Limitations of liver biopsy and non-invasive diagnostic tests for the diagnosis of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis

It is estimated that 30%of the adult population in Japan is affected by nonalcoholic fatty liver disease(NAFLD).Fatty changes of the liver are generally diagnosed using imaging methods such as abdominal ultrasonography(US)and computed tomography(CT),but the sensitivity of these imaging techniques is low in cases of mild steatosis.Alanine aminotransferase levels may be normal in some of these patients,warranting the necessity to establish a set of parameters useful for detecting NAFLD,and the more severe form of the disease,nonalcoholic steatohepatitis(NASH).Although liver biopsy is currently the gold standard for diagnosing progressive NASH,it has many drawbacks,such as sampling error,cost,and risk of complications.Furthermore,it is not realistic to perform liver biopsies on all NAFLD patients.Diagnosis of NASH using various biomarkers,scoring systems and imaging methods,such as elastography,has recently been attempted.The NAFIC score,calculated from the levels of ferritin,fasting insulin,and typeⅣcollagen 7S,is useful for the diagnosis of NASH,while the NAFLD fibrosis score and the FIB-4 index are useful for excluding NASH in cases of advanced fibrosis.This article reviews the limitations and merits of liver biopsy and noninvasive diagnostic tests in the diagnosis of NAFLD/NASH.

Regenerative therapy for neuronal diseases with transplantation of somatic stem cells

Pluripotent stem cells, which are capable of differentiating in various species of cells, are hoped to be donor cells in transplantation in regenerative medicine. Embryonic stem(ES) cells and induced pluripotent stem cells have the potential to differentiate in approximately all species of cells. However, the proliferating ability of these cells is high and the cancer formation ability is also recognized. In addition, ethical problems exist in using ES cells. Somatic stem cells with the ability to differentiate in various species of cells have been used as donor cells for neuronal diseases, such as amyotrophic lateral sclerosis, spinal cord injury, Alzheimer disease,cerebral infarction and congenital neuronal diseases.Human mesenchymal stem cells derived from bone marrow, adipose tissue, dermal tissue, umbilical cord blood and placenta are usually used for intractable neuronal diseases as somatic stem cells, while neural progenitor/stem cells and retinal progenitor/stem cells are used for a few congenital neuronal diseases and retinal degenerative disease, respectively. However,non-treated somatic stem cells seldom differentiate to neural cells in recipient neural tissue. Therefore, the contribution to neuronal regeneration using non-treated somatic stem cells has been poor and various differential trials, such as the addition of neurotrophic factors,gene transfer, peptide transfer for neuronal differentiation of somatic stem cells, have been performed. Here,the recent progress of regenerative therapies using various somatic stem cells is described.

Clinicopathological features of early gastric cancers arising in Helicobacter pylori uninfected patients

BACKGROUND Persistent Helicobacter pylori(H.pylori)infection causes chronic inflammation,atrophy of the gastric mucosa,and a high risk of developing gastric cancer.In recent years,awareness of eradication therapy has increased in Japan.As H.pylori infections decrease,the proportion of gastric cancers arising from H.pylori uninfected gastric mucosa will increase.The emergence of gastric cancer arising in H.pylori uninfected patients though rarely reported,is a concern to be addressed and needs elucidation of its clinicopathological features.AIM To evaluate the clinicopathological features of early gastric cancer in H.pyloriuninfected patients.METHODS A total of 2462 patients with 3375 instances of early gastric cancers that were treated by endoscopic submucosal dissection were enrolled in our study between May 2000 and September 2019.Of these,30 lesions in 30 patients were diagnosed as H.pylori-uninfected gastric cancer(Hp UIGC).We defined a patient as H.pylori-uninfected using the following three criteria:(1)The patient did not receive treatment for H.pylori,which was determined by investigating medical recordsand conducting patient interviews;(2)Lack of endoscopic atrophy;and(3)The patient was negative for H.pylori after being tested at least twice using various diagnostic methods,including serum anti-H.pylori-Ig G antibody,urease breath test,rapid urease test,and microscopic examination.RESULTS The frequency of Hp UIGC was 1.2%(30/2462)for the patients in our study.The study included 19 males and 11 females with a mean age of 59 years.The location of the stomach lesions was divided into three sections;upper third(U),middle third(M),lower third(L).Of the 30 lesions,15 were U,1 was M,and 14 were L.Morphologically,17 lesions were protruded and flat elevated type(0-I,0-IIa,0-IIa+IIc),and 13 lesions were flat and depressed type(0-IIb,0-IIc).The median tumor diameter was 8 mm(range 2-98 mm).Histological analysis revealed that22 lesions(73.3%)were differentiated type.The Hp UIGC lesions were classified into fundic gland type adenocarcinoma(7 cases),foveolar type welldifferentiated adenocarcinoma(8 cases),intestinal phenotype adenocarcinoma(7 cases),and pure signet-ring cell carcinoma(8 cases).Among 30 Hp UIGCs,24 lesions(80%)were limited to the mucosa;wherein,the remaining 6 lesions showed submucosal invasion.One of the submucosal invasive lesions showed more than 500μm invasion.The mucin phenotype analysis identified 7 Hp UIGC with intestinal phenotype and 23 with gastric phenotype.CONCLUSION We elucidated the clinicopathological characteristics of Hp UIGC,revealing recognition not only undifferentiated-type but also differentiated-type.In addition,intestinal phenotype tumors were also observed and could be an important tip.

Accumulation of aberrant DNA methylation during colorectal cancer development

Despite the recent advances in the therapeutic modalities,colorectal cancer(CRC)remains to be one of the most common causes of cancer-related death.CRC arises through accumulation of multiple genetic and epigenetic alterations that transform normal colonic epithelium into adenocarcinomas.Among crucial roles of epigenetic alterations,gene silencing by aberrant DNA methylation of promoter regions is one of the most important epigenetic mechanisms.Recent comprehensive methylation analyses on genome-wide scale revealed that sporadic CRC can be classified into distinct epigenotypes.Each epigenotype cooperates with specific genetic alterations,suggesting that they represent different molecular carcinogenic pathways.Precursor lesions of CRC,such as conventional and serrated adenomas,already show similar methylation accumulation to CRC,and can therefore be classified into those epigenotypes of CRC.In addition,specific DNA methylation already occurs in the normal colonic mucosa,which might be utilized for prediction of the personal CRC risk.DNA methylation is suggested to occur at an earlier stage than carcinoma formation,and may predict the molecular basis for future development of CRC.Here,we review DNA methylation and CRC classification,and discuss the possible clinical usefulness of DNA methylation as biomarkers for the diagnosis,prediction of the prognosis and the response to therapy of CRC.

characteristics of intestinal pseudo-obstruction in patients with mitochondrial diseases

AIM: To reveal the frequency, characteristics and prognosis of chronic intestinal pseudo-obstruction (CIP) in mitochondrial disease patients. METHODS: Between January 2000 and December 2010, 31 patients (13 males and 18 females) were di-agnosed with mitochondrial diseases at our hospital. We conducted a retrospective review of the patients' sex, subclass of mitochondrial disease, age at onset of mitochondrial disease, frequency of CIP and the age at its onset, and the duration of survival. The age at onset or at the first diagnosis of the disorder that led to the clinical suspicion of mitochondrial disease was also examined. RESULTS: Twenty patients were sub-classified with mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS), 8 with chronic progressive external ophthalmoplegia (CPEO), and 3 with myoclonus epilepsy associated with ragged-red fibers (MERRF). Nine patients were diagnosed with CIP, 8 of the 20 (40.0%) patients with MELAS, 0 of the 8 (0.0%) patients with CPEO, and 1 of the 3 (33.3%) patients with MERRF. The median age (range) at the diagnosis and the median age at onset of mitochondrial disease were 40 (17-69) and 25 (12-63) years in patients with CIP, and 49 (17-81) and 40 (11-71) years in patients without CIP. During the survey period, 5 patients (4 patients with MELAS and 1 with CPEO) died. The cause of death was cardiomyopathy in 2 patients with MELAS, cerebral infarction in 1 patient with MELAS, epilepsy and aspiration pneumonia in 1 patient with MELAS, and multiple metastases from gastric cancer and aspiration pneumonia in 1 patient with CPEO. CONCLUSION: Patients with CIP tend to have disorders that are suspected to be related to mitochondrial diseases at younger ages than are patients without CIP.

Visual distraction alone for the improvement of colonoscopy-related pain and satisfaction

AIM: To evaluate the effect of a relaxing visual distraction alone on patient pain, anxiety, and satisfaction during colonoscopy.METHODS: This study was designed as an endoscopistblinded randomized controlled trial with 60 consecutively enrolled patients who underwent elective colonoscopy at Yokohama City University Hospital, Japan. Patients were randomly assigned to two groups: group 1 watched a silent movie using a head-mounted display, while group 2 only wore the display. All of the colonoscopies were performed without sedation. We examined pain, anxiety, and the satisfaction of patients before and after the procedure using questionnaires that included the Visual Analog Scale. Patients were also asked whether they would be willing to use the same method for a repeat procedure.RESULTS: A total of 60 patients were allocated to two groups. Two patients assigned to group 1 and one patient assigned to group 2 were excluded after the randomization. Twenty-eight patients in group 1 and 29 patients in group 2 were entered into the final analysis. The groups were similar in terms of gender, age, history of prior colonoscopy, and pre-procedural anxiety score. The two groups were comparable in terms of the cecal insertion rate, the time to reach the cecum, the time needed for the total procedure, and vital signs. The median anxiety score during the colonoscopy didnot differ significantly between the two groups(median scores, 20 vs 24). The median pain score during the procedure was lower in group 1, but the difference was not significant(median scores, 24.5 vs 42). The patients in group 1 reported significantly higher median post-procedural satisfaction levels, compared with the patients in group 2(median scores, 89 vs 72, P = 0.04). Nearly three-quarters of the patients in group 1 wished to use the same method for repeat procedures, and the difference in rates between the two groups was statistically significant(75.0% vs 48.3%, P = 0.04). Patients with greater levels of anxiety before the procedure tended to feel a painful sensation. Among patients with a pre-procedural anxiety score of 50 or higher, the anxiety score during the procedure was significantly lower in the group that received the visual distraction(median scores, 20 vs 68, P = 0.05); the pain score during the colonoscopy was also lower(median scores, 23 vs 57, P = 0.04). No adverse effects arising from the visual distraction were recognized.CONCLUSION: Visual distraction alone improves satisfaction in patients undergoing colonoscopy and decreases anxiety and pain during the procedure among patients with a high pre-procedural anxiety score.

Histopathological validation of magnifying endoscopy for diagnosis of mixed-histological-type early gastric cancer

BACKGROUND The undifferentiated-type(UDT)component profoundly affects the clinical course of early gastric cancers(EGCs).However,an accurate preoperative diagnosis of the histological types is unsatisfactory.To date,few studies have investigated whether the UDT component within mixed-histological-type(MT)EGCs can be recognized preoperatively.AIM To clarify the histopathological characteristics of the endoscopically-resected MT EGCs for investigating whether the UDT component could be recognized preoperatively.METHODS This was a single-center retrospective study.First,we attempted to clarify the histopathological characteristics of the endoscopically-resected MT EGCs with emphasis on the UDT component.Histopathological examination investigated each lesion’s UDT component:(1)Whole mucosal layer occupation of the UDT component;(2)UDT component exposure to the surface of the mucosa;and(3)existence of a clear border between the differentiated-type and UDT components.Then,preoperative endoscopic images with magnifying endoscopy with narrowband imaging(ME-NBI)were examined to identify whether the endoscopic UDT component finding was recognizable within the area where it was present in the histopathological examination.The preoperative biopsy results and comparative relationships between endoscopic and histopathological findings were also examined.RESULTS In the histopathological examination,the whole mucosal layer occupation of the UDT component and exposure of the UDT component to the mucosal surface were observed in 67.3%(33/49)and 79.6%(39/49)of samples,respectively.A clear distinction of the border between the differentiated-type and UDT components could not be drawn in 65.3%(32/49)of MT lesions.In the endoscopic examination,the preoperative endoscopic images showed that only 24.5%(12/49)of MT EGCs revealed the UDT component within the area where it was present histopathologically.Histopathological UDT predominance was the single significant factor associated with the presence of the endoscopic UDT component finding(61.5%vs 11.1%,P=0.0009).Only 26.5%(13/49)of the lesions were diagnosed from the pretreatment biopsy as having a UDT component.Combined results of the pretreatment biopsy and ME-NBI showed the preoperative presence of the UDT component in 40.8%(20/49)of MT EGCs.CONCLUSION Recognition of a UDT component within MT EGCs is difficult even when pretreatment biopsy and ME-NBI are combined.Endoscopic resection plays a significant role in both treatment and diagnosis.

Oral esomeprazole vs injectable omeprazole for the prevention of hemorrhage after endoscopic submucosal dissection

AIM To evaluate the effectiveness of oral esomeprazole(EPZ) vs injectable omeprazole(OPZ) therapy to prevent hemorrhage after endoscopic submucosal dissection(ESD).METHODS A case-control study was conducted using a quasirandomized analysis with propensity score matching. A total of 258 patients were enrolled in this study. Patients were treated with either oral EPZ or injectable OPZ. The endpoint was the incidence of hemorrhage after ESD.RESULTS Data of 71 subjects treated with oral EPZ and 172 subjects treated with injectable OPZ were analyzed. Analysis of 65 matched samples revealed no difference in the incidence of hemorrhage after ESD between the oral EPZ and injectable OPZ groups(OR = 0.89, 95%CI:0.35-2.27, P ≥ 0.99).CONCLUSION We conclude that oral EPZ therapy is a useful alternative to injectable PPI therapy for the prevention of hemorrhage after ESD.

Shape of Barrett's epithelium is associated with prevalence of erosive esophagitis

AIM:To test the hypothesis that the shape and length of Barrett's epithelium are associated with prevalence of erosive esophagitis.METHODS:A total study population comprised 869 patients who underwent endoscopy during a health checkup at our hospital.The presence and extent of Barrett's epithelium were diagnosed based on the Prague C & M Criteria.We originally classified cases of Barrett's epithelium into two types based on its shape,namely,flamelike and lotus-like Barrett's epithelium,and into two groups based on its length,its C extent < 2 cm,and ≥ 2 cm.Correlation of shape and length of Barrett's epithelium with erosive esophagitis was examined.RESULTS:Barrett's epithelium was diagnosed in 374 cases(43%).Most of these were diagnosed as shortsegment Barrett's epithelium.The prevalence of erosive esophagitis was significantly higher in subjects with flame-like than lotus-like Barrett's epithelium,and in those with a C extent of ≥ 2 cm than < 2 cm.CONCLUSION:Flame-like rather than lotus-like Barrett's epithelium,and Barrett's epithelium with a longer segment were more strongly associated with erosive esophagitis.

Gender differences of low-dose aspirin-associated gastroduodenal ulcer in Japanese patients

AIM:To clarify the gender differences about the clini-cal features and risk factors of low-dose aspirin (LDA) (81-100 mg daily)-associated peptic ulcer in Japanese patients.METHODS: There were 453 patients under treatment with LDA (298 males, 155 females) who underwent esophagogastroduodenoscopy at the Department of Gastroenterology and Hepatology of Hiratsuka City Hospital between January 2003 and December 2007. They had kept taking the LDA or started treatmentduring the study period and kept taking LDA during the whole period of observation. Of these, 119 patients (87 males, 32 females) were diagnosed as having LDA-associated peptic ulcer. We examined the clinical factors associated with LDA-associated peptic ulcer in both sexes.RESULTS: A history of peptic ulcer was found to be the risk factor for LDA-associated peptic ulcer common to both sexes. In female patients, age greater than 70 years (prevalence ORs 8.441, 95% CI: 1.797-33.649, P = 0.0069) was found to be another significant risk fac-tor, and the time to diagnosis as having LDA-associat-ed peptic ulcer by endoscopy was significantly shorter than that in the male patients (P = 0.0050). CONCLUSION: We demonstrated gender differences about the clinical features and risk factors of LDA-asso-ciated peptic ulcer. Special attention should be paid to aged female patients taking LDA.

Case of a tumor comprising gastric cancer and duodenal neuroendocrine tumor

The present report describes a rare case of a tumor composed of early gastric cancer and a duodenal neuroendocrine tumor(NET). A 78-year-old woman underwent esophagogastroduodenoscopy at a local institution for screening of the upper gastrointestinal tract which revealed a protruded tumor through the pyloric ring from the pyloric antrum. The tumor was too large to treat at the facility; consequently, she was referred to our hospital for further management. Esophagogastroduodenoscopy with tumor biopsy of the lesion revealed the diagnosis of early gastric cancer. Endoscopic submucosal dissection was performed with sufficient free margins in both vertical and horizontal directions. Histopathological findings showed NET confined to the submucosal layer and covered by welldifferentiated adenocarcinoma. Immunohistochemical stainings showed that the two lesions existed continuously. While the possibility of a collision cancer was considered, it was suggested that the two lesions existed continuously. Finally, the tumor was diagnosed as gastric cancer composed of duodenal NET G1, with a lymphatic invasion of NET component.

Rescue case of low birth weight infant with acute hepatic failure

We report a case involving a rescued low birth weight infant(LBWI) with acute liver failure. Case: The patient was 1594 g and 32^(3/7) gestational wk at birth. At the age of 11 d, she developed acute liver failure due to gestational alloimmune liver disease. Exchange transfusion and high-dose gamma globulin therapy were initiated, and body weight increased with enteral nutrition. Exchange transfusion was performed a total of 33 times prior to living donor liver transplantation(LDLT). Her liver dysfunction could not be treated by medications alone. At 55 d old and a body weight of 2946 g, she underwent LDLT using an S2 monosegment graft from her mother. Three years have passed with no reports of intellectual disability or liver dysfunction. LBWIs with acute liver failure may be rescued by LDLT after body weight has increased to over 2500 g.

Consensus of primary care in acute pancreatitis in Japan

在日本的尖锐胰腺炎的发生正在增加并且每百万张人口从 187 ～ 347 个盒子。盒子命运是 0.2% 为对温和中等，并且 9.0% 为在在 2003 的日本的严重尖锐胰腺炎。在日本的胰腺炎的专家做了与尖锐胰腺炎在病人的早管理集中于实际方面的这个文件。尖锐胰腺炎和严厉层化的正确诊断应该为尖锐胰腺炎的诊断用标准在所有病人被做并且多，因素得分系统尽早由胰的难处理的疾病的研究委员会求婚了。与尖锐胰腺炎诊断的所有病人应该在医院里被管理。血压监视，脉搏和呼吸率，体温，时时尿的体积，和血氧饱和水平在如此的病人的管理是必要的。早精力旺盛的静脉内的水和具有最前的重要性稳定循环动力学。有鸦片剂的足够的疼痛地势也是重要的。在严重尖锐胰腺炎，在一个早阶段的抗菌素的预防静脉内的管理被推荐。一旦尖锐胰腺炎的诊断被证实，朊酶禁止者的管理应该被开始。如果没有肠塞痛并且胃肠的流血的清楚的症状，从早舞台用非肠道的营养喂的肠内的联合被推荐。有严重尖锐胰腺炎的病人应该尽早被转移到 ICU 执行象朊酶的连续地区性的动脉的注入那样的特殊措施禁止者和抗菌素，和连续牙齿过敏过滤。日本政府为难处理的疾病作为关于措施的研究的工程之一为严重尖锐胰腺炎盖住医疗保健开销。

Rate of local tumor progression following radiofrequency ablation of pathologically early hepatocellular carcinoma

AIM To evaluate whether pathologically early hepatocellular carcinoma(HCC) exhibited local tumor progression after radiofrequency ablation(RFA) less often than typical HCC.METHODS Fifty pathologically early HCCs [tumor diameter(mm): mean, 15.8; range, 10-23; follow-up days after RFA: median, 1213; range, 216-2137] and 187 typical HCCs [tumor diameter(mm): mean, 15.6; range, 6-30; follow-up days after RFA: median, 1116; range, 190-2328] were enrolled in this retrospective study. The presence of stromal invasion(namely, tumor cell invasion into the intratumoral portal tracts) was considered to be the most important pathologic finding for the diagnosis of early HCCs. Typical HCC was defined as the presence of a hyper-vascular lesion accompanied by delayed washout using contrastenhanced computed tomography or contrast-enhanced magnetic resonance imaging. Follow-up examinations were performed at 3-mo intervals to monitor for signs of local tumor progression. The local tumor progression rates of pathologically early HCCs and typical HCCs were then determined using the Kaplan-Meier method.RESULTS During the follow-up period for the 50 pathologically early HCCs, 49(98%) of the nodules did not exhibit local tumor progression. However, 1 nodule(2%) was associated with a local tumor progression found 636 d after RFA. For the 187 typical HCCs, 46(24.6%) of the nodules exhibited local recurrence after RFA. The follow-up period until the local tumor progression of typical HCC was a median of 605 d, ranging from 181 to 1741 d. Among the cases with typical HCCs, local tumor progression had occurred in 7.0%(7/187), 16.0%(30/187), 21.9%(41/187) and 24.6%(46/187) of the cases at 1, 2, 3 and 4 years, respectively. Pathologically early HCC was statistically associated with a lower rate of local tumor progression, compared with typical HCC, when evaluated using a log-rank test(P = 0.002). CONCLUSION The rate of local tumor progression for pathologically early HCCs after RFA was significantly lower than that for typical HCCs.

Two-stage treatment of an unusual haemobilia caused by intrahepatic pseudoaneurysm

A 84-year-old man with a surgical history of subtotal gastrectomy for gastric cancer was transferred to our department because of a disorder of consciousness. Septic shock due to obstructive suppurative cholangitis secondary to choledocholithiasis was diagnosed. Anemia was also present,and upper gastrointestinal tract endoscopy revealed blood emerging from the Papilla of Vater.The cause of the anemia was identified as haemobilia.Angiography showed a small aneurysm over the artery on segment 3(A3) .The cause of the haemobilia was suspected to be the bleeding into the biliary tree from this aneurysm.Because the patient's general condition was poor,minimally invasive therapy was needed.Transcatheter arterial embolization(TAE) was selected initally.Later,lateral sectionectomy was performed in order to remove the aneurysm on A3. No surgical complication occurred and,after surgery,no haemobilia was identified.In conclusion,a twostage treatment,namely,surgery following TAE,is recommended for patients in a physically poor condition who have haemobilia due to intrahepatic aneurysm.

Predicting differentiation potential of human pluripotent stem cells:Possibilities and challenges

The capability of human pluripotent stem cell(hPSC)lines to propagate indefinitely and differentiate into derivatives of three embryonic germ layers makes these cells be powerful tools for basic scientific research and promising agents for translational medicine.However,variations in differentiation tendency and efficiency as well as pluripotency maintenance necessitate the selection of hPSC lines for the intended applications to save time and cost.To screen the qualified cell lines and exclude problematic cell lines,their pluripotency must be confirmed initially by traditional methods such as teratoma formation or by highthroughput gene expression profiling assay.Additionally,their differentiation potential,particularly the lineage-specific differentiation propensities of hPSC lines,should be predicted in an early stage.As a complement to the teratoma assay,RNA sequencing data provide a quantitative estimate of the differentiation ability of hPSCs in vivo.Moreover,multiple scorecards have been developed based on selected gene sets for predicting the differentiation potential into three germ layers or the desired cell type many days before terminal differentiation.For clinical application of hPSCs,the malignant potential of the cells must also be evaluated.A combination of histologic examination of teratoma with quantitation of gene expression data derived from teratoma tissue provides safety-related predictive information by detecting immature teratomas,malignancy marker expression,and other parameters.Although various prediction methods are available,distinct limitations remain such as the discordance of results between different assays and requirement of a long time and high labor and cost,restricting their wide applications in routine studies.Therefore,simpler and more rapid detection assays with high specificity and sensitivity that can be used to monitor the status of hPSCs at any time and fewer targeted markers that are more specific for a given desired cell type are urgently needed.

Relapse of both small cell lung cancer and Lambert-Eaton myasthenic syndrome after a 13-year disease-free survival period

Lambert-Eaton myasthenic syndrome(LEMS) is a paraneoplastic syndrome and only 3%of small cell lung carcinoma(SCLC) patients have LEMS.Moreover,the recurrence of SCLC after a disease-free survival(DFS) of more than 10 years is rare.We report a patient who had a recurrence of both SCLC and LEMS after a 13-year DFS period.A 69-year-old man was diagnosed with LEMS and SCLC(cT0N2M0,stage ⅢA) 13 years ago.Chemoradiotherapy was performed and a complete response was achieved.With anticancer treatment,the LEMS symptoms was alleviated.At the age of 82 years,gait disturbance appeared followed by left supraclavicular lymphadenopathy and further examination revealed the recurrence of SCLC.Careful screening for the recurrence of SCLC might be needed when the patient has recurrent or secondary paraneoplastic neurological syndrome even after a long DFS period.

Efficacy of neoadjuvant chemotherapy for initially resectable colorectal liver metastases:A retrospective cohort study

BACKGROUND The liver is the most common metastatic site of colorectal cancer.Hepatectomy is the mainstay of treatment for patients with colorectal liver metastases(CRLMs).However,there are cases of early recurrence after upfront hepatectomy alone.In selected high-risk patients,neoadjuvant chemotherapy(NAC)may improve longterm survival.AIM To determine the efficacy of NAC for initially resectable CRLMs.METHODS Among 644 patients who underwent their first hepatectomy for CRLMs at our institution,297 resectable cases were stratified into an upfront hepatectomy group(238 patients)and a NAC group(59 patients).Poor prognostic factors for upfront hepatectomy were identified using multivariate logistic regression analysis.Propensity score matching was used to compare clinical outcomes between the upfront hepatectomy and NAC groups,according to the number of poor prognostic factors.Survival curves were estimated using the Kaplan-Meier method and compared using the log-rank test.RESULTS Preoperative carcinoembryonic antigen levels(≥10 ng/mL)(P=0.003),primary histological type(other than well/moderately differentiated)(P=0.04),and primary lymph node metastases(≥1)(P=0.04)were identified as independent poor prognostic factors for overall survival(OS)in the upfront hepatectomy group.High-risk status was defined as the presence of two or more risk factors.After propensity score matching,50 patients were matched in each group.Among high-risk patients,the 5-year OS rate was significantly higher in the NAC group(13 patients)than in the upfront hepatectomy group(18 patients)(100%vs 34%;P=0.02).CONCLUSION NAC may improve the prognosis of high-risk patients with resectable CRLMs who have two or more risk factors.

Effectiveness of entecavir in preventing hepatocellular carcinoma development is genotype-dependent in hepatitis B virus-associated liver cirrhosis

BACKGROUND The oral nucleos(t)ide analogue,entecavir(ETV)was demonstrated to reduce the rate of hepatocellular carcinoma(HCC)in patients with hepatitis B virus(HBV)-associated liver cirrhosis.However,the reduction of HCC differs in various regions of the world.AIM To investigate the reduction of HCC development due to ETV therapy by metaanalysis.METHODS We surveyed the differences in HCC development following ETV treatment based on published articles using PubMed(2004-2019).RESULTS The regions with the most marked reduction in HCC development due to ETV therapy were Spain(1.0%/year)and Canada(Southern part,1.3%/year),and the most ineffective areas were South Korea(3.6%-3.8%/year),China(3.3%/year),Taiwan(2.4%-3.1%/year),and Hong Kong(2.8%/year).Following ETV administration,the incidence of HCC in genotype D regions(1.89%±0.28%/year,mean±SE)was significantly lower than that in genotype C regions(2.91%±0.24%/year,P<0.01).With regard to the initial HBV-DNA level,in genotype C patients(average:5.61 Log10IU/mL)this was almost the same as that in genotype D patients(average:5.46 Log10IU/mL).Moreover,there was no association between the prevalence ratio of HBV and the incidence of HCC on ETV treatment.CONCLUSION The effectiveness of ETV in preventing HCC development in HBV-associated liver cirrhosis is genotype-dependent.

Comparison of unenhanced magnetic resonance imaging and ultrasound in detecting very small hepatocellular carcinoma

BACKGROUND In hepatocellular carcinoma(HCC),detection and treatment prior to growth beyond 2 cm are important as a larger tumor size is more frequently associated with microvascular invasion and/or satellites.In the surveillance of very small HCC nodules(≤2 cm in maximum diameter,Barcelona clinical stage 0),we demonstrated that the tumor markers alpha-fetoprotein and PIVKA-Ⅱare not so useful.Therefore,we must survey with imaging modalities.The superiority of magnetic resonance imaging(MRI)over ultrasound(US)to detect HCC was confirmed in many studies.Although enhanced MRI is now performed to accurately diagnose HCC,in conventional clinical practice for HCC surveillance in liver diseases,unenhanced MRI is widely performed throughout the world.While,MRI has made marked improvements in recent years.AIM To make a comparison of unenhanced MRI and US in detecting very small HCC that was examined in the last ten years in patients in whom MRI and US examinations were performed nearly simultaneously.METHODS In 394 patients with very small HCC nodules,those who underwent MRI and US at nearly the same time(on the same day whenever possible or at least within 14 days of one another)at the first diagnosis of HCC were selected.The detection rate of HCC with unenhanced MRI was investigated and compared with that of unenhanced US.RESULTS The sensitivity of unenhanced MRI for detecting very small HCC was 95.1%(97/102,95%confidence interval:90.9-99.3)and that of unenhanced US was 69.6%(71/102,95%confidence interval:60.7-78.5).The sensitivity of unenhanced MRI for detecting very small HCC was significantly higher than that of unenhanced US(P<0.001).Regarding the location of HCC in the liver in patients in whom detection by US was unsuccessful,S7-8 was identified in 51.7%.CONCLUSION Currently,unenhanced MRI is a very useful tool for the surveillance of very small HCC in conventional clinical follow-up practice.