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.

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.

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.

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.

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.

[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.

Prediction of recurrence following hepatectomy in patients with hepatitis C virus infection-related hepatocellular carcinoma who achieved a sustained virological response.

AIM: The risk of hepatitis C virus infection-related hepatocellular carcinoma (HCC) is lower, with a better prognosis, in patients who achieve a sustained virological response (SVR) than in those who do not. We aimed to identify risk factors of post-hepatectomy HCC recurrence in patients who achieved a SVR. METHODS: This retrospective study included 349 HCC patients who underwent an initial radical hepatectomy at our institution between January 2005 and December 2014. Sixty-eight patients had achieved a SVR (the SVR group) and 281 patients had not (the non-SVR group). Clinical characteristics and long-term outcomes were compared between the two groups. Univariate and multivariate analyses identified variables associated with recurrence-free survival in the SVR group. RESULTS: Post-hepatectomy overall and recurrence-free survival rates were significantly higher in the SVR group than the non-SVR group (P < 0.01 and <0.05, respectively). Univariate analysis of post-hepatectomy recurrence-free survival in the SVR group revealed multiple significant factors: aspartate aminotransferase, 25 IU/L or more (P = 0.01); indocyanine green retention rate at 15 min, 20.0% or less (P < 0.05); hepatic vascular invasion (P < 0.05); and an interval of months or less between achieving a SVR and hepatectomy (P < 0.01). Multivariate analysis confirmed an interval of 30 months or less between achieving a SVR and hepatectomy as an independent prognostic factor of recurrence-free survival (hazard ratio, 2.30; 95.0% confidence interval, 1.04-5.13; P < 0.05). CONCLUSION: The interval between achieving a SVR and hepatectomy is an important predictor of recurrence in hepatitis C virus infection-related HCC patients who achieved a SVR.

[A Case of Myxofibrosarcoma of the Retroperitoneum].

Myxofibrosarcoma(MFS)is one of the most common sarcomas in the extremities of elderly patients.We report a rare case of MFS originating in the retroperitoneum.A 65-year-old man presented to our hospital with an intraabdominal tumor, which was identified by abdominal CT during an investigation of an abdominal protuberance.Contrast -enhanced CT and MRI revealed a 18×12 cm mass in the left retroperitoneum.The patient underwent retroperitoneum tumor resection.Operative findings showed that there was an indistinct area between the left side of the tumor and the abdominal wall.There was no residual tumor macroscopically after the operation.The histopathological diagnosis was MFS arising from the retroperitoneum. Four months later, local recurrence and para-aortic lymph node metastasis were diagnosed.We performed tumor resection; however, the recurrent tumor had invaded the iliopsoas and iliac muscles.Additionally, there was peritoneal dissemination around the tumor.Five months after the initial surgery, a recurrence on the back was identified.He died 7 months after the first operation.According to previous reports, patients who undergo an operation with pathologically negative margins achieve better surgical outcomes.Therefore, it is important to perform expanded resection with enough surgical margin as possible.

[A Case of Angiomyolipoma Occurring in the Mesentery of the Transverse Colon and Treated Using Laparoscopic Excision].

A 65-year-old woman had received chemotherapy for malignant lymphoma since 2011. After the 8th course, computed tomography revealed the disappearance of lymph node metastasis, except for 22mm of the mass located on the tail side of the antrum. MRI showed a low intensity mass on the T1 and T2-weighted images. FDG-PET did not show abnormal uptake in the tumor. EUS-FNA did not reveal a definitive diagnosis. We performed a laparotomy for diagnosis and treatment. Intraoperative findings showed that the tumor occurred in the mesentery of the transverse colon. The pathological diagnosis was angiomyolipoma. The patient has been free from recurrent disease for 2 years and 6 months. Angiomyolipoma originating in the transverse mesentery region is rare and, due to various percentage of tissue factors, there are no fixed view of image findings. Furthermore, a large tissue volume is need for histological diagnosis. Laparotomy is useful for diagnosis and therapy for angiomyolipoma occurring in the mesentery of the transverse colon.

[A Case of Ovarian Cancer with Lymph Node Metastasis in the Lesser Curvature of the Stomach Resected Using Laparoscopic Surgery].

A 67-year-old woman, who was diagnosed with ovarian cancer with multiple metastases, underwent abdominal total hysterectomy, bilateral salpingo-oophorectomy, para-aortic lymph node dissection(b2), omental subtotal hysterectomy, and lower anterior rectal resection after receiving a combination of PTX plus CBDCA chemotherapy. Macroscopically, complete resection was achieved and histopathological examination of the resectedspecimen showedpoorly differentiatedserous adenocarcinoma. After surgery, additional chemotherapy was administered. However, increasing only lesser curvature of stomach lymph node, we performed laparoscopic lymph node resection as debulking surgery. It is often said that macroscopic complete resection of ovarian cancer improves the prognosis. In particular, we hope that this patient will survive longer with a sustainable quality of life as a result of laparoscopic stomach- andnerve -sparing surgery.

[Usefulness of Metallic Stent for Left-Sided Obstructive Colon Cancer].

The aim of this study was to compare the efficacy of self-expandable metallic stent (SEMS) and transanal tube as preoperative treatments for left-sided obstructive colon cancer. Forty-three patients (the SEMS group: 28 cases, the tube group: 15 cases) were included in this study. Clinicopathological data (age, sex, tumor location, depth, histological type, stage) were comparable between the 2 groups. In addition, there was no difference in intestinal decompression rate between the SEMS group and the tube group (technical success rate: 100% vs 86.7%, clinical success rate: 92.8% vs 73.3%, complication rate: 7.1% vs 0%). A significantly higher number of patients in the SEMS group underwent laparoscopic surgery because of difference of historical background. However, no significant difference was observed between the 2 groups in postoperative outcome(complication rate, hospital stay duration). SEMS insertion had several benefits compared to transanal tube placement, such as the resumption of oral intake because of rapid resolution of obstruction and easier management because SEMSs do not require washing. SEMS insertion could be a safe and effective bridge to subsequent surgery in patients with left-sided obstructive colon cancer.

[A Case of Radical Resection of Rectal Cancer with Multiple Liver and Lung Metastases after Preoperative Chemotherapy].

We report a case of radical resection of rectal cancer with multiple liver and lung metastases after preoperative chemotherapy. A 54-year-old woman presented with abdominal pain and loss of body weight due to rectal cancer with multiple liver and lung metastases. Therefore, the patient received 14 courses of bevacizumab+mFOLFOX6, and 7 courses of panitumumab+FOLFIRI. After the chemotherapy, the size of the distant metastases reduced by 62% on computed tomography, according to RECIST. Due to the reduction in size, a conversion surgery was attempted. First, an abdominal operation with laparoscopy was performed, and 2 months later an operation to resect the lung metastases via thoracoscopy was performed. Currently, 3 months after surgery, the patient is alive, without recurrence.

[A Case of Locally Advanced Rectal Cancer Successfully Treated by Conversion Surgery after Multidisciplinary Treatment].

A 70-year-old woman who complained of abdominal pain and a prolapsed tumor from the anus was diagnosed with an intestinal obstruction resulting from anal canal cancer. Computed tomography (CT) and magnetic resonance imaging revealed a huge tumor (11×5×12 cm) invading the vagina and levator ani muscle. Enlarged inguinal lymph nodes on both sides indicated metastasis. The clinical stage was T4b (vagina, levator ani muscle, and pudenda) N0H0M1a (LYM), stage IV (Japanese Classification of Colorectal Carcinoma: 8th edition). As curative resection was not possible, a transvers colostomy was performed to relieve the intestinal obstruction. This was followed by chemoradiotherapy (45 Gy/1.8 Gy×25; TS-1, 80 mg/body for 2 weeks and a 1-week interval, for 2 courses) and up to 10 courses of Bev+mFOLFOX6 continuously. After this regimen, there was a remarkable reduction in tumor size. Positron emission tomography-CT revealed no FDG uptake in the primary rectal site or inguinal lymph nodes, but a maximum standardized uptake value (SUVmax) of 6.3 was detected in the vagina. Six weeks after chemotherapy, the patient underwent a pelvic exenteration including resection of the vagina, bladder, and pudenda. The pathological stage was yp T4b (vagina) N0H0M0, stageⅡ. Curative resection was performed, and the patient had a Grade 2 pathological response after chemoradiotherapy.

[A Case of Small Bowel Cancer Treated with Laparoscopic Surgery].

We report a case of small intestinal adenocarcinoma treated with laparoscopic surgery. A 70-year-old woman had abdominal pain and epigastralgia. There were no abnormal findings on upper and lower endoscopy. The symptoms continued for 4 months after endoscopy, so she presented to our hospital. After CT examination, small bowel cancer with ileus was suspected. An ileus tube was inserted to relieve the bowel pressure and she was diagnosed with ileum cancer by enteroscopy. Laparoscopic surgery was performed and the pathological stage was determined as pStage Ⅲa. She was treated with oral chemotherapy (UFT plus LV) and had no recurrence 6 months after surgery.

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.

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.

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.