pathway analysis using gene set enrichment analysis. We extracted ARHGEF2 from GSE21501 as a gene with a high hazard ratio (HR) for early recurrence within 1 year. The high ARHGEF2 expression group had significantly poorer recurrence-free survival (RFS) and poorer overall survival (OS) than the low ARHGEF2 expression group. Multivariate analysis demonstrated that high ARHGEF2 expression was an independent poor prognostic factor for RFS (HR 1.92) and OS (HR 1.63). In vitro, ARHGEF2 suppression resulted in reduced cell growth and invasiveness. Bioinformatic analysis revealed that ARHGEF2 expression was associated with MYC, G2M, E2F, and CDC25A expression, suggesting that c-Myc and cell cycle genes are associated with high ARHGEF2 expression. IHC revealed a positive correlation between ARHGEF2 and c-Myc expression. High ARHGEF2 expression is associated with cell cycle progression, and predicts early recurrence and poor survival in patients with pancreatic cancer.

Background The predictive significance of programmed death ligand 1 (PD-L1) for programmed death 1 (PD-1) inhibitors remains unclear in gastric cancer (GC) due to the dynamic alteration by treatments. We aimed to elucidate the effects of trastuzumab (Tmab) on PD-L1 expression in GC. Methods PD-L1 expression was evaluated by multicolour flow cytometry analysis after co-culturing GG cell lines and immune cells with Tmab. IFN-γ in the co-culture experiments was quantified. Immunohistochemistry (IHC) for PD-L1 expression using clinical samples was also performed to confirm PD-L1 alteration by Tmab. Results PD-L1 expression was significantly upregulated by Tmab in HER2-amplified GC cell lines co-cultured with peripheral blood mononuclear cells (PBMCs). PD-L1 upregulation by Tmab was also observed in the GC cells co-cultured with NK cells in time-dependent manner, but not with monocytes. IFN-γ concentration in conditioned media from co-cultured PBMCs and NK cells with Tmab was significantly higher and anti-IFN-γ significantly suppress the Tmab-induced PD-L1 upregulation. IHC also suggested PD-L1 upregulation after Tmab treatment. Conclusions Tmab can upregulate PD-L1 expression on GC cells through interaction with NK cells. These results suggest clinical implications in the assessment of the predictive significance of PD-L1 expression for PD-1 inhibitors.

The prediction of prognostic outcomes can provide the most suitable strategy for patients with pancreatic ductal adenocarcinoma (PDAC). This study aimed to evaluate the clinical value of the preoperative tumor marker index (pre-TI) in predicting prognostic outcomes after resection for PDAC. For 183 patients who underwent pancreatic resection of PDAC, adjusted carbohydrate antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA), pancreatic cancer-associated antigen-2 (DUpan-2), and s-pancreas-1 antigen (SPan-1) were retrospectively evaluated, and the positive number of these markers was scored as the pre-TI. A high pre-TI (≥ 2) was significantly associated with a larger tumor and lymph node metastases, and the patients with a high pre-TI had worse prognostic outcomes in terms of both relapse-free survival (RFS) (P

Preoperative biliary drainage (PBD) prior to pancreatoduodenectomy (PD) is controversial. The aim of this study was to clarify how PBD leads to postoperative complications of PD. The subjects of this retrospective study were 230 patients who underwent PD between January, 2008 and January, 2018. We analyzed how PBD was associated with severe postoperative complications (Clavien-Dindo ≥ IIIB) with special reference to its links with bacterial contamination. Preoperative biliary drainage (PBD) was correlated with the contamination of both bile juice collected at surgery (p

The aim of this study was to verify the efficacy of wound protection with a plastic ring wound protector (ring drape) and using new sterile instruments when closing the abdominal wall (wound closure set), both of which were used to prevent incisional surgical site infection (SSI) after hepatectomy.The incidence of incisional SSIs and the clinical courses of 572 patients who underwent hepatectomy between January 2010 and December 2015 were studied retrospectively. The patients were divided into three period groups according to the period when each infection countermeasure was started.Incisional SSI incidence decreased significantly with additional countermeasures: 1Incisional SSI incidence was significantly reduced by using ring drape after hepatectomy.

Programmed death ligand 1 (PD-L1) is a key target for the treatment of several malignancies. The present study was conducted to clarify the role of serum PD-L1 in hepatocellular carcinoma (HCC). Serum PD-L1 (sPD-L1) was examined by an enzyme-linked immunosorbent assay in 153 patients with HCC who underwent curative hepatectomy at Kumamoto University in 2011–2016. The expression of PD-L1 in tissue (tPD-L1) was investigated by immunohistochemistry. The clinical roles of the PD-L1 expression in both serum and tissue were examined. The sPD-L1 was significantly elevated in HCC patients compared to patients without any malignant or inflammatory disease (234 vs. 93 pg/mL, p

INTRODUCTION The aim of this study was to evaluate the safety and efficacy of interval laparoscopic appendectomy after antibiotic therapy in elderly patients with appendiceal abscess. METHODS We retrospectively analyzed data for 50 patients with appendiceal abscess aged ≥18 years who had initially planned to undergo interval laparoscopic appendectomy after antibiotic therapy and 50 patients with appendicitis aged ≥70 years who had undergone early laparoscopic appendectomy. All patients were treated at the National Hospital Organization Kumamoto Medical Center between 2012 and 2018. We compared perioperative outcomes after interval appendectomy between patients aged

Whether perioperative allogeneic blood transfusion (PABT) negatively influences patient survival after hepatectomy (HR) for hepatocellular carcinoma (HCC) remains controversial. Five hundred two patients who underwent HR for initial HCC between 1994 and 2015 were enrolled in this study. All patients were divided into two groups: the PABT group and the non-PABT group. Differences of clinicopathological factors, overall survival (OS), recurrence-free survival (RFS), and the recurrence pattern between the two groups were evaluated. Using propensity score matching for tumor-related factors, liver functions, and surgical factors (total 11 factors), the survival impact of PABT was also analyzed. In the entire cohort, 78 patients (15.5%) received PABT such as red cell concentrate, fresh-frozen plasma, or platelets. OS (5-year OS: 55% vs. 76%; p = 0.0005) and RFS (2-year RFS: 47% vs. 56%; p = 0.0131) were significantly worse in the PABT group. The extrahepatic recurrence happened more frequently in the PABT group (15% vs. 5.4%; p = 0.0039). There were many significant clinicopathological differences between the two groups: more advanced tumor stage (tumor diameter, stage III or IV, microvascular invasion), worse liver functions (albumin, indocyanine green retention rate at 15 min), and more surgical stress (blood loss, operation time) in the PABT group. After propensity score matching, 43 pairs of patients were extracted. In this matched cohort, the survival curves of the PABT and non-PABT groups almost completely overlapped both in OS (5-year OS: 62% vs. 62%; p = 0.4384) and in RFS (2-year RFS: 49% vs. 47%; p = 0.8195). The significant difference of the extrahepatic recurrence rate disappeared in the matched cohort (p = 0.5789). Using propensity score matching, we found that PABT does not influence patient survival after HR for HCC.

Background/aim Identifying malignancy in intraductal papillary mucinous neoplasm (IPMN) of the pancreas remains challenging. This study aimed to evaluate the usefulness of 18-fluorodeoxyglucose positron emission tomography/computed tomography (18-FDG PET/CT) in distinguishing malignant from benign IPMN of the pancreas. Patients and methods The cases of 79 patients with IPMN of the pancreas who underwent surgical resections between 1996 and 2016 at our Institution were enrolled in the present retrospective analysis of predictors for malignancy in IPMN of the pancreas. 18-FDG PET/CT evaluations were performed in 38 patients, and the usefulness of 18-FDG PET/CT for detecting malignancy in IPMN of the pancreas was evaluated. Results Three factors were significantly related to malignancy in IPMN; the diameter of the main pancreatic duct, the serum value of carcinoembryonic antigen (CEA), and the neutrophil-to-lymphocyte ratio (NLR). 18-FDG PET accumulation was significantly related to malignancy in IPMN; sensitivity 0.82 and specificity 0.71. Independent predictors for malignancy in IPMN were as follows: 18-FDG PET accumulation, CEA >1.0 ng/ml, and NLR >2.63. Conclusion 18-FDG PET accumulation is a potent new marker for distinguishing malignant from benign IPMNs of the pancreas.

With population aging, the number of frail patients with pancreatic cancer has increased. The Clinical Frailty Scale (CFS) is a simple and validated tool to assess frailty, and higher scores predict worse clinical outcomes after cardiovascular surgery. In this retrospective study, we aimed to examine the association of preoperative frailty with prognosis after resection for pancreatic cancer. We retrospectively analyzed data from 142 consecutive patients undergoing resection for pancreatic cancer between April 2010 and December 2018. We used the CFS: 1 (very fit) to 9 (terminally ill) to assess frailty and examined associations of the CFS scores with recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). Multivariable Cox proportional hazards models were used to calculate hazard ratios (HRs), controlling for potential confounders. Of the 142 patients, 113 (80%) had CFS scores of ≤ 3, 13 (9.2%) scores of 4, and 16 (11%) scores of ≥ 5. Scores of ≥ 5 on the CFS were associated with worse CSS (univariable HR: 2.62, 95% confidence interval [CI]: 1.19–5.18, P = 0.019; multivariable HR: 2.49, 95% CI 1.05–5.34, P = 0.039) and OS (univariable HR: 2.42, 95% CI 1.19–4.46, P = 0.016; multivariable HR: 2.25, 95% CI 1.05–4.43, P = 0.038). The association between CFS scores and RFS was not significant in multivariable analysis (univariable HR: 2.11, 95% CI 1.08–3.79, P = 0.030; multivariable HR: 1.47, 95% CI 0.71–2.83, P = 0.29). Higher scores on the CFS are associated with worse CSS and OS after resection for pancreatic cancer. Preoperative measurement of frailty may improve risk assessment among patients with pancreatic cancer.

Early recurrence (ER) is a strong predictor of poor prognosis in patients with hepatocellular carcinoma (HCC) after hepatectomy. The aim of this study was to examine manageable factors associated with ER.Overall, 475 consecutive patients with primary HCC who underwent curative hepatectomy were included (R0/R1). We defined ER as recurrence within 2 years after hepatectomy and analyzed predictors for ER. We also defined postoperative complication as Clavien-Dindo classification grade III or IV.ER after hepatectomy was observed in 209 cases (44.0%). Patients with ER had a significantly poor prognosis compared with those with late recurrence (log-rank p 0.0001) and were more likely to be diagnosed with extrahepatic metastasis (p = 0.009). Significant predictors for ER were des-γ-carboxyprothrombin 40 mAU/mL (odds ratio (OR) 2.06, 95% confidence interval (CI) 1.36-3.14, p = 0.001), multiple tumors (OR 2.80 95%CI 1.83-4.32, p 0.0001), cirrhosis (OR 1.53, 95%CI 1.01-2.32, p = 0.043), and postoperative complications (OR 1.72, 95% CI 1.05-2.85, p = 0.032). Blood loss (OR 1.09, 95%CI 1.05-1.13, p 0.0001) and cirrhosis (OR 1.74, 95%CI 1.05-2.86, p = 0.031) were significant predictors for postoperative complications.We should pay close attention to surgical associated- and disease-specific factors in hepatectomy for HCC to prevent ER.

Background Postoperative complications after pancreaticoduodenectomy (PD) is still a major concern. The aim of this study was to propose how to choose antibiotics, based on bacterial sensitivity profiling involved in postoperative complications after PD. Methods Two hundred and thirty patients underwent PD between 2008 and 2018 at Kumamoto University Hospital. We enrolled 121 patients who had both intraoperative bile culture and drain culture on postoperative day (POD) 3. The clinical impact of the bacterial profile on postoperative outcome was retrospectively analyzed. Results Multivariate regression analysis revealed that intraperitoneal contamination on POD3 was independently associated with postoperative complications (odds ratio 2.62, P =0.02). The bacteria in intraperitoneal drain on POD3 showed 94.9% similarity with those in bile collected during surgery. The major species were Enterococcus (44.6%) and Enterobacter (38.5%). Enterobacter species caused a higher rate of postoperative complications than others (83% vs 54%, P =0.04). Three out of five Enterococcus faecium were resistant to carbapenems that were active against all Gram-negative rods. Conclusions Intraperitoneal contamination on POD3, which had similar bacterial species as bile collected during surgery, was correlated with postoperative complications. The bacterial antibiotic sensitivity profile may help selecting optimal antibiotics against infectious postoperative complications in PD.

Focal nodular hyperplasia (FNH) is a relatively common benign liver tumor with rare indications to surgery. Budd–Chiari syndrome is a rare condition caused by interrupted hepatic venous outflow in the hepatic veins and inferior vena cava (IVC). A 42-year-old woman was referred to our department with a hepatic tumor. Patient’s chief complaint was leg edema. Because of this symptom, it was difficult for the patient to stand for more than 20 min in the evening. Computed tomography (CT) showed a hypervascular mass compressing IVC in the caudate lobe of the liver. Fine needle aspiration was performed, and preoperative diagnosis was focal nodular hyperplasia (FNH). Hepatic resection of the right caudate lobe was performed. Postoperative histological examination revealed that the tumor was FNH. After surgery, the patient’s leg edema disappeared, and postoperative CT revealed that severe IVC stenosis was improved. Although there have been several reports of giant FNH causing Budd–Chiari syndrome, this case shows the stenosis of IVC below the root of hepatic veins causing Budd–Chiari-like syndrome without portal hypertension. The location of the tumor considerably attributed to the congestion of venous flow in IVC causing various symptoms and intrahepatic inferior right hepatic vein–right hepatic vein bypass. The surgical indication of FNH is limited in most cases; however, the current report alerts that the location of FNH should be taken into account when monitoring it.

MicroRNA (miRNA) expression abnormalities are implicated in tumor progression. Previous reports have indicated that microRNA-25 (miR-25) acts as a tumor suppressor or oncogene in diverse cancers. However, its molecular mechanisms in hepatocellular carcinoma (HCC) are still unclear. F-box and WD repeat domain 7 (Fbxw7) is a critical tumor suppressor and is one of the most important deregulated proteins of the ubiquitin–proteasome system in cancer. Our objective was to elucidate the role of miR-25 and Fbxw7 in HCC and to clarify the mechanism by which Fbxw7 is regulated. Fbxw7 expression was estimated in 210 fixed paraffin-embedded HCC samples by immunohistochemistry, and miR-25 expression was evaluated in 142 frozen HCC tissue samples by quantitative real-time PCR. Oncogenic functions of miR-25 and its role in the regulation of Fbxw7 expression were assayed in vitro. miR-25 was overexpressed in HCC tissue compared with adjacent normal tissue and significantly correlated with a poorer prognosis. Moreover, it was inversely correlated with Fbxw7 expression in HCC tissues. Furthermore, miR-25 inhibition significantly reduced the proliferation, migration, and invasion of HCC cells in vitro. miR-25 may promote tumor progression in HCC patients by repression of Fbxw7 and could serve as a promising molecular target for HCC treatment.

Highlights • Neuroendocrine carcinoma of the esophagus is a rare and highly aggressive disease. • A case of large-cell neuroendocrine carcinoma of the esophagus in a 73-year-old male patient with aggressive surgical treatment. • We performed subtotal esophagectomy, partial hepatectomy, radiotherapy and chemotherapy using cisplatin and irinotecan. • We believe that aggressive treatment can become one treatment option with the aim of extending survival., Introduction Neuroendocrine carcinoma of the esophagus is a rare and highly aggressive disease, and the biological features are poorly understood. Presentation of case We report a case of large-cell neuroendocrine carcinoma of the esophagus in a 73-year-old male patient with aggressive surgical treatment. Upper gastrointestinal endoscopy revealed an esophageal large mass. Histological examination of biopsy specimens indicated a neuroendocrine carcinoma. First, we performed subtotal esophagectomy with lymphadenectomy, but he experienced metastasis at the liver and rib 5 months later. Next, we performed partial hepatectomy and radiotherapy for rib metastasis, but he experienced metastasis at the left pulmonary hilar lymph node and sacral bone. Finally, we performed chemotherapy using cisplatin and irinotecan. Discussion The therapeutic strategy for large-cell NEC of the esophagus is unestablished. Thus, accumulating the therapeutic results garnered from various treatment tools is considerably important. Conclusion Aggressive multimodal treatments including surgery have a possibility to gain better survival in patients with large-cell NEC of the esophagus.

Portal vein embolization (PVE) was developed for patients with insufficient future liver remnant volume and function and has gained relevant support worldwide before major hepatectomy. However, the efficacy of preoperative PVE for hepatocellular carcinoma (HCC) patients with impaired liver function remains uncertain. Ninety-seven HCC patients who were scheduled for PVE followed by hepatectomy were enrolled in this study. Their short- and long-term outcomes were investigated, according to the liver damage classification defined by the Liver Cancer Study Group of Japan. Of 97 patients who underwent preoperative PVE, 30 (32.4%) could not undergo subsequent hepatectomy. Dropout rate from treatment strategy was significantly higher in patients with liver damage B (n = 13, 61.5%) than in those with liver damage A (n = 84, 26.2%) (P = 0.014). Among the 67 patients who underwent planned hepatectomy after PVE, 53 were categorized to liver damage A, and 14 were categorized to liver damage B at the point of hepatectomy. Although major complication and mortality rates were comparable between the two groups, the cumulative overall survival (OS) and disease-free survival (DFS) after hepatectomy were markedly worse in patients with liver damage B than in those with liver damage A (5-year OS rate: 23.1% vs 74.6%, P = 0.014, 5-year DFS rate: 7.8% vs 33.5%, P = 0.054, respectively). The treatment strategy of PVE followed by hepatectomy might be a contraindication for HCC patients with impaired liver function categorized as liver damage B because of the higher dropout rate and poorer long-term outcomes after hepatectomy.

Aim Combined hepatocellular cholangiocarcinoma (cHCC-CCA) is a very rare subtype of primary liver carcinoma; therefore, its clinicopathological characteristics have not yet been elucidated in detail. The aim of the study was to reveal the clinicopathological characteristics and prognostic factors of cHCC-CCA after hepatic resection (HR) METHODS: A total of 124 patients who underwent curative HR for cHCC-CCA between 2000 and 2016 were enrolled in this multi-institutional study conducted by the Kyushu Study Group of Liver Surgery. Clinicopathological analysis was performed from the viewpoint of patient prognosis. Results A total of 62 patients (50%) had early recurrence within 1.5 years after HR, including 36 patients (58%) with extrahepatic recurrence. In contrast, just four patients (3%) had late recurrence occurring >3 years after HR. The independent predictors of early recurrence were as follows: des-gamma carboxyprothrombin >40 mAU/mL (odds ratio 26.2, P = 0.0117), carbohydrate antigen 19-9>37 IU/l (odds ratio 18.0, P = 0.0200), and poorly differentiated HCC or CCA (odds ratio 11.2, P = 0.0259). Conclusions Half of the patients with cHCC-CCA had early recurrence after HR. Preoperative elevation of des-gamma carboxyprothrombin or carbohydrate antigen 19-9 and the existence of poorly differentiated components of HCC or CCA in resected specimens are predictors of its early recurrence.

Clinical predictive markers for the malignant potential of pancreatic neuroendocrine tumors (PNETs) are limited without histological investigation. We reported previously that a loss of the regular enhancement pattern in preoperative computed tomography (CT) was correlated with the malignant tumor phenotype. This study aimed to establish whether the metabolic aspect of the tumor evaluated by fludeoxyglucose (18F) positron emission tomography/computed tomography 18F-FDG PET/CT is associated with the tumor imaging characteristics and postoperative oncological outcome. Among 77 patients who underwent surgery with curative intent for a PNET at our institution between 2001 and 2017, 24 who received 18F-FDG PET/CT before surgery were enrolled in this study. The clinical importance of the standardized uptake value (SUVmax) was investigated with regard to tumor progression and prognosis after curative surgery. There were four (16%) patients with insulinoma. The mean tumor size was 17 mm and when the median value of the SUVmax (= 2.0) was measured as the cut-off value, the SUVmax ≥ 2.0 group (n = 12) was associated with large tumor size (p = 0.021), high tumor grade (p = 0.015), and irregular pattern on CT (p = 0.0055). The SUVmax was not correlated with age, gender, whether the tumor was functioning or non-functioning, or lymph node metastasis. The SUVmax ≥ 2.0 group had significantly poorer disease-free survival (median, 3.5 vs 16.2 months; p = 0.023) and poorer overall survival (median, 8.8 vs 16.2 months; p = 0.042). An SUVmax ≥ 2.0 on 18F-FDG PET/CT might be associated with higher malignant potential of PNETs.

Background Small hepatocellular carcinomas (HCC ≤3 cm) are generally considered to have low malignant potential; however, some of them display pathological microvascular invasion (MVI). Methods Between 1991 and 2013, 414 patients with a single HCC ≤3 cm underwent curative hepatic resection (HR). Predictors for MVI were identified. Using another cohort (149 patients during 2000‐2014), our predictors for MVI in HCC ≤3 cm were validated. In 428 patients with a single HCC ≤3 cm who had predictors for MVI, survival was compared among anatomical HR (n = 149), partial HR (n = 227), and radiofrequency ablation (RFA) (n = 52). Results The positive rate of MVI reached 40.6% (168/414 patients). Independent predictors for MVI were as follows: tumor diameter ≥2 cm (odds ratio 1.84, P = .0052), alpha‐fetoprotein (AFP) ≥200 ng/mL (odds ratio 1.82, P = .0466), and des‐gamma‐carboxy prothrombin (DCP) ≥40 mAU/mL (odds ratio 1.79, P = .0126). Matching at least one predictor among these three could predict MVI in HCC ≤3 cm well (sensitivity 82.8%, positive predictive value [PPV] 48.7%). This criterion could also predict MVI in HCC ≤3 cm well in another cohort (sensitivity 82.8%, PPV 30.3%). In patients with single HCC ≤3 cm matching our criterion for predicting MVI, anatomical HR led to significantly better survival in both disease‐free (hazard ratio 0.689, P = .0231) and overall (hazard ratio 0.589, P = .0316) survivals. Conclusion Matching at least one factor among three (tumor diameter ≥2 cm, AFP ≥200 ng/mL, or DCP ≥40 mAU/mL) can predict MVI in HCC ≤3 cm. In such patients, anatomical HR would be recommended to improve survival., Matching at least one factor among three (tumor diameter ≥2 cm, AFP ≥200 ng/mL, or DCP ≥40 mAU/mL) can predict MVI in HCC ≤3 cm. In such patients, anatomical HR should be recommended to improve survival.

Metastases to the kidney are extremely rare and intrahepatic cholangiocarcinoma (ICC) is difficult to treat. In this study, we report a case of renal metastasis from ICC. A 72-year-old man who had been followed-up for chronic hepatitis C was diagnosed with ICC in the segment 8 and underwent S8 segmentectomy in 2014. During follow-up, the serum levels of carcinoembryonic antigen and carbohydrate antigen 19-9 were slightly elevated, and abdominal contrast-enhanced computed tomography revealed a low-density mass preceded by rim enhancement in the arterial phase measuring 1.5 × 1.5 cm in the segment 6, and a hypovascular mass measuring 2.2 × 2.0 cm in the upper pole of the left kidney in 2017. He underwent partial hepatectomy and partial nephrectomy. Based on postoperative histological findings combined with immunohistochemical analysis, the tumors both in the liver and kidney were diagnosed as recurrent ICC.

Growth factors (GFs) are signaling molecules that are principle mediators in tissue regeneration. Biomaterial scaffolds employed as wound dressings are often hampered by their limitations to deliver GFs exogenously due to their instability and low half-life. The key to overcome this challenge lies in the better organization and use of endogenous pro-regenerative GFs released at regenerative site, with an aim to minimize the sole dependency on exogenous factors. Considering such challenges, this research utilizes the exogenous and endogenous GFs sequestering capability of heparin functionalized PCL/gelatin co-spun nanofabrics to mediate synergistically driven tissue regeneration by utilizing combined therapeutic effect of exogenous and endogenous GFs, and thereby minimizing the sole dependency on exogenous GFs for tissue regeneration. Basic fibroblast growth factor (bFGF) was chosen as GF for exogenous loading whereas vascular endothelial growth factor (VEGF) was chosen as a representative example to demonstrate the endogenous pro-regenerative GF sequestration capability of fabricated nanofabrics. From our results, the fabricated nanofabrics showed loading efficiency of 80% for exogenous bFGF and can sequester 15-fold more amount of endogenous VEGF compared to non-heparin functionalized nanofibrous dressings. When applied as wound dressings, heparin functionalized nanofibers showed better therapeutic capability compared to control groups that were treated using patches without heparin functionalization, indicating endogenously driven tissue regeneration. This was indicated by significant higher number of newly formed skin appendages, lesser scarring and lower inflammatory levels in newly formed granulation. Additionally, further improvements in therapeutic effect was observed when exogenous bFGF was employed indicating effectiveness of synergistically mediated tissue regeneration.

Background/aim Prognoses of patients with cancer can be predicted on the basis of preoperative nutrition- or inflammation-based scores; however, predicting the prognostic impact of undergoing surgery remains challenging. In this study, we investigated the usefulness of the perioperative C-reactive protein/albumin (CRP/Alb) ratio in patients with intrahepatic cholangiocarcinoma (ICC). Patients and methods We retrospectively investigated 80 patients who had undergone curative resection of primary ICC between April 2002 and December 2017. We identified the time at which perioperative CRP/Alb ratio most influences the prognosis, and investigated the correlations among the perioperative CRP/Alb ratio, clinicopathological features and patient outcomes. Results The only perioperative CRP/Alb ratios significantly associated with shorter overall survival (OS) was a high CRP/Alb ratio on POD14. High CRP/Alb ratio on POD 14 was significantly associated with older age, male sex, and the presence of postoperative complications. Finally, a high CRP/Alb ratio at POD 14 was an independent prognostic factor for poor OS. Conclusion CRP/Alb ratio on POD 14 may be a useful prognostic factor in patients with ICC who have undergone curative resections.

A 72-year-old man with hepatocellular carcinoma (HCC) was diagnosed with acute perforated cholecystitis requiring emergency surgery. Unexpectedly, a bile duct tumor thrombus was found to have spread into the intracystic space, mimicking a gall stone and presumably causing the severe acute cholecystitis. We herein report an extremely rare subtype of bile duct tumor thrombus of HCC.

Background Removal of an isolated portal vein (PV) thrombus is still a difficult problem in liver surgery. In this report, we present technical details of the ultrasonography (US)-guided suction thrombectomy for an isolated PV thrombus in a case with PV tumor thrombus extending into the main PV trunk of a patient undergoing right hemi-hepatectomy and tumor thrombectomy for hepatocellular carcinoma (HCC). Patients and methods Three cases were treated with US-guided suction thrombectomy for an isolated PV thrombus in liver surgeries. All three patients had HCC; however, two cases had a blood clot PV thrombus, and one case had an isolated PV tumor thrombus. Results In all three cases, the isolated PV thrombus was successfully removed by suction thrombectomy without intraoperative and postoperative problems. Conclusion US-guided suction thrombectomy is a promising method for removal of an isolated PV thrombus in liver surgery.

Background Portal vein embolization has been used worldwide to induce hypertrophy of the future liver remnant and to reduce the risk of hepatic insufficiency and death after major hepatectomy. However, whether disease progression after portal vein embolization can affect long-term oncologic outcomes in patients with hepatocellular carcinoma is uncertain. Methods From a total of 107 patients who underwent portal vein embolization and subsequent hepatectomy between 2000 and 2016, 57 patients with hepatocellular carcinoma were enrolled. We evaluated their long-term oncologic outcomes and investigated whether the disease progression between portal vein embolization and subsequent hepatectomy affected survival. Results The 5-year overall survival and disease-free survival after hepatectomy were 74.5% and 31.7%, respectively. Multivariate analyses revealed that tumor number before hepatectomy ≥3 (hazard ratio 3.59, P = .019), des-γ-carboxy prothrombin >200 mAU/mL (hazard ratio 3.36, P = .045), and red blood cell transfusion (hazard ratio 11.03, P = .0008) were independent prognostic factors for overall survival. Male sex (hazard ratio 3.74, P = .029), bilobar tumor distribution (hazard ratio 3.65, P = .004), and red blood cell transfusion (hazard ratio 6.22, P = .0026) were independent prognostic factors for disease-free survival. Disease progressions after portal vein embolization, including increases in tumor size, tumor number, α-fetoprotein, lens culinaris agglutinin-reactive fraction of α-fetoprotein, and des-γ-carboxy prothrombin, were observed in 22.8%, 14.0%, 29.8%, 19.3%, and 47.4% of patients, respectively. Only an increase of tumor number significantly decreased the disease-free survival rate after hepatectomy in a univariate analysis, and none of the variables affected overall survival. Conclusion Disease progression after portal vein embolization did not affect long-term survival in patients with hepatocellular carcinoma if the planned subsequent hepatectomy could be completed.

Clinical predictive markers for the malignant potential of pancreatic neuroendocrine tumors (PNETs) are limited without histological investigation. We reported previously that a loss of the regular enhancement pattern in preoperative computed tomography (CT) was correlated with the malignant tumor phenotype. This study aimed to establish whether the metabolic aspect of the tumor evaluated by fludeoxyglucose (Among 77 patients who underwent surgery with curative intent for a PNET at our institution between 2001 and 2017, 24 who receivedThere were four (16%) patients with insulinoma. The mean tumor size was 17 mm and when the median value of the SUVmax (= 2.0) was measured as the cut-off value, the SUVmax ≥ 2.0 group (n = 12) was associated with large tumor size (p = 0.021), high tumor grade (p = 0.015), and irregular pattern on CT (p = 0.0055). The SUVmax was not correlated with age, gender, whether the tumor was functioning or non-functioning, or lymph node metastasis. The SUVmax ≥ 2.0 group had significantly poorer disease-free survival (median, 3.5 vs 16.2 months; p = 0.023) and poorer overall survival (median, 8.8 vs 16.2 months; p = 0.042).An SUVmax ≥ 2.0 on

Background The benefit of preoperative chemotherapy for colorectal liver metastases (CRLM) remains uncertain. The aim was to clarify the effect of preoperative chemotherapy on CRLM according to the primary tumor location. Methods Among a total cohort of 163 patients who underwent curative hepatectomy for CRLM, 36 patients had a right-sided and 127 had a left-sided primary tumor. According to the performance of preoperative chemotherapy, survival analysis was conducted and prognostic factors were identified. Results Preoperative chemotherapy was administered to 17 patients (47.2%) with a right-sided and 74 (58.3%) with a left-sided primary tumor (P = 0.24). Among the patients who received preoperative chemotherapy, overall survival (OS) and disease-free survival (DFS) were similar between patients with right- and left-sided primary tumors (P = 0.36 and P = 0.44, respectively). Among the patients who underwent upfront hepatectomy, the OS and DFS of patients with a right-sided primary tumor were worse than those with a left-sided primary tumor (P = 0.02 and P = 0.025, respectively). Among the patients who underwent upfront surgery, the right-sided primary tumor was identified as an independent poor prognostic factor for OS (hazard ratio 3.44, P = 0.021). Conclusion The existence of a right-sided primary tumor may be an indication of preoperative chemotherapy for patients with CRLM.

BACKGROUND/AIM The significance of microvascular invasion (MVI) of hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA) is unknown. PATIENTS AND METHODS We studied 149 patients with solitary small-sized HCC (≤3 cm) who underwent hepatectomy, and developed a predictive model of MVI using independent factors related to the presence of MVI. The predictive model was applied to 159 patients who underwent RFA, and their outcomes were examined. RESULTS A multivariate analysis revealed that α-fetoprotein ≥15 ng/ml (relative risk (RR) 3.05, p=0.02), des-γ-carboxy prothrombin ≥100 mAU/ml (RR 4.19, p=0.003), and tumor size ≥2 cm (RR 3.37, p=0.03) were independent risk factors of MVI. Among the patients who underwent RFA, the survival in patients with risk factors 2-3 was significantly worse, and local recurrence was more frequently obserbed than those with 0-1. CONCLUSION When an HCC tumor is expected to display MVI, RFA may not be suitable in terms of poorer survival and local disease-control rates.

Background: Pancreatic cancer remains a lethal malignancy with a dismal five year survival rate of less than ten percent. ARHGEF2 is one of the Rho guanine exchange factor (RhoGEF). RhoGEF is a microtubule-associated guanine nucleotide exchange factor for the Rho family of small GTPases. We aimed to reveal the association between ARHGEF2 expression and patients’ prognosis, or the downstream pathways of ARHGEF in pancreatic cancer. Methods: For the gene selection, we used the cohort of 102 patients who underwent curative resection for pancreatic cancer from GSE21501 in which the DNA microarray were performed to assess the association with molecular pathways and the prognosis of patients. Pathway analysis was performed by GSEA (gene set enrichment analysis) using HALLMARK geneset. As a validation cohort, 200 patients underwent curative resection for pancreatic cancer at Kumamoto University from April 2004 to March 2018 were enrolled. The immunohistochemical (IHC) staining was performed to evaluate the expression of ARHGEF2 and c-Myc. IHC was evaluated with the intensity and area of immunoreactivity of ARHGEF2 and c-Myc and scored each factors from 0 to 2. The staining index (ranging from 0 to 4) was calculated by multiplying intensity and area. Low expression was defined from 0 to 1, and high expression was from 2 to 4. Result: In GSE21501 (n=102), the patients were separated into high- (upper 50%, n = 51) and low- (lower 50%, n = 51) ARHGEF2 groups. High-ARHGEF2 group had significantly poor overall survival than low-ARHGEF group (p = 0.01). Moreover, high ARHGEF2 group was associated with high lymph node metastasis (p=0.03). The GSEA analysis revealed that the high ARHGEF expression was significantly associated with “HALLMARK-MYC-TARGET-V2” geneset (p=0.04). Also high ARHGEF expression was significantly associated with CDC25A (p=0.006) which is the downstream gene of c-MYC pathway and regulates cell cycle, suggesting that ARHGEF promote cell cycle via MYC signaling. In immunohistochemistry, the high ARHGEF2 group (n = 122) had shorter recurrence free survival (RFS) (p = 0.0014) and poor overall survival (OS) (p = 0.0036). In addition, in the comparisons of clinicopathological factors between the high ARHGEF2 and the low ARHGEF2 groups, there were significantly larger tumor size and higher lymph node positive rate in the high ARHGEF2 group. In the multivariate analysis for RFS, high CA19-9 value, R1 resection and high ARHGEF2 expression were independent poor prognostic factors. In the multivariate analysis for OS, high CA19-9 value, tumor size (> 40 mm), lymph node metastasis and high ARHGEF2 expression were independently associated with poor prognosis. According to immunohistochemistry, ARHGEF2 and c-Myc have a significant positive correlation. Conclusion: High expression of ARHGEF2 is associated with poor prognosis via c-Myc signaling in patients with pancreatic cancer. Citation Format: Yosuke Nakao, Shigeki Nakagawa, Yo-ichi Yamashita, Rumi Itoyama, Toshihiko Yusa, Naoki Umezaki, Takanobu Yamao, Tatsunori Miyata, Hirohisa Okabe, Katsunori Imai, Hiromitsu Hayashi, Akira Chikamoto, Hideo Baba. High expression of ARHGEF2 is associated with poor prognosis via c-Myc signaling in patients with pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1766.

Background: Pancreatic cancer is one of the most malignant tumors. The prognosis of patients with pancreatic cancer remains poor, with a 5-year survival rate of less than 10%. Therefore, identification of new biomarkers and development of therapeutic drugs are urgent issues. As a result of genetic research using public database, we focused on Cofilin-1. In recent years, it has been revealed that cancer cells form invadopodia to destroy extracellular matrix and cause hematogenous metastasis, and it is suggested that Cofilin-1 has a key role in stabilizing the structure of the invadopodia. However the significance of Cofilin-1 expression in cancer invasion is not clear. The purpose of this study is to verify the relationship between the expression of Cofilin-1 and patient’s prognosis in pancreatic cancer. Methods: At first, we examined the relationship between Cofilin-1 expression level and clinicopathological factors or prognosis using GSE21501 and TCGA, which are public databases of patients with pancreatic cancer. We set the cut-off value, and divided into the two groups, the high Cofilin-1 and low groups. Then, we evaluated expression of Cofilin-1 with immunohistochemical (IHC) staining in 200 pancreatic cancer patients who underwent curative surgery during April 2004 to March 2018 at the department of gastroenterological surgery, Kumamoto University. After that, we examined the relationship between Cofilin-1 expression and prognosis. Results: In silico analyses using GSE21501 and TCGA dataset, high expression of Cofilin-1 is associated with early recurrence and poor prognosis. Then, we evaluated expression of Cofilin-1 with IHC staining using original scoring. The score is calculated by multiplying each scores classified into 4 stages from 0 to 3 in intensity of Cofilin-1 expression and area of that. 0 to 3 of the score was the low expression group (n=93), 4 to 9 is the high expression group (n=107). The result showed that high Cofilin-1 expression is associated with high occurrence of lymph node metastasis. In addition, both the relapse free and overall survivals were significantly worse in the high Cofilin-1 group. Cox proportional hazard analysis revealed that the high Cofilin-1 expression was an independent poor prognostic predictor. Conclusion: In both silico analysis and IHC staining, high Cofilin-1 expression is associated with poor prognosis, especially high recurrence rate in patients with pancreatic cancer. Cofilin-1 may be useful as a biomarker for early recurrence in pancreatic cancer. Citation Format: Rumi Itoyama, Shigeki Nakagawa, Toshihiko Yusa, Yosuke Nakao, Takanobu Yamao, Naoki Umezaki, Tatsunori Miyata, Hirohisa Okabe, Hiromitsu Hayashi, Katsunori Imai, Yo-ichi Yamashita, Akira Chikamoto, Hideo Baba. Clinical significance of Cofilin-1 expression in pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2854.

Background: The role of cellular senescence of cancer associated fibroblasts (CAFs) in the development of cancer is controversial. In this study, we investigated how senescence of CAFs, represented by Caveolin-1 (CAV1) expression, affects tumor progression in pancreatic cancers (PC). Methods: We used CAV1 expression to monitor cellular senescence, because CAV1 has been reported to play a major role in cellular senescence. A total 157 consecutive patients with PC underwent curative resections between January 2004 and December 2017 were enrolled. Patients were divided into two groups according to CAV1 expression in CAFs (high and low CAV1, measured by immunohistochemistry). We investigated the relationship between the CAV1 expression in CAFs and the patients’ clinicopathological characteristics, including survival. We also established ten CAFs cell lines using PC clinical samples and and evaluated the relationship between CAV1 and senescence marker expression, such as p21 and p53. We chose high CAV1 CAFs to knock down CAV1 expression using siRNA. Finally, we cultured a PC cell line (MIAPaCa-2) with CAFs-conditioned medium (CM) to evaluate the effect of cellular senescence in CAFs on proliferation and invasion of PC cell lines. Results: The high CAV1 group counts of 49 patients (31%), and the low CAV1 group counts of 110 patients (69%). As for patients’ clinicopatholoical factors, the serum levels of CA19-9 (p=0.024) and pathological T factor stage (T0,1/T2,3,4) (p=0.014), defined by Japan Pancreas Society as the “General Rules for the Study of Pancreatic Cancer” were significantly higher in the high CAV1 group. The high CAV1 group had significantly worse outcomes in overall (log-rank p=0.0062) and disease-free survivals (log-rank p=0.0018). Multivariate analysis revealed that high CAV1 group was the independent prognostic factors for OS (p=0.043) and DFS (p=0.018). In coculture assays using CAFs-CM and MIAPaCa-2 cells, we found that knockdown of CAV1 in CAFs negatively affected the invasion of the PC cells compared to that with si control (p Conclusion: The present results suggest that, in PC, CAV1 expression in CAFs is associated with patients’ poor prognosis and the downregulation of CAV1 in CAFs reduces the invasive ability of PC cells. Therefore, CAV1 of CAFs might be a new target for the treatment of PC. Citation Format: Takanobu Yamao, Yo-ichi Yamashita, Kensuke Yamamura, Naoki Umezaki, Rumi Itoyama, Yosuke Nakao, Toshihiko Yusa, Tatsunori Miyata, Shigeki Nakagawa, Hirohisa Okabe, Katsunori Imai, Hiromitsu Hayashi, Akira Chikamoto, Takatoshi Ishiko, Hideo Baba. Cellular senescence, represented by expression of caveolin-1, in cancer-associated fibroblasts promotes tumor Invasion in pancreatic cancer cellular [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2023.

In this study, we propose a microfluidic cell culture device mimicking the microscopic structure in liver tissue called hepatic cords. The cell culture area of the device was designed to align hepatocytes in two lines in a similar way to hepatic cords. Thanks to the structural design together with a cell seeding procedure, rat primary hepatocytes were successfully aligned in two lines and cultured under perfusion condition. It is shown that aligned hepatocytes gradually self-organize and form bile canaliculi along the hepatic cord-like structure. The present technique to culture hepatocytes with functional bile canaliculi could be used as an alternative to animal testing in the field of drug discovery and toxicological studies, and also be beneficial to tissue engineering applications.