Transarterial chemoembolization for hepatocellular carcinoma: A review of techniques

Hepatocellular carcinoma(HCC)is one of the most common malignant diseases worldwide.While curative therapies,including resection,liver transplantation,and percutaneous ablation(percutaneous ethanol injection and radiofrequency ablation),are applicable for only a portion of the HCC population,transcatheter arterial chemoembolization(TACE)has been recognized as an effective palliative treatment option for patients with advanced HCC.TACE is also used even for single HCCs in which it is difficult to perform surgical resection or locoregional treatment due to systemic co-morbidities or anatomical problems.TACE has become widely adopted in the treatment of HCC.By using computed tomography-angiography,TACE is capable of performing diagnosis and treatment at the same time.Furthermore,TACE plays an important role in the multidisciplinary treatment for HCC when combined with other treatment.In this review,we first discuss the history of TACE,and then review the previous findings about techniques of achieving a locoregional treatment effect(liver infarction treatment,e.g.,ultra-selective TACE,balloon-occluded TACE),and the use of TACE as a drugdelivery system for anti-cancer agents(palliative,e.g.,platinum complex agents,drug-eluting beads)for multiple lesions.

Utility of linked color imaging for endoscopic diagnosis of early gastric cancer

BACKGROUND Linked color imaging(LCI) is a method of endoscopic imaging that emphasizes slight differences in red mucosal color.AIM To evaluate LCI in diagnostic endoscopy of early gastric cancer and to compare LCI and pathological findings.METHODS Endoscopic images were obtained for 39 patients(43 lesions) with early gastric cancer. Three endoscopists evaluated lesion recognition with white light imaging(WLI) and LCI. Color values in Commission Internationale de l'Eclairage(CIE)1976 L*a*b* color space were used to calculate the color difference(ΔE) between cancer lesions and non-cancer areas. After endoscopic submucosal dissection,blood vessel density in the surface layer of the gastric epithelium was evaluated pathologically. The identical region of interest was selected for analyses of endoscopic images(WLI and LCI) and pathological analyses.RESULTS LCI was superior for lesion recognition(P < 0.0001), and ΔE between cancer and non-cancer areas was significantly greater with LCI than WLI(29.4 vs 18.6, P <0.0001). Blood vessel density was significantly higher in cancer lesions(5.96% vs4.15%, P = 0.0004). An a* cut-off of ≥ 24 in CIE 1976 L*a*b* color space identified a cancer lesion using LCI with sensitivity of 76.7%, specificity of 93.0%, and accuracy of 84.9%.CONCLUSION LCI is more effective for recognition of early gastric cancer compared to WLI as a result of improved visualization of changes in redness. Surface blood vessel density was significantly higher in cancer lesions, and this result is consistent with LCI image analysis.

Endoscopic ultrasound-guided fine needle aspiration in the differentiation of type 1 and type 2 autoimmune pancreatitis

AIM:To investigate the usefulness of endoscopic ultrasound-guided fine needle aspiration(EUS-FNA) in the differentiation of autoimmune pancreatitis(AIP).METHODS:We retrospectively reviewed 47 of 56 AIP patients who underwent EUS-FNA and met the Asian diagnostic criteria.On 47 EUS-FNA specimens,we evaluated the presence of adequate material and characteristic features of lymphoplasmacytic sclerosing pancreatitis(LPSP) and idiopathic duct-centric pancreatitis(IDCP) mentioned in the International Consensus Diagnostic Criteria and examined if these findings make a contribution to the differential diagnosis of type 1 and type 2 AIP.A disposable 22-gauge needle was used for EUS-FNA.RESULTS:Adequate specimens including pancreatic tissue for differentiating AIP from cancer were obtained from 43 of 47 patients who underwent EUSFNA.EUS-FNA was performed from the pancreatic head in 21 cases,which is known to be technically difficult when performed by core biopsy;there was no significant difference in the results compared with pancreatic body-tail.Nine of 47 patients met level 1 findings of LPSP and 5 patients met level 2 findings of LPSP.No one met level 1 findings of IDCP,but 3 patients met level 2 findings of IDCP.Of 10 seronegative cases,2 cases were diagnosed with "definitive type 1 AIP",and 3 cases were diagnosed with "probable type 2 AIP" when considering both the level 2 histological findings and response to steroids.CONCLUSION:EUS-FNA is useful in the differentiation of type 1 and type 2 AIP,particularly in seronegative cases.

Analysis of the risk factors for severity in post endoscopic retrograde cholangiopancreatography pancreatitis: The indication of prophylactic treatments

AIM To determine the risk factors of severe post endoscopic retrograde cholangiopancreatography pancreatitis(s PEP) and clarify the indication of prophylactic treatments.METHODS At our hospital, endoscopic retrograde cholangiopancreatography(ERCP) was performed on 1507 patients from May 2012 to December 2015. Of these patients, we enrolled all 121 patients that were diagnosed with post endoscopic retrograde PEP. Fourteen of 121 patients diagnosed as s PEP were analyzed.RESULTS Forty-one patients had contrast media remaining in the pancreatic duct after completion of ERCP. Seventy-one patients had abdominal pain within three hours after ERCP. These were significant differences for s PEP(P < 0.05). The median of Body mass index, the median time for ERCP, the median serum amylase level of the next day, past histories including drinking and smoking, past history of pancreatitis, sphincter of Oddi dysfunction, whether emergency or not, expertise of ERCP procedure, diverticulum nearby Vater papilla, whether there was sphincterotomy or papillary balloon dilation, pancreatic duct cannulation, use of intraductal ultrasonography enforcement, and transpapillary biopsies had no significant differences with s PEP.CONCLUSION Contrast media remaining in the pancreatic duct and the appearance of abdominal pain within three hours after ERCP were risk factors of s PEP.

Use of color Doppler ultrasonography in the diagnosis of anomalous connection in pancreatobiliary disease

AIM: To estimate the detectability of anomalous connection in pancreatobiliary disease (ACPBD) cases, measuring gallbladder wall blood flow (GWBF).METHODS: In the retrospective study, we enrolled 42subjects with gallbladder wall thickening. GWBF velocity was determined as an average value of the peak velocity of color signals on the gallbladder wall, three times in each case. Based on the findings on endoscopic ultrasonography (EUS) or endoscopic retrograde cholangiopancreatography (ERCP), the 42 subjects were divided into 11 cases with ACPBD and 31 cases without ACPBD. In the prospective study, the subjects were 92 cases with gallbladder wall thickening. Using the cut-off level of the flow velocity obtained in the retrospective study, the usefulness of measuring GWBF velocity in diagnosing ACPBD was evaluated.RESULTS: In the retrospective study, imaging of GWBF was obtained in 40 of the 42 subjects. The mean GWBF velocity of the ACPBD cases was 29.4±3.9 cm/s(mean±SD), which was significantly different (P＜0.0001;95% CI 5.48-13.2) from that of the without ACPBD cases(20.1±5.9 cm/s). Based on this result, we prepared a receiver operating characteristic curve, and the cut-off level appropriate for diagnosing ACPBD was estimated to be 25 cm/s. In the prospective study, GWBF was detected in 86 of the 92 subjects. Based on the EUS or ERCP findings, the 92 subjects were divided into 15 cases with ACPBD and 77 cases without ACPBD. When a cut-off level of 25 cm/s was employed, ACPBD could be diagnosed with a sensitivity of 87.0% (13/15) and a specificity of87.3% (62/71).CONCLUSION: Measurement of GWBF velocity, which is less invasive and provides objective values, is very useful for diagnosing ACPBD prior to the development of malignant tumors in cases with gallbladder wall thickening.

In vivo histological diagnosis for gastric cancer using endocytoscopy

AIM To examine usefulness of virtual biopsy using endocytoscopy by comparing the in vivo endocytoscopic and histopathological images of gastric cancers.METHODS Endocytoscopy was performed in 30 patients with early gastric cancer. Of these, 26 patients showed well differentiated adenocarcinomas, while 4 patients showed poorly differentiated adenocarcinomas(including one signet ring cell carcinoma). Cancerous and non-cancerous areas were observed after double staining with 0.05% crystal violet and 0.1% methylene blue. The endocytoscopic images obtained were evaluated by an expert endoscopist and an expert pathologist without knowledge of patient clinical data, and endocytoscopic and histopathological diagnoses were compared.RESULTS The endocytoscopic images of the cancerous area were assessed as evaluable in 25(83.3%) and 27(90%) patients by endoscopist A and pathologist B, respectively, and those of the non-cancerous area as evaluable in 28(93.3%) and 23(76.7%) patients by the endoscopist and pathologist, respectively. The sensitivity, specificity, and diagnostic accuracy of gastric cancer diagnosis using evaluable endocytoscopic images were 88.0% and 92.9%, and 90.6% by endoscopist A, and 88.9% and 91.3%, and 90.0% by pathologist B, respectively. Evaluation of the diagnostic concordance rate between the endoscopist and the pathologist by inter-observer agreement calculation revealed no significant difference between the two observers. The inter-observer agreement(κ-value) for endocytoscopic diagnosis was 0.745. CONCLUSION Endocytoscopy is useful for the differentiation of cancerous from non-cancerous gastric mucosa, making it a promising tool for virtual biopsy.

Characteristic endoscopic findings and risk factors for cytomegalovirus-associated colitis in patients with active ulcerative colitis

AIM: To identify characteristic endoscopic findings and risk factors for cytomegalovirus(CMV)-associated colitis in patients with active ulcerative colitis(UC).METHODS: A total of 149 UC patients admitted to the Department of Gastroenterology, Nagoya University Hospital, from January 2004 to December 2013 with exacerbation of UC symptoms were enrolled in this retrospective study. All medical records, including colonoscopy results, were reviewed. CMV infection was determined by the presence of CMV antigen, CMV inclusion bodies in biopsy specimens, or positive specific immunohistochemical staining for CMV. Multivariate analysis was used to identify independent risk factors for CMV colitis.RESULTS: Multivariate analysis indicated independent associations with the extent of disease(pancolitis) anduse of > 400 mg corticosteroids for the previous 4 wk. In contrast, no association was seen with sex, age at UC diagnosis, immunomodulator use, or infliximab use. Punched-out ulceration was also significantly associated with CMV infection in patients with active UC(odds ratio = 12.672, 95%CI: 4.210-38.143).CONCLUSION: Identification of a total corticosteroid dose > 400 mg for 4 wk, extensive colitis and a specific endoscopic finding of punched-out ulcer might facilitate the more rapid diagnosis and timely initiation of antiviral therapy for CMV-associated colitis in patients with active UC.

Modified docetaxel, cisplatin and capecitabine for stage Ⅳ gastric cancer in Japanese patients: A feasibility study

AIM To evaluate the feasibility of chemotherapy including fluoropyrimidine, platinum and taxane with modified dosages for unresectable gastric cancer in Japanese patients.METHODS We performed a feasibility study of a modified docetaxel, cisplatin and capecitabine (DCX) regimen for stage Ⅳ gastric cancer. In particular, 30 or 40 mg/m^2 of docetaxel on day 1, 60 mg/m^2 of cisplatin on day 1, and 2000 mg/m^2 of capecitabine for 2 wk were administered every three weeks.RESULTS Three patients were treated with modified DCX(m DCX) with 30 mg/m^2 docetaxel, and five patients were treated with this regimen with 40 mg/m^2 docetaxel. Grade 3 or 4 neutropenia was observed in six of the eight patients; no patients exhibited febrile neutropenia. Partial response was achieved in four of the eight patients. Three patients underwent gastrectomy, which achieved R0 resection without residual tumors in dissected lymph nodes. In one of these three patients, resected specimens revealed pathological complete response in the primary lesion and in lymph nodes.CONCLUSION m DCX was well tolerated by Japanese patients with stage Ⅳ gastric cancer. This regimen might be useful for allowing gastric cancer patients with distant lymph node metastasis to undergo conversion surgery.

Double-balloon endoscopic retrograde cholangiopancreatography for patients who underwent liver operation: A retrospective study

BACKGROUND Double-balloon endoscopic retrograde cholangiography (DB-ERC) is widely performed for biliary diseases after reconstruction in gastrointestinal surgery,but there are few reports on DB-ERC after hepatectomy or living donor liver transplantation (LDLT).AIM To examine the success rates and safety of DB-ERC after hepatectomy or LDLT METHODS The study was performed retrospectively in 26 patients (45 procedures) who underwent hepatectomy or LDLT (liver operation:LO group) and 40 control patients (59 procedures) who underwent pancreatoduodenectomy (control group).The technical success (endoscope reaching the choledochojejunostomy site),diagnostic success (performance of cholangiography),therapeutic success(completed interventions) and overall success rates,insertion and procedure(completion of DB-ERC) time,and adverse events were compared between these groups.RESULTS There were no significant differences between LO and control groups in the technical [93.3%(42/45) vs 96.6%(57/59),P=0.439],diagnostic [83.3%(35/42) vs83.6%(46/55),P=0.968],therapeutic [97.0%(32/33) vs 97.7%(43/44),P=0.836],and overall [75.6%(34/45) vs 79.7%(47/59),P=0.617] success rates.The median insertion time (22 vs 14 min,P <0.001) and procedure time (43.5 vs 30 min,P=0.033) were significantly longer in the LO group.The incidence of adverse events showed no significant difference [11.1%(5/45) vs 6.8%(4/59),P=0.670].CONCLUSION DB-ERC after liver operation is safe and useful but longer time is required,so should be performed with particular care.

Endoscopic papillectomy of minor papillar adenoma associated with pancreas divisum

Tumors of the minor papilla of the duodenum are quite rare.We successfully and safely treated an 18-mm adenoma of the minor papilla associated with pancreas divisum using endoscopic papillectomy.A 64-year-old man was admitted to our hospital for treatment of an asymptomatic mass in the minor papilla detected by upper gastrointestinal endoscopy.Endscopic analysis showed an 18-mm,whitish,sessile mass,located in the duodenum proximal to a normal-appearing major papilla.Endoscopic retrograde pancreatography did not reveal the pancreatic duct.Magnetic resonance cholangiopancreatography showed a lack of the ventral pancreatic duct.We suspected this case was associated with pancreatic divisum;therefore,we performed endoscopic papillectomy of the minor papilla tumor.Subsequently,endoscopic pancreatic stent placement in the minor papilla was done to prevent drainage disturbance.The patient has been asymptomatic without recurrence of tumor or stenosis of the Santorini orifice upon endoscopic examination for the past 2 years.

Clinical utility of a new endoscopic scoring system for Crohn's disease

AIM:To evaluate the clinical value of the newly modified Simple Endoscopic Score for Crohn's disease(m SES-CD).METHODS:Seventy-six Crohn's disease(CD) patients who underwent transanal double balloon endoscopy(DBE) in our hospital between 2003 and 2012 were retrospectively reviewed. DBE is defined as small intestinal endoscopy using two attached balloons. We included patients with stenosis which hampered passage of the scope and those who underwent DBE with observation for at least 80 cm from the ileocecal valve. Our new m SES-CD assesses the endoscopic activity of two consecutive small intestinal segments located 0-40 cm and 40-80 cm from the ileocecal valve by DBE,in addition to the activity of four colorectal segments. To compare the usefulness of m SES-CD with SES-CD,we similarly divided the patients into two groups according to total m SES-CD score(low disease activity group,< 4; high disease activity group,≥ 4). The clinical value of m SES-CD in predicting clinical outcome in patients with CD was evaluated using the occurrence of surgery after DBE as an endpoint.RESULTS:Median age of the 76 CD patients was 36 years(range,16-71). Thirty-nine patients had stenosis which hampered passage of the DBE to 80 cm on the proximal side from the ileocecal valve. Median evaluable length of small intestine by DBE was 80 cm(range,3-200). A total of 74 patients had one or more small intestinal lesions detected by DBE,of which 62(83.8%) were within 80 cm of the ileocecal valve on the proximal side. Only two patients(2.7%) with proximal-side lesions more than 80 cm from the ileocecal valve did not have lesions within 80 cm. Patients with high m SES-CD scores showed significantly shorter surgeryfree survival than those with low scores(P < 0.05). In contrast,surgery-free survival did not significantly differ between the low and high SES-CD groups(P > 0.05). Multivariate analysis by a Cox proportional hazards model identified m SES-CD as an independent factor for surgery-free survival.CONCLUSION:m SES-CD is useful in evaluating the risk of surgery-free survival in patients with CD.

Colorectal endoscopic submucosal dissection in special locations

Colorectal endoscopic submucosal dissection(ESD) is considered one of the most challenging endoscopic procedures for novice endoscopists. When compared with the stomach, the colon and rectum have a narrower tubular lumen, greater angulation at the flexures, and a thinner muscle layer. These factors make endoscopic control and maneuverability difficult. ESD of the colorectum was considered more difficult than gastric and esophageal ESD. However, with learning from the experts, practicing, and selecting an appropriate technique,most of colorectal ESD could be performed successfully. Nevertheless, some colorectal locations are extremely specialized either from unique anatomy or given unstable scope position. Accordingly, the objective of this review was to provide endoscopists with an overview of the techniques and outcomes associated with ESD at these special colorectal locations. ESD at the discussed special locations of the ileo-colo-rectum was found to be feasible, and outcomes were comparable to those of ESD performed in non-special locations of the ileocolo-rectum. Practice for skill improvement and awareness of the unique characteristics of each special location is the key to performing successful ESD.

Change of strategies and future perspectives against hepatitis B virus recurrence after liver transplantation

A few decades ago,liver transplantation in patients with chronic hepatitis B virus(HBV) infection was considered a relative contraindication because of the high rate of graft infections and poor prognosis. Since then,remarkable progress was introduced by using nucleos(t)ide analogues and/or hepatitis B immunoglobulin(HBIg) and liver transplantation for HBV-related disease is now becoming one of the good indication. However,high cost burden is the main problem for this combination prophylaxis for a long time use,and this issue should be emerged to be resolved. In this review,we show the progress of post antiHBV strategies showing the history from introduction of HBIg and nucleos(t)ide analogues to recent new strategies with hepatitis B vaccine or saving or stopping protocols of HBIg,and clarify and discuss how to do for further improvement of prevention strategies with better quality.

Clinical oncology for pancreatic and biliary cancers:Advances and current limitations

In the early 2000s,the main stream of endoscopic ultrasonography(EUS)changed from a mechanical scanning method to electronic radial or linear scanning methods.Subsequently,useful applications in trans-abdominal ultrasonography came within reach of EUS.In particular,contrast-enhanced EUS(CE-EUS)and EUS-elastography became cutting-edge diagnostic modalities for pancreatic disorders.Each type of pancreatic disorder has characteristic hemodynamics.CE-EUS uses color Doppler flow imaging and harmonic imaging to classify pancreatic lesions.EUS-elastography can assess tissue hardness by measuring its elasticity.This parameter appears to correlate with the malignant potential of the lesions.Tissue elasticity studies can provide information on both its pattern and distribution.The former is the conventional method of morphological diagnosis,but it is restricted to observations made in a region of interest(ROI).The latter is an unbiased analysis that can be performed by image analysis software and is theoretically constant,regardless of the ROI.Though EUSfine needle aspiration(FNA)is also a very useful diagnostic tool,there are several limitations.Diagnostic EUS-FNA of pancreatic cystic lesions has marginal utility mainly due to low sensitivity.Therefore,in particular,endoscopists should keep this limitation in mind.

胆道肿瘤临床实践指南(英文第三版)

日本肝胆胰外科学会(JSHBPS)于2007年出版第一版胆道肿瘤(胆管癌、胆囊癌及壶腹癌)临床实践指南,于2014年更新第二版,2021年英文第三版胆道肿瘤临床实践指南围绕6个主题提出若干临床问题,基于相关循证医学证据并组织专家讨论后,最终确定推荐意见、推荐强度以及推荐说明。根据证据推荐分级的评估、制订与评价(GRADE)系统,推荐强度被分为1级(强)或者2级(弱)。英文第三版胆道肿瘤临床实践指南中提出的31个临床问题涵盖:(1)预防性治疗;(2)诊断;(3)胆道引流;(4)外科治疗;(5)化疗;(6)放疗。31个临床问题中,14个问题给予推荐强度为强的推荐意见,14个问题给予推荐强度为弱的推荐意见,剩余的3个问题未给予推荐意见。每条推荐意见都进行推荐强度说明。最新版指南基于循证医学证据,为临床提供了重要建议。未来与癌症登记数据库协作将是评估指南和建立新证据的关键。

Copper Accumulates in Hemosiderins in Livers of Patients with Iron Overload Syndromes

In biology,redox reactions are essential and sometimes harmful,and therefore,iron metabolism is tightly regulated by cuproproteins.Since the state of copper in iron overload syndromes remains unclear,we investigated whether copper metabolism is altered in these syndromes.Eleven patients with iron overload syndromes participated in this study.The clinical diagnoses were aceruloplasminemia (n=2),hemochromatosis (n=5),ferroportin disease (n=2),and receiving excess intravenous iron supplementation (n=2).Liver specimens were analyzed using a light microscope and transmission electron microscope equipped with an X-ray analyzer.In addition to a large amount of iron associated with oxygen and phosphorus,the iron-rich hemosiderins of hepatocytes and Kupffer cells contained small amounts of copper and sulfur,regardless of disease etiology.Two-dimensional imaging clearly showed that cuproproteins were distributed homogenously with iron complexes within hemosiderins.Copper stasis was unlikely in noncirrhotic patients.The enhanced induction of cuproproteins by excess iron may contribute to copper accumulation in hemosiderins.In conclusion,we have demonstrated that copper accumulates in hemosiderins in iron overload conditions,perhaps due to alterations in copper metabolism.