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Background An accurate diagnosis of the primary cancer or metastatic tumor is quite important because misdiagnosis may lead to the selection of incorrect adjuvant therapy and worse long-term outcomes after surgery. Here, we present a rare case with an unusual metastatic pattern mimicking a hilar cholangiocarcinoma originated from colon cancer Case presentation A 69-year-old man was referred to our hospital because of an upper bile duct stenosis. He had the past history of the sigmoidectomy for the primary colon cancer and the partial hepatectomy with radiofrequency ablation (RFA) for synchronous liver metastases 4 years ago. After 2 years from the initial operation, he had experienced the local recurrence of post-RFA lesion and had undergone a partial hepatectomy. According to the radiological findings of the bile duct stenosis, we diagnosed a hilar cholangiocarcinoma (Bismuth type II), and then he underwent the extended right hepatectomy with extrahepatic bile duct resection. Histological findings including the immune-histochemical examinations (CK7−, CK20+, CDX2+ and SATB2+) uncovered the metastatic tumor into extrahepatic bile duct originated from the primary colon cancer. Conclusion We experienced an extremely rare case with a colon cancer metastasis mimicking a hilar cholangiocarcinoma. In this case with a past history of colon cancer, an immunohistochemical staining led us to distinguish the primary hilar cholangiocarcinoma and the mimicking tumor.

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

Background An ectopic hepatocellular carcinoma (EHCC) arises from the ectopic liver which is defined as a hepatic organ or tissue not connected to surrounding tissues. EHCC is a rare disease and it is difficult to diagnose preoperatively. Furthermore, the clinical features are not fully elucidated. Case summary A retroperitoneal tumor (6 cm) was located at the dorsal side of the pancreas head on abdominal ultrasonography in an 81-year old woman positive for hepatitis C virus antibody. Contrast enhanced-computed tomography and gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging showed viable HCC patterns with early enhancement and delayed washout. The tumor markers - serum alpha-fetoprotein and alpha-fetoprotein-L3% - were increased to 30.1 ng/mL and 83.1%, respectively. Protein induced by vitamin K absence or antagonist-II was within normal levels (17 mAU/mL). Positron emission tomography-computed tomography showed strong accumulation into the tumor (Standardized Uptake Value max: 13.8), and the tumor cytology following endoscopic ultrasound-guided fine needle aspiration showed poorly differentiated carcinoma. Tumor extirpation was performed, and operative findings showed that the retroperitoneal tumor was disconnected from the pancreas and the liver. Swollen lymph nodes near the tumor were histologically normal. On histological examination, the tumor was finally diagnosed as EHCC with Arginase-1 positive expression. Conclusion We report our experience of a rare EHCC which was difficult to diagnose, and we present a review of the literature.

Background/Purpose We examined therapeutic strategies for pancreatic neuroendocrine neoplasm (pNEN) associated with MEN1 (M‐pNEN) by investigating clinicopathological features and menin expression. Methods Seventy‐seven patients who underwent resection of pNEN at our department from January 2001 to December 2017 were retrospectively analyzed. Immunohistochemical analysis of menin was performed using resected specimens. Results Seven patients (9%) met the diagnostic criteria for MEN1. M‐pNEN had more tumors (P, This study aimed to describe therapeutic strategies for pancreatic neuroendocrine neoplasm associated with multiple endocrine neoplasia type 1 (M‐pNEN) by investigating the clinicopathological features and menin expression. Sonoda and colleagues concluded that minimal resection with strict follow‐up is recommended rather than extensive pancreatic resections for consideration of recurrence in M‐pNEN.

Background/aim Preoperative evaluation of resectability of pancreatic cancer (PC) is difficult, so that staging laparoscopy (SL) has come to be used for detecting occult metastases. We aimed to evaluate the prognostic impact of SL in comparison with exploratory laparotomy (EL) in unresectable PC. Patients and methods Between 2010 and 2016, 57 patients with PC underwent SL after conventional tumor staging. Patient characteristics, operative findings and survival rates were compared between SL and EL group. Results Twenty patients (35%) were identified as having unresectable factors in SL group. In contrast, laparotomy showed unresectable factors in 8 patients who did not receive preoperative SL (EL group). The time between the surgery to the induction of chemotherapy was significantly shorter in the SL group (mean=6 days, range=2-17) than in the EL group (mean=10 days, range=6-15). There was no significant difference in overall survival between the two groups; however, EL was associated with shorter survival in the early postoperative period. Conclusion SL was associated with a shorter time interval to chemotherapy and lead to the prevention of unnecessary laparotomy.

Background/aim The aim of this study was to elucidate the clinical impact of coagulation disorders on outcomes after curative resection of pancreatic ductal adenocarcinoma. Patients and methods Preoperative coagulation activity in 135 patients, who had undergone curative resections for pancreatic ductal adenocarcinoma was retrospectively evaluated and the impact on survival outcomes analyzed. Results A prolonged prothrombin time-international normalized ratio (PT-INR) (≥1.1) was detected in 23/135 patients (17%). Univariate analysis that showed prolonged PT-INR was associated with worse relapse-free (hazard ratio=1.79, p=0.044) and overall (hazard ratio=2.18, p=0.004) survival. Multivariate analyses showed prolonged PT-INR, large tumor (>30 mm), and lymph node metastasis were independent predictors of poor overall survival. Conclusion Prolonged PT-INR may be a predictor of poor prognosis in patients with pancreatic ductal adenocarcinoma who have undergone curative resection. Coagulation disorders may be a therapeutic target for improving outcomes of pancreatic ductal adenocarcinoma.

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 objective of this study was to describe the surgical techniques for a thoracoscopic approach to treat hepatocellular carcinoma in the hepatic dome. Also, safety, feasibility, and long-term outcomes were evaluated. Methods Surgical procedures were selected based on liver function, the extent and location of the tumor, and each patient's general condition. Thoracoscopic hepatic resection was performed under direct vision through a diaphragmatic incision. Thoracoscopic radiofrequency ablation (TRFA) was performed either with a transdiaphragmatic puncture for deeply located tumors or under direct vision through a diaphragmatic incision for subcapsular tumors. Results Thoracoscopic surgery was indicated for 107 patients with hepatocellular carcinoma in the hepatic dome. Among these patients, 5 underwent hepatectomy and 102 underwent radiofrequency ablation, which was more frequently employed in patients with impaired liver function. Of the patients who underwent radiofrequency ablation, 43 (42.2%) required a diaphragmatic incision. In the thoracoscopic hepatic resection group and TRFA group, the median operating time was 350 and 197 minutes, the median blood loss was 200 and 5 mL, and the complication rate was 12.7% and 20.0%, respectively. The 5-year overall and disease-free survival rates were 100% and 50.0% in the thoracoscopic hepatic resection group, respectively, and 60.7% and 18.1% in the TRFA group, respectively. Local recurrence after TRFA was observed in 10 patients (9.8%). Conclusion The thoracoscopic approach is safe and feasible, with promising short- and long-term outcomes. It could serve as a treatment option for hepatocellular carcinoma in the hepatic dome.

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.

In recent years, studies on liver graft construction using the decellularized liver as a template for transplantation therapy have attracted much attention. However, the therapeutic effect of constructed liver grafts in hepatic failure has not been evaluated. Therefore, we aimed to develop a novel evaluation system demonstrating the curative effect of a constructed liver graft in animals with hepatic failure. First, we developed a highly reproducible rat model of hepatic failure by combining 80% partial hepatectomy with warm ischemia. In this model, severity could be controlled by the warm ischemic period. We also constructed a liver graft by recellularization of decellularized liver, and confirmed the ammonia metabolic function in the graft in vitro as one of the most important functions for recovery from hepatic failure. The graft was then applied to our developed hepatic failure rat model using a blood extracorporeal circulation system. In this application, the graft metabolized the ammonia in the blood of animals with hepatic failure and was thus suggested to be effective for the treatment of hepatic failure. In summary, a novel evaluation system for whole-organ-engineered liver graft as a preliminary stage of transplantation was developed. This system was expected to provide much information about the curative effect of a constructed liver graft.

Background The aim of this study was to verify the significance of high Lens culinaris agglutinin-reactive fraction of α-fetoprotein (AFP-L3) in patients with hepatocellular carcinoma (HCC) with low AFP. Materials and methods There were 283 patients with low AFP who underwent initial hepatic resection with or without radiofrequency ablation for HCC. Patients were divided into two groups based on AFP-L3 values: >10%: high AFP-L3 (n=24); and ≤10%: low AFP-L3 (n=259). Overall survival (OS) and 2-year recurrence rates were compared, and independent prognostic factors were identified. Results The OS and 2-year recurrence rates of the high AFP-L3 group were significantly worse than those of the low AFP-L3 group. The independent prognostic factors for poor OS were des-gamma-carboxy prothrombin (DCP) of >40 mAU/ml, microvascular invasion, and invasive growth, and those for 2-year recurrence were 99mTc-galactosyl human serum albumin uptake ratio of 40 mAU/ml, multiple tumors, microvascular invasion, and poor differentiation. DCP levels increased with AFP-L3, and cases with high DCP and AFP-L3 had worse prognoses and higher 2-year recurrence rates compared to those with elevation of only one of these. Conclusion Patients with high AFP-L3 but low AFP have poor prognosis and high 2-year recurrence rates. DCP strongly reflects HCC malignancy in patients with low AFP.

Neuroendocrine tumors usually develop in the gastrointestinal tract, pancreas, and lung. Therefore, a neuroendocrine tumor of the bile duct is quite rare. We present a 59-year-old-male patient whose preoperative diagnosis was hilar cholangiocarcinoma. One month after embolization of the left branch and anterior branch of the portal vein, he underwent left hepatic trisegmentectomy and extrahepatic bile duct resection. Pathological examination revealed the neuroendocrine tumor in the submucosal layer of the hilar bile duct. Because there was no neuroendocrine tumor in other organs, the tumor was considered a primary neuroendocrine tumor of the hilar bile duct, rather than a liver metastasis from other organs. We also present a review of the English literature regarding neuroendocrine tumors of the bile duct.

The objective of this study was to describe the detailed technique and clinical outcomes of portal vein embolization via the round ligament (RL-PVE) prior to major hepatectomy. Between January 2010 and March 2020, a total of 50 portal vein embolization (PVE) procedures were performed in 50 patients. Of them, seven patients who underwent RL-PVE were enrolled in this study. Percutaneous transhepatic portal vein embolization (PTPE) was not indicated due to the following reasons: bile duct dilation (n = 4), difficulty in visualizing the portal vein on ultrasonography because of severe fatty liver (n = 1), large tumor size (n = 1), and combined surgery with staging laparoscopy (n = 1). The following were reasons for avoiding trans-ileocecal PVE: past laparotomy (n = 5), difficulty in accessing the portal vein due to a large tumor (n = 1), and purpose of preventing small intestinal adhesions before hepatopancreatoduodenectomy (n = 1). The percentage of functional hepatic remnant rates was calculated before and after RL-PVE. Technical success was achieved in all cases. Five patients underwent embolization of the right portal vein, while two underwent embolization of the left portal vein. The median operative time and blood loss during RL-PVE were 181 min and 33 g, respectively. Morbidity and mortality related to RL-PVE were not observed. The median functional hepatic remnant rate before and after PVE was 55.6% and 63.2%, respectively. Liver functions including Child–Pugh classification were equivalent before and after RL-PVE. The RL-PVE technique may be useful in elective cases for which it is difficult to safely perform PTPE or trans-ileocecal approaches.

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.

Background Schwannomas originate from Schwann cells, which are constituents of peripheral nerve sheaths, and can occur anywhere in the body at any age. Most occur in soft tissues such as subcutaneous tissues and muscles, occurrence in the abdominal cavity being relatively rare. In particular, schwannomas of the gallbladder are extremely rare. We herein report a rare case of a schwannoma that coexisted with systemic sarcoidosis and presented as a steroid-resistant mass in the gallbladder wall. Case presentation A 40-year-old woman was found to have thickening of the gallbladder wall during a routine medical examination and was referred to our hospital, where she was found to have granular shadows in the lungs; mediastinal, cervical, intraperitoneal, and inguinal lymphadenopathy; parotid gland enlargement; and an erythematous skin rash. She was diagnosed as having systemic sarcoidosis by transbronchial lung biopsy and bronchoalveolar lavage. All her systemic mass lesions except for the one in the gallbladder resolved or became smaller with steroid treatment. The steroid-resistant gallbladder lesion showed enhancement on contrast-enhanced computed tomography and was shown by endoscopic ultrasonography to be a 30-mm-diameter gallbladder wall lesion. We performed laparoscopic cholecystectomy, which resulted in diagnosis of the steroid-resistant tumor as a schwannoma. Five months after surgery, the patient’s prednisolone dosage had been gradually reduced to 5 mg/day and she was doing well with no evidence of recurrence. Conclusion Resection of a steroid-resistant tumor resulted in diagnosis of schwannoma, enabling reduction in the patient’s steroid dosage for sarcoidosis.

The prognostic value of the prognostic nutrition index (PNI) in pancreatic ductal adenocarcinoma (PDAC) is still controversial. This study aimed to assess the correlation between PNI and the outcome for PDAC patients and to generate a new score from PNI and serum markers.This study investigated 151 patients who underwent pancreatic resection for PDAC between April 2002 and June 2012. Disease-free survival (DFS), overall survival, and clinicopathological parameters were analyzed according to the PNI value.The low PNI patients had poorer 5-year DFS rate than high-PNI patients (10.7% and 34.8%, respectively). Multivariate analyses revealed that independent risk factors for poor DFS were high carcinoembryonic antigen (hazard ratio [HR], 1.53; P = 0.038), high carbohydrate antigen 19-9 (HR, 1.67; P = 0.017), positive lymph node metastasis (HR, 1.98; P = 0.017), R1 or 2 resection (HR, 3.50; P0.001), and low PNI (HR, 0.37 [high/low]; P = 0.029]. Scoring based on the formula -0.49 × (PNI) + 0.41 × (carcinoembryonic antigen) + 0.67 × (carbohydrate antigen 19-9) was significantly associated with poor DFS (P0.001) and overall survival (P = 0.0019).Low PNI and serum marker score are significantly associated with poor DFS.

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 Patients' prognoses have been predicted by the preoperative inflammation-based score, but predicting a patient's risk for operative load remains challenging. This study investigates the usefulness of the postoperative C-reactive protein/albumin (CRP/Alb) ratio in patients with pancreatic ductal adenocarcinoma (PDAC). Methods This study retrospectively assessed 142 patients who underwent pancreatic resection for PDAC between 2004 and 2014. The time at which perioperative CRP/Alb ratio most influences the prognosis was identified, and the correlations among the perioperative CRP/Alb ratio, clinicopathological factors, and patient outcomes were investigated. Results Among the perioperative CRP/Alb ratios, only a high CRP/Alb ratio at postoperative day 14 (POD14) was significantly associated with shorter overall survival (OS) and relapse-free survival (RFS). High CRP/Alb ratio at POD 14 was related to high BMI, large amount of intraoperative bleeding, and the presence of complications. Finally, high CRP/Alb at POD14 was an independent prognostic factor of poor OS and RFS. Conclusions The CRP/Alb ratio at POD14 is a useful predictive marker of surgical invasion, biological reaction, and prognosis in PDAC patients.

// Tatsunori Miyata 1 , Yo-Ichi Yamashita 1 , Yoshifumi Baba 1 , Kazuto Harada 1 , Takanobu Yamao 1 , Naoki Umezaki 1 , Masayo Tsukamoto 1 , Yuki Kitano 1 , Kensuke Yamamura 1 , Kota Arima 1 , Shigeki Nakagawa 1 , Hirohisa Okabe 1 , Katsunori Imai 1 , Daisuke Hashimoto 1 , Akira Chikamoto 1 , Mototsugu Shimokawa 2 and Hideo Baba 1 1 Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan 2 Clinical Research Institute, National Kyushu Cancer Center, Fukuoka, Japan Correspondence to: Hideo Baba, email: hdobaba@kumamoto-u.ac.jp Keywords: LINE-1; methylation; epigenetics; primary liver cancer; prognosis Received: October 18, 2017 Accepted: March 22, 2018 Published: April 17, 2018 ABSTRACT Background: The methylation level of long interspersed nucleotide element-1 (LINE-1) is a good surrogate marker of the global DNA methylation level. The relationship between LINE-1 methylation level and prognosis in primary liver cancer (PLC) patients remains unclear. Results: LINE-1 methylation levels were significantly lower in HCC and cHCC-CC tissues, but not in ICC tissues, than those in noncancerous liver parenchyma (HCC: p < 0.0001; cHCC-CC: p < 0.001; and ICC: p = 0.053). HCC cases with hypomethylated LINE-1 had significantly shorter relapse-free survival (RFS) (log-rank, p = 0.008); however, this was not observed for the cHCC-CC or ICC cases. Multivariate Cox regression analysis revealed a significantly higher HCC recurrence rate in the group with hypomethylated LINE-1 (hazard ratio, 1.62; 95% confidence interval, 1.06–2.58; p = 0.025). Conclusions: The genome-wide DNA hypomethylation status estimated via LINE-1 methylation levels might be indicative of poor RFS in patients with HCC but not ICC or cHCC-CC. Methods: We evaluated the level of LINE-1 methylation in 321 cases of curatively resected PLC {231 hepatocellular carcinoma (HCC), 19 combined hepatocellular and cholangiocarcinoma (cHCC-CC) and 71 intrahepatic cholangiocarcinoma (ICC)} via pyrosequencing of formalin-fixed paraffin-embedded (FFPE) tissues and examined its prognostic value.

Gastrointestinal tract metastasis from pancreatic cancer is quite rare. We present the case of a 58-year-old male patient who underwent distal pancreatectomy for pancreatic body cancer 5 years prior. Four years after the initial operation, a 15-mm cystic submucosal tumor was found in the antrum of the stomach. Because the tumor had grown to 25 mm and the level of carcinoembryonic antigen in the cystic fluid derived by ultrasound-guided fine-needle aspiration biopsy was high, partial resection of the stomach was performed 5 years after the distal pancreatectomy. Pathological diagnosis was gastric metastasis of pancreatic cancer. The patient has been alive without recurrence for 13 months after the resection of the cystic tumor. We are not aware of any similar cases of cystic gastric metastasis from pancreatic cancer published in the English literature.

Background Although hilar cholangiocarcinoma (HCCA) has a very poor prognosis, there are cases in which long-term survival is rarely obtained by multidisciplinary treatment. Case presentation A 61-year-old man diagnosed with HCCA was referred to our hospital. We performed an extended left hemi-hepatectomy and caudate lobectomy with extrahepatic bile duct resection. The tumor stage was T2aN0M0, stage II, based on the TNM classification, seventh edition. R0 resection was successfully performed. Adjuvant chemotherapy was not administered. After 38 months, computed tomography revealed peritoneal dissemination. The patient received chemotherapy with tegafur-gimeracil-oteracil-potassium (S-1) and gemcitabine. The peritoneal dissemination was successfully controlled for more than 50 months. During the treatment, levels of CEA and CA19-9 kept rising slowly, which was followed by bowel obstruction due to peritoneal dissemination of HCCA. The patient underwent resection of transverse colon with tumor nodules, and the tumor was pathologically diagnosed as metastasis of HCCA. Tumor markers decreased to normal levels, and the patient has been free from tumor relapse for 6 months. Conclusions We here report a rare case of HCCA patient with recurrent peritoneal dissemination 3 years after R0 surgery which was sensitive to chemotherapy. The patient successfully received resection of peritoneal dissemination 50 months after the induction of chemotherapy and survived for 10 years.

Multicystic biliary hamartoma (MCBH) is a rare cystic disease of the liver. We herein report a case of MCBH associated with extremely elevated levels of serum carbohydrate antigen (CA) 19-9. A 53-year-old man was referred to our hospital because of extremely elevated CA19-9 levels (more than 12,000 U/mL). Enhanced abdominal computed tomography and magnetic resonance imaging (MRI) revealed a multicystic tumor with a calcified wall in the left lobe of the liver, although no apparent intracystic nodule was detected. Because of the possibility of a malignant tumor, such as intraductal papillary neoplasm of the bile duct or cystadenocarcinoma, the patient underwent left hepatectomy. Based on the postoperative pathological findings, the lesion was diagnosed as MCBH. The serum CA19-9 level drastically decreased after surgery. We encountered a rare case of MCBH with extremely elevated CA19-9 levels.

Background/aim The prognostic effect of lymph node dissection (LND) in intrahepatic cholangiocarcinoma (ICC) remains unclear. The aim of this study was to reveal the clinical benefits of LND in patients with ICC after curative hepatic resections. Patients and methods We retrospectively analyzed 64 patients with ICC who underwent primary curative resections between June 2002 and February 2016 and evaluated the survival benefits of LND. Results We performed LND on patients suspected to have LN metastasis before operation (23/64 cases; 35.9%). There was no significant difference in prognosis between the LND(+) group (n=22) and the LND(-) group (n=41); relapse-free survival (RFS): p=0.635 and overall survival (OS): p=0.347. Among the groups, pN0 (n=17), pN1 (n=7) and pNX (without LND or LN sampling; n=39), the survival curves of pN0 and pNX groups were similar (p=0.568). Conclusion Special attention should be given to the indication of LND and the practice of secure operation.

Patients with cholangiocarcinoma sometimes show very slow progression and thereby exhibit long-term survival under treatment of the disease. A 72-year-old male with hilar cholangiocarcinoma underwent extended-right hemi-hepatectomy and caudate lobectomy. Pathological finding revealed a well differentiated tumor and carcinoma in situ at the bile duct margin. Routine imaging follow-up was continued for 5 years. Ten years after the surgery, the patient noticed a right-hand chest wall mass formation of 5 cm without any symptoms, and the tumor was diagnosed metastatic cholangiocarcinoma by needle biopsy. Radical resection of the metastatic tumor was performed. The pathological findings of the primary tumor and the metastatic tumor were similar. Three months later, recurrent multiple lesions were identified in the chest wall and the liver. The patient received chemotherapy. We here report a rare case of metastatic cholangiocarcinoma 10 years after hepatectomy with positive ductal margin of carcinoma in situ, implying that rare event of very late recurrence of patients with hilar cholangiocarcinoma should be taken into consideration.

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.

Background Carcinosarcoma is a rare tumor that includes both carcinoma and sarcoma components. It develops commonly in the female reproductive tract, most often in the uterus. However, as there are a small number of similar cases in the English literature, we would like to present a rare case of a carcinosarcoma in Vater’s papilla. Case presentation A 76-year-old female patient was preoperatively diagnosed with a papillary adenocarcinoma in Vater’s papilla by endoscopic biopsy. The patient underwent subtotal stomach-preserving pancreaticoduodenectomy, and postoperative pathological examination diagnosed the carcinosarcoma. The patient received adjuvant chemotherapy with gemcitabine, but multiple liver metastases were found 3 months after the operation. Though chemotherapy with gemcitabine and cisplatin was introduced, she died owing to tumor progression 7 months after the operation. Conclusion Because carcinosarcoma of Vater’s papilla is a rare disease, a suitable treatment strategy has been unclear. We also present a review of the English literature regarding carcinosarcoma of Vater’s papilla.

Background Several reported complications associated with radiofrequency ablation for liver tumors are due to thermal damage of neighboring organs. We herein report a first case of esophageal perforation due to thermal injury of laparoscopic radiofrequency ablation (RFA). Case presentation A 75-year-old woman was treated repeatedly with RFA (percutaneous and laparoscopic) and transcatheter arterial chemoembolization for hepatocellular carcinoma. One week after laparoscopic RFA for recurrent HCC located in segment 2 of the liver, dysphagia and thoracic pain occurred. Upper gastrointestinal endoscopy revealed a perforated esophageal ulcer at the esophago-gastric junction. Inflammation was localized because of severe intra-abdominal adhesion due to repeat surgery, so we decided to treat the patient conservatively. The perforation of the esophagus gradually scarred, and exacerbation did not occur after restarting oral intake. Conclusions When patients with a history of abdominal surgery or intra-abdominal inflammation undergo thermal ablation therapy, caution is required, as there is a possibility of thermal injury of unexpected organs.

Less invasiveness is an important consideration for the treatment of hepatocellular carcinoma (HCC) especially in patients with severe cirrhosis. Between April 2000 and September 2016, 100 patients with liver damage B underwent multimodal radiofrequency ablation (RFA; n = 62) or laparoscopic hepatic resection (Lap-HR; n = 38) for primary HCC as defined by the Milan criteria. We compared the operative outcomes and patients’ survival between the two groups. The RFA group showed worse liver functions as indicated by indocyanine green retention rate (32.9 vs. 22.4%; p

Background Radiofrequency ablation (RFA) is an alternative to hepatic resection and one of the major therapeutic options for hepatocellular carcinoma (HCC). Here, we investigated the long-term outcomes of RFA as an initial treatment for HCC. Patients and methods From January 2000 to December 2014, we treated 1,043 patients with RFA for HCC at the Kumamoto University Hospital; 327 of these patients (31.4%) were treated for primary HCC. After exclusion of 75 patients who underwent combined therapy, data for 252 patients were examined. We retrospectively analyzed the long-term outcomes of RFA and identified factors of poor prognosis. Results The median platelet count, prothrombin activity and indocyanine green retention rate at 15 min were 9.1×104/μl, 83% and 26%, respectively. The 5-year overall survival (OS) rate was 69% and the median survival time was 7.0 years. The 5-year recurrence-free survival (RFS) rate was 17%, and the median RFS was 2.0 years. A multivariate analysis revealed that age >80 years [hazard ratio (HR)=7.76, p=0.011], tumor diameter >2 cm (HR=1.68, p=0.047) and multiple tumors (HR=1.87, p=0.014) were independent prognostic factors for poor OS. For RFS, des-γ-carboxy prothrombin (DCP) ≥40 mAU/ml (HR=1.47, p=0.038) and multiple tumors (HR=1.63, p=0.0056) were independent prognostic factors. Local recurrence at the ablated site occurred in 33/252 patients (13%), and in 33/372 tumors (8.9%). Conclusion Although our cohort included patients with relatively worse liver function, a favorable 5-year survival rate 69% was obtained by RFA. DCP ≥40 mAU/ml and multiple HCCs contribute to a higher risk of recurrence. Patients with these factors should therefore be followed-up intensively.

Background/aim Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer after hepatocellular carcinoma, and has a poor prognosis. Surgical resection is the only option for a cure of ICC. Here we attempted to define the cure rate after hepatic resection for ICC and to identify the predictors for a cure. Patients and methods Among the 96 patients who underwent R0 resections for primary ICC between 1990 and 2011 at the Kumamoto University Hospital and Kyushu University Hospital, those who were followed for ≥5 years after surgery were enrolled. "Cure" was defined as recurrence-free survival (RFS) of ≥5 years after surgery. Results A total of 81 patients were eligible. A cure was achieved in 37 patients (45.7%). The 5-year overall survival and RFS rates were 55.0% and 41.7%, respectively. A multivariate logistic regression analysis identified the absence of lymph node metastasis (relative risk (RR) 7.5, p=0.011) and the absence of microvascular invasion (RR 5.5, p=0.0137) as the independent predictors of achieving a cure. Conclusion R0 resections achieved a cure in 45.7% of this series of ICC patients. The predictors of a cure identified here, i.e., absence of lymph node metastasis and absence of microvascular invasion, could contribute to the selection of patients who are not candidates for adjuvant chemotherapy.

AIM The prognostic value of lymphocyte infiltration into hepatocellular carcinoma (HCC) is still controversial, and it has not been reported in hepatitis B virus (HBV)-positive or non-B non-C (NBNC) HCC. The aim of this study is to assess the prognostic significance of lymphocyte infiltrate in tumor for HBV-positive and NBNC HCC patients. METHODS This study investigated 145 HBV-positive or NBNC patients who underwent hepatectomy for HCC between January 2001 and May 2009. Cumulative recurrence rate, overall survival (OS), and clinicopathological parameters were analyzed according to lymphocyte infiltration in tumor. RESULTS In patients with low lymphocyte infiltration, the 5-year recurrence rate was higher and OS was poor (86.4 and 44.1%, respectively) than that of the patients with high lymphocyte infiltration (55.3 and 83.7%, respectively). Multivariate analyses revealed that independent risk factors for recurrence were low albumin value (hazard ratio [HR] 2.33, P = 0.009), high American Joint Committee on Cancer (AJCC) T stage (HR 2.31, P

Acquired factor V deficiency is a rare condition associated with a wide variety of causes. We herein report the case of a 75-year-old man who developed acquired factor V deficiency associated with gastrointestinal bleeding after transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma. Laboratory data revealed prolonged prothrombin time (PT) and activated partial thromboplastin time (APTT) and a significant reduction in the factor V (FV) activity. Infusion of fresh-frozen plasma (FFP) was unable to correct the prolonged PT and APTT. Four weeks after onset, his coagulation parameters improved spontaneously with no particular treatment. The patient developed acquired FV deficiency after TACE treatment using cisplatin, and thus, cisplatin was suspected as the cause of this coagulopathy. If coagulopathy that is not corrected by FFP transfusion after TACE is observed, acquired factor V deficiency, although extremely rare, should be considered.

Background To compare the survival impacts of radiofrequency ablation (RFA) as an initial treatment for hepatocellular carcinoma (HCC) in patients with impaired liver functional reserve compared to those of hepatic resection (HR). Methods In total, 104 patients with liver damage B as defined by the Liver Cancer Study Group of Japan underwent RFA (n = 33) or HR (n = 71) as an initial treatment for hepatocellular carcinoma. The overall survival (OS) and disease-free survival (DFS) rates were compared, and independent prognostic factors were identified. Results The OS tended to be better in the RFA group than in the HR group. There was no significant difference in the DFS rate between the two groups. Independent poor prognostic factors for OS were tumor size >3 cm and red blood cell transfusion, and those for DFS were aspartate aminotransferase level >35 IU/L and multiple tumors. Subgroup analyses revealed that the OS with RFA was significantly better in patients with aspartate aminotransferase >35 IU/L, serum albumin 99m Tc-galactosyl human serum albumin Conclusions RFA offers comparable results with HR and may be preferable for HCC in the particular setting of liver damage B, especially in those with poorer liver functional reserve.

The incidence of postoperative pancreatic fistula (POPF) remains high at approximately 30% of cases with distal pancreatectomy (DP) and is associated with higher incidence of life-threatening complications. However, the most appropriate closure technique for the pancreatic stump during DP remains controversial. We, herein, present details of the use of a linear stapling device with pre-attached bioabsorbable polyglycolic acid (PGA) felt for pancreatic stump closure during DP. Grade B or C POPF occurred in only one case (5%) among 22 consecutive patients.

The postoperative complication is one of an indicator of poor prognosis in patients with several gastroenterological cancers after curative operations. We, herein, examined prognostic impacts of postoperative complications in patients with intrahepatic cholangiocarcinoma after curative operations. We retrospectively analyzed 60 patients with intrahepatic cholangiocarcinoma who underwent primary curative operations from June 2002 to February 2016. Prognostic impacts of postoperative complications were analyzed using log-rank test and Cox proportional hazard model. Postoperative complications (Clavien-Dindo classification grade 3 or more) occurred in 13 patients (21.7%). Overall survival of patients without postoperative complications was significantly better than that of patients with postoperative complications (p = 0.025). Postoperative complications are independent prognostic factor of overall survival (hazard ratio 3.02; p = 0.030). In addition, bile duct resection and reconstruction (Odds ratio 59.1; p = 0.002) and hepatitis C virus antibody positive (Odds ratio 7.14; p= 0.022), and lymph node dissection (Odds ratio 6.28; p = 0.040) were independent predictors of postoperative complications. Postoperative complications may be an independent predictor of poorer survival in patients with intrahepatic cholangiocarcinoma after curative operations. Lymph node dissection and bile duct resection and reconstruction were risk factors for postoperative complications, therefore we should pay attentions to perform lymph node dissections, bile duct resection and reconstruction in patients with intrahepatic cholangiocarcinoma.

We report two cases of (18)F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) fusion imaging showing false-positive findings of bone metastases from esophagogastric cancer. Although multiple bone metastases from esophagogastric cancer were suggested by several images, ultimately, degeneration of the bone marrow was diagnosed histologically. We discuss the value of imaging modalities and the importance of a comprehensive diagnosis based on a combination of physical examination, laboratory test results, and imaging studies.

The purpose of this study was to determine the relationship between serum zinc (Zn) level and clinicopathological profiles in patients with hepatocellular carcinoma (HCC). Furthermore, we investigate the influence of serum Zn level on the long-term prognosis after hepatectomy. A retrospective analysis was conducted of 310 patients who underwent initial hepatectomy for HCC. The correlation between serum Zn level and preoperative liver functional indicator, pathological features, including the degree of hepatic fibrosis, and perioperative outcome were evaluated. The patients were divided into two groups (serum Zn ≤ 65 mg/dL; n = 71 and Zn > 65 mg/dL; n = 239), and their long-term prognosis were compared. There were strong correlations between preoperative serum Zn level and serum albumin (r = 0.47, P

Graphical abstract, Highlights • A rare case of colon cancer metastasis mimicking IPNB at the extra-hepatic bile duct. • Immunohistochemical staining of cytokeratin was useful to identify the primary site. • There may be an incidental metastatic route via the bile stream from liver metastases., Introduction An accurate diagnosis of the primary cancer in cases with metastatic lesions is quite important because misdiagnosis may lead to the selection of incorrect adjuvant therapy and worse long-term outcomes after surgery. The metastatic sites associated with the dissemination of colon cancer are well known and normally predictable, which includes the lymphatic, haematogenous, or peritoneal regions, while other locations are quite rare. Presentation of case In this report, we present a case of colon cancer with an unusual metastatic pattern mimicking an intraductal papillary neoplasm of the bile duct (IPNB) present in the extra-hepatic bile duct with a cytokeratin (CK)-7–negative and CK-20–positive profile (intestinal type). Discussion In the case of this patient who had a history of colon cancer, immunohistochemical staining for the CKs was useful for distinguishing between primary IPNB and colon cancer metastases. We suspect that the metastatic pattern of this case of colon cancer that mimicked IPNB at the extra-hepatic bile duct developed incidentally via the bile stream. Conclusion This is a rare case of colon cancer metastasis mimicking IPNB at the extra-hepatic bile duct. Our findings also suggest that there may be an incidental 4th metastatic route via the bile stream.

Background /Objectives: Enoxaparin is low-molecular-weight heparin that is used for postoperative thromboprophylaxis. The purpose of this study was to evaluate the efficacy and safety of enoxaparin after pancreatic resection. We additionally carried out a literature review regarding venous thromboembolism (VTE) and postoperative bleeding mainly after hepatobiliary-pancreatic surgery. Methods This was a prospective, single-arm study. Patients aged 20–79 years who planned to undergo pancreatic resection followed by postoperative anticoagulation therapy with enoxaparin were enrolled from 2013 to 2016. The exclusion criteria were low renal function, active bleeding, clinical signs of VTE at screening, or evidence of thromboembolic disease before surgery. The primary endpoint was the incidence of postoperative VTE. The secondary endpoint was the incidence of postoperative complications. For the literature review, PubMed was searched for relevant articles and the PRISMA guidelines were used. Results In total, 103 patients were analyzed. Two patients (1.9%) developed asymptomatic VTE, and no patients developed symptomatic VTE. No in-hospital mortality occurred. Morbidities (Clavien–Dindo grade ≥ IIIa) occurred in 29 patients (28.1%). Three patients (2.9%) developed intra-abdominal hemorrhage due to pseudoaneurysm formation after pancreaticoduodenectomy or distal pancreatectomy. The literature review included nine articles, and all indicated that the results of this study were feasible. Conclusion This is the first prospective trial to focus on pharmacologic prophylaxis with enoxaparin after pancreatic surgery. Postoperative anticoagulant therapy with enoxaparin was used in patients who underwent pancreatic surgery with a low incidence of VTE and no increase in postoperative bleeding events compared with existing evidence.

Background & Aims: HCC risk-predictive biomarkers will enable identification of patients who most need close monitoring and cancer preventive intervention. We previously reported a stromal liver gene signature predictive of HCC risk in multiple independent patient cohorts mainly affected with HCV (Hoshida 2008, Hoshida 2013, King 2014). We aimed to determine whether the gene signature is similarly prognostic in HBV, alcohol abuse, and NAFLD/NASH patients. Methods: The liver gene signature was analyzed using an FDA-approved diagnostic platform (NanoString), and an independent cohort of curatively resected early-stage HCC patients (n=223, median follow up 4.5 years, HCV [n=67, 30%], HBV [n=39, 17%], alcohol [n=51, 23%], NAFLD [n=66, 30%], and NASH [n=52, 23%, a subset of 66 NAFLD patients]) were analyzed. Complete surgical resection was radiologically and histologically confirmed, and HCC recurrence in the cohort was confirmed to be mainly late recurrence, i.e., de novo carcinogenesis, based on a recurrence hazard plot. Prognostic prediction was performed by using a previously developed model without making any modification, and evaluated for association with de novo HCC recurrence in multivariable modeling and subgroup analyses. Results: The gene signature assay classified the patients into high- (n=49, 22%), intermediate- (n=127, 57%), and low- (n=47, 21%) risk groups. The high-risk prediction was associated with higher HCC recurrence (HR=4.8, p&lt0.001) as well as overall death (HR=4.8, p&lt0.001) in multivariable modeling. The association with HCC risk remained significant in subgroups of patients with HCV (HR=3.0, p=0.028), HBV (HR=6.1, p&lt0.001), alcohol (HR=6.1, p=0.023), and NASH (HR=10.9, p=0.03) in multivariable models including cirrhosis and AJCC stage 2/3. The association was diminished in NAFLD patients (HR=3.02, p=0.16), suggesting that presence of active inflammation and/or fibrosis is critical for the signature to predict HCC risk in NAFLD. Established cirrhosis was less frequent in NAFLD/NASH (23%/21%) compared to other etiologies (50%). Conclusions: The prognostic liver gene signature was implemented in a clinically applicable assay, and successfully validated for de novo HCC recurrence after curative resection of early-stage HCC in all major etiologies of chronic liver disease and HCC. The assay will enable prioritization of patients for HCC surveillance and enrichment of high risk patients for more cost-effective clinical trials of new HCC chemopreventive therapies. Citation Format: Shigeki Nakagawa, Naoki Umesaki, Takanobu Yamao, Yuki Kitano, Kensuke Yamamura, Kota Arima, Tatsunori Miyata, Takayoshi Kaida, Yujin Hoshida, Katsunori Imai, Daisuke Hashimoto, Yo-ichi Yamashita, Akira Chikamoto, Hideo Baba. A stromal liver gene signature predictive of HCC risk across all liver disease etiologies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5000. doi:10.1158/1538-7445.AM2017-5000

741 Background: The number of patients with colorectal cancer has been increasing in all over the world. Approximately 10 percent of CRC is complicated by obstructive symptoms at the time of their diagnosis. Obstructive colorectal cancer (OCRC) could be a fatal because of perforation peritonitis or sepsis, and it is necessary to immediate treatment. The aim of this study was to explore the treatment strategies for patients with OCRC. Methods: Between April 2008 and December 2014, six hundred seventy two patients underwent surgery in out institute. The numbers of OCRC were 82 cases (12.2%). We evaluated the feasibility and effectiveness of our treatments for OCRC. Results: Treatment strategies were adopted according to the location of CRC. For patients with right-sided OCRC, we performed one-stage surgery. They underwent primary tumor resection and anastomosis at the same time. For left-sided OCRC, patients were treated by two-stage surgery. At first, they were managed by decompression of their colon with colostomy or transanal ileus tube, and then, underwent colectomy. The cases of right-side OCRC were 23 cases, and all of them underwent one-stage surgery. We could find no cases of anastomotic leakage in these cases. The cases of left-side OCRC were 59 cases, and 50 patients (86%) of them were treated two-stage surgery. Stage IV OCRC patients tended to undergo colostomy only. Conclusions: One-stage surgery was feasible for patients with right-sided OCRC. For left-sided OCRC cases, two-stage surgery was effective to prevent perioperative complications.