Parallel pathways:A chronicle of evolution in rectal and breast cancer surgery

In this editorial,we have analyzed the historical evolution of rectal and breast cancer surgery,focusing on the progressive reduction of demolitive approaches and the increasing use of more conservative strategies,accompanied by a growing emphasis on perioperative treatments aimed at enhancing surgical outcomes.All of these changes have been made possible due to an increased awareness and understanding of oncological diseases and improved perioperative treatments.

Regional Block Anesthesia in Breast Surgery: What Do We Know So Far?

Breast cancer is the most prevalent cancer in women worldwide, and pain following mastectomy is a major post-surgical complication. This paper highlights the risk factors for chronic pain in breast surgery and evaluates various regional block techniques used to reduce post-operative pain, and minimize hospital stays in high-risk patients. Further research is needed to evaluate the effectiveness of novel regional anaesthesia techniques in an enhanced recovery context, and to assess their role in preventing or reducing chronic pain.

New direction for surgery:Super minimally invasive surgery

The top goal of modern medicine is treating disease without destroying organ structures and making patients as healthy as they were before their sickness.Minimally invasive surgery(MIS)has dominated the surgical realm because of its lesser invasiveness.However,changes in anatomical structures of the body and reconstruction of internal organs or different organs are common after traditional surgery or MIS,decreasing the quality of life of patients post-operation.Thus,I propose a new treatment mode,super MIS(SMIS),which is defined as“curing a disease or lesion which used to be treated by MIS while preserving the integrity of the organs”.In this study,I describe the origin,definition,operative channels,advantages,and future perspectives of SMIS.

Fully automatic AI segmentation of oral surgery-related tissues based on cone beam computed tomography images

Accurate segmentation of oral surgery-related tissues from cone beam computed tomography(CBCT)images can significantly accelerate treatment planning and improve surgical accuracy.In this paper,we propose a fully automated tissue segmentation system for dental implant surgery.Specifically,we propose an image preprocessing method based on data distribution histograms,which can adaptively process CBCT images with different parameters.Based on this,we use the bone segmentation network to obtain the segmentation results of alveolar bone,teeth,and maxillary sinus.We use the tooth and mandibular regions as the ROI regions of tooth segmentation and mandibular nerve tube segmentation to achieve the corresponding tasks.The tooth segmentation results can obtain the order information of the dentition.The corresponding experimental results show that our method can achieve higher segmentation accuracy and efficiency compared to existing methods.Its average Dice scores on the tooth,alveolar bone,maxillary sinus,and mandibular canal segmentation tasks were 96.5%,95.4%,93.6%,and 94.8%,respectively.These results demonstrate that it can accelerate the development of digital dentistry.

Circular RNAs in breast cancer diagnosis,treatment and prognosis

Breast cancer has surpassed lung cancer to become the most common malignancy worldwide.The incidence rate and mortality rate of breast cancer continue to rise,which leads to a great burden on public health.Circular RNAs(circRNAs),a new class of noncoding RNAs(ncRNAs),have been recognized as important oncogenes or suppressors in regulating cancer initiation and progression.In breast cancer,circRNAs have significant roles in tumorigenesis,recurrence and multidrug resistance that are mediated by various mechanisms.Therefore,circRNAs may serve as promising targets of therapeutic strategies for breast cancer management.This study reviews the most recent studies about the biosynthesis and characteristics of circRNAs in diagnosis,treatment and prognosis evaluation,as well as the value of circRNAs in clinical applications as biomarkers or therapeutic targets in breast cancer.Understanding the mechanisms by which circRNAs function could help transform basic research into clinical applications and facilitate the development of novel circRNA-based therapeutic strategies for breast cancer treatment.

Reversal of tamoxifen resistance by artemisinin in ER+breast cancer:bioinformatics analysis and experimental validation

Breast cancer is the leading cause of cancer-related deaths in women worldwide,with Hormone Receptor(HR)+being the predominant subtype.Tamoxifen(TAM)serves as the primary treatment for HR+breast cancer.However,drug resistance often leads to recurrence,underscoring the need to develop new therapies to enhance patient quality of life and reduce recurrence rates.Artemisinin(ART)has demonstrated efficacy in inhibiting the growth of drug-resistant cells,positioning art as a viable option for counteracting endocrine resistance.This study explored the interaction between artemisinin and tamoxifen through a combined approach of bioinformatics analysis and experimental validation.Five characterized genes(ar,cdkn1a,erbb2,esr1,hsp90aa1)and seven drug-disease crossover genes(cyp2e1,rorc,mapk10,glp1r,egfr,pgr,mgll)were identified using WGCNA crossover analysis.Subsequent functional enrichment analyses were conducted.Our findings confirm a significant correlation between key cluster gene expression and immune cell infiltration in tamoxifen-resistant and-sensitized patients.scRNA-seq analysis revealed high expression of key cluster genes in epithelial cells,suggesting artemisinin’s specific impact on tumor cells in estrogen receptor(ER)-positive BC tissues.Molecular target docking and in vitro experiments with artemisinin on LCC9 cells demonstrated a reversal effect in reducing migratory and drug resistance of drug-resistant cells by modulating relevant drug resistance genes.These results indicate that artemisinin could potentially reverse tamoxifen resistance in ER-positive breast cancer.

Enhanced recovery after surgery in elderly patients with non-small cell lung cancer who underwent video-assisted thoracic surgery

BACKGROUND This study was designed to investigate the clinical outcomes of enhanced recovery after surgery(ERAS)in the perioperative period in elderly patients with nonsmall cell lung cancer(NSCLC).AIM To investigate the potential enhancement of video-assisted thoracic surgery(VATS)in postoperative recovery in elderly patients with NSCLC.METHODS We retrospectively analysed the clinical data of 85 elderly NSCLC patients who underwent ERAS(the ERAS group)and 327 elderly NSCLC patients who received routine care(the control group)after VATS at the Department of Thoracic Surgery of Peking University Shenzhen Hospital between May 2015 and April 2017.After propensity score matching of baseline data,we analysed the postoperative stay,total hospital expenses,postoperative 48-h pain score,and postoperative complication rate for the 2 groups of patients who underwent lobectomy or sublobar resection.RESULTS After propensity score matching,ERAS significantly reduced the postoperative hospital stay(6.96±4.16 vs 8.48±4.18 d,P=0.001)and total hospital expenses(48875.27±18437.5 vs 55497.64±21168.63 CNY,P=0.014)and improved the satisfaction score(79.8±7.55 vs 77.35±7.72,P=0.029)relative to those for routine care.No significant between-group difference was observed in postoperative 48-h pain score(4.68±1.69 vs 5.28±2.1,P=0.090)or postoperative complication rate(21.2%vs 27.1%,P=0.371).Subgroup analysis showed that ERAS significantly reduced the postoperative hospital stay and total hospital expenses and increased the satisfaction score of patients who underwent lobectomy but not of patients who underwent sublobar resection.CONCLUSION ERAS effectively reduced the postoperative hospital stay and total hospital expenses and improved the satisfaction score in the perioperative period for elderly NSCLC patients who underwent lobectomy but not for patients who underwent sublobar resection.

Diagnostic challenges and individualized treatment of cervical adenocarcinoma metastases to the breast:A case report

BACKGROUND Cervical cancer is a rare primary tumor resulting in metastases to the breast with few cases reported in literature.Breast metastases are associated with poor prognosis.The following case highlights the diagnostic challenges associated with metastatic cervical cancer to the breast along with individualized treatment.CASE SUMMARY A 44-year-old G7P5025 with no significant past medical or surgical history presented with heavy vaginal to an outside emergency department where an exam and a pelvic magnetic resonance imaging showed a 4.5 cm heterogenous lobulated cervical mass involving upper two thirds of vagina,parametria and lymph node metastases.Cervical biopsies confirmed high grade adenocarcinoma with mucinous features.A positron emission tomography/computed tomography(PET/CT)did not show evidence of metastatic disease.She received concurrent cisplatin with external beam radiation therapy.Follow up PET/CT scan three months later showed no suspicious fluorodeoxyglucose uptake in the cervix and no evidence of metastatic disease.Patient was lost to follow up for six months.She was re-imaged on re-presentation and found to have widely metastatic disease including breast disease.Breast biopsy confirmed programmed death-ligand 1 positive metastatic cervical cancer.The patient received six cycles of carboplatin and paclitaxel with pembrolizumab.Restaging imaging demonstrated response.Patient continued on pembrolizumab with disease control.CONCLUSION Metastatic cervical cancer to the breast is uncommon with nonspecific clinical findings that can make diagnosis challenging.Clinical history and immunohistochemical evaluation of breast lesion,and comparison to primary tumor can support diagnosis of metastatic cervical cancer to the breast.Overall,the prognosis is poor,but immunotherapy can be considered in select patients and may result in good disease response.

Tumor deposits in axillary adipose tissue in patients with breast cancer:Do they matter?

Tumor deposits(TDs)are defined as discrete,irregular clusters of tumor cells lying in the soft tissue adjacent to but separate from the primary tumor,and are usually found in the lymphatic drainage area of the primary tumor.By definition,no residual lymph node structure should be identified in these tumor masses.At present,TDs are mainly reported in colorectal cancer,with a few reports in gastric cancer.There are very few reports on breast cancer(BC).For TDs,current dominant theories suggest that these are the result of lymph node metastasis of the tumor with complete destruction of the lymph nodes by the tumor tissue.Even some pathologists classify a TD as two lymph node metastases for calculation.Some pathologists also believe that TDs belong to the category of disseminated metastasis.Therefore,regardless of the origin,TDs are an indicator of poor prognosis.Moreover,for BC,sentinel lymph node biopsy is generally used at present.Whether radical axillary lymph node dissection should be adopted for BC with TDs in axillary lymph nodes is still inconclusive.The present commentary of this clinical issue has certain guiding significance.It is aimed to increase the awareness of the scientific community towards this under-recognized problem in BC pathology.

RARRES2 regulates lipid metabolic reprogramming to mediate the development of brain metastasis in triple negative breast cancer

Background Triple negative breast cancer(TNBC),the most aggressive subtype of breast cancer,is characterized by a high incidence of brain metastasis(BrM)and a poor prognosis.As the most lethal form of breast cancer,BrM remains a major clinical challenge due to its rising incidence and lack of effective treatment strategies.Recent evidence suggested a potential role of lipid metabolic reprogramming in breast cancer brain metastasis(BCBrM),but the underlying mechanisms are far from being fully elucidated.Methods Through analysis of BCBrM transcriptome data from mice and patients,and immunohistochemical validation on patient tissues,we identified and verified the specific down-regulation of retinoic acid receptor responder 2(RARRES2),a multifunctional adipokine and chemokine,in BrM of TNBC.We investigated the effect of aberrant RARRES2 expression of BrM in both in vitro and in vivo studies.Key signaling pathway components were evaluated using multi-omics approaches.Lipidomics were performed to elucidate the regulation of lipid metabolic reprogramming of RARRES2.Results We found that downregulation of RARRES2 is specifically associated with BCBrM,and that RARRES2 deficiency promoted BCBrM through lipid metabolic reprogramming.Mechanistically,reduced expression of RARRES2 in brain metastatic potential TNBC cells resulted in increased levels of glycerophospholipid and decreased levels of triacylglycerols by regulating phosphatase and tensin homologue(PTEN)-mammalian target of rapamycin(mTOR)-sterol regulatory element-binding protein 1(SREBP1)signaling pathway to facilitate the survival of breast cancer cells in the unique brain microenvironment.Conclusions Our work uncovers an essential role of RARRES2 in linking lipid metabolic reprogramming and the development of BrM.RARRES2-dependent metabolic functions may serve as potential biomarkers or therapeutic targets for BCBrM.

Metochalcone induces senescence-associated secretory phenotype via JAK2/STAT3 pathway in breast cancer

Breast and lung cancers are the leading causes of mortality and most frequently diagnosed cancers in women and men,respectively,worldwide.Although the antitumor activity of chalcones has been extensively studied,the molecular mechanisms of isoliquiritigenin analog 2',4',4-trihydroxychalcone(metochalcone;TEC)against carcinomas remain less well understood.In this study,we found that TEC inhibited cell proliferation of breast cancer BT549 cells and lung cancer A549 cells in a concentration-dependent manner.TEC induced cell cycle arrest in the S-phase,cell migration inhibition in vitro,and reduced tumor growth in vivo.Moreover,transcriptomic analysis revealed that TEC modulated the activity of the JAK2/STAT3 and P53 pathways.TEC triggered the senescence-associated secretory phenotype(SASP)by repressing the JAK2/STAT3 axis.The mechanism of metochalcone against breast cancer depended on the induction of SASP via deactivation of the JAK2/STAT3 pathway,highlighting the potential of chalcone in senescence-inducing therapy against carcinomas.

Glaucoma surgery experiments using digital microscope-integrated optical coherence tomography and OCT-compatible instruments

There is a certain failure rate in traditional glaucoma surgery because of the lack of depth information in microscope images.In this work,we present a digital microscope-integrated optical coherence tomography(MIOCT)system and several custom-made OCT-compatible instruments for glaucoma surgery.Sixteen ophthalmologists were asked to perform trabeculectomy and canaloplasty on live porcine eyes using the system and instruments.After surgery,a subjective feedback survey about the user experience was taken.The experiment results showed that our system can help surgeons easily locate important tissue structures during surgery.The custom-made instruments also solved the shadowing problem in OCT imaging.Surgeons preferred to use the system in their future practice.

Is recovery enhancement after gastric cancer surgery really a safe approach for elderly patients?

BACKGROUND This study aimed to evaluate the safety of enhanced recovery after surgery(ERAS)in elderly patients with gastric cancer(GC).AIM To evaluate the safety of ERAS in elderly patients with GC.METHODS The PubMed,EMBASE,and Cochrane Library databases were used to search for eligible studies from inception to April 1,2023.The mean difference(MD),odds ratio(OR)and 95%confidence interval(95%CI)were pooled for analysis.The quality of the included studies was evaluated using the Newcastle-Ottawa Scale scores.We used Stata(V.16.0)software for data analysis.RESULTS This study consists of six studies involving 878 elderly patients.By analyzing the clinical outcomes,we found that the ERAS group had shorter postoperative hospital stays(MD=-0.51,I2=0.00%,95%CI=-0.72 to-0.30,P=0.00);earlier times to first flatus(defecation;MD=-0.30,I²=0.00%,95%CI=-0.55 to-0.06,P=0.02);less intestinal obstruction(OR=3.24,I2=0.00%,95%CI=1.07 to 9.78,P=0.04);less nausea and vomiting(OR=4.07,I2=0.00%,95%CI=1.29 to 12.84,P=0.02);and less gastric retention(OR=5.69,I2=2.46%,95%CI=2.00 to 16.20,P=0.00).Our results showed that the conventional group had a greater mortality rate than the ERAS group(OR=0.24,I2=0.00%,95%CI=0.07 to 0.84,P=0.03).However,there was no statistically significant difference in major complications between the ERAS group and the conventional group(OR=0.67,I2=0.00%,95%CI=0.38 to 1.18,P=0.16).CONCLUSION Compared to those with conventional recovery,elderly GC patients who received the ERAS protocol after surgery had a lower risk of mortality.

Treatment of hemolymphangioma by robotic surgery: A case report

BACKGROUND Hemolymphangioma of the jejunum is rare and lacks clinical specificity,and can manifest as gastrointestinal bleeding,abdominal pain,and intestinal obstruction.Computed tomography,magnetic resonance imaging,and other examinations show certain characteristics of the disease,but lack accuracy.Although capsule endoscopy and enteroscopy make up for this deficiency,the diagnosis also still re-quires pathology.CASE SUMMARY A male patient was admitted to the hospital due to abdominal distension and abdominal pain,but a specific diagnosis by computed tomography examination was not obtained.Partial resection of the small intestine was performed by robotic surgery,and postoperative pathological biopsy confirmed the diagnosis of hemo-lymphangioma.No recurrence in the follow-up examination was observed.CONCLUSION Robotic surgery is an effective way to treat hemolymphangioma through minima-lly invasive techniques under the concept of rapid rehabilitation.

Effect of ankle versus thigh tourniquets on post-operative pain in foot and ankle surgery

BACKGROUND Tourniquets are commonly used in elective extremity orthopaedic surgery to reduce blood loss,improve visualization in the surgical field,and to potentially reduce surgical time.There is a lack of consensus in existing guidelines regarding the optimal tourniquet pressure,placement site,and duration of use.There is a paucity of data on the relationship between the site of a tourniquet and postoperative pain in foot and ankle surgery.AIM To explore the relationship between tourniquet site and intensity of post-operative pain scores in patients undergoing elective foot and ankle surgery.METHODS Retrospective analysis of prospectively collected data on 201 patients who underwent foot and ankle surgery in a single institution was undertaken.Intraoperative tourniquet duration,tourniquet pressure and site,and postoperative pain scores using Visual Analogue Score were collected in immediate recovery,at six hours and at 24 h post-op.Scatter plots were used to analyse the data and to assess for the statistical correlation between tourniquet pressure,duration,site,and pain scores using Pearson correlation coefficient.RESULTS All patients who underwent foot and ankle surgery had tourniquet pressure of 250 mmHg for ankle tourniquet and 300 mmHg for thigh.There was no correlation between the site of the tourniquet and pain scores in recovery,at six hours and after 24 h.There was a weak correlation between tourniquet time and Visual Analogue Score immediately post-op(r=0.14,P=0.04)but not at six or 24 h post-operatively.CONCLUSION This study shows that there was no statistically significant correlation between tourniquet pressure,site and postop pain in patients undergoing foot and ankle surgery.The choice of using a tourniquet is based on the surgeon's preference,with the goal of minimizing the duration of its application at the operative site.

Cardiac rehabilitation after cardiac surgery:An important underutilized treatment strategy

Physical inactivity remains in high levels after cardiac surgery,reaching up to 50%.Patients present a significant loss of functional capacity,with prominent muscle weakness after cardiac surgery due to anesthesia,surgical incision,duration of cardiopulmonary bypass,and mechanical ventilation that affects their quality of life.These complications,along with pulmonary complications after surgery,lead to extended intensive care unit(ICU)and hospital length of stay and significant mortality rates.Despite the well-known beneficial effects of cardiac rehabilitation,this treatment strategy still remains broadly underutilized in patients after cardiac surgery.Prehabilitation and ICU early mobilization have been both showed to be valid methods to improve exercise tolerance and muscle strength.Early mobilization should be adjusted to each patient’s functional capacity with progressive exercise training,from passive mobilization to more active range of motion and resistance exercises.Cardiopulmonary exercise testing remains the gold standard for exercise capacity assessment and optimal prescription of aerobic exercise intensity.During the last decade,recent advances in healthcare technology have changed cardiac rehabilitation perspectives,leading to the future of cardiac rehabilitation.By incorporating artificial intelligence,simulation,telemedicine and virtual cardiac rehabilitation,cardiac surgery patients may improve adherence and compliance,targeting to reduced hospital readmissions and decreased healthcare costs.

Breast Cancer in a Supernumerary Breast at the Yaoundé Gynaeco-Obstetric and Paediatric Hospital: About a Case

Accessory or ectopic breast tissue is an anomaly in the development of the breast. It is a rare condition that occurs along the embryological mammary line. In less than 1% of all breast cancers, supernumerary breast cancer is reported, with the axillary location being the most common in 60% to 90% of cases. Cancerous degeneration of this supernumerary breast tissue can pose a dual diagnostic and therapeutic problem. We report the case of locally advanced adenocarcinoma in a right supernumerary breast. This is a 75-year-old, grand-multiparous, postmenopausal, and known hypertensive patient on treatment. Family history was remarkable for brain cancer in her sister and oesophageal cancer in her mother. She consulted for a mass in the right axillary cavity on supernumerary breast evolving for a year. Clinical examination revealed a large, fixed, budding and haemorrhagic-ulcerated mass of the right axilla, with long axis measuring about 15 cm. There was as wella supernumerary breast on the left, but without particularity. A soft tissue ultrasound showed a large hypoechoicmass in the right axillary region of 116 mm with areas of central necrobiosis. Morphologically, the breasts were normal. A breast MRI revealed a subcutaneous mass in the right axillary cavity with skin ulceration and satellite lymphadenopathy. The extension assessment revealed liver metastases, and a biopsy of the mass revealed a breast adenocarcinoma. The case was the subject of a multidisciplinary consultation meeting following which a wide excision of the mass was indicated. The histo-pathology analysis results of the surgical specimen were in favour of a triple negative papillary adenocarcinoma. After a post-operative multidisciplinary consultation meeting, adjuvant chemotherapy was indicated. The development of supernumerary breasts depends on hormones, just like normal breasts. Breast cancer in accessory breast tissue is quite rare with the incidence being 6%. The most common pathology is invasive carcinoma (50% - 75%). It is usually located in the armpit (60% - 70%) although it can be present in other less common locations such as the inframammary region (5% - 10%) and rarely the thighs, perineum, groin and the vulva. Since accessory axillary breast tissue is not considered during breast screening examination, it is necessary for clinicians to be aware of this entity and associated pathologies. Their preventive excision in women at high risk can also be considered.

Impact of frailty on short-term postoperative outcomes in patients undergoing colorectal cancer surgery:A systematic review and meta-analysis

BACKGROUND Colorectal cancer is a major global health challenge that predominantly affects older people.Surgical management,despite advancements,requires careful consideration of preoperative patient status for optimal outcomes.AIM To summarize existing evidence on the association of frailty with short-term postoperative outcomes in patients undergoing colorectal cancer surgery.METHODS A literature search was conducted using PubMed,EMBASE and Scopus databases for observational studies in adult patients aged≥18 years undergoing planned or elective colorectal surgery for primary carcinoma and/or secondary metastasis.Only studies that conducted frailty assessment using recognized frailty assess-ment tools and had a comparator group,comprising nonfrail patients,were included.Pooled effect sizes were reported as weighted mean difference or relative risk(RR)with 95%confidence intervals(CIs).RESULTS A total of 24 studies were included.Compared with nonfrail patients,frailty was associated with an increased risk of mortality at 30 d(RR:1.99,95%CI:1.47-2.69),at 90 d(RR:4.76,95%CI:1.56-14.6)and at 1 year(RR:5.73,95%CI:2.74-12.0)of follow up.Frail patients had an increased risk of any complications(RR:1.81,95%CI:1.57-2.10)as well as major complications(Clavien-Dindo classification grade≥III)(RR:2.87,95%CI:1.65-4.99)compared with the control group.The risk of reoperation(RR:1.18,95%CI:1.07-1.31),readmission(RR:1.70,95%CI:1.36-2.12),need for blood transfusion(RR:1.67,95%CI:1.52-1.85),wound complications(RR:1.49,95%CI:1.11-1.99),delirium(RR:4.60,95%CI:2.31-9.16),risk of prolonged hospitalization(RR:2.09,95%CI:1.22-3.60)and discharge to a skilled nursing facility or rehabilitation center(RR:3.19,95%CI:2.0-5.08)was all higher in frail patients.CONCLUSION Frailty in colorectal cancer surgery patients was associated with more complications,longer hospital stays,higher reoperation risk,and increased mortality.Integrating frailty assessment appears crucial for tailored surgical management.

Dermatofibrosarcoma Protuberans of the Breast: A Rare Localization

The dermatofibrosarcoma protuberans (DFP) is a rare skin tumor. It represents 0.1% of the malignant skin tumor. Surgery is its only treatment. The breast involvement is exceptional. We report our cases, 13 years old patient we have dermatofibrosarcoma protuberans in her breast.

Advances in regional nodal management of early-stage breast cancer

With the continuous improvement of systemic treatment, reasonable local regional control of early-stage breast cancer can be translated into survival benefits. The optimization of regional nodal management in patients with limited sentinel lymph node(SLN) metastasis needs to be weighed by surgical complications, regional recurrence risk, and lymph node status, as well as other escalating treatment(systemic/radiotherapy) that may result from deescalating surgery. With the effective support and supplementation of systemic therapy and radiotherapy, the management of axillary surgery is developing in a de-escalating trend. The widespread application of neoadjuvant therapy has contributed to optimizing the management of patients with clinically node-negative/imaging nodepositive disease. In clinical practice, it is necessary to consider the residual tumor burden of regional lymph nodes when formulating the optimal irradiation fields in patients with limited positive SLN without axillary lymph node dissection. The combined application of genomic tests and American College of Surgeons Oncology Group Z0011/AMAROS criteria could provide patients with a better strategy of dual de-escalation treatment, which includes the de-escalation of both axillary surgery and systemic treatment. In the era of sentinel lymph node biopsy(SLNB), the regional nodal management of breast cancer should adhere to the concept of “updating ideas, making bold assumptions, and carefully seeking proof”, make full use of the benefits of systemic therapy and radiotherapy to reduce the scope of surgery and complications, and expand the “net benefit” of efficacy and quality of life. This review discusses the optimization of regional nodal management in the era of SLNB, in order to provide reference information for clinicians.