Tumor size discrepancy between endoscopic and pathological evaluations in colorectal endoscopic submucosal dissection

BACKGROUND Tumor size impacts the technical difficulty and histological curability of colorectal endoscopic submucosal dissection(ESD);however,the preoperative evaluation of tumor size is often different from histological assessment.Analyzing influential factors on failure to obtain an accurate tumor size evaluation could help prepare optimal conditions for safer and more reliable ESD.METHODS This was a retrospective study conducted at a single institution.A total of 377 lesions removed by colorectal ESD at our hospital between April 2018 and March 2022 were collected.We first assessed the difference in size with an absolute per-centage of the scaling discrepancy.Subsequently,we compared the clinicopatho-logical characteristics of the correct scaling group(>-33%and<33%)with that of the incorrect scaling group(<-33%or>33%),which was further subdivided into the underscaling group(-33%or less of the discrepancy)and overscaling group(33%or more of the discrepancy),respectively.As secondary outcome measures,parameters on size estimation were compared between the underscaling and correct scaling groups,as well as between the overscaling and correct scaling groups.Finally,multivariate analysis was performed in terms of the following relevant parameters on size estimation:Pathological size,location,and possible influential factors(P<0.1)in the univariate analysis.RESULTS The mean of absolute percentage in the scaling discordance was 21%,and 91 lesions were considered to be incorrectly estimated in size.The incorrect scaling was significantly remarkable in larger lesions(40 mm vs 28 mm;P<0.001)and less experience(P<0.001),and these two factors were influential on the underscaling(75 lesions;P<0.001).Conversely,compared with the correct scaling group,16 lesions in the overscaling group were significantly small(20 mm vs 28 mm;P<0.001),and the small lesion size was influential on the overscaling(P=0.002).CONCLUSION Lesions indicated for colorectal ESD tended to be underestimated in large tumors,but overestimated in small ones.This discrepancy appears worth understanding for optimal procedural preparation.

New methods for the management of esophageal varices

Bleeding from esophageal varices (EVs) is a catastrophic complication of chronic liver disease. Many years ago, surgical procedures such as esophageal transection or distal splenorenal shunting were the only treatments for EVs. In the 1970s, interventional radiology procedures such as transportal obliteration, left gastric artery embolization, and partial splenic artery embolization were introduced, improving the survival of patients with bleeding EVs. In the 1980s, endoscopic treatment, endoscopic injection sclerotherapy (EIS), and endoscopic variceal ligation (EVL), further contributed to improved survival. We combined IVR with endoscopic treatment or EIS with EVL. Most patients with EVs treated endoscopically required follow- up treatment for recurrent varices. Proper management of recurrent EVs can significantly improve patients’ quality of life. Recently, we have performed EVL at 2-mo (bimonthly) intervals for the management of EVs. Longer intervals between treatment sessions resulted in a higher rate of total eradication and lower rates of recurrence and additional treatment.

Interventional treatment for unresectable hepatocellular carcinoma

Hepatocellular carcinoma(HCC) is the sixth most common cancer and third leading cause of cancer-related death in the world. The Barcelona clinic liver cancer classification is the current standard classification system for the clinical management of patients with HCC and suggests that patients with intermediate-stage HCC benefit from transcatheter arterial chemoembolization(TACE). Interventional treatments such as TACE, balloon-occluded TACE, drug-eluting bead embolization, radioembolization, and combined therapies including TACE and radiofrequency ablation, continue to evolve, resulting in improved patient prognosis. However, patients with advanced-stage HCC typically receive only chemotherapy with sorafenib, a multi-kinase inhibitor, or palliative and conservative therapy. Most patients receive palliative or conservative therapy only, and approximately 50% of patients with HCC are candidatesfor systemic therapy. However, these patients require therapy that is more effective than sorafenib or conservative treatment. Several researchers try to perform more effective therapies, such as combined therapies(TACE with radiotherapy and sorafenib with TACE), modified TACE for HCC with arterioportal or arteriohepatic vein shunts, TACE based on hepatic hemodynamics, and isolated hepatic perfusion. This review summarizes the published data and data on important ongoing studies concerning interventional treatments for unresectable HCC and discusses the technical improvements in these interventions, particularly for advanced-stage HCC.

One-step palliative treatment method for obstructive jaundice caused by unresectable malignancies by percutaneous transhepatic insertion of an expandable metallic stent

AIM： To describe a simple one-step method involving percutaneous transhepatic insertion of an expandable metal stent （EMS） used in the treatment of obstructive jaundice caused by unresectable malignancies. METHODS： Fourteen patients diagnosed with obstructive jaundice due to unresectable malignancies were included in the study. The malignancies in these patients were a result of very advanced carcinoma or old age. Percutaneous transhepatic cholangiography was performed under ultrasonographic guidance. After a catheter with an inner metallic guide was advanced into the duodenum, an EMS was placed in the common bile duct, between a point 1 cm beyond the papilla of Vater and the entrance to the hepatic hilum. In cases where it was difficult to span the distance using just a single EMS, an additional stent was positioned. A drainage catheter was left in place to act as a hemostat. The catheter was removed after resolution of cholestasis and stent patency was confirmed 2 or 3 d post-procedure. RESULTS： One-step insertion of the EMS was achieved in all patients with a procedure mean time of 24.4 min. Out of the patients who required 2 EMS, 4 needed a procedure time exceeding 30 min. The mean time for removal of the catheter post-procedure was 2.3 d. All patients died of malignancy with a mean follow-up time of 7.8 mo. No stent-related complication or stent obstruction was encountered. CONCLUSIONS： One-step percutaneous transhepaticinsertion of EMS is a simple procedure for resolving biliary obstruction and can effectively improve the patient＇s quality of life.

Nestin:A novel angiogenesis marker and possible target for tumor angiogenesis

Abnormal vasculature,termed tumor vessels,is a hallmark of solid tumors.The degree of angiogenesis is associated with tumor aggressiveness and clinical outcome.Therefore,exact quantification of tumor vessels is useful to evaluate prognosis.Furthermore,selective detection of newly formed tumor vessels within cancer tissues using specific markers raises the possibility of molecular targeted therapy via the inhibition of tumor angiogenesis.Nestin,an intermediate filament protein,is reportedly expressed in repair processes,various neoplasms,and proliferating vascular endothelial cells.Nestin expression is detected in endothelial cells of embryonic capillaries,capillaries of the corpus luteum,which replenishes itself by angiogenesis,and proliferating endothelial progenitor cells,but not in mature endothelial cells.Therefore,expression of nestin is relatively limited to proliferating vascular endothelial cells and endothelial progenitor cells.Nestin expression is also reported in blood vessels within glioblastoma,prostate cancer,colorectal cancer,and pancreatic cancer,and its expression is more specific for newly formed blood vessels than other endothelial cell markers.Nestin-positive blood vessels form smaller vessels with high proliferation activity in tumors.Knockdown of nestin in vascular endothelial cells suppresses endothelial cell growth and tumor formation ability of pancreatic cancers in vivo.Using nestin to more accurately evaluate microvessel density in cancer specimens may be a novel prognostic indicator.Furthermore,nestin-targeted therapy may suppress tumor proliferation via inhibition of angiogenesis in numerous malignancies,including pancreatic cancer.In this review article,we focus on nestin as a novel angiogenesis marker and possible therapeutic target via inhibition of tumor angiogenesis.

New methods for the management of gastric varices

Bleeding from gastric varices has been successfully treated by endoscopic modalities. Once the bleeding from the gastric varices is stabilized, endoscopic treatment and/or interventional radiology should be performed to eradicate varices completely. Partial splenic artery embolization is a supplemental treatment to prolong the obliteration of the veins feeding and/or draining the varices. The overall incidence of bleeding from gastric varices is lower than that from esophageal varices. No studies to date have defi nitively characterized the causal factors behind bleeding from gastric varices. The initial episodes of bleeding from esophageal varices or gastric varices without prior treatment may be at least partly triggered by a violation of the mucosal barrier overlying varices. This is especially likely in the case of varices of the fundus. In view of the high rate of hemostasis achieved among bleeding gastric varices, treatment should be administered in selective cases. Among untreated cases, steps to prevent gastric mucosal injury confer very important protection against gastric variceal bleeding.

Nestin in gastrointestinal and other cancers: Effects on cells and tumor angiogenesis

Nestin is a class Ⅵ intermediate filament protein that was originally described as a neuronal stem cell marker during central nervous system (CNS) development, and is currently widely used in that capacity. Nestin is also expressed in non-neuronal immature or progenitor cells in normal tissues. Under pathological conditions, nestin is expressed in repair processes in the CNS, muscle, liver, and infarcted myocardium. Furthermore, increased nestin expression has been reported in various tumor cells, including CNS tumors, gastrointestinal stromal tumors, pancreatic cancer, prostate cancer, breast cancer, malignant melanoma, dermatofibrosarcoma protuberances, and thyroid tumors. Nestin is reported to correlate with aggressive growth, metastasis, and poor prognosis in some tumors; however, the roles of nestin in cancer cells have not been well characterized. Furthermore, nestin is more specifically expressed in proliferating small-sized tumor vessels in glioblastoma and gastric, colorectal, and prostate cancers than are other tumor vessel markers. These findings indicate that nestin may be a marker for newly synthesized tumor vessels and a therapeutic target for tumor angiogenesis. It has received a lot of attention recently as a cancer stem cell marker in various cancer cells including brain tumors, malignant rhabdoid tumors, and uterine, cervical, prostate, bladder, head and neck, ovarian, testicular, and pancreatic cancers. The purpose of this review is to clarify the roles of nestin in cancer cells and in tumor angiogenesis, and to examine the association between nestin and cancer stem cells. Nestin has the potential to serve as a molecular target for cancers with nestin-positive cancer cells and nestin-positive tumor vasculature.

What are the effects of proton pump inhibitors on the small intestine?

Generally, proton-pump inhibitors(PPIs) have great benefit for patients with acid related disease with less frequently occurring side effects. According to a recent report, PPIs provoke dysbiosis of the small intestinal bacterial flora, exacerbating nonsteroidal anti-inflammatory drug-induced small intestinal injury.Several meta-analyses and systematic reviews have reported that patients treated with PPIs, as well as post-gastrectomy patients, have a higher frequency of small intestinal bacterial overgrowth(SIBO) compared to patients who lack the aforementioned conditions.Furthermore, there is insufficient evidence that these conditions induce Clostridium difficile infection. At this time, PPI-induced dysbiosis is considered a type of SIBO. It now seems likely that intestinal bacterial flora influence many diseases, such as inflammatory bowel disease, diabetes mellitus, obesity, nonalcoholic fatty liver disease, and autoimmune diseases.When attempting to control intestinal bacterial flora with probiotics, prebiotics, and fecal microbiota transplantation, etc., the influence of acid suppression therapy, especially PPIs, should not be overlooked.

Progress in elucidating the relationship between Helicobacter pylori infection and intestinal diseases

Helicobacter pylori(H.pylori)infection causes changes to the intestinal flora,such as small intestinal bacterial overgrowth,and increases gastric acid secretionstimulating gastrointestinal hormones,mainly gastrin,due to a decrease in gastric acid caused by atrophic gastritis.In addition,the cellular components of H.pylori travel through the intestinal tract,so the bacterial infection affects the immune system.Therefore,the effects of H.pylori infection are observed not only in the stomach and the proximal duodenum but also in the small and large intestines.In particular,meta-analyses reported that H.pylori-infected individuals had an increased risk of colorectal adenoma and colorectal cancer.Moreover,a recent study reported that the risk of developing colorectal cancer was increased in subjects carrying H.pylori vacuolating cytotoxin A antibody.In addition,it has been reported that H.pylori infection exacerbates the symptoms of Fabry’s disease and familial Mediterranean fever attack and is involved in irritable bowel syndrome and small intestinal ulcers.On the other hand,some studies have reported that the frequency of ulcerative colitis,Crohn’s disease,and celiac disease is low in H.pylori-infected individuals.Thus,H.pylori infection is considered to have various effects on the small and large intestines.However,few studies have reported on these issues,and the details of their effects have not been well elucidated.Therefore,additional studies are needed.

Evaluation of the relationship between hepatocellular carcinoma location and transarterial chemoembolization efficacy

AIM To evaluate the relationship between the location of hepatocellular carcinoma(HCC) and the efficacy of transarterial chemoembolization(TACE).METHODS We evaluated 115 patients(127 nodules), excluding recurrent nodules, treated with TACE between January 2011 and June 2014. TACE efficacy was evaluated according to m RECIST. The HCC location coefficient was calculated as the distance from the central portal portion to the HCC center(mm)/liver diameter(mm) on multiplanar reconstruction images rendered(MPR) to visualize bifurcation of the right and left branches of the portal vein and HCC center. The HCC location coefficient was compared between complete response(CR) and non-CR groups in Child-Pugh grade A and B patients.RESULTS The median location coefficient of HCC among all nodules, the right lobe, and the medial segment was significantly higher in the CR group than in the non-CR group in the Child-Pugh grade A patients(0.82 vs 0.62, P < 0.001; 0.71 vs 0.59, P < 0.01; 0.81 vs 0.49, P < 0.05, respectively). However, there was no significant difference in the median location coefficient of the HCC in the lateral segment between in the CR and in the non-CR groups(0.67 vs 0.65, P > 0.05). On the other hand, in the Child-Pugh grade B patients, the HCC median location coefficient in each lobe and segment was not significantly different between in the CR and in the non-CR groups.CONCLUSION Improved TACE efficacy may be obtained for HCC in the peripheral zone of the right lobe and the medial segment in Child-Pugh grade A patients.

Host cellular micro RNA involvement in the control of hepatitis B virus gene expression and replication

A large number of studies have demonstrated that the synergistic collaboration of a number of micro RNAs(mi RNAs), their growth factors and their downstream agents is required for the initiation and completion of pathogenesis in the liver. mi RNAs are thought to exert a profound effect on almost every aspect of liver biology and pathology. Accumulating evidence indicates that several mi RNAs are involved in the hepatitis B virus(HBV) life cycle and infectivity, in addition to HBVassociated liver diseases including fibrosis, cirrhosis and hepatocellular carcinoma(HCC). In turn, HBV can modulate the expression of several cellular mi RNAs, thus promoting a favorable environment for its replication and survival. In this review, we focused on the involvement of host cellular mi RNAs that are directly and indirectly associated with HBV RNA or HBV associated transcription factors. Exploring different facets of the interactions among mi RNA, HBV and HCV infections, and the carcinogenesis and progress of HCC, could facilitate the development of novel and effective treatment approaches for liver disease.

Supportive techniques and devices for endoscopic submucosal dissection of gastric cancer

The indications for endoscopic treatment have expanded in recent years,and relatively intestinal-type mucosal stomach carcinomas with a low potential for metastasis are now often resected en bloc by endoscopic submucosal dissection(ESD),even if they measure over 20 mm in size.However,ESD requires complex maneuvers,which entails a long operation time,and is often accompanied by complications such as bleeding and perforation.Many technical developments have been implemented to overcome these complications.The scope,cutting device,hemostasis device,and other supportive devices have been improved.However,even with these innovations,ESD remains a potentially complex procedure.One of the major difficulties is poor visualization of the submucosal layer resulting from the poor countertraction afforded during submucosal dissection.Recently,countertraction devices have been developed.In this paper,we introduce countertraction techniques and devices mainly for gastric cancer.

Pathologic complete response confirmed by surgical resection for liver metastases of gastrointestinal stromal tumor after treatment with imatinib mesylate

A 39-year-old male underwent distal gastrectomy for a high grade gastrointestinal stromal tumor(GIST) . Computed tomography(CT) and magnetic resonance imaging(MRI) 107 mo after the operation,revealed a cystic mass(14 cm in diameter) and a solid mass(9 cm in diameter) in the right and left lobes of the liver,respectively. A biopsy specimen of the solid mass showed a liver metastasis of GIST. The patient received imatinib mesylate(IM) treatment,400 mg/day orally. Following the IM treatment for a period of 35 mo,the patient underwent partial hepatectomy(S4 + S5) . The effect of IM on the metastatic lesions was interpreted as pathologic complete response(CR) . Pathologically verified cases showing therapeutic efficacy of IM have been rarely reported.

Endovascular treatment of post-laparoscopic pancreatectomy splenic arteriovenous fistula with splenic vein aneurysm

Splenic arteriovenous fistulas(SAVFs) with splenic vein aneurysms are extremely rare entities. There have been no prior reports of SAVFs developing after laparoscopic pancreatectomy. Here, we report the first case. A 40-year-old man underwent a laparoscopic, spleen-preserving, distal pancreatectomy for an endocrine neoplasm of the pancreatic tail. Three months after surgery, a computed tomography(CT) scan demonstrated an SAVF with a dilated splenic vein. The SAVF, together with the splenic vein aneurysm, was successfully treated using percutaneous transarterial coil embolization of the splenic artery, including the SAVF and drainage vein. After the endovascular treatment, the patient's recovery was uneventful. He was discharged on postoperative day 6 and continues to be well 3 mo after discharge. An abdominal CT scan performed at his 3-mo follow-up demonstrated complete thrombosis of the splenic vein aneurysm, which had decreased to a 40 mm diameter. This is the first reported case of SAVF following a laparoscopic pancreatectomy and demonstrates the usefulness of endovascular treatment for this type of complication.

Ribavirin contributes to eradicate hepatitis C virus through polarization of T helper 1/2 cell balance into T helper 1 dominance

The mechanism of action of ribavirin(RBV) as an immunomodulatory and antiviral agent and its clinical significance in the future treatment of patients with hepatitis C virus(HCV) infection are reviewed.RBV up-regulates type 1 and/or 2 cytokines to modulate the T helper(Th) 1/2 cell balance to Th1 dominance.Examination of co-stimulatory signaling indicated that RBV down-modulates inducible co-stimulator on Th cells,which contributes to differentiating na?ve Th cells into Th2 cells while reducing their interleukin-10 production.The effects on T-regulatory(Treg) cells were also investigated,and RBV inhibited the differentiation of na?ve Th cells into adaptive Treg cells by downmodulating forkhead box-P3.These findings indicate that RBV mainly down-regulates the activity of Th2 cells,resulting in the maintenance of Th1 activity that contributes to abrogating HCV-infected hepatocytes.Although an interferon-free treatment regimen exhibits almost the same efficacy without serious complications,regimens with RBV will be still be used because of their ability to facilitate the cellular immune response,which may contribute to reducing the development of hepatocellular carcinogenesis in patients infected with HCV.

Maintenance for healed erosive esophagitis:PhaseⅢcomparison of vonoprazan with lansoprazole

AIM To compare vonoprazan 10 and 20 mg vs lansoprazole 15 mg as maintenance therapy in healed erosive esophagitis(EE).METHODS A total of 607 patients aged ≥ 20 years, with endoscopically-confirmed healed EE following 8 wk of treatment with vonoprazan 20 mg once daily, were randomized 1:1:1 to receive lansoprazole 15 mg(n = 201), vonoprazan 10 mg(n = 202), or vonoprazan 20 mg(n = 204), once daily. The primary endpoint of the study was the rate of endoscopically-confirmed EE recurrence during a 24-wk maintenance period. The secondary endpoint was the EE recurrence rate at Week 12 during maintenance treatment. Additional efficacy endpoints included the incidence of heartburn and acid reflux, and the EE healing rate 4 wk after the initiation of maintenance treatment. Safety endpoints comprised adverse events(AEs), vital signs, electrocardiogram findings, clinical laboratory results, serum gastrin and pepsinogen Ⅰ/Ⅱ levels, and gastric mucosa histopathology results.RESULTS Rates of EE recurrence during the 24-wk maintenance period were 16.8%, 5.1%, and 2.0% with lansoprazole 15 mg, vonoprazan 10 mg, and vonoprazan 20 mg, respectively. Vonoprazan was shown to be non-inferior to lansoprazole 15 mg(P < 0.0001 for both doses). In a post-hoc analysis, EE recurrence at Week 24 was significantly reduced with vonoprazan at both the 10 mg and the 20 mg dose vs lansoprazole 15 mg(5.1% vs 16.8%, P = 0.0002, and 2.0% vs 16.8%, P < 0.0001, respectively); by contrast, the EE recurrence rate did not differ significantly between the two doses of vonoprazan(P = 0.1090). The safety profiles of vonoprazan 10 and 20 mg were similar to that of lansoprazole 15 mg in patients with healed EE. Treatment-related AEs were reported in 11.4%, 10.4%, and 10.3% of patients in the lansoprazole 15 mg, vonoprazan 10 mg, and vonoprazan 20 mg arms, respectively.CONCLUSION Our findings confirm the non-inferiority of vonoprazan 10 and 20 mg to lansoprazole 15 mg as maintenance therapy for patients with healed EE.

Postoperative bile leakage managed successfully by intrahepatic biliary ablation with ethanol

We report a case of postoperative refractory bile leakage managed successfully by intrahepatic biliary ablation with ethanol. A 75-year-old man diagnosed with hepatocellular carcinoma underwent extended posterior segmentectomy including the caudate lobe and a part of the anterior segment. The hepatic tumor attached to the anterior branch of the bile duct was detached carefully and resected. Fluid drained from the liver surface postoperatively contained high concentrations of total bilirubin, at a constant volume of 150 mL per day. On d 32 after surgery, a fistulogram of the drainage tube demonstrated an enhancement of the anterior bile duct. Endoscopic retrograde cholangiography demonstrated complete obstruction of the proximal anterior bile duct and no enhancement of the peripheral anterior bile duct. On d 46 after surgery, a retrograde transhepatic biliary drainage （RTBD） tube was inserted into the anterior bile duct under open surgery. However, a contrast study of RTBD taken 7 mo post-surgery revealed that the fistula remained patent despite prolonged conservative man- agement, so we decided to perform ethanol ablation of the isolated bile duct. Four mL pure ethanol was injected into the isolated anterior bile duct for ten minutes, the procedure being repeated five times a week. Following 23 attempts, the volume of bile juice reached less than 10 mL per day. The RTBD was clamped and removed two days later. After RTBD removal, the patient had no complaints or symptoms. Follow-up magnetic resonance imaging demonstrated atrophy of the ethanol-injected anterior segment without liver abscess formation.

Diagnosis and initial management of cholangiocarcinoma with obstructive jaundice

Cholangiocarcinoma is the second most common primary hepatic cancer. Despite advances in diagnostic techniques during the past decade, cholangiocarcinoma is usually encountered at an advanced stage. In this review, we describe the classification, diagnosis, and initial management of cholangiocarcinoma with obstructive jaundice.

Coronary atherosclerosis is already ongoing in pre-diabetic status: Insight from intravascular imaging modalities

Diabetes mellitus is a powerful risk factor of coronary artery disease(CAD), leading to death and disability. In recent years, given the accumulating evidence that prediabetes is also related to increasing risk of CAD including cardiovascular events, a new guideline has been proposed for the treatment of blood cholesterolfor primary prevention of cardiovascular events. This guideline recommends aggressive lipid-lowering statin therapy for primary prevention in diabetes and other patients. The ultimate goal of patient management is to inhibit progression of systemic atherosclerosis and prevent fatal cardiovascular events such as acute coronary syndrome(ACS). Because disruption of atherosclerotic coronary plaques is a trigger of ACS, the high-risk atheroma is called a vulnerable plaque. Several types of novel diagnostic imaging technologies have been developed for identifying the characteristics of coronary atherosclerosis before the onset of ACS, especially vulnerable plaques. According to coronary angioscopic evaluation, atherosclerosis severity and plaque vulnerability were more advanced in prediabetic than in nondiabetic patients and comparable to that in diabetic patients. In addition, pharmacological intervention by statin therapy changed plaque color and complexity, and the dynamic changes in plaque features are considered plaque stabilization. In this article, we review the findings of atherosclerosis in prediabetes, detected by intravascular imaging modalities, and the therapeutic implications.

Neoatherosclerosis:Coronary stents seal atherosclerotic lesions but result in making a new problem of atherosclerosis

Chronic inflammation of the native vessel wall with infiltration of lipid-laden foamy macrophages through impaired endothelium results in atherosclerosis. Percutaneous coronary intervention, including metallic stent implantation, is now widely utilized for the treatment of atherosclerotic lesions of the coronary artery. Baremetal stents and the subsequently developed drugeluting stents seal the atherosclerosis and resolve lumen stenosis or obstruction of the epicardial coronary artery and myocardial ischemia. After stent implantation, neointima proliferates within the stented segment. Chronic inflammation caused by a foreign body reaction to the implanted stent and subsequent neovascularization, which is characterized by the continuous recruitment of macrophages into the vessel, result in the transformation of the usual neointima into an atheromatous neointima. Neointima with an atherosclerotic appearance, such as that caused by thin-cap fibroatheromas, is now recognized as neoatherosclerosis, which can sometimes cause in-stent restenosis and acute thrombotic occlusion originating from the stent segment following disruption of the atheroma. Neoatherosclerosis is emerging as a new coronary stent-associated problem that has not yet been resolved. In this review article, we will discuss possible mechanisms, clinical challenges, and the future outlook of neoatherosclerosis.