Double contrast-enhanced ultrasonography improves diagnostic accuracy of T staging compared with multi-detector computed tomography in gastric cancer patients

BACKGROUND Gastric cancer(GC)is the most common malignant tumor and ranks third for cancer-related deaths among the worldwide.The disease poses a serious public health problem in China,ranking fifth for incidence and third for mortality.Knowledge of the invasive depth of the tumor is vital to treatment decisions.AIM To evaluate the diagnostic performance of double contrast-enhanced ultrasonography(DCEUS)for preoperative T staging in patients with GC by comparing with multi-detector computed tomography(MDCT).METHODS This single prospective study enrolled patients with GC confirmed by preoperative gastroscopy from July 2021 to March 2023.Patients underwent DCEUS,including ultrasonography(US)and intravenous contrast-enhanced ultrasonography(CEUS),and MDCT examinations for the assessment of preoperative T staging.Features of GC were identified on DCEUS and criteria developed to evaluate T staging according to the 8th edition of AJCC cancer staging manual.The diagnostic performance of DCEUS was evaluated by comparing it with that of MDCT and surgical-pathological findings were considered as the gold standard.RESULTS A total of 229 patients with GC(80 T1,33 T2,59 T3 and 57 T4)were included.Overall accuracies were 86.9%for DCEUS and 61.1%for MDCT(P<0.001).DCEUS was superior to MDCT for T1(92.5%vs 70.0%,P<0.001),T2(72.7%vs 51.5%,P=0.041),T3(86.4%vs 45.8%,P<0.001)and T4(87.7%vs 70.2%,P=0.022)staging of GC.CONCLUSION DCEUS improved the diagnostic accuracy of preoperative T staging in patients with GC compared with MDCT,and constitutes a promising imaging modality for preoperative evaluation of GC to aid individualized treatment decision-making.

Contrast-enhanced guided endoscopic ultrasound procedures

Contrast-enhanced endoscopic ultrasound(CH-EUS)can overcome the limi-tations of endoscopic ultrasound-guided acquisition by identifying microvessels inside inhomogeneous tumours and improving the characterization of these tumours.Despite the initial enthusiasm that oriented needle sampling under CH-EUS guidance could provide better diagnostic yield in pancreatic solid lesions,further studies did not confirm the supplementary values in cases of tissue acquisition guided by CH-EUS.This review details the knowledge based on the available data on contrast-guided procedures.The indications for CH-EUS tissue acquisition include isoechoic EUS lesions with poor visible delineation where CH-EUS can differentiate the lesion vascularisation from the surrounding parenchyma and also the mural nodules within biliopancreatic cystic lesions,which occur in select cases.Additionally,the roles of CH-EUS-guided therapy in patients whose pancreatic fluid collections or bile ducts that have an echogenic content have indications for drainage,and patients who have nonvisualized vessels that need to be highlighted via Doppler EUS are presented.Another indication is represented if there is a need for an immediate assessment of the post-radiofrequency ablation of pancreatic neuroendocrine tumours,in which case CH-EUS can be used to reveal the incomplete tumour destruction.

Survival Analysis of Patients Undergoing Intraoperative Contrast-enhanced Ultrasound in the Surgical Treatment of Malignant Glioma

Objective:Complete resection of malignant gliomas is often challenging.Our previous study indicated that intraoperative contrast-enhanced ultrasound(ICEUS)could aid in the detection of residual tumor remnants and the total removal of brain lesions.This study aimed to investigate the survival rates of patients undergoing resection with or without the use of ICEUS and to assess the impact of ICEUS on the prognosis of patients with malignant glioma.Methods:A total of 64 patients diagnosed with malignant glioma(WHO grade HI and IV)who underwent surgery between 2012 and 2018 were included.Among them,29 patients received ICEUS.The effects of ICEUS on overall survival(OS)and progression-free survival(PFS)of patients were evaluated.A quantitative analysis was performed to compare ICEUS parameters between gliomas and the surrounding tissues.Results:The ICEUS group showed better survival rates both in OS and PFS than the control group.The univariate analysis revealed that age,pathology and ICEUS were significant prognostic factors for PFS,with only age being a significant prognostic factor for OS.In multivariate analysis,age and ICEUS were significant prognostic factors for both OS and PFS.The quantitative analysis showed that the intensity and transit time of microbubbles reaching the tumors were significantly different from those of microbubbles reaching the surrounding tissue.Conclusion:ICEUS facilitates the identification of residual tumors.Age and ICEUS are prognostic factors for malignant glioma surgery,and use of ICEUS offers a better prognosis for patients with malignant glioma.

Evaluating microvascular invasion in hepatitis B virus-related hepatocellular carcinoma based on contrast-enhanced computed tomography radiomics and clinicoradiological factors

BACKGROUND Microvascular invasion(MVI)is a significant indicator of the aggressive behavior of hepatocellular carcinoma(HCC).Expanding the surgical resection margin and performing anatomical liver resection may improve outcomes in patients with MVI.However,no reliable preoperative method currently exists to predict MVI status or to identify patients at high-risk group(M2).AIM To develop and validate models based on contrast-enhanced computed tomo-graphy(CECT)radiomics and clinicoradiological factors to predict MVI and identify M2 among patients with hepatitis B virus-related HCC(HBV-HCC).The ultimate goal of the study was to guide surgical decision-making.METHODS A total of 270 patients who underwent surgical resection were retrospectively analyzed.The cohort was divided into a training dataset(189 patients)and a validation dataset(81)with a 7:3 ratio.Radiomics features were selected using intra-class correlation coefficient analysis,Pearson or Spearman’s correlation analysis,and the least absolute shrinkage and selection operator algorithm,leading to the construction of radscores from CECT images.Univariate and multivariate analyses identified significant clinicoradiological factors and radscores associated with MVI and M2,which were subsequently incorporated into predictive models.The models’performance was evaluated using calibration,discrimination,and clinical utility analysis.RESULTS Independent risk factors for MVI included non-smooth tumor margins,absence of a peritumoral hypointensity ring,and a high radscore based on delayed-phase CECT images.The MVI prediction model incorporating these factors achieved an area under the curve(AUC)of 0.841 in the training dataset and 0.768 in the validation dataset.The M2 prediction model,which integrated the radscore from the 5 mm peritumoral area in the CECT arterial phase,α-fetoprotein level,enhancing capsule,and aspartate aminotransferase level achieved an AUC of 0.865 in the training dataset and 0.798 in the validation dataset.Calibration and decision curve analyses confirmed the models’good fit and clinical utility.CONCLUSION Multivariable models were constructed by combining clinicoradiological risk factors and radscores to preoper-atively predict MVI and identify M2 among patients with HBV-HCC.Further studies are needed to evaluate the practical application of these models in clinical settings.

Gastrointestinal contrast-enhanced ultrasonography for diagnosis and treatment of peptic ulcer in children

BACKGROUND The detection rate of peptic ulcer in children is improving,with development of diagnostic procedures.Gastroscopy is the gold standard for the diagnosis of peptic ulcer,but it is an invasive procedure.Gastrointestinal contrast-enhanced ultrasonography(CEUS)has the advantages of being painless,noninvasive,nonradioactive,easy to use,and safe.AIM To investigate the clinical value of CEUS for diagnosis and treatment of peptic ulcer in children.METHODS We investigated 43 children with digestive tract symptoms in our hospital from January 2021 to June 2022.All children were examined by routine ultrasound,gastrointestinal CEUS,and gastroscopy.The pathological results of gastroscopy were taken as the gold standard.Routine ultrasonography was performed before gastrointestinal CEUS.Conventional ultrasound showed the thickness of the gastroduodenal wall,gastric peristalsis,and the adjacent organs and tissues around the abdominal cavity.Gastrointestinal CEUS recorded the thickness of the gastroduodenal wall;the size,location and shape of the ulcer;gastric peristalsis;and adjacent organs and tissues around the abdominal cavity.The results of routine ultrasound and gastrointestinal ultrasound were compared with those of gastroscopy to evaluate the diagnostic results and coincidence rate of routine ultrasound and gastrointestinal CEUS.All children received informed consent from their guardians for CEUS.This study was reviewed and approved by the hospital medical ethics committee.RESULTS Among the 43 children,17(15 male,2 female)were diagnosed with peptic ulcer by gastroscopy.There were 26 children with nonpeptic ulcer.There were eight cases of peptic ulcer and 35 of nonpeptic ulcer diagnosed by conventional ultrasound.The diagnostic coincidence rate of peptic ulcer in children diagnosed by conventional ultrasound was 79.1%(34/43),which was significantly different from that of gastroscopy(P=0.033).It indicates that the coincidence rate of gastrointestinal contrast-enhanced ultrasound and gastroscope is low.Fifteen cases of peptic ulcer and 28 of nonpeptic ulcer were diagnosed by CEUS.The diagnostic coincidence rate of peptic ulcer in children was 95.3%(41/43).There was no significant difference between CEUS and gastroscopy(P=0.655).It indicates that the coincidence rate of gastrointestinal contrast-enhanced ultrasound and gastroscope is high.CONCLUSION Gastrointestinal CEUS has a high coincidence rate in the diagnosis of peptic ulcer in children,and can be used as a preliminary examination method.

Correlation of dynamic contrast-enhanced ultrasonography and the Ki-67 labelling index in pancreatic ductal adenocarcinoma

BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly malignant and aggressive tumor,and high Ki-67 expression indicates poor histological differentiation and prognosis.Therefore,one of the challenges in diagnosing preoperatively patients with PDAC is predicting the degree of malignancy.Dynamic contrast-enhanced ultrasonography(DCE-US)plays a crucial role in abdominal tumor diagnosis,and can adequately show the microvascular composition within the tumors.However,the relationship between DCE-US and the Ki-67 labelling index remains unclear at the present time.AIM To predict the correlation between Ki-67 expression and the parameters of DCEUS.METHODS Patients with PDAC who underwent DCE-US were retrospectively analyzed.Patients who had received any treatment(radiotherapy or chemotherapy)prior to DCE-US;had incomplete clinical,imaging,or pathologic information;and had poor-quality image analysis were excluded.Correlations between Ki-67 expression and the parameters of DCE-US in patients with PDAC were assessed using Spearman’s rank correlation analysis.The diagnostic performances of these parameters in high Ki-67 expression group were evaluated according to receiver operating characteristic curve.RESULTS Based on the Ki-67 labelling index,30 patients were divided into two groups,i.e.,the high expression group and the low expression group.Among the relative quantitative parameters between the two groups,relative half-decrease time(rHDT),relative peak enhancement,relative wash-in perfusion index and relative wash-in rate were significantly different between two groups(P=0.018,P=0.025,P=0.028,P=0.035,respectively).The DCE-US parameter rHDT was moderately correlated with Ki-67 expression,and rHDT≥1.07 was more helpful in accurately diagnosing high Ki-67 expression,exhibiting a sensitivity and specificity of 53.8%and 94.1%,respectively.CONCLUSION One parameter of DCE-US,rHDT,correlates with high Ki-67 expression.It demonstrates that parameters obtained noninvasively by DCE-US could better predict Ki-67 expression in PDAC preoperatively.

Clinical value of oral contrast-enhanced ultrasonography in diagnosis of gastric tumors

BACKGROUND The incidence of gastric cancer remains high,and it is the sixth most common cancer and the fourth leading cause of cancer deaths worldwide.Oral contrastenhanced ultrasonography is a simple,non-invasive,and painless method for the diagnosis of gastric tumors.AIM To explore the diagnostic value of oral contrast-enhanced ultrasonography for the detection of gastric tumors.METHODS The screening results based on oral contrast-enhanced ultrasonography and electronic gastroscopy were compared with those of the postoperative pathological examination.RESULTS Among 42 patients with gastric tumors enrolled in the study,the diagnostic accordance rate was 95.2%for oral contrast-enhanced ultrasonography(n=40)and 90.5%for electronic gastroscopy(n=38)compared with postoperative pathological examination.The Kappa value of consistency test with pathological findings was 0.812 for oral contrast-enhanced ultrasonography and 0.718 for electronic gastroscopy,and there was no significant difference between them(P=0.397).For the TNM staging of gastric tumors,the accuracy rate of oral contrast enhanced ultrasonography was 81.9%for the overall T staging and 50%,77.8%,100%,and 100%for T1,T2,T3,and T4 staging,respectively.The sensitivity and specificity were both 100%for stages T3 and T4.The diagnostic accuracy rate of oral contrast-enhanced ultrasonography was 93.8%,80%,100%,and 100%for stages N0,N1-N3,M0,and M1,respectively.CONCLUSION The accordance rate of qualitative diagnosis by oral contrast-enhanced ultrasonography is comparable to that of gastroscopy,and it could be used as the preferred method for the early screening of gastric tumors.

Clinical application of oral contrast-enhanced ultrasound in evaluating the preoperative T staging of gastric cancer

BACKGROUND Oral contrast-enhanced ultrasound(OCEUS)is widely used in the noninvasive diagnosis and screening of gastric cancer(GC)in China.AIM To investigate the clinical application of OCEUS in evaluating the preoperative T staging of gastric cancer.METHODS OCEUS was performed before the operation,and standard ultrasound images were retained.The depth of infiltration of GC(T-stage)was evaluated according to the American Joint Committee on Cancer 8th edition of the tumor-nodemetastasis staging criteria.Finally,with postoperative pathological staging as the gold standard reference,the sensitivity,specificity,negative predictive value,positive predictive value,and diagnostic value of OCEUS T staging were evaluated.RESULTS OCEUS achieved diagnostic accuracy rates of 76.6%(T1a),69.6%(T1b),62.7%(T2),60.8%(T3),88.0%(T4a),and 88.7%(T4b),with an average of 75.5%.Ultrasonic T staging sensitivity exceeded 62%,aside from T1b at 40.3%,while specificity was over 91%,except for T3 with 83.5%.The Youden index was above 60%,with T1b and T2 being exceptions.OCEUS T staging corresponded closely with pathology in T4b(kappa>0.75)and moderately in T1a,T1b,T2,T3,and T4a(kappa 0.40-0.75),registering a concordance rate exceeding 84%.CONCLUSION OCEUS was effective,reliable,and accurate in diagnosing the preoperative T staging of GC.As a noninvasive diagnostic technique,OCEUS merits clinical popularization.

Evaluating the efficacy of percutaneous puncture biopsy guided by contrast-enhanced ultrasound for peripheral pulmonary lesions

BACKGROUND The incidence and mortality of lung cancer have increased annually.Accurate diagnosis can help improve therapeutic efficacy of interventions and prognosis.Percutaneous lung biopsy is a reliable method for the clinical diagnosis of lung cancer.Ultrasound-guided percutaneous lung biopsy technology has been widely promoted and applied in recent years.AIM To investigate the diagnostic value of contrast-enhanced ultrasound(CEUS)-guided percutaneous biopsy in peripheral pulmonary lesions.METHODS We retrospectively collected data on 237 patients with peripheral thoracic focal lesions who underwent puncture biopsy at Wuxi People’s Hospital.The patients were randomly divided into two groups:The CEUS-guided before lesion puncture group(contrast group)and conventional ultrasound-guided group(control group).Analyze the diagnostic efficacy of the puncture biopsy,impact of tumor size,and number of puncture needles and complications were analyzed and compared between the two groups.RESULTS Accurate pathological results were obtained for 92.83%(220/237)of peripheral lung lesions during the first biopsy,with an accuracy rate of 95.8%(113/118)in the contrast group and 89.9%(107/119)in the control group.The difference in the area under the curve(AUC)between the contrast and the control groups was not statistically significant(0.952 vs 0.902,respectively;P>0.05).However,when the lesion diameter≥5 cm,the diagnostic AUC of the contrast group was higher than that of the control group(0.952 vs 0.902,respectively;P<0.05).In addition,the average number of puncture needles in the contrast group was lower than that in the control group(2.58±0.53 vs 2.90±0.56,respectively;P<0.05).CONCLUSION CEUS guidance can enhance the efficiency of puncture biopsy of peripheral pulmonary lesions,especially for lesions with a diameter≥5 cm.Therefore,CEUS guidance has high clinical diagnostic value in puncture biopsy of peripheral focal lung lesions.

Ultrasomics in liver cancer: Developing a radiomics model for differentiating intrahepatic cholangiocarcinoma from hepatocellular carcinoma using contrast-enhanced ultrasound

BACKGROUND Hepatocellular carcinoma(HCC)and intrahepatic cholangiocarcinoma(ICC)represent the predominant histological types of primary liver cancer,comprising over 99%of cases.Given their differing biological behaviors,prognoses,and treatment strategies,accurately differentiating between HCC and ICC is crucial for effective clinical management.Radiomics,an emerging image processing technology,can automatically extract various quantitative image features that may elude the human eye.Reports on the application of ultrasound(US)-based radiomics methods in distinguishing HCC from ICC are limited.METHODS In our retrospective study,we included a total of 280 patients who were diagnosed with ICC(n=140)and HCC(n=140)between 1999 and 2019.These patients were divided into training(n=224)and testing(n=56)groups for analysis.US images and relevant clinical characteristics were collected.We utilized the XGBoost method to extract and select radiomics features and further employed a random forest algorithm to establish ultrasomics models.We compared the diagnostic performances of these ultrasomics models with that of radiologists.RESULTS Four distinct ultrasomics models were constructed,with the number of selected features varying between models:13 features for the US model;15 for the contrast-enhanced ultrasound(CEUS)model;13 for the combined US+CEUS model;and 21 for the US+CEUS+clinical data model.The US+CEUS+clinical data model yielded the highest area under the receiver operating characteristic curve(AUC)among all models,achieving an AUC of 0.973 in the validation cohort and 0.971 in the test cohort.This performance exceeded even the most experienced radiologist(AUC=0.964).The AUC for the US+CEUS model(training cohort AUC=0.964,test cohort AUC=0.955)was significantly higher than that of the US model alone(training cohort AUC=0.822,test cohort AUC=0.816).This finding underscored the significant benefit of incorporating CEUS information in accurately distin-guishing ICC from HCC.CONCLUSION We developed a radiomics diagnostic model based on CEUS images capable of quickly distinguishing HCC from ICC,which outperformed experienced radiologists.

Ultrasound,contrast-enhanced ultrasound and pyelonephritis:A narrative review

Acute pyelonephritis(APN)is a bacterial infection resulting in kidney inflammation,typically arising as a complication of an ascending urinary tract infection that ascends from the bladder to the kidneys.Clinical diagnosis is generally based on clinical and laboratory findings.Recent guidelines recommend not performing diagnostic imaging unless a complicated APN is suspected or the infection affects high-risk patients such as the elderly,immunocompromised individuals,or diabetics.Contrast-enhanced ultrasound(CEUS)is a valuable tool in both the diagnosis and follow-up of APN.It aids in distinguishing small simple nephritic involvement from abscess complications and monitoring their evolution over time during antibiotic therapy.Given its lack of ionizing radiation and nephrotoxicity,CEUS is a valid diagnostic modality for approaching and monitoring pyelonephritis,improving early identification and characterization of inflammatory lesions.This review aims to summarize the main evidence on the use of ultrasound and CEUS in the diagnosis of APN and its follow-up.

Radiomics model based on contrast-enhanced computed tomography to predict early recurrence in patients with hepatocellular carcinoma after radical resection

BACKGROUND Radical resection remains an effective strategy for patients with hepatocellular carcinoma(HCC).Unfortunately,the postoperative early recurrence(recurrence within 2 years)rate is still high.AIM To develop a radiomics model based on preoperative contrast-enhanced computed tomography(CECT)to evaluate early recurrence in HCC patients with a single tumour.METHODS We enrolled a total of 402 HCC patients from two centres who were diagnosed with a single tumour and underwent radical resection.First,the features from the portal venous and arterial phases of CECT were extracted based on the region of interest,and the early recurrence-related radiomics features were selected via the least absolute shrinkage and selection operator proportional hazards model(LASSO Cox)to determine radiomics scores for each patient.Then,the clinicopathologic data were combined to develop a model to predict early recurrence by Cox regression.Finally,we evaluated the prediction performance of this model by multiple methods.RESULTS A total of 1915 radiomics features were extracted from CECT images,and 31 of them were used to determine the radiomics scores,which showed a significant difference between the early recurrence and nonearly recurrence groups.Univariate and multivariate Cox regression analyses showed that radiomics scores and serum alphafetoprotein were independent indicators,and they were used to develop a combined model to predict early recurrence.The area under the receiver operating characteristic curve values for the training and validation cohorts were 0.77 and 0.74,respectively,while the C-indices were 0.712 and 0.674,respectively.The calibration curves and decision curve analysis showed satisfactory accuracy and clinical utilities.Kaplan-Meier curves based on recurrence-free survival and overall survival showed significant differences.CONCLUSION The preoperative radiomics model was shown to be effective for predicting early recurrence among HCC patients with a single tumour.

Detection and classification of breast lesions using multiple information on contrast-enhanced mammography by a multiprocess deep-learning system: A multicenter study

Objective: Accurate detection and classification of breast lesions in early stage is crucial to timely formulate effective treatments for patients. We aim to develop a fully automatic system to detect and classify breast lesions using multiple contrast-enhanced mammography(CEM) images.Methods: In this study, a total of 1,903 females who underwent CEM examination from three hospitals were enrolled as the training set, internal testing set, pooled external testing set and prospective testing set. Here we developed a CEM-based multiprocess detection and classification system(MDCS) to perform the task of detection and classification of breast lesions. In this system, we introduced an innovative auxiliary feature fusion(AFF)algorithm that could intelligently incorporates multiple types of information from CEM images. The average freeresponse receiver operating characteristic score(AFROC-Score) was presented to validate system’s detection performance, and the performance of classification was evaluated by area under the receiver operating characteristic curve(AUC). Furthermore, we assessed the diagnostic value of MDCS through visual analysis of disputed cases,comparing its performance and efficiency with that of radiologists and exploring whether it could augment radiologists’ performance.Results: On the pooled external and prospective testing sets, MDCS always maintained a high standalone performance, with AFROC-Scores of 0.953 and 0.963 for detection task, and AUCs for classification were 0.909[95% confidence interval(95% CI): 0.822-0.996] and 0.912(95% CI: 0.840-0.985), respectively. It also achieved higher sensitivity than all senior radiologists and higher specificity than all junior radiologists on pooled external and prospective testing sets. Moreover, MDCS performed superior diagnostic efficiency with an average reading time of 5 seconds, compared to the radiologists’ average reading time of 3.2 min. The average performance of all radiologists was also improved to varying degrees with MDCS assistance.Conclusions: MDCS demonstrated excellent performance in the detection and classification of breast lesions,and greatly enhanced the overall performance of radiologists.

Value of contrast-enhanced ultrasound in deep angiomyxoma using a biplane transrectal probe:A case report

BACKGROUND Deep angiomyxoma(DAM)is a very rare tumor type.Magnetic resonance imaging(MRI)is considered the best imaging modality for diagnosing DAM.Computed tomography(CT)is used mainly to assess the invasion range of DAM.The value of ultrasonography in the diagnosis of DAM is still controversial.Through a literature review,we summarized the current state of ultrasonic examination for DAM and reported for the first time the contrast-enhanced ultrasound(CEUS)features of DAM seen using a biplane transrectal probe.CASE SUMMARY A 37-year-old woman presented with a sacrococcygeal mass that had gradually increased in size over the previous 6 mo.MRI and CT examinations failed to allow a definite diagnosis to be made.Transperineal core needle biopsy(CNB)guided by transrectal ultrasound and CEUS was suggested after a multidisciplinary discussion.Grayscale ultrasound of the lesion showed a layered appearance with alternating hyperechoic and hypoechoic patterns.Transrectal CEUS showed a laminated distribution of the contrast agent that was consistent with the layered appearance of the tumor on grayscale ultrasound.We performed transperineal CNB of the enhanced area inside the tumor under transrectal CEUS guidance and finally made a definitive diagnosis of DAM through histopathology.The patient underwent laparoscopic-assisted transabdominal surgery combined with transperineal surgery for large pelvic tumor resection and pelvic floor peritoneal reconstruction.No recurrence or metastasis was found at the ninemonth follow-up.CONCLUSION Transrectal CEUS can show the layered perfusion characteristics of the contrast agent,guiding subsequent transperineal CNB of the enhanced area within the DAM.

Back to the drawing board:Overview of the next generation of combination therapy for inflammatory bowel disease

Inflammatory bowel disease(IBD)is entering a potentially new era of combined therapeutics.Triantafillidis et al provide an insightful review of the current state of combination therapy,with a focus on the use of a combined biologic and immunomodulator,as well as emerging data on the future potential of dual-biologic therapy(DBT).While current evidence for DBT is limited,encouraging safety profiles and ongoing trials suggest a brighter future for this approach.The importance of controlled trials should be stressed in establishing new treatment paradigms.Ongoing prospective randomized trials of DBT and perhaps future combinations of biologics and small molecule therapies will hopefully guide the next generation of IBD care.

Combination treatment of inflammatory bowel disease:Present status and future perspectives

The treatment of patients with inflammatory bowel disease(IBD),especially those with severe or refractory disease,represents an important challenge for the clinical gastroenterologist.It seems to be no exaggeration to say that in these patients,not only the scientific background of the gastroenterologist is tested,but also the abundance of“gifts”that he should possess(insight,intuition,determ-ination,ability to take initiative,etc.)for the successful outcome of the treatment.In daily clinical practice,depending on the severity of the attack,IBD is treated with one or a combination of two or more pharmaceutical agents.These combin-ations include not only the first-line drugs(e.g.,mesalazine,corticosteroids,antibiotics,etc)but also second-and third-line drugs(immunosuppressants and biologic agents).It is a fact that despite the significant therapeutic advances there is still a significant percentage of patients who do not satisfactorily respond to the treatment applied.Therefore,a part of these patients are going to surgery.In recent years,several small-size clinical studies,reviews,and case reports have been published combining not only biological agents with other drugs(e.g.,immunosuppressants or corticosteroids)but also the combination of two biologi-cal agents simultaneously,especially in severe cases.In our opinion,it is at least a strange(and largely unexplained)fact that we often use combinations of drugs in a given patient although studies comparing the simultaneous administration of two or more drugs with monotherapy are very few.As mentioned above,there is a timid tendency in the literature to combine two biological agents in severe cases unresponsive to the applied treatment or patients with severe extraintestinal manifestations.The appropriate dosage,the duration of the administration,the suitable timing for checking the clinical and laboratory outcome,as well as the treatment side-effects,should be the subject of intense clinical research shortly.In this editorial,we attempt to summarize the existing data regarding the already applied combination therapies and to humbly formulate thoughts and suggestions for the future application of the combination treatment of biological agents in a well-defined category of patients.We suggest that the application of biomarkers and artificial intelligence could help in establishing new forms of treatment using the available modern drugs in patients with IBD resistant to treatment.

Bridging the gap:Unveiling the crisis of physical inactivity in inflammatory bowel diseases

In this editorial we comment on the article titled“Inflammatory bowel diseases patients suffer from significant low levels and barriers to physical activity:The BE-FIT-IBD study”published in a recent issue of the World Journal of Gastroen-terology 2023;29(41):5668-5682.Inflammatory bowel diseases(IBD)are emerging as a significant global health concern as their incidence continues to rise on a global scale,with detrimental impacts on quality of life.While many advances have been made regarding the management of the disease,physical inactivity in these patients represents an underexplored issue that may hold the key for further and better understanding the ramifications of IBD.Chronic pain,fatigue,and fear of exacerbating symptoms promotes physical inactivity among IBD patients,while the lack of clear guidelines on safe exercise regimens contributes to a norm of physical inactivity.Physical activity(PA)is accepted to have a positive effect on disease outcomes and quality of life,while inactivity exacerbates comorbidities like cardiovascular disease and mental health disorders.The“BE-FIT-IBD”study,focusing on PA levels and barriers in IBD patients of Southern Italy,revealed that a significant proportion(42.9%)were physically inactive.This lack of PA is attributed to barriers such as fear of flare-ups and misconceptions about exercise exacerbating the disease.The study also highlighted the need for better communication between healthcare providers and patients regarding the benefits of PA and safe incorporation into lifestyles.Moreover,physical inactivity may also contribute to disability in IBD patients,having a great impact on employment status.Of note is the fact that IBD also comes with an important psychological burden with relevant evidence suggesting that regular PA can improve mood,reduce anxiety,and enhance mental health.The“BE-FIT-IBD”study advocated for the integration of PA into IBD management,emphasizing the bidirectional link between PA and IBD.Regular exercise can influence the course of IBD,potentially reducing symptom severity and prolonging remission periods.As such,it is mandatory that healthcare providers actively educate patients,dispel misconceptions,and tailor exercise recommendations to improve the quality of life and reduce IBD-related complications.

Interaction between inflammatory bowel disease,physical activity,and myokines:Assessment of serum irisin levels

Inflammatory bowel disease(IBD),including Crohn’s disease and ulcerative colitis,showed a wide spectrum of intestinal and extra-intestinal manifestations,which rendered the patients physically inactive and impaired their quality of life.It has been found that physical activity is a non-pharmacological intervention that improves the quality of life for those patients.Irisin is one member of the myokines secreted by muscle contraction during exercise and could be used as an antiinflammatory biomarker in assessing the physical activity of IBD patients.In addition,experimental studies showed that exogenous irisin significantly decreased the inflammatory markers and the histological changes of the intestinal mucosa observed in experimental colitis.Furthermore,irisin produces changes in the diversity of the microbiota.Therefore,endogenous or exogenous irisin,via its anti-inflammatory effects,will improve the health of IBD patients and will limit the barriers to physical activity in patients with IBD.

Effects of proton pump inhibitors on inflammatory bowel disease:An updated review

Inflammatory bowel disease(IBD)is believed to be caused by various factors,including abnormalities in disease susceptibility genes,environmental factors,immune factors,and intestinal bacteria.Proton pump inhibitors(PPIs)are the primary drugs used to treat acid-related diseases.They are also commonly prescribed to patients with IBD.Recent studies have suggested a potential association between the use of certain medications,such as PPIs,and the occurrence and progression of IBD.In this review,we summarize the potential impact of PPIs on IBD and analyze the underlying mechanisms.Our findings may provide insights for conducting further investigations into the effects of PPIs on IBD and serve as an important reminder for physicians to exercise caution when prescribing PPIs to patients with IBD.

Perianal disease in inflammatory bowel disease:Broadening treatment and surveillance strategies for anal cancer

The perianal disease affects up to one-third of individuals with Crohn's disease(CD),causing disabling symptoms and significant impairment in quality of life,particularly for those with perianal fistulising CD(PFCD).The collaborative effort between gastroenterologists and surgeons is essential for addressing PFCD to achieve fistula closure and promote luminal healing.Limited fistula healing rates with conventional therapies have prompted the emergence of new biological agents,endoscopic procedures and surgical techniques that show promising results.Among these,mesenchymal stem cells injection is a particularly hopeful therapy.In addition to the burden of fistulas,individuals with perianal CD may face an increased risk of developing anal cancer.This underscores the importance of surveillance programmes and timely interventions to prevent late diagnoses and poor outcomes.Currently,there is no established formal anal screening programme.In this review,we provide an overview of the current state of the art in managing PFCD,including novel medical,endoscopic and surgical approaches.The discussion also focuses on the relevance of establishing an anal cancer screening programme in CD,intending to propose a risk-based surveillance algorithm.The validation of this surveillance programme would be a significant step forward in improving patient care and outcomes.