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Patients diagnosed with resectable pancreatic ductal adenocarcinoma often experience early recurrence even after upfront R0 resection. This study aimed to define early recurrence and identify preoperative risk factors for early recurrence after upfront pancreaticoduodenectomy in patients with resectable pancreatic ductal adenocarcinoma of the pancreatic head.This multicenter, retrospective study involved 500 patients who underwent pancreaticoduodenectomy resectable pancreatic ductal adenocarcinoma of the pancreatic head at 10 institutions between 2007 and 2016. Preoperative, intraoperative, and postoperative clinicopathological results were compared between early and non-early recurrence groups. Predictors of early recurrence were determined using statistical analyses.Log-rank tests revealed a significant difference (P.001) between recurrence within 3 to 6 months and 6 to 9 months. Early recurrence was subsequently defined as recurrence within 6 months. Patients were categorized into early recurrence (n = 104) and non-early recurrence groups (n = 389). The median overall survival of the early and non-early recurrence groups was 8.6 months and 42.6 months (P.001), respectively. Preoperatively, high carbohydrate antigen 19-9 levels ≥120 U/mL, retroperitoneal invasion, and diabetes mellitus were identified as independent predictive risk factors for early recurrence according to multivariate analysis. Comparing survival rates among patients with 3, 2, 1, or none of these factors, the median overall survival was 17.6 (n = 90), 21.2 (n = 184), 47 (n = 141), and 61.5 (n = 73) months, respectively.The optimal period that defines the early recurrence for resectable pancreatic ductal adenocarcinoma of the pancreatic head is 6 months. Tumor size ≥20 mm, preoperative carbohydrate antigen 19-9 levels ≥120 U/mL, retroperitoneal invasion of the tumor, and the presence of diabetes mellitus are independently associated with early recurrence.

Effects of YAP overexpression on phosphorylation of Erk1/2 in HuH1 cells.

Supplemental methods

Supplementary Figure Legends

Knockdown of TAZ or YAP expression by siRNA duplex oligonucleotides.

Transcriptional coactivator with PDZ-binding motif (TAZ) and yes-associated protein (YAP) are equivalently placed downstream effectors of the Hippo pathway with oncogenic roles in human cancers. However, the expression profiles of TAZ/YAP differ depending on the cancer cell type, suggesting that these proteins have different roles during cancer progression, yet no studies have examined the biologic significance of the balance between TAZ and YAP expression levels. Here we examined the functional roles of TAZ/YAP in hepatocellular carcinoma progression. We found that TAZ, but not YAP, was predominantly expressed in HCC. TAZ knockdown under normal conditions attenuated cell growth in HCC cells; however, TAZ knockdown combined with 5-fluorouracil treatment significantly increased chemoresistance compared with control cells. Notably, TAZ knockdown induced compensatory YAP expression and was accompanied by upregulation of CD90, a HCC–specific cancer stem cell marker. Continuous treatment with 5-fluorouracil also induced YAP expression and promoted tumor formation in vivo. Conversely, double knockdown of TAZ/YAP reduced chemoresistance and tumorigenicity. Moreover, YAP knockdown aggravated HCC cell growth to a greater degree than TAZ knockdown, and YAP overexpression was strongly associated with poor prognoses in patients with HCC. Collectively, these studies demonstrate that TAZ and YAP exhibit different functional roles in cancer progression, and a shift to predominant YAP expression upon TAZ depletion conferred cancer stem cell–like properties including chemoresistance and tumorigenicity in HCC. Therefore, targeting of both TAZ/YAP will be required for a complete antitumor response in HCC. Cancer Res; 75(22); 4985–97. ©2015 AACR.

Changes in cyclin D1 mRNA expression by TAZ knockdown in HCC cells

Characteristics of 110 patients with hepatocellular carcinoma

Association between TAZ or YAP mRNA expression and patient's characteristics in hepatocellular carcinoma

YAP knockdown in other gastrointestinal cancer cells (SW620 and TE-1 cells) with high YAP expression.

qPCR analysis of EpCAM, CD133, and CD44 expressions in response to TAZ knockdown.

BACKGROUND: Liver inflammation is a reaction to disease-causing stress in the liver that induces fibrosis and cirrhosis. However, its prognostic impact after hepatectomy remains unclear. This study aimed to evaluate the prognostic and oncologic impacts of liver inflammation on patients after curative hepatectomy for hepatocellular carcinoma (HCC). METHODS: The study enrolled 500 consecutive patients with primary HCC who underwent curative and primary hepatectomy. Patient characteristics and prognoses were evaluated according to histologic liver inflammation assessed by the New Inuyama Classification. RESULTS: Severe liver inflammation (A3) was observed in 97 patients (19.4%) and nonsevere liver inflammation (A0-2) in 403 patients (80.6%). The patients with A3 had a significantly poorer prognosis than those with A0-2 in terms of relapse-free survival (p < 0.0001, log-rank) and overall survival (p = 0.0013, log-rank). The study showed that A3 is an independent poor prognostic factor (hazard ratio, 1.36; 95% confidence interval [Cl], 1.02-1.81; p = 0.039), and that Child-Pugh grade B and multiple tumors are associated with relapse-free survival. Furthermore, The significant predictors of early recurrence (within 2 years after hepatectomy) were A3 (odds ratio, 2.10; 95% CI, 1.25-3.55; p = 0.005), a des-I³-carboxyprothrombin level higher than 40 mAU/mL, and multiple tumors. CONCLUSIONS: Severe liver inflammation was associated with poor short- and long-term prognoses independently of cirrhosis. Controlling liver inflammation in the perioperative period may be essential to improving the prognosis of patients with HCC after hepatectomy.

Falling is a representative incident in hospitalization and can cause serious complications. In this study, we constructed an algorithm that nurses can use to easily recognize essential fall risk factors and appropriately perform an assessment. A total of 56,911 inpatients (non-fall, 56,673; fall; 238) hospitalized between October 2017 and September 2018 were used for the training dataset. Correlation coefficients, multivariable logistic regression analysis, and decision tree analysis were performed using 36 fall risk factors identified from inpatients. An algorithm was generated combining nine essential fall risk factors (delirium, fall history, use of a walking aid, stagger, impaired judgment/comprehension, muscle weakness of the lower limbs, night urination, use of sleeping drug, and presence of infusion route/tube). Moreover, fall risk level was conveniently classified into four groups (extra-high, high, moderate, and low) according to the priority of fall risk. Finally, we confirmed the reliability of the algorithm using a validation dataset that comprised 57,929 inpatients (non-fall, 57,695; fall, 234) hospitalized between October 2018 and September 2019. Using the newly created algorithm, clinical staff including nurses may be able to appropriately evaluate fall risk level and provide preventive interventions for individual inpatients.

Background Hepatocellular carcinoma has a high recurrence rate even after curative surgery, and hepatocellular carcinoma risk–predictive biomarkers will enable identification of patients who most need close monitoring and cancer-preventive intervention. Hepatocellular carcinoma has 2 different recurrence patterns—a multicentric recurrence and an intrahepatic metastasis. We have reported that the molecular gene signature from the gene expression of adjacent liver can be used to predict multicentric recurrence of hepatocellular carcinoma, but the signature to predict recurrence from intrahepatic metastasis has not been established. We aimed to identify the recurrence from intrahepatic metastasis gene signature from the gene expression of tumor to predict recurrence from intrahepatic metastasis. Methods The intrahepatic metastasis-risk signature was created based on the exhaustive analysis using a microarray transcriptome database of hepatocellular carcinoma. The intrahepatic metastasis-risk signature was measured in a cohort of 80 hepatocellular carcinoma patients, and the correlation with hepatocellular carcinoma recurrence and overall survival and each gene signature were analyzed and validated. Results The gene signature assay classified the patients into high- (n = 20), intermediate- (n = 40), and low-risk (n = 20) groups. The high-risk prediction was independently associated with higher early hepatocellular carcinoma recurrence (hazard ratio = 3.7, P = .03) in multivariable modeling adjusted by tumor size, tumor number, and microvascular invasion. Gene set enrichment analysis demonstrates that the gene sets associated with “cell cycle” or “histone modulation” are highly enriched in the high intrahepatic metastasis gene signature group Conclusion The intrahepatic metastasis gene signature predicts early recurrence and is associated with malignant potential related to the promoted cell cycle.

The aim of this study was to show the real impact of perioperative red blood cell transfusion (PBT) on prognosis in patients who underwent pancreatectomy for pancreatic ductal adenocarcinoma.Patients who underwent pancreatectomy between 2004 and 2018 were enrolled. Short- and long-term outcomes in patients who received PBT (PBT group) were compared with those who did not (non-PBT group).From a total of 197 patients, 55 (27.9%) received PBT, and 142 (72.1%) did not. The PBT group displayed a higher level of carbohydrate antigen 19-9 (P = 0.02), larger tumor size (P0.001), and a higher rate of lymph node metastasis (P = 0.02), and underwent more frequent pancreaticoduodenectomy (P0.001) and portal vein resection (P0.001). Before matching, recurrence-free survival (RFS) and overall survival (OS) in the PBT group were significantly worse than the non-PBT group (RFS: hazard ratio [HR], 1.73 [P = 0.002]; OS: HR, 2.06 [P0.001]). After matching, RFS and OS in the PBT group were not significantly different from the non-PBT group (RFS: HR, 1.44 [P = 0.15]; OS: HR, 1.53 [P = 0.11]).Our results show that PBT has no survival impact in patients who underwent pancreatectomy for pancreatic ductal adenocarcinoma.

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

Total pancreatectomy is required to completely clear tumours that are locally advanced or located in the centre of the pancreas. However, reports describing clinical outcomes after total pancreatectomy are rare. The aim of this retrospective observational study was to assess clinical outcomes following total pancreatectomy using a nationwide registry and to create a risk model for severe postoperative complications.Patients who underwent total pancreatectomy from 2013 to 2017, and who were recorded in the Japan Society of Gastroenterological Surgery and Japanese Society of Hepato-Biliary-Pancreatic Surgery database, were included. Severe complications at 30 days were defined as those with a Clavien-Dindo grade III needing reoperation, or grade IV-V. Occurrence of severe complications was modelled using data from patients treated from 2013 to 2016, and the accuracy of the model tested among patients from 2017 using c-statistics and a calibration plot.A total of 2167 patients undergoing total pancreatectomy were included. Postoperative 30-day and in-hospital mortality rates were 1·0 per cent (22 of 2167 patients) and 2·7 per cent (58 of 167) respectively, and severe complications developed in 6·0 per cent (131 of 2167). Factors showing a strong positive association with outcome in this risk model were the ASA performance status grade and combined arterial resection. In the test cohort, the c-statistic of the model was 0·70 (95 per cent c.i. 0·59 to 0·81).The risk model may be used to predict severe complications after total pancreatectomy.La pancreatectomía total está indicada cuando se requiere la resección completa de tumores localmente avanzados o ubicados en el centro del páncreas. Sin embargo, existen pocos artículos que describan los resultados clínicos después de una pancreatectomía total. El objetivo de este estudio observacional retrospectivo fue evaluar los resultados clínicos después de una pancreatectomía total utilizando un registro nacional y crear un modelo de riesgo de complicaciones postoperatorias graves. MÉTODOS: Se incluyeron aquellos pacientes que se sometieron a una pancreatectomía total entre 2013 y 2017 y que fueron registrados en la base de datos de la Sociedad Japonesa de Cirugía Gastrointestinal y de la Sociedad Japonesa de Cirugía Hepato-Bilio-Pancreática. Las complicaciones graves a los 30 días se definieron como Clavien-Dindo grado III con reintervención o grado IV/V. Se analizó la aparición de complicaciones graves de los pacientes desde 2013 a 2016 y se evaluó la precisión del modelo entre los pacientes operados desde 2017 usando estadísticos c y un gráfico de calibración.Se incluyeron 2.167 pacientes sometidos a una pancreatectomía total. La mortalidad postoperatoria a los 30 días y la mortalidad hospitalaria fueron del 1,0% (22/2167) y del 2,7% (58/2167), respectivamente, y las complicaciones graves ocurrieron en el 6,0% (131/2167) de los pacientes. Los factores que mostraron una fuerte asociación positiva con los resultados en este modelo de riesgo fueron el estado funcional según la Sociedad Americana de Anestesiología y la resección arterial combinada. En la cohorte de prueba, el estadístico c del modelo fue de 0,70 (i.c. del 95% 0,59-0,81). CONCLUSIÓN: El modelo de riesgo puede usarse para predecir las complicaciones graves después de una pancreatectomía total.

In this study, we reviewed our experiences and previous studies on surgery for recurrent cholangiocarcinoma (CCA).We analyzed outcomes of 117 patients with recurrent CCA between 2000 and 2015. Twenty-one patients (17.9%) underwent surgical resection for recurrence, and the remaining 96 patients (82.1%) did not undergo resection. We evaluated patients' clinicopathological features and prognoses between the two groups.Patients who underwent surgery were significantly associated with better overall survival after recurrence (HR = 0.22, P 0.0001). In patients with recurrent CCA, surgery for recurrence was an independent better prognostic factor after recurrence (HR = 0.27, P = 0.0002), and in patients who underwent surgery for recurrent CCA, the presence of lymph node metastasis of primary cancer was an independent worse prognostic factor (HR = 9.45, P = 0.04).Surgery for recurrent CCA may provide good survival impact in selected patients. Patients with lymph node metastasis of primary CCA should not undergo surgery for recurrent CCA.

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

Although the relationship between cardiovascular diseases and malignant diseases has recently attracted attention, the associations of cardiovascular risk factors and clinical outcomes in cancer patients remain to be elucidated. We performed a retrospective, observational study that explored the clinical outcomes of patients with cancer or with a history of cancer. We enrolled 30,706 consecutive adult cancer patients from Kumamoto University Hospital. We investigated mortality and morbidity, including cardiovascular conditions (dyslipidemia [DL]/diabetes mellitus [DM]/hypertension [HT]). The primary endpoint was all-cause mortality. Of the enrolled patients, 9032 patients (29.4%) died within the follow-up period. The Kaplan–Meier analysis demonstrated that in the groups classified according to the number of DL/DM/HT (LDH) factors, the LDH1 and LDH2 groups had a significantly higher probability of the primary endpoint than the LDH0 group (P

Falling is a representative incident in hospitalization and can cause serious complications. In this study, we constructed an algorithm that nurses can use to easily recognize essential fall risk factors and appropriately perform an assessment. A total of 56,911 inpatients (non-fall, 56,673; fall; 238) hospitalized between October 2017 and September 2018 were used for the training dataset. Correlation coefficients, multivariable logistic regression analysis, and decision tree analysis were performed using 36 fall risk factors identified from inpatients. An algorithm was generated combining nine essential fall risk factors (delirium, fall history, use of a walking aid, stagger, impaired judgment/comprehension, muscle weakness of the lower limbs, night urination, use of sleeping drug, and presence of infusion route/tube). Moreover, fall risk level was conveniently classified into four groups (extra-high, high, moderate, and low) according to the priority of fall risk. Finally, we confirmed the reliability of the algorithm using a validation dataset that comprised 57,929 inpatients (non-fall, 57,695; fall, 234) hospitalized between October 2018 and September 2019. Using the newly created algorithm, clinical staff including nurses may be able to appropriately evaluate fall risk level and provide preventive interventions for individual inpatients.

Background Radiofrequency ablation (RFA) is widely used as a minimally invasive treatment for hepatocellular carcinoma (HCC). RFA has a low risk of complications, especially compared with liver resection. Nevertheless, various complications have been reported after RFA for HCC; however, diaphragmatic hernia (DH) is extremely rare. Case presentation A 78-year-old man underwent thoracoscopic RFA for HCC located at the medial segment adjacent to the diaphragm approximately 7 years before being transported to the emergency department due complaints of nausea and abdominal pain. Computed tomography revealed a prolapsed small intestine through a defect in the right diaphragm, and emergency surgery was performed. The cause of diaphragmatic hernia was the scar of RFA. We confirmed that the small intestine had prolapsed into the right diaphragm, and we resected the necrotic small intestine and repaired the right diaphragm. Herein, we report a case of ileal strangulation due to diaphragmatic hernia after thoracoscopic RFA. Conclusions Care should be taken when performing thoracoscopic RFA, especially for tumors located on the liver surface adjacent to the diaphragm. Patients should be carefully followed up for possible DH, even after a long postoperative interval.

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.

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.

A decrease in skeletal muscle mass and function, defined as sarcopenia, is associated with poor postoperative outcome in patients with cancers. Although systemic or local immune status impacts cancer progression, the relationship between sarcopenia and these statuses remains unclear. The aim of this study is to investigate the clinical impact of sarcopenia and its relationship to immune systems in patients with extrahepatic cholangiocarcinoma (ECC). A total of 110 consecutive ECC patients with curative resection between 2005 and 2014 were enrolled. Sarcopenia was determined from skeletal muscle index, assessed by a L3 skeletal muscle mass on axial computed tomography images, and their relationships with patients’ clinicopathological characteristics and survival were evaluated. Systemic immune status was calculated using preoperative laboratory data, and tumor-infiltrating (TI) immune cells (CD8+ T cells, CD66b+ neutrophils, CD163+ M2 macrophages) assayed by immunohistochemistry, and their relationship to sarcopenia were evaluated. Sarcopenia was present in 31 patients (28.2%). Patients with sarcopenia had a worse recurrence-free survival (HR 1.87, p = 0.009) and overall survival (OS) (HR 2.47, p = 0.0004) than patients without sarcopenia. Moreover, patients with sarcopenia had a higher level of platelet–lymphocyte ratio (159 vs. 119; p = 0.003) and lower number of TI CD8+ T cells (47 vs. 66 cells/spot; p = 0.03) than patients without sarcopenia. On multivariate analysis, the presence of sarcopenia (HR 2.60, p = 0.0008) was an independent predictor of poor OS. Our data showed that sarcopenia and systemic or local immune cells may interact with each other and play a pivotal role in clinical outcomes of patients with ECC.

We report a 64-year-old woman with a 9-cm liver tumor in the left lateral section. The patient had neither hepatitis B or C virus infection, nor cirrhosis. Carbohydrate antigen 19-9 (CA 19-9) level was 1,889 U/ml. We also suspected bulky hilar lymph node metastasis, and a left lateral sectionectomy without lymph node dissection (R2) was performed. The pathological findings led to diagnosis of combined hepatocellular and cholangiocarcinoma. Three weeks post-operation, the patient underwent hepatic arterial infusion chemotherapy with cisplatin, fluorouracil, and mitomycin C. In addition, a total dose of 45 Gy of irradiation for the hilar lymph node was performed; while oral tegafur-uracil (UFT) has been administered for 10 years at a dose of 400 mg/day. The CA19-9 level of the patient was normalized after hepatectomy, hepatic arterial infusion, irradiation for hilar lymph node, and oral UFT administration. Currently, the patient is alive without any relapse for 12 years post-operation.

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.

After initial pancreatic resection, local recurrence of pancreatic cancer (PC) or new primary PC can develop in the remnant. There are limited data available regarding this so-called remnant PC. The aim of this retrospective study was to clarify the clinical features and establish a treatment strategy for remnant PC. A multicenter retrospective study with the Kyushu Study Group of Clinical Cancer was carried out. Clinical data from 50 patients who developed remnant PC were analyzed. RAS mutation analysis of the initial tumor and of remnant PC was performed in 17 cases. The initial pancreatic resections were performed for 37 invasive ductal carcinomas, and for 13 other tumors. Thirty-seven patients underwent a second pancreatectomy for remnant PC (resected group), while thirteen patients were not operated (unresected group). The median overall survival times were 42.2 months in the resected group and 12.3 months in the unresected group (HR 0.374; 95% CI 0.17–0.83). In RAS mutation analysis, 14 cases had at least 1 missense variant of KRAS, HRAS, or NRAS in the initial pancreatic tumor and/or remnant PC. The same missense variants between the initial tumor and remnant PC were discovered only in KRAS of one patient, and in HRAS of one patient. No case had completely consistent missense variants between the initial tumor and remnant PC. This study found that repeated pancreatectomy for remnant PC can prolong patient survival, and RAS mutation analysis indicated that many remnant PCs are developed from metachronous multifocal origins.

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.

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.

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.

A 54-year-old woman finished the treatment for chronic hepatitis C and achieved sustained virological response. She was identified with some tumor lesions at her liver during follow-up observation by ultrasonography. From contrast-enhanced computed tomography, there were four tumors at sub-segment 4/5, S5, S6, and S7. These lesions are slightly enhanced on arterial phase and washed out on delayed phase. Contrast-enhanced magnetic resonance imaging showed slight enhancement on arterial phase and defect on hepatocyte phase. Tumor markers including alpha fetoprotein, Des-Gamma-Carboxy Prothrombin, carcinoembryonic antigen, and carbohydrate antigen (CA19-9) were within normal range. The patient underwent partial hepatectomies of four tumors at S4/5, S5, S6, and S7. The patient was recovering well, so he discharged our hospital after 10 days from the operation. The histological assay of the resected specimen showed accumulation of lymphocyte with hyperplasia of lymphoid follicles accordant with tumor lesions. Immunohistochemical staining assay revealed a positive for CD3, CD20, CD10, and bcl-2. These findings eventually made a diagnosis of all four tumors as mucosa-associated lymphoid tissue lymphoma. Since previously published case reports and our case described nonspecific clinical features of this rare disease, it was difficult to get the certain diagnosis before histological confirmation and non-anatomical partial liver resection may be a good choice for both diagnosis and local therapy.