Modulation of valosin-containing protein by Kyoto University Substances(KUS) as a novel therapeutic strategy for ischemic neuronal diseases

Retinal ischemia causes several vision-threatening diseases, including diabetic retinopathy, retinal artery occlusion, and retinal vein occlusion. Intracellular adenosine triphosphate（ATP） depletion and subsequent induced endoplasmic reticulum（ER） stress are proposed to be the underlying mechanisms of ischemic retinal cell death. Recently, we found that a naphthalene derivative can inhibit ATPase activity of valosin-containing protein, universally expressed within various types of cells, including retinal neural cells, with strong cytoprotective activity. Based on the chemical structure, we developed novel valosin-containing protein modulators, Kyoto University Substances（KUSs）, that not only inhibit intracellular ATP depletion, but also ameliorate ER stress. Suppressing ER stress by KUSs is associated with neural cell survival in animal models of several neurodegenerative diseases, such as glaucoma and retinal degeneration. Given that a major pathology of ischemic retinal diseases, other than intracellular ATP depletion, is ER stress-induced cell death, KUSs may provide a novel strategy for cell protection in ischemic conditions. Hence, we investigated the efficacy of KUS121 in a rat model of retinal ischemic injury. Intravitreal injections of KUS121, which is clinically preferable route of drug administration in retinal diseases, significantly suppressed inner retinal thinning and retinal cell death, and maintained visual functions. Valosin-containing protein modulation by KUS is a promising novel therapeutic strategy for ischemic retinal diseases.

Stage at diagnosis of colorectal cancer through diagnostic route:Who should be screened?

BACKGROUND Colorectal cancer(CRC)is a global health concern,with advanced-stage diagnoses contributing to poor prognoses.The efficacy of CRC screening has been well-established;nevertheless,a significant proportion of patients remain unscreened,with>70%of cases diagnosed outside screening.Although identifying specific subgroups for whom CRC screening should be particularly recommended is crucial owing to limited resources,the association between the diagnostic routes and identification of these subgroups has been less appreciated.In the Japanese cancer registry,the diagnostic routes for groups discovered outside of screening are primarily categorized into those with comorbidities found during hospital visits and those with CRC-related symptoms.AIM To clarify the stage at CRC diagnosis based on diagnostic routes.METHODS We conducted a retrospective observational study using a cancer registry of patients with CRC between January 2016 and December 2019 at two hospitals.The diagnostic routes were primarily classified into three groups:Cancer screening,follow-up,and symptomatic.The early-stage was defined as Stages 0 or I.Multivariate and univariate logistic regressions were exploited to determine the odds of early-stage diagnosis in the symptomatic and cancer screening groups,referencing the follow-up group.The adjusted covariates were age,sex,and tumor location.RESULTS Of the 2083 patients,715(34.4%),1064(51.1%),and 304(14.6%)belonged to the follow-up,symptomatic,and cancer screening groups,respectively.Among the 2083 patients,CRCs diagnosed at an early stage were 57.3%(410 of 715),23.9%(254 of 1064),and 59.5%(181 of 304)in the follow-up,symptomatic,and cancer screening groups,respectively.The symptomatic group exhibited a lower likelihood of early-stage diagnosis than the follow-up group[P<0.001,adjusted odds ratio(aOR),0.23;95%confidence interval(95%CI):0.19-0.29].The likelihood of diagnosis at an early stage was similar between the follow-up and cancer screening groups(P=0.493,aOR for early-stage diagnosis in the cancer screening group vs follow-up group=1.11;95%CI=0.82-1.49).CONCLUSION CRCs detected during hospital visits for comorbidities were diagnosed earlier,similar to cancer screening.CRC screening should be recommended,particularly for patients without periodical hospital visits for comorbidities.

Therapeutic applications of curcumin for patients with pancreatic cancer

A number of preclinical studies have demonstrated anticancer effects for curcumin in various types of tumors,including pancreatic cancer.Curcumin has anticancer effects both alone and in combination with other anticancer drugs(e.g.,gemcitabine,5-fluorouracil,and oxaliplatin),and it has been shown to modulate a variety of molecular targets in preclinical models,with more than30 molecular targets identified to date.Of these various molecules,NF-kB is thought to be one of the primary targets of curcumin activity.Based on these promising preclinical results,several research groups,including our own,have progressed to testing the anticancer effects of curcumin in clinical trials;however,the poor bioavailability of this agent has been the major challenge for its clinical application.Despite the ingestion of gram-level doses of curcumin,plasma curcumin levels remain at low(ng/mL)levels in patients,which is insufficient to yield the anticancer benefits of curcumin.This problem has been solved by the development of highly bioavailable forms of curcumin(THERACURMIN),and higher plasma curcumin levels can now be achieved without increased toxicity in patients with pancreatic cancer.In this article,we review possible therapeutic applications of curcumin in patients with pancreatic cancer.

Progressive familial intrahepatic cholestasis

BACKGROUND:Three types of progressive familial intrahepatic cholestasis(PFIC)have been identified,but their etiologies include unknown mechanisms. DATA SOURCES:A PubMed search on'progressive familial intrahepatic cholestasis'and'PFIC'was performed on the topic,and the relevant articles were reviewed. RESULTS:The etiologies of the three PFIC types still include unknown mechanisms.Especially in PFIC type 1,enterohepatic circulation of bile acid should be considered.Ursodeoxycholic acid,partial external biliary diversion and liver transplantation have been used for the treatment of PFIC patients according to disease course. CONCLUSIONS:Since the etiologies and disease mechanisms of PFIC are still unclear,detailed studies are urgently required. Strategies for more advanced therapies are also needed.These developments in the future are indispensable,especially for PFIC type 1 patients.

Comprehensive and innovative techniques for livertransplantation in rats: A surgical guide

AIM: To investigate our learning curves of orthotopic liver transplantation (OLT) in rats and the most important factor for successful surgery. METHODS: We describe the surgical procedures for our rat OLT model, and determined the operator learning curves. The various factors that contributed to successful surgery were determined. The most important surgical factors were evaluated between successful and unsuccessful surgeries.RESULTS: Learning curve data indicated that 50 cases were required for operator training to start a study. Operative time, blood loss, warm ischemic time, anhepatic phase, unstable systemic hemodynamic state, and body temperature after surgery significantly affected surgery success by univariate analysis, while the anhepatic phase was the most critical factor for success by multivariate analysis. CONCLUSION: OLT in rats is the only liver transplantation model that provides clinically relevant and reliable results. Shortened anhepatic phase is key to success in this model.

Is biliary bile acid a good predictor for acute cellular rejection in living donor liver transplantation?

BACKGROUND:In liver transplantation,acute cellular rejection(ACR)is still a major complication that can lead to mortality.Bile secretion has been considered as a marker of early graft function. METHODS:The study included 41 adults who received living donor liver transplantation(LDLT)at Kyoto University Hospital between April 2007 and February 2008. The patients were stratified according to the presence or absence of ACR.Bile samples were collected from donors once and from recipients every other day for the first 2 weeks after transplantation.Total bile acid(BA)and taurine-conjugated bile acid(TCBA)in bile were measured by magnetic resonance spectroscopy.The recipient/donor (R/D)BA ratio and R/D TCBA ratio were calculated. RESULTS:The ACR group(n=12)showed a greater decrease in BA post-transplantation than the non-ACR group,but this difference was not statistically significant. On both day 7 and day 9 post-transplantation the R/D TCBA was significantly different between the two groups (P=0.038 on day 7 and P=0.036 on day 9).The R/D TCBA ratio≥0.5 on days 7 and 9,and≥0.38 on day 11 post- transplantation were associated with better ACR-free survival. CONCLUSION:The recipient/donor TCBA ratio can be a predictor for ACR after LDLT as early as post- transplantation day 7.

Effect of ONO-4057 and tacrolimus on ischemia-reperfusion injury of the liver

AIM: To investigate the effects of a novel Leukotriene B4 receptor antagonist and/or tacrolimus on ischemia-reperfusion in a rat liver model. METHODS: Male Lewis rats were pretreated with ONO-4057 (100 mg/kg) and/or tacrolimus (1 mg/kg) orally, and divided into four experimental groups; group 1 (control), group 2 (ONO-4057), group 3 (tacrolimus), group 4 (ONO-4057 + tacrolimus). RESULTS: There was a tendency for long survival in the groups treated with tacrolimus alone and ONO-4057 plus tacrolimus. Post-reperfusion serum aspartate aminotransferase levels decreased more signif icantly in ONO-4057 plus tacrolimus group (P < 0.01), than in the tacrolimus alone group (P < 0.05), compared to controls. CONCLUSION: This study demonstrated that pretreat-ment with ONO-4057 in combination with tacrolimus produced additive effects in a rat model of liver isch-emia-reperfusion injury.

Protocol for laparoscopic cholecystectomy: Is it rocket science?

Laparoscopic cholecystectomy(LC) does not require advanced techniques, and its performance has therefore rapidly spread worldwide. However, the rate of biliary injuries has not decreased. The concept of the critical view of safety(CVS) was first documented two decades ago. Unexpected injuries are principally due to misidentification of human factors. The surgeon's assumption is a major cause of misidentification, and a high level of experience alone is not sufficient for successful LC. We herein describe tips and pitfalls of LC in detail and discuss various technical considerations.Finally, based on a review of important papers and our own experience, we summarize the following mandatory protocol for safe LC:(1) consideration that a high level of experience alone is not enough;(2) recognition of the plateau involving the common hepatic duct and hepatic hilum;(3) blunt dissection until CVS exposure;(4) Calot's triangle clearance in the overhead view;(5) Calot's triangle clearance in the view from underneath;(6) dissection of the posterior right side of Calot's triangle;(7) removal of the gallbladder body; and(8) positive CVS exposure. We believe that adherence to this protocol will ensure successful and beneficial LC worldwide, even in patients with inflammatory changes and rare anatomies.

Systemic hemodynamics in advanced cirrhosis: Concerns during perioperative period of liver transplantation

Advanced liver cirrhosis is usually accompanied by portal hypertension. Long-term portal hypertension results in various vascular alterations. The systemic hemodynamic state in patients with cirrhosis is termed a hyperdynamic state. This peculiar hemodynamic state is characterized by an expanded blood volume, high cardiac output, and low total peripheral resistance. Vascular alterations do not disappear even long after liver transplantation(LT), and recipients with cirrhosis exhibit a persistent systemic hyperdynamic state even after LT. Stability of optimal systemic hemodynamics is indispensable for adequate portal venous flow(PVF) and successful LT, and reliable parameters for optimal systemic hemodynamics and adequate PVF are required. Even a subtle disorder in systemic hemodynamics is precisely indicated by the balance between cardiac output and blood volume. The indocyanine green(ICG) kinetics reflect the patient's functional hepatocytes and effective PVF, and PVF is a major determinant of the ICG elimination constant(kICG) in the well-preserved allograft. The kICG value is useful to set the optimal PVF during living-donor LT and to evaluate adequate PVF after LT. Perioperative management has a large influence on the postoperative course and outcome; therefore, key points and unexpected pitfalls for intensive management are herein summarized. Transplant physicians should fully understand the peculiar systemic hemodynamic behavior in LT recipients with cirrhosis and recognize the critical importance of PVF after LT.

Laparoscopic approach for choledochojejunostomy

Laparoscopic hepatobiliary and pancreatic (HBP) surgery has been developed slowly because of technical challenges and a protracted learning curve with the exception of laparoscopic cholecystectomy [1]. Surgical treatments for benign diseases of the extrahepatic bile duct (EHBD) are classified according to their therapeutic purpose as lithotomy (i.e., choledocholithotomy) or diversion (i.e., choledochojejunostomy)[2].

Unexpected metastasis of intraductal papillary neoplasm of the bile duct without an invasive component to the brain and lungs:A case report

BACKGROUND Despite an expanding number of studies on intraductal papillary neoplasm of the bile duct(IPNB),distant metastasis remains unexplained especially in cases of carcinoma in situ.In the present study,we report a rare and interesting case of IPNB without invasive components that later metastasized to lungs and brain.CASE SUMMARY A 69-year-old male was referred to our hospital due to suspected cholangiocarcinoma.Laboratory tests on admission reported a mild elevation of alkaline phosphatase,γ-glutamyl transpeptidase,and total bilirubin in serum.Endoscopic retrograde cholangiography revealed a filling defect in the common bile duct(CBD)extending to the left hepatic duct.Peroral cholangioscopy delineated a tumor in the CBD that had a papillary pattern.Multidetector computed tomography and magnetic resonance cholangiopancreatography detected partial blockage ot interlude in the CBD leading to cholestasis without evidence of metastasis.Therefore,a diagnosis of IPNB cT1N0M0 was established.Left hepatectomy with bile duct reconstruction was performed.Pathological examination confirmed an intraepithelial neoplasia pattern without an invasive component and an R0 resection achievement.The patient was monitored carefully by regular examinations.However,at 32 mo after the operation,a 26 mm tumor in the lungs and a 12 mm lesion in the brain were detected following a suspicious elevated CA 19-9 level.Video-assisted thoracoscopic surgery of left upper lobectomy and stereotactic radiotherapy are indicated.In addition to histopathological results,a genomic profiling analysis using whole exome sequencing subsequently confirmed lung metastasis originating from bile duct cancer.CONCLUSION This case highlights the important role of genomic profiling analysis using whole exome sequencing in identifying the origin of metastasis in patients with IPNB.

Thrombotic microangiopathy-like disorder after living-donor liver transplantation:A single-center experience in Japan

AIM:To investigate thrombotic microangiopathy (TMA)in liver transplantion,because TMA is an infrequent but life-threatening complication in the transplantation field. METHODS:A total of 206 patients who underwent living-donor liver transplantation (LDLT) were evaluated,and the TMA-like disorder (TMALD) occurred in seven recipients. RESULTS:These TMALD recipients showed poor outcomes in comparison with other 199 recipients. Although two TMALD recipients successfully recovered,the other five recipients finally died despite intensive treatments including repeated plasma exchange (PE) and re-transplantation. Histopathological analysis of liver biopsies after LDLT revealed obvious differences according to the outcomes. Qualitative analysis of antibodies against a disintegrin-like domain and metalloproteinase with thrombospondin type 1 motifs (ADAMTS-13) were negative in all patients. The fragmentation of red cells,the microhemorrhagic macules and the platelet counts were early markers for the suspicion of TMALD after LDLT. Although the absolute values of von Willebrand factor (vWF) and ADAMTS-13 did not necessarily reflect TMALD,the vWF/ADAMTS-13 ratio had a clear diagnostic value in all cases. The establishment of adequate treatments for TMALD,such as PE for ADAMTS-13 replenishment or treatments against inhibitory antibodies,must be decided according to each case. CONCLUSION:The optimal induction of adequate therapies based on early recognition of TMALD by the reliable markers may confer a large advantage for TMALD after LDLT.

Overexpression of ETS-1 is associated with malignan＇ biological features of prostate cancer

E26 transformation-specific-1 （ETS-1）, an ETS family transcription factor, has been reported to play an important role in a variety of physiological and pathological processes, but clinical implications of ETS-1 expression in prostate cancer （PCa）, particularly high-risk cases, including response to androgen-deprivation therapy （ADT） have yet to be elucidated. We examined the expression of ETS- 1 using immunohistochemical staining of paraffin-embedded prostate carcinoma tissue obtained by needle biopsy from 69 mostly advanced PCa patients. ETS-1 expression was compared with the clinicopathological characteristics of the 69 patients, including 25 who underwent ADT as a primary treatment. As a result, PCa patients with higher expression of ETS-1 were significantly more likely to be of high stage and high Gleason score （P〈O.05）. There was no significant association between ETS-1 expression and the initial prostate-specific antigen （PSA） level. In the 25 patients treated by ADT, the staining score for ETS-1 was significantly associated with rapid development of castration-resistant disease within 24 months （P〈O.05）, whereas the Gleason score and PSA level were not. In conclusion, increased ETS-1 expression was associated with a higher stage, higher Gleason score and shorter time to castration-resistant progression. These data suggest that immunostaining for ETS-1 could be a molecular marker for predicting a poor clinical outcome for PCa patients, oarticularlv those with hi^h-risk disease.

Spontaneous necrosis of solid gallbladder adenocarcinoma accompanied with pancreaticobiliary maljunction

A 71-year-old Japanese man with acute cholecystitis and an incarcerated gallbladder (GB) stone was admitted. Plain ultrasonography (US) incidentally detected a mass-like lesion in the fundus. Doppler US revealed that this elevated lesion had no blood flow. Computed tomography showed a relatively low-density mass, measuring 5 cm x 4 cm in diameter, with no positive enhancement. Magnetic resonance imaging showed a mass in the fundus with a slightly low intensity on T1-weighted images and a slightly high intensity on T2-weighted images. We were agonized in making the qualitative diagnosis of mass-like lesions of the fundus, such as a benign tumor, cancer, or debris. We performed laparoscopic cholecystectomy, because the incarcerated GB stone clearly caused acute cholecystitis. Intra-operative cholangiography clearly revealed pancreaticobiliary maljunction. Amylase levels in the common bile duct and gallbladder were quite high. The elevated lesion in the fundus clearly showed severe necrosis. Although this necrotic nodule included non-viable adenocarcinoma cells, viable cancer cell nests were located in the muscularis propria and subcutaneous layer. Histopathological examinationconfirmed a solid adenocarcinoma. Thus, we diagnosed it as a gallbladder cancer, based on histopathological analysis of the resected specimen. We therefore undertook radical surgery, including wedge resection of the liver, radical dissection of regional lymph nodes, and resection of the extrahepatic bile duct. Histopathological findings revealed no cancer, hyperplasia or dysplasia in the additionally resected specimens. The patient was finally staged as T2, N0, H0, P0, M(-), stage Ⅱ. We present the first case of spontaneous necrosis of solid gallbladder adenocarcinoma, with a review of previous studies.

Stability of cirrhotic systemic hemodynamics ensures sufficient splanchnic blood flow after living-donor liver transplantation in adult recipients with liver cirrhosis

AIM: To investigate the correlation between systemic hemodynamics and splanchnic circulation in recipients with cirrhosis undergoing living-donor liver transplantation (LDLT), and to clarify how systemic hemodynamics impact on local graft circulation after LDLT. METHODS: Systemic hemodynamics, indocyanine green (ICG) elimination rate (KICG) and splanchnic circulation were simultaneously and non-invasively investigated by pulse dye densitometry (PDD) and ultrasound. Accurate estimators of optimal systemic hyperdynamics after LDLT [i.e., balance of cardiac output (CO) to blood volume (BV) and mean transit time (MTT), defined as the timerequired for half the administered ICG to pass through an attached PDD sensor in the first circulation] were also measured. Thirty recipients with cirrhosis were divided into two groups based on clinical outcomes corresponding to postoperative graft function. RESULTS: Cirrhotic systemic hyperdynamics characterized by high CO, expanded BV and low total peripheral resistance (TPR) were observed before LDLT. TPR reflecting cirrhotic vascular alterations was slowly restored after LDLT in both groups. Although no significant temporal differences in TPR were detected between the two groups, CO/BV and MTT differed significantly. Recipients with good outcomes showed persistent cirrhotic systemic hyperdynamics after LDLT, whereas recipients with poor outcomes presented with unstable cirrhotic systemic hyperdynamics and severely decreased KICG. Systemic hyperdynamic disorders after LDLT impacted on portal venous flow but not hepatic arterial flow. CONCLUSION: We conclude that subtle systemic hyperdynamics disorders impact on splanchnic circulation, and that an imbalance between CO and BV decreases portal venous flow, which results in critical outcomes.

Assessment of cardiac output in liver transplantation recipients

BACKGROUND:Liver cirrhosis causes peculiar systemic hemodynamics,and accurate evaluation of systemic hemodynamic state is important for cirrhotic recipients who underwent living donor liver transplantation(LDLT). We investigated the clinical advantages of a novel non- invasive method for measuring systemic hemodynamic parameters using indocyanine green(ICG). METHODS:Twenty-eight LDLT recipients were evaluated. Simultaneous measurements of cardiac output(CO)using Swan-Ganz catheters and pulse dye densitometry(PDD) were performed every 12 hours after LDLT.A total of 155 sets of simultaneous CO measurements were obtained. RESULTS:The CO values obtained by PDD correlated well with those obtained by the invasive catheter technique.In addition,none of the recipients developed any side-effects, and we verified the safety of repeated ICG injections.ICG is safe,even for repeated use over time in the same recipient. Moreover,PDD can measure the blood volume(BV).CONCLUSIONS:Since the cirrhotic systemic hemody- namics characterized by high CO and large BV remains, even after LDLT,the ability to measure CO and BV in a non-invasive,simple and real-time manner using PDD has advantages for cirrhotic LDLT recipients.

Redox regulation of mast cell histamine release in thioredoxin-1 （TRX） transgenic mice

Thioredoxin-1 (TRX ) 是有抗氧化、反煽动性的效果的压力可诱导的氧化还原作用规章的蛋白质。这里，我们证明从高亲密关系的受体的 cross-linking 为 IgE (FcepsilonRI ) 得到的桅杆房间的组织安的版本显著地在 TRX 被压制转基因(TRX-tg ) 与野类型(WT ) 相比的老鼠老鼠。IgE 和抗原刺激的桅杆房间的细胞内部的反应的氧种类(ROS ) 也与 WT 老鼠相比在 TRX-tg 老鼠被减少。而从响应 2,4-dinitrophenylated 的桅杆房间在 cytokines (IL-6 和 TNF-alpha ) 的生产没有差别在 TRX-tg 和 WT 老鼠的牛的浆液白朊(DNP-BSA ) 刺激。TRX-tg 老鼠的免疫学的地位倾向了 T 助手(Th ) 2 在主要有免疫力的反应主导，尽管在树枝状的房间(DC ) 和规章的 T 房间的人口没有差别。我们断定从在 TRX-tg 老鼠的桅杆房间的组织安版本被 ROS 产生的抑制压制。当 ROS 涉及桅杆房间激活并且便于调停人版本， TRX 可以是在在桅杆房间和过敏发炎发信号的 IgE 调整早事件的一个关键发信号分子。

Inferior mesenteric arteriovenous fistula during treatment with bevacizumab in colorectal cancer patient: A case report

BACKGROUND Fistula formation is a severe adverse event related to antiangiogenetic agents such as bevacizumab and inferior mesenteric arteriovenous fistula(IMAVF) is a result of acquired factor, especially colon surgery. However, IMAVF occurs very rarely and there are few reports in patients during chemotherapy. We report a case of a patient who developed IMAVF during treatment with bevacizumab in metastatic colorectal cancer(mCRC) after colon surgery.CASE SUMMARY An 81-year-old man was diagnosed with descending colon cancer and underwent left hemicolectomy without any complications. He was definitely diagnosed with high-risk stage 2 and received tegafur-uracil plus leucovorin as adjuvant chemotherapy. Three years and 6 mo after the operation, the cancer relapsed with peritoneal dissemination. The patient underwent CyberKnife radiosurgery targeting the recurrent tumor and received chemotherapy with S-1 plus bevacizumab. At 1 year after chemotherapy, he complained of severe diarrhea, which is suspected drug-induced colitis. As diarrhea worsened despite the termination of treatment, he underwent colonoscopy and computed tomography (CT) scans that revealed edematous change from sigmoid to rectosigmoid colon. CT scans also revealed an aneurysm adjacent to the inferior mesenteric vein and multidetector CT angiography showed the IMAVF. Elective angiography confirmed the diagnosis of an IMAVF and it was successfully treated by arterial embolization. The patient resumed chemotherapy with only S-1 6 mo after embolization.CONCLUSION Clinicians should keep in mind the probability of severe diarrhea arose from IMAVF in mCRC patients treated with bevacizumab.

Fifty-Year-Follow-up Results Compared with Shorter Follow-up of Breast Cancer Patients Undergoing Radical Mastectomy with or without Adjuvant Radiotherapy

Background: To evaluate the effect of follow-up length on the outcome of breast cancer patients, we compared the 50- and 25-year follow-up results in terms of cure rate, overall mortality and mortalities from breast cancer, second cancer, and benign diseases. Methods: 763 patients treated for breast cancer between February 1953 and September 1976, were followed up until December 2014. They were divided into two cohorts;earlier cohort exclusively underwent radical mastectomy plus adjuvant radiotherapy, while later cohort had radical mastectomy alone. Assuming that in all patients follow-up was terminated at 50 or 25 years after diagnosis, likelihood ratio test and stratified Log-rank tests were performed to evaluate the differences in cure rate and overall survival between the two cohorts. Results: During the 50 years, radical mastectomy alone compared with radical mastectomy plus adjuvant radiotherapy is associated with a significantly higher cure rate, and higher survivals regardless of whether the death was from breast cancer, second cancer, benign causes or any causes. However, if follow-up information is limited to 25 years, the advantage of radical mastectomy alone is partly offset and the survival difference between the two cohorts becomes less significant. Conclusion: Radiotherapy to breast cancer may adversely affect not only mortality from breast cancer, but mortalities unrelated to breast cancer. Since such deaths occur later, they may fail to be detected unless follow-up is long enough. Thus, deleterious effects of radiotherapy may be underestimated. Exceedingly long follow-up is required to accurately estimate the cure rate and the long-term effect of radiotherapy.

Diagnostic Accuracy and Complication Rates of Fusion Images Created Using Real-Time Ultrasound with CT for Identification of Peripheral Lung Lesions in Patients Undergoing Biopsy

Background: Fusion image improves lesion detectability and can be an effective tool for percutaneous ultrasound (US)-guide procedure. We describe the clinical benefit of US-guided lung biopsy using fusion image. Purpose: To retrospectively compare the diagnostic accuracy and complication rates of US-guided lung biopsy with B-mode alone and those of a fusion image created using real-time US and computed tomography (CT). Materials and Methods: Between September, 2013 and September, 2016, 50 peripheral lung lesions in 50 patients (40 males, 10 females;median, 74 years old) were performed by US-guided percutaneous cutting needle biopsy using the B-mode alone or fusion image. Final diagnoses were based on surgical outcomes or clinical follow-up results for at least 12 months after biopsy. To assess prebiopsy characteristics, all lesions were divided into two groups: group 1 (identification on B-mode) and group 2 (identification on fusion image). Results: Of 50 peripheral lesions, 40 lesions (80%) were detected by means of B-mode alone (group 1), and 10 lesions (20%) were identified by fusion image (group 2). The diagnostic accuracy of group 1 was 90% (36/40 lesions), and the diagnostic accuracy of group 2 was 100% (10/10 lesions). Nodule type and the size of the lesions showed significant group wise differences (p Conclusion: Fusion images created using real-time US and CT may be useful for identification of the minimal size of potential target lung lesions and may be more suitable for improved yields with US-guided lung biopsy.