Risk Factors for Hepatocellular Carcinoma After Splenectomy in Liver Cirrhotic Patients.

BACKGROUND: Splenectomy is sometimes indicated for portal hypertension caused by cirrhosis, which is a risk for hepatic carcinogenesis. This study aimed to identify risk factors for hepatocellular carcinoma (HCC) development after splenectomy. METHODS: This retrospective study included 65 patients who underwent splenectomy for portal hypertension between 2009 and 2017. Cox regression analyses were performed to identify factors related to HCC development after splenectomy. The predictive index for HCC development was constructed from the results of multivariate analysis, and 3 risk-dependent groups were defined. Discrimination among the groups was estimated using Kaplan-Meier curves and the log-rank test. RESULTS: Post-splenectomy, 36.9% of patients developed HCC. In the univariate analysis, the etiology of cirrhosis (hepatitis C virus antibody, P = .005, and hepatitis B surface antigen, P = .008, referring to non-B and non-C patients, respectively), presence of HCC history (P < .001), and preoperative hemoglobin level (P = .007) were related to HCC development, and the presence of HCC history (P = .002) and preoperative hemoglobin level (P = .022) were independent risk factors. The predictive index classified three groups at risk; the hazards in each group were significantly different (low vs middle risk, P = .035, and middle vs high risk, P = .011). DISCUSSION: The etiology of cirrhosis, presence of HCC history, and hemoglobin level were associated with HCC development after splenectomy. The predictive model may aid in HCC surveillance after splenectomy for patients with portal hypertension.

Downregulation of thrombomodulin contributes to ischemia-reperfusion injury in mice with steatotic liver.

AIM: Ischemia-reperfusion (IR) injury is one of the most critical complications commonly associated with liver surgery, including liver transplantation. Steatotic livers are particularly vulnerable to IR injury. However, the underlying mechanisms of this increased susceptibility have not fully been understood. In the present study, we used heterogeneous thrombomodulin (TM)-knockout (KO) (TM+/- ) mice, which express about 50% functional activity of TM as compared with wild type, to investigate whether dysregulation of TM enhances IR injury in steatotic livers. METHODS: Steatotic livers were induced using choline-deficient diets (CDD) in mice. The biological activity of TM was assessed using the productivity of protein C. Susceptibility to IR injury was compared between steatotic livers and non-steatotic livers and also assessed in TM-KO mice. We investigated whether recombinant TM (rTM) and the lectin-like domain of TM (rTM-D1) ameliorated IR injury in steatotic livers. RESULTS: Protein C activity was significantly decreased to less than 20% in CDD-fed mice compared with mice with non-steatotic livers. Steatotic livers showed exaggerated IR injury compared with non-steatotic livers. Recombinant TM (rTM) and the lectin-like domain of TM (rTM-D1), which has anti-inflammatory effects, ameliorated IR injury in steatotic livers. TM+/- mice showed increased susceptibility to IR injury, and rTM ameliorated the increased IR injury in TM+/- mice. CONCLUSION: We conclude that downregulation of TM increases susceptibility to hepatic IR injury in steatotic livers and that rTM ameliorates hepatic IR injury through anti-inflammatory action.

Application of MinION Amplicon Sequencing to Buccal Swab Samples for Improving Resolution and Throughput of Rumen Microbiota Analysis.

The Illumina MiSeq platform has been widely used as a standard method for studying the rumen microbiota. However, the low resolution of taxonomic identification is the only disadvantage of MiSeq amplicon sequencing, as it targets a part of the 16S rRNA gene. In the present study, we performed three experiments to establish a high-resolution and high-throughput rumen microbial profiling approach using a combination of MinION platform and buccal swab sample, which is a proxy for rumen contents. In experiment 1, rumen contents and buccal swab samples were collected simultaneously from cannulated cattle (n = 6) and used for microbiota analysis using three different analytical workflows: amplicon sequencing of the V3-V4 region of the 16S rRNA gene using MiSeq and amplicon sequencing of near full-length 16S rRNA gene using MinION or PacBio Sequel II. All reads derived from the MinION and PacBio platforms were classified at the species-level. In experiment 2, rumen fluid samples were collected from beef cattle (n = 28) and used for 16S rRNA gene amplicon sequencing using the MinION platform to evaluate this sequencing platform for rumen microbiota analysis. We confirmed that the MinION platform allowed species-level taxa assignment for the predominant bacterial groups, which were previously identified at the family- and genus-level using the MiSeq platform. In experiment 3, buccal swab samples were collected from beef cattle (n = 30) and used for 16S rRNA gene amplicon sequencing using the MinION platform to validate the applicability of a combination of the MinION platform and buccal swab samples for rumen microbiota analysis. The distribution of predominant bacterial taxa in the buccal swab samples was similar to that in the rumen samples observed in experiment 2. Based on these results, we concluded that the combination of the MinION platform and buccal swab samples may be potentially applied for rumen microbial analysis in large-scale studies.

Crystallization of charged gold particles mediated by nonadsorbing like-charged polyelectrolyte.

We report that the aqueous dispersions of negatively charged submicron-sized colloidal Au particles formed non-close-packed colloidal crystals by the addition of a like-charged linear polyelectrolyte, sodium polyacrylate (NaPAA). Au particles often form irregular aggregates in dispersions because of a strong van der Waals force acting between them. To prevent aggregation, we introduced negative electric charges on particle surfaces. By the addition of NaPAA, colloidal crystals were formed on the bottom of a sample cell because of the supply of Au particles by sedimentation and 2D diffusion even under very dilute conditions. Interparticle potential calculations demonstrated that the addition of NaPAA caused depletion attraction between the particles as well as a significant reduction in the interparticle repulsion because of the electrostatic screening effect. However, the electrostatic repulsion was strong enough to prevent the direct contact of particles in the excluded region between Au particles. Large-area crystals could be obtained by tilting the sample cell. By drying the sample, the Au particles came into contact and the non-space-filling crystals changed into closest packed crystals. These closest packed crystals exhibited a significant enhancement of Raman scattering intensity because of high hot-spot density.

Acute diffuse thyroid swelling after fine-needle aspiration: A case report and review of the literature.

Fine-needle aspiration (FNA) is the first-line and a cost-effective examination method of nonfunctional thyroid nodules. Acute transient thyroid swelling after an FNA is a rare complication, and to date, only 14 cases have been reported in the English literature. Herein, we report a case of a 26-year-old woman with acute transient thyroid swelling, which occurred after an ultrasound-guided FNA of a thyroid nodule. Although the patient had undergone an FNA without complication 2 years previously, the second FNA caused acute thyroid swelling. The present case emphasizes the potential risk of acute thyroid swelling associated with every FNA procedure.

Laparoscopic excision of a solitary fibrous tumor originating from the abdominal wall: a case report.

Solitary fibrous tumors (SFTs) are mesenchymal fibroblastic tumors, and forms of SFTs that originate from the abdominal wall are extremely rare. Here we report a case of a nonpalpable SFT along the abdominal wall. Abdominal magnetic resonance (MR) imaging showed a well-circumscribed mass measuring 5 cm in diameter with heterogeneous signal intensity on T2-weighted MR images; this mass was diagnosed as a benign abdominal tumor of unknown origin. Successful laparoscopic excision of the tumor was performed. Histological examination revealed a benign extrapleural SFT. No tumor recurrence was observed after 20-month follow-up. This is the first case of laparoscopic excision of an SFT originating from the abdominal wall. Our report highlights the safety and usefulness of laparoscopic excision of abdominal wall tumors such as SFTs. This approach is an underutilized surgical treatment that can be applied to select cases of SFT in the abdominal cavity.

Successful diagnosis and treatment of double common bile duct with cholelithiasis by laparoscopic cholecystectomy.

Double common bile duct (DCBD) is an extremely rare congenital anomaly of the biliary system associated with serious complications. An association between DCBD and inadvertent bile duct injury during surgery has been reported. However, DCBD is difficult to diagnose preoperatively. We report a rare case of DCBD (type 3b), combined with cholelithiasis and cholecystitis, diagnosed preoperatively, and treated safely by laparoscopic cholecystectomy. A 79-year-old woman was admitted with a 1-week history of chest pain. Abdominal computed tomography revealed gallbladder distension with obvious wall thickening. Laparoscopic cholecystectomy was planned to determine the presence of stones in the common bile duct and an anomalous biliary tract. Magnetic resonance cholangiopancreatography (MRCP) was performed, and anomalous anatomy of the biliary tract was suspected. Drip infusion cholangiography with computed tomography (DIC-CT) showed type 3b DCBD. On hospital day 7, laparoscopic cholecystectomy was performed without accessory common bile duct resection. The postoperative course was uneventful, and the patient was discharged on postoperative day 5. To our knowledge, this is the first report of the successful diagnosis of DCBD using DIC-CT. MRCP and DIC-CT can be useful for the pre-operative diagnosis of DCBD to decrease the risk of bile duct injury during surgery.

Impact of postoperative bile leakage on long-term outcome in patients following liver resection for hepatocellular carcinoma.

BACKGROUND/PURPOSE: The incidence of bile leakage after liver resection for hepatocellular carcinoma (HCC) remains a cause for concern. There are limited reports on the impacts of postoperative bile leakage on long-term clinical outcomes. This study aims to evaluate the effects of postoperative bile leakage on recurrence-free survival (RFS) and overall survival (OS). METHODS: A total of 1,178 patients who underwent curative liver resection for HCC between 1986 and 2012 were included in the present study. Postoperative bile leakage was defined using the International Study Group of Liver Surgery definition, and the primary end points of the study were OS and RFS at 5 years. RESULTS: Forty-three (3.7%) patients had bile leakage following liver resection. The median follow-up was 5 years. A follow-up analysis revealed that patients with bile leakage had poor 5-year rates of OS (41.0% vs 56.4%, P = .013) and RFS (14.6% vs 28.7%, P < .001). Additionally, bile leakage was an independent factor for both OS [hazard ratio (HR) 1.559, P = .022] and RFS (HR 1.517, P = .024). Furthermore, bile leakage was the only factor affecting prognosis among postoperative complications. CONCLUSIONS: Postoperative bile leakage worsens long-term clinical outcomes following liver resection in HCC patients.

Feasibility and efficacy of repeat laparoscopic liver resection for recurrent hepatocellular carcinoma.

BACKGROUND: Repeat hepatectomy is an acceptable treatment for recurrent hepatocellular carcinoma (HCC). However, repeat laparoscopic liver resection (LLR) has not been widely adopted due to its technical difficulty. This study aimed to assess the feasibility and efficacy of repeat LLR compared with repeat open liver resection (OLR) for recurrent HCC. METHODS: We performed 42 repeat OLR and 30 repeat LLR for cases of recurrent HCC between January 2007 and March 2018. This study retrospectively compared the patients' clinicopathological characteristics and operative and short-term outcomes including surgical time, intraoperative blood loss, duration of hospital stay, and postoperative complications between the two groups. RESULTS: There were no significant differences in patient characteristics between the two groups except in terms of Child-Pugh grade. The repeat LLR group had lower median intraoperative blood loss (100 mL vs. 435 mL; P = 0.001) and shorter median postoperative hospital stay (10 days vs. 14.5 days; P = 0.002). The other results including postoperative complications were comparable between the two groups. Further, comparison of two subpopulations of the repeat LLR group stratified by previous hepatectomy type (open or laparoscopic) or tumor location (segments 7 and 8 or other) revealed no significant differences in the postoperative clinical characteristics between them, although the morbidity rate tended to be higher in patients who underwent open hepatectomy for primary HCC than in patients who underwent laparoscopic hepatectomy. CONCLUSIONS: Repeat LLR for recurrent HCC is feasible and useful with good short-term outcomes although an appropriate patient selection seems to be necessary.

Verification of inflammation-based prognostic marker as a prognostic indicator in hepatocellular carcinoma.

AIM: Although inflammation-based markers in cancer have been used for prognostic prediction, the most useful marker for hepatocellular carcinoma (HCC) has not been established. We investigated the usefulness of various inflammation-based markers in HCC patients after hepatectomy. METHODS: A total of 478 patients who underwent initial hepatectomy for HCC from 2009 to 2015 and were diagnosed with pathological HCC were included in this retrospective study. Inflammation-based markers consisted of the C-reactive protein to albumin ratio (CAR), Glasgow prognostic score (GPS), neutrophil to lymphocyte ratio, lymphocyte to monocyte ratio, platelet to lymphocyte ratio and prognostic index. Univariate and multivariate analyses for overall survival (OS) and disease-free survival (DFS) using the Cox proportional hazard model were carried out. Kaplan-Meier analysis and log-rank test were used for comparison of OS and DFS. To reduce influences of selection bias and confounders for stratifying CAR, clinicopathological characteristics of patients were balanced by propensity score matching. RESULTS: Multivariate analysis identified only high CAR (>0.027) as an indicator of poor OS, and high CAR and high GPS (1-2) as indicators of poor DFS among inflammation-based markers. After propensity score matching, 124 patients each with low CAR and high CAR were matched. High CAR was correlated with both poor OS and DFS. CONCLUSION: C-reactive protein to albumin ratio was the most valuable prognostic indicator after hepatectomy for HCC among inflammation-based markers.

A case of hepatic pseudolymphoma in a patient with primary biliary cirrhosis.

Hepatic pseudolymphoma is a very rare benign reactive lymphoid hyperplasia associated with autoimmunity and chronic inflammatory liver diseases such as primary biliary cirrhosis and may mimic hepatocellular carcinoma. This diagnosis should be suspected in female with a suspicious single tumor. Close monitoring is needed in view of its premalignant nature.

Experience and outcomes in living donor liver procurement using the water jet scalpel.

BACKGROUND: The aim of the present study was to clarify treatment outcomes of living donor liver procurement using the water jet scalpel (WJS). METHODS: This single-center, retrospective cohort study included 40 living donors who underwent liver procurement from January 2014 to December 2018. One living donor who underwent posterior segmentectomy was excluded. Clinical data and outcomes after surgery for 20 WJS donors and 19 Cavitron Ultrasonic Surgical Aspirator (CUSA) donors were compared. RESULTS: Preoperative and excised graft data did not differ significantly between the WJS and CUSA groups. Operation time (P = 0.025) and parenchymal transection time (P = 0.007) were significantly shorter in the WJS group. There was no difference between the groups in terms of short-term outcomes after surgery. Multivariate analysis revealed that WJS offered significant advantages over CUSA in terms of shortening parenchymal transection time (P = 0.017). CONCLUSION: Living donor liver procurement using WJS contributes to shortening of parenchymal transection time while maintaining the same level of safety as when using CUSA.

Validation of Addenbrooke's cognitive examination III for detecting mild cognitive impairment and dementia in Japan.

BACKGROUND: Early detection of mild cognitive impairment (MCI) and dementia is very important to begin appropriate treatment promptly and to prevent disease exacerbation. We investigated the screening accuracy of the Japanese version of Addenbrooke's Cognitive Examination III (ACE-III) to diagnose MCI and dementia. METHODS: The original ACE-III was translated and adapted to Japanese. It was then administered to a Japanese population. The Hasegawa Dementia Scale-revised (HDS-R) and Mini-mental State Examination (MMSE) were also applied to evaluate cognitive dysfunction. In total, 389 subjects (dementia = 178, MCI = 137, controls = 73) took part in our study. RESULTS: The optimal ACE-III cut-off scores to detect MCI and dementia were 88/89 (sensitivity 0.77, specificity 0.92) and 75/76 (sensitivity 0.82, specificity 0.90), respectively. ACE-III was superior to HDS-R and MMSE in the detection of MCI or dementia. The internal consistency, test-retest reliability, and inter-rater reliability of ACE-III were excellent. CONCLUSIONS: ACE-III is a useful cognitive test to detect MCI and dementia. ACE-III may be widely useful in clinical practice.

Clinical characteristics of elderly depressive patients with low metaiodobenzylguanidine uptake.

BACKGROUND: Recently, depression with Lewy body pathology before the appearance of parkinsonism and cognitive dysfunction has been drawing attention. Low cardiac metaiodobenzylguanidine (MIBG) uptake is helpful for early differentiation of Lewy body disease (LBD) from late-onset psychiatric disorders even before parkinsonism or dementia appears. In this study, we used MIBG uptake as a tool in suspected LBD, and evaluated the relationship of MIBG results to clinical characteristics and depressive symptoms. METHODS: Fifty-two elderly inpatients with depression were included in this study. The Hamilton Depression Rating Scale (HDRS) was administered at admission, and 123 I-MIBG cardiac scintigraphy was performed. Of 52 patients, 38 had normal and 14 had reduced MIBG uptake. RESULTS: Correlation analyses of the late phase heart-to-mediastinum (H/M) ratio on the MIBG test and each item of the HDRS revealed that the H/M ratio was significantly correlated with scores of 'agitation', 'anxiety-somatic', and 'retardation' on the HDRS. Mean HDRS composite scores of 'somatic and psychic anxiety (Marcos)' and 'somatic anxiety/somatization factor (Pancheri)' were higher in the low uptake group than in the normal uptake group. CONCLUSION: Elderly patients with depression who manifested an obvious somatic anxiety tend to show low MIBG uptake, and are more likely to have Lewy body pathology.

Antithrombin Insufficiency Promotes Susceptibility to Liver Tumorigenesis.

BACKGROUND: Antithrombin (AT) is not only a major regulator of hemostasis, but it shows anti-inflammatory properties as well. We aimed to investigate whether AT-insufficient mice increase susceptibility to liver tumorigenesis. METHODS: We induced the development of liver tumor in AT-insufficient (AT+/-) mice and wild-type (AT+/+) mice by treating them with diethylnitrosamine (DEN) and CCl4. The development of liver tumors and liver inflammation were compared between these mouse groups. Following this, AT was administered to the AT-insufficient mice treated with DEN and CCl4. RESULTS: Tumor size and the number of DEN and CCl4-induced liver tumors significantly increased in AT-insufficient mice compared with the wild-type mice. Serum transaminase levels, cell death, and the expression of cleaved caspase-3 in liver were increased in AT+/-. Furthermore, hepatic neutrophil infiltrations and serum interleukin 6 and tumor necrosis factor-α levels were significantly elevated in AT-insufficient mice. The levels of 8-OHdG, oxidative DNA damage marker, in liver were significantly increased in AT-insufficient mice. Administration of AT led to a significant decrease in DEN- and CCl4-induced liver injury and inflammation in AT-insufficient mice, compared with the wild-type group. CONCLUSIONS: AT insufficiency led to increased susceptibility to liver tumorigenesis by increasing hepatic inflammation.

Down-regulation of pyruvate decarboxylase gene of white-rot fungus Phlebia sp. MG-60 modify the metabolism of sugars and productivity of extracellular peroxidase activity.

Ethanologenic white-rot fungus Phlebia sp. MG-60-P2 produces ethanol directly from several lignocelluloses. Efficient gene silencing methods are needed for metabolic engineering of this fungus for biorefinery use. In this study, we evaluated the effectiveness of RNAi-mediated silencing of the pyruvate decarboxylase gene of Phlebia sp. MG-60-P2 (MGpdc1). The RNAi lines generated showed a variety of suppression levels of ethanol production and MGpdc1 expression, and two selected strains led to different metabolic fluxes, resulting in rapid accumulation of xylitol from xylose. Knockdown lines KD2 and KD10 showed different strength of silencing. The moderate-inhibition line (KD10) showed faster xylitol accumulation from xylose than the severe-inhibition line (KD2). KD2, KD10 and knockout line KO77 showed higher extracellular peroxidase activity than the wild-type. Gene silencing using RNAi for MGpdc1 in the ethanologenic white-rot fungus Phlebia sp. MG-60-P2 is an effective first step in metabolic engineering to produce other chemicals besides ethanol. This high efficiency of transformation and silencing effect will make it possible to cotransform with multiple expression vectors which enhance the minor metabolic pathway or introduce exogenous metabolic reaction in Phlebia sp. MG-60-P2.

Independent risk factors that predict bile leakage after hepatectomy for hepatocellular carcinoma: Cohort study.

BACKGROUND: Bile leakage is a major cause of morbidity after hepatectomy. This study aimed to identify the predictive factors for bile leakage after hepatectomy. MATERIALS AND METHODS: Between January 2011 and December 2016, 556 patients underwent a liver resection for hepatocellular carcinoma with curative intent, and were enrolled to participate in this study. The incidence of postoperative bile leakage (POBL) was determined and the predictive factors for POBL were identified using univariate and multivariate analysis. RESULTS: POBLs occurred in 28 patients (5.0%). The multivariate analysis identified a history of stereotactic body radiotherapy, a body mass index <20 kg/m2, Child-Pugh class B cirrhosis, a central hepatectomy, and an operation time ≥375 min as risk factors that were associated with POBL. When the study cohort was grouped according to the number of the predictive factors present, the incidence of POBL increased as the number of the extant independent predictive factors increased. The POBL rate was 45.0% in patients with ≥3 predictive factors. CONCLUSION: We determined that POBL was associated with operative mortality and identified five independent predictive factors associated with POBL. Risk stratification using these predictive factors may be useful for identifying patients at a high risk of POBL.

Aneurysm of the inferior vena cava with thrombosis.

Inferior vena cava (IVC) aneurysms are extremely rare. Patients can be asymptomatic, have thrombosis, rupture, or pulmonary embolism. Thrombosis of the IVC aneurysm may mimic a retroperitoneal tumor. Surgical treatment of abdominal venous aneurysms with thrombosis is warranted and is necessary for the management of intraoperative bleeding and thrombosis.

[A Resectable Case of TS-1 Therapy Useful in Distinguishing Primary Lung Cancer from Lung Metastases of Pancreatic Cancer].

We report a case of pneumonectomy followed by radical pancreatectomy after oral administration of TS-1 for pancreatic cancer with complications ofa lung tumor. The patient was a 66-year-old woman. A pancreatic tail tumor and 2 lung nodules were detected on CT scans, and were diagnosed as pancreatic cancer and metastatic lung cancer. During a total of1 1 courses ofTS -1 therapy, the pancreatic tumor tended to contract, but both pulmonary nodules remained unchanged. Due to differences in treatment effect, double cancers of the lung and pancreas were suspected, rather than metastatic lung cancers. We performed a VATS partial resection of the left lower lobe for diagnostic therapy. The pathological diagnosis revealed an inflammatory myofibroblastic tumor and a primary lung cancer. We diagnosed that a radical pancreatectomy was possible and performed distal pancreatectomy. Pathological diagnosis confirmed an invasive pancreatic ductal carcinoma. Oral administration ofTS -1 was performed as adjuvant chemotherapy after surgery. Liver metastasis was observed 10 months after pancreatectomy, and GEM therapy was initiated. Peritoneal dissemination was observed at 2 years following pancreatectomy, and the patient died at 2 years and 9 months. TS-1 therapy for synchronous lung tumors and pancreatic cancer with careful observation allowed for a definitive radical resection. This method was an effective treatment for lung nodules with pancreatic cancer.

Significance of the Glasgow Prognostic Score for patients with colorectal liver metastasis.

BACKGROUND: Systemic inflammation and nutritional status are strongly associated with tumor progression. Inflammation-based prognostic scores, such as the Glasgow Prognostic Score (GPS), reflect these states and are predictive in patients with several types of advanced cancers. The aim of this study was to evaluate the significance of GPS in patients with colorectal liver metastasis (CRLM). PATIENTS AND METHODS: Study subjects were 134 patients with CRLM who underwent initial radical liver resection at Hiroshima University Hospital between January 2000 and December 2013. Univariate and multivariate analyses were performed to identify variables associated with overall and recurrence-free survival following liver resection in two groups based on GPS. RESULTS: There was no significant relationship between overall survival and GPS. Recurrence-free survival was significantly poorer in patients with GPS 1-2 than in those with GPS 0 (p < 0.01). In multivariate analysis for recurrence-free survival, moderate histologic differentiation, carcinoembryonic antigen level ≥10 ng/mL, and GPS 1-2 were identified as independent prognostic factors. CONCLUSION: We suggest that GPS is an important predictor of recurrence following liver resection in patients with CRLM, and it should be considered one of the evaluation criteria for liver resection.