Systemic treatments for resectable carcinoma of the esophagus

One of the most prevalent malignancies in the world is esophageal cancer(EC).The 5-year survival rate of EC remains pitiful despite treatment advancements.Neoadjuvant chemoradiotherapy in conjunction with esophagectomy is the standard of care for patients with resectable disease.The pathological complete response rate,however,is not acceptable.A distant metastasis or a locoregional recurrence will occur in about half of the patients.To increase the clinical effectiveness of therapy,it is consequently vital to investigate cutting-edge and potent therapeutic modalities.The approach to the management of resectable EC using immunotherapy has been considerably altered by immune checkpoint inhibitors.Systemic immunotherapy has recently been shown to have the potential to increase the survival of patients with resectable EC,according to growing clinical data.A combination of chemotherapy,radiation,and immunotherapy may have a synergistic antitumor impact because,according to mounting evidence,these treatments can stimulate the immune system via a number of different pathways.In light of this,it makes sense to consider the value of neoadjuvant immunotherapy for patients with surgically treatable EC.In this review,we clarify the rationale for neoadjuvant immunotherapy in resectable EC patients,recap the clinical outcomes of these approaches,go through the upcoming and ongoing investigations,and emphasize the difficulties and unmet research requirements.

Systemic treatment for metastatic colorectal cancer

Significant progress has been achieved in the treatment of metastatic colorectal cancer(mCRC)patients during the last 20 years.There are currently numerous treatments available for the first-line treatment of mCRC.Sophisticated molecular technologies have been developed to reveal novel prognostic and predictive biomarkers for CRC.The development of next-generation sequencing and wholeexome sequencing,which are strong new tools for the discovery of predictive molecular biomarkers to facilitate the delivery of customized treatment,has resulted in tremendous breakthroughs in DNA sequencing technology in recent years.The appropriate adjuvant treatments for mCRC patients are determined by the tumor stage,presence of high-risk pathologic characteristics,microsatellite instability status,patient age,and performance status.Chemotherapy,targeted therapy,and immunotherapy are the main systemic treatments for patients with mCRC.Despite the fact that these novel treatment choices have increased overall survival for mCRC,survival remains optimal for individuals with non-metastatic disease.The molecular technologies currently being used to support our ability to practice personalized medicine;the practical aspects of applying molecular biomarkers to regular clinical practice;and the evolution of chemotherapy,targeted therapy,and immunotherapy strategies for the treatment of mCRC in the front-line setting are all reviewed here.

Systemic treatment for advanced pancreatic cancer

Pancreatic cancer is a deadly disease with an extremely poor 5-year survival rate due to treatment resistance and late-stage detection.Despite numerous years of research and pharmaceutical development,these figures have not changed.Treatment options for advanced pancreatic cancer are still limited.This illness is typically detected at a late stage,making curative surgical resection impossible.Chemotherapy is the most commonly utilized technique for treating advanced pancreatic cancer but has poor efficacy.Targeted therapy and immunotherapy have made significant progress in many other cancer types and have been proven to have extremely promising possibilities;these therapies also hold promise for pancreatic cancer.There is an urgent need for research into targeted treatment,immunotherapy,and cancer vaccines.In this review,we emphasize the founda-tional findings that have fueled the therapeutic strategy for advanced pancreatic cancer.We also address current advancements in targeted therapy,immuno-therapy,and cancer vaccines,all of which continue to improve the clinical outcome of advanced pancreatic cancer.We believe that clinical translation of these novel treatments will improve the low survival rate of this deadly disease.

Therapeutic response and safety of different treatments for cutaneous leishmaniasis in patients: A retrospective cross-sectional study

Objective:To analyze the therapeutic response and safety of different treatments for cutaneous leishmaniasis,received by patients in the Program for the Study and Control of Tropical Diseases-PECET-Medellín-Colombia.Methods:This is a retrospective cross-sectional study of patients attended at PECET Research Center during 2016-2021.Relevant information regarding sociodemographic characteristics,history of leishmaniasis,characterization of current infection,treatment received,follow-up of therapeutic response and safety was collected from the medical records.Data were analyzed with Pearson's Chi-square association tests and Mann-Whitney U test using statistical software.Results:A total of 486 clinical records of patients were analyzed,and 356 received treatment.Eight different therapeutic alternatives(systemic,local and in combination)were analyzed.The therapeutic response of the different alternatives used(except thermotherapy)was higher than 50%.Most frequent adverse events were myalgias,arthralgias and headache,and vesicles for systemic and local treatment,respectively.Conclusions:Safety profile and performance of local therapeutic alternatives and combined schemes for the treatment of uncomplicated cutaneous leishmaniasis are an interesting option for the management of the disease.

Efficacy of hepatic arterial infusion chemotherapy and its combination strategies for advanced hepatocellular carcinoma:A network meta-analysis

BACKGROUND With the rapid progress of systematic therapy for hepatocellular carcinoma(HCC),therapeutic strategies combining hepatic arterial infusion chemotherapy(HAIC)with systematic therapy arised increasing concentrations.However,there have been no systematic review comparing HAIC and its combination strategies in the first-line treatment for advanced HCC.AIM To investigate the efficacy and safety of HAIC and its combination therapies for advanced HCC.METHODS A network meta-analysis was performed by including 9 randomized controlled trails and 35 cohort studies to carry out our study.The outcomes of interest comprised overall survival(OS),progression-free survival(PFS),tumor response and adverse events.Hazard ratios(HR)and odds ratios(OR)with a 95% confidence interval(CI)were calculated and agents were ranked based on their ranking probability.RESULTS HAIC outperformed Sorafenib(HR=0.55,95%CI:0.42-0.72;HR=0.51,95%CI:0.33-0.78;OR=2.86,95%CI:1.37-5.98;OR=5.45,95%CI:3.57-8.30;OR=7.15,95%CI:4.06-12.58;OR=2.89,95%CI:1.99-4.19;OR=0.48,95%CI:0.25-0.92,respectively)and transarterial chemoembolization(TACE)(HR=0.50,95%CI:0.33-0.75;HR=0.62,95%CI:0.39-0.98;OR=3.08,95%CI:1.36-6.98;OR=2.07,95%CI:1.54-2.80;OR=3.16,95%CI:1.71-5.85;OR=2.67,95%CI:1.59-4.50;OR=0.16,95%CI:0.05-0.54,respectively)in terms of efficacy and safety.HAIC+lenvatinib+ablation,HAIC+ablation,HAIC+anti-programmed cell death 1(PD-1),and HAIC+radiotherapy had the higher likelihood of providing better OS and PFS outcomes compared to HAIC alone.HAIC+TACE+S-1,HAIC+lenvatinib,HAIC+PD-1,HAIC+TACE,and HAIC+sorafenib had the higher likelihood of providing better partial response and objective response rate outcomes compared to HAIC.HAIC+PD-1,HAIC+TACE+S-1 and HAIC+TACE had the higher likelihood of providing better complete response and disease control rate outcomes compared to HAIC alone.CONCLUSION HAIC proved more effective and safer than sorafenib and TACE.Furthermore,combined with other interventions,HAIC showed improved efficacy over HAIC monotherapy according to the treatment ranking analysis.

Development of systemic therapy for hepatocellular carcinoma at 2013:Updates and insights

A growing number of multi-targeted tyrosine kinase inhibitor (TKI) has undergone testing for hepatocellular carcinoma (HCC). Unfortunately, this enthusiasm has recently been discouraged by a number of negative phase III studies on several anti-angiogenic TKIs in HCC. Several postulations have been made to account for this phenomenon, namely the plateau effects of anti-angiogenesis approach, the heterogeneity of HCC in terms of background hepatitis/cirrhosis and tumor biology, as well as the way how clinical trials are designed. Regardless of the underlying reasons, these results suggested that alternative strategies are necessary to further develop systemic therapy for HCC. Several new strategies are currently evaluated: for examples, molecular agents with activities against targets other than vascular endothelial growth factor receptor are being evaluated in on-going clinical trials. In addition, different approaches of targeted agents in combination with various treatment modalities, such as concurrently with another molecular agent, cytotoxic chemotherapy or transarterial chemoembolization, are being developed. This review aims to give a summary on the results of recently released clinical trials on TKIs, followed by discussion on some of the potential novel agents and combinational approaches. Future directions for testing innovative systemic agents for HCC will also be discussed.

Intratympanic vs systemic use of steroids as first-line treatment for sudden hearing loss:A meta-analysis of randomized,controlled trials

Background Sudden sensorineural hearing loss(SSNHL)is a common disease in otology,and steroids play an important role in its treatment.Steroids can be administered systemically or locally,and the efficacies of different administration routes remain controversial.Methods We searched the Cochrane,EMBASE,PubMed,Web of Science,CNKI,Wanfang and Weipu databases for randomized controlled trials(RCTs)on glucocorticoid treatments for SSNHL to compare the efficacy of topical and systemic steroid administration.The Review Manager 5.4 software was used for synthesis of data:the rate of reported hearing improvement and change in pure-tone audiometry(PTA).Results In all the included studies,when intratympanic administration was compared to systemic therapies,the risk difference(RD)using reported hearing improvement as an outcome measure was 0.08(95%CI:0.01–0.14,I2=45%).Using PTA changes as an outcome measure in 4 studies,the mean difference(MD)was 10.43 dB(95%CI:3.68–17.18,I2=81%).Hearing improvement RD was also compared among different types of steroid,recovery criteria,follow-up times and diagnostic criteria,and showed no significant differences exception for recovery criteria(>10 dB)(RD-0.06,95%CI:0.14-0.2,I2=0%).Conclusion As the initial treatment for SSNHL,topical steroids seem to be superior to systemic steroid administration,especially in patients with contraindications to systemic steroids usage.However,further verification based on high-quality research is needed.

Advances in Diagnosis and Treatment of Neuropsychiatric Systemic Lupus Erythematosus

1 Introduction Neuropsychiatric systemic lupus erythematosus(NPSLE)is a serious complication of systemic lupus erythematosus(SLE),with an incidence of about 30%to 40%[1].No matter early or late SLE patients are prone to concurrent,so early diagnosis and treatment of NPSLE is extremely important.

Strategy for Detecting Systemic Treatment Sensitivity of Primary Liver Cancer Based on a Novel Infrared-emissive Organic Nanoparticle

In this study,we synthesized an organic material with near-infrared emission capabilities:4-(2-(4-(9-(4-(diphenylamino)phenyl)naphtho[2,3-c][1,2,5]thiadiazol-4-yl)phenyl)-1H-phenol-1-ylidene)malononitrile(TPA).Furthermore,TPA-PEG2000 fluorescent nanoparticles were prepared via coating the shells with PEG2000.TPA-PEG2000 exhibited strong near-infrared emission near 700 nm,with a photoluminescence quantum yield of 15.09%,indicating a high emission efficiency.Molecular biology experiments have confirmed its low toxicity and excellent biocompatibility.Increased cholesterol and phospholipid levels in liver cancer cell membranes with low sensitivity or high drug resistance lead to increased rigidity,reduced membrane fluidity,reduced endocytic efficiency,and reduced uptake.Therefore,the uptake of TPA-PEG2000 nanoparticles into cells and the near-infrared fluorescence intensity can be used to evaluate the sensitivity of systemic liver cancer treatment in a simple and efficient manner.

Computed tomography-based delta radiomics of tumor core_edge combination for systemic treatment response evaluation in pancreatic cancer

Background:As a systemic disease,pancreatic cancer(PC)can be treated systemically to raise the R0 resection rate and enhance patient prognosis.The best ways to assess the treatment response to systemic treatment of patients with PC are still lacking.Methods:A total of 122 PC patients were enrolled;25 of these patients were used as an independent testing set.According to the pathologic response,PC patients were classified into the responder and nonresponder groups.The whole tumor,core,edge,and peritumoral were segmented from the enhanced computed tomography(CT)images.Machine-learning models were created by extracting the variations in radionics features before and after therapy(delta radiomics features).Finally,we compared the performance of models based on radiomics features,changes in tumor markers,and radiologic evaluation.Results:The model based on the core(area under curve[AUC]=0.864)and edge features(AUC=0.853)showed better performance than that based on the whole tumor(AUC=0.847)or peritumoral area(AUC=0.846).Moreover,the tumor core_edge combination model(AUC=0.899)could better increase confidence in treatment response than using either of them alone.The accuracies of models based on changes in tumor markers and radiologic evaluation were relatively poorer than of the radiomics model.Moreover,Patients predicted to respond to therapy using the radiomics model showed a relatively longer overall survival(43 vs 27 months),although there were no significant differences(P=.063).Conclusions:The tumor core_edge combination delta radiomics model is an effective approach to evaluate pathologic response in PC patients with systemic treatment.

MALE BREAST CANCER: A REPORT OF 34 CASES

Objective： To study the biological characteristics, the therapeutic procedure and the prognosis of male breast cancer. Methods： 34 patients with male breast cancer were retrospectively analyzed, who were diagnosed and treated in the First Hospital of Jilin University between 1980 and March 2005. Results： Clinical TNM stage of the patients were stage Ⅰ, 6 patients, stage Ⅱ, 24 patients and stage Ⅲ, 4 patients＇. Positive lymph nodes were found in 35.3% of the patients. All these patients received modified radical mastectomy. The 5-year survival rate was 65.3%. Postoperation recurrence rate was 11.8%. Conclusions： Patients with male breast cancer should receive surgical treatment, assisted with adjuvant treatment, such as radiotherapy, chemotherapy, endocrine therapy and so on. TNM stage and expression of hormone receptor may be the main factors affecting the prognosis.

Current management strategy of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) still remains a considerable challenge for surgeons.Surgery,including liver transplantation,is the most important therapeutic approach for patients with this disease.HCC is frequently diagnosed at advanced stages and has a poor prognosis with a high mortality rate even when surgical resection has been considered potentially curative.This brief report summarizes the current status of the management of this malignancy and includes a short description of new pharmacological approaches in HCC treatment.

Evaluation of Biological Characteristics of Bacteria Contributing to Biofilm Formation

Biofilm-associated microorganisms play crucial roles in terrestrial and aquatic nutrient cycling and in the biodegradation of environmental pollutants. Biofilm formation was determined for a total of 18 bacterial isolates obtained from the biofilms of wastewater treatment systems and of little carpolite in soil. Among these isolates, seven showed strong biofilm-forming capacity. The phylogenetic affiliation of the isolates showing high biofilm formation capacity was determined through 16S rDNA sequencing and the isolates were grouped into 7 bacterial species including Pseudornonas sp., Pseudomonas putida, Aeromonas caviae, Bacillus cereus, Pseudornonas plecoglossicida, Aeromonas hydrophila, and Comamonas testosteroni. The biofilm-forming capacity was closely related with flagella, exopolysaccharide, and extracellular protein. According to the coefficient of determination, the relative importance of the five biological characteristics to biofilm formation was, in order from greatest to least, exopolysaccharide 〉 flagella 〉 N-acyl-homoserine lactones （AHLs） signaling molecules 〉 extracellular protein 〉 swarming motility.

Evolving treatment landscape for early and advanced pancreatic cancer

Pancreatic ductal adenocarcinoma is an infrequent cancer with a high disease related mortality rate, even in the context of early stage disease. Until recently, the rate of death from pancreatic cancer has remained largely similar whereby gemcitabine monotherapy was the mainstay of systemic treatment for most stages of disease. With the discovery of active multiagent chemotherapy regimens, namely FOLFIRINOX and gemcitabine plus nab-paclitaxel, the treatment landscape of pancreatic cancer is slowly evolving. FOLFIRINOX and gemcitabine plus nab-paclitaxel are now considered standard first line treatment options in metastatic pancreatic cancer. Studies are ongoing to investigate the utility of these same regimens in the adjuvant setting. The potential of these treatments to downstage disease is also being actively examined in the locally advanced context since neoadjuvant approaches may improve resection rates and surgical outcomes. As more emerging data become available, the management of pancreatic cancer is anticipated to change significantly in the coming years.

Will the collaboration of surgery and external radiotherapy open new avenues for hepatocellular carcinoma with portal vein thrombosis?

Portal invasion of hepatocellular carcinoma(HCC)occurs in 12.5%-40%of patients diagnosed with cancer and yields poor clinical outcomes.Since it is a common cause of inoperability,sorafenib was regarded as the standard treatment for HCC in the Barcelona Clinic of Liver Cancer guidelines.However,the median survival of the Asian population was only approximately 6 mo,and the tumor response rate was less than moderate(<5%).Various locoregional modalities were performed,including external beam radiotherapy(EBRT),transarterial chemoembolization,hepatic arterial infusion chemotherapy,and surgery,alone or in combination.Among them,EBRT is a noninvasive method and can safely treat tumors involving the major vessels.Palliative EBRT has been commonly performed,especially in East Asian countries,where locally invasive HCC is highly prevalent.Although surgery is not commonly indicated,pioneering studies have demonstrated encouraging results in recent decades.Furthermore,the combination of neo-or adjuvant EBRT and surgery has been recently used and has significantly improved the outcomes of HCC patients,as reported in a few randomized studies.Regarding systemic modality,a combination of novel immunotherapy and vascular endothelial growth factor inhibitor showed results superior to that of sorafenib as a first-line agent.Future clinical trials investigating the combined use of these novel agents,surgery,and EBRT are expected to improve the prognosis of HCC with portal invasion.

Hepatocellular carcinoma Liver Imaging Reporting and Data Systems treatment response assessment: Lessons learned and future directions

Hepatocellular carcinoma(HCC)is a leading cause of morbidity and mortality worldwide,with rising clinical and economic burden as incidence increases.There are a multitude of evolving treatment options,including locoregional therapies which can be used alone,in combination with each other,or in combination with systemic therapy.These treatment options have shown to be effective in achieving remission,controlling tumor progression,improving disease free and overall survival in patients who cannot undergo resection and providing a bridge to transplant by debulking tumor burden to downstage patients.Following locoregional therapy(LRT),it is crucial to provide treatment response assessment to guide management and liver transplant candidacy.Therefore,Liver Imaging Reporting and Data Systems(LI-RADS)Treatment Response Algorithm(TRA)was created to provide a standardized assessment of HCC following LRT.LIRADS TRA provides a step by step approach to evaluate each lesion independently for accurate tumor assessment.In this review,we provide an overview of different locoregional therapies for HCC,describe the expected post treatment imaging appearance following treatment,and review the LI-RADS TRA with guidance for its application in clinical practice.Unique to other publications,we will also review emerging literature supporting the use of LI-RADS for assessment of HCC treatment response after LRT.

Update on the treatment of metastatic renal cell carcinoma

Metastatic renal cell cancer(mRCC)management has undergone a paradigm shift in recent decades.The first revolution came with the emergence of vascular endothelial growth factor inhibitors;there was a second wave with the unprecedented success of checkpoint inhibitors,and then the latest approach,which is becoming the new care standard in mRCC,of combining these two strategies in different ways.Updated results of Checkmate-214 after 42 mo of follow-up were consistent with previously published results showing the superiority of nivolumab/ipilimumab over sunitinib in progression free survival(PFS),overall survival(OS),and objective response rate(ORR)in intermediate and high-risk patients.However,several studies presented at the American Society of Clinical Oncology 2020 suggested that the best place,and so far,the only one for nivolumab/ipilimumab is the frontline setting.The update on Keynote-426 after 23 mo of follow-up showed no superiority of pembrolizumab/axitinib over sunitinib in favorable-risk mRCC,suggesting that it should no longer be the first line of choice in low-risk patients.Finally,the phase III Checkmate 9ER trial results revealed the superiority of nivolumab/cabozantinib vs sunitinib in PFS,OS,and ORR,providing a new first-line option among all International Metastatic RCC Database Consortium risk patients.Some phase II clinical trials also presented this year showed promising results with new combination therapies such as nivolumab/sitravatinib,cabozantinib/atezolizumab,and lenvatinib/pembrolizumab,providing promising grounds upon which to start phase III studies.In addition,other works are using novel therapeutic agents with different mechanisms of action,including telaglenastat(a glutaminase inhibitor),entinostat[an inhibitor of histone deacetylases(HDACs)],and olaparib and talazoparib,poly(ADP-ribose)polymerase inhibitors widely used in other tumors.However,some questions regarding mRCC management still need to be addressed,such as head-to-head comparisons between the current options,treatment sequencing,non-clear cell mRCC,and the role of biomarkers to ascertain the best treatment choice.

Therapeutic strategies for post-transplant recurrence of hepatocellular carcinoma

Despite stringent selection criteria,hepatocellular carcinoma recurrence after liver transplantation(LT)still occurs in up to 20%of cases,mostly within the first 2–3 years.No adjuvant treatments to prevent such an occurrence have been developed so far.However,a balanced use of immunosuppression with minimal dose of calcineurin inhibitors and possible addition of mammalian target of rapamycin inhibitors is strongly advisable.Moreover,several pre-and posttransplant predictors of recurrence have been identified and may help determine the frequency and duration of post-transplant follow-up.When recurrence occurs,the outcomes are poor with a median survival of 12 mo according to most retrospective studies.The factor that most impacts survival after recurrence is timing(within 1–2 years from LT according to different authors).Several therapeutic options may be chosen in case of recurrence,according to timing and disease presentation.Surgical treatment seems to provide a survival benefit,especially in case of late recurrence,while the benefit of locoregional treatments has been suggested only in small retrospective studies.When systemic treatment is indicated,sorafenib has been proved safe and effective,while only few data are available for lenvatinib and regorafenib in second line.The use of immune checkpoint inhibitors is controversial in this setting,given the safety warnings for the risk of acute rejection.

Real-life multi-center retrospective analysis on nivolumab in difficult-to-treat patients with advanced hepatocellular carcinoma

BACKGROUND Hepatocellular carcinoma(HCC)is one of the leading causes of cancer-related death worldwide.The landscape of the systemic treatment for advanced HCC is changing quickly,and recently,the standard of care became either atezolizumab plus bevacizumab or tremelimumab plus durvalumab in the single tremelimumab regular interval durvalumab regimen.Nivolumab monotherapy has proven to be effective sometimes for advanced HCC and could be a valuable treatment option for patients outside current treatment indications and reimbursement criteria for the standard of care.This is a particular population of interest.AIM To evaluate the real-world effectiveness of nivolumab monotherapy in patients with advanced HCC who are not eligible for other treatment.METHODS We conducted a retrospective,multicentric study including 29 patients with advanced HCC from 3 Belgian tertiary hospitals.All patients had had prior chemotherapy or were intolerant or ineligible for treatments.All study subjects received nivolumab 3 mg/kg in monotherapy,administered once every two weeks intravenously.Treatment continued until disease progression,severe adverse events or death.Data were retrieved from patients'medical records.The outcome parameters such as radiological response according to response evaluation criteria in solid tumors(RECIST)criteria,the biological response through the evolution of the alpha-fetoprotein(AFP)level,and clinical response considering both the Child–Pugh(CP)score and the World Health Organization(WHO)performance status(PS)were reported.A safety profile was also reported.Statistical analysis was performed using the SPSS Statistics 27 statistical software package.RESULTS The radiological overall response rate(defined as complete or partial response according to the immune RECIST and modified RECIST criteria)to nivolumab monotherapy was 24.1%.The biological overall response rate(defined as a decrease of≥25%in AFP blood level)was 20.7%.Radiological and biological responses were significantly associated both with each other(P<0.001)and with overall survival(P<0.005 for radiological response and P<0.001 for biological response).Overall survival was 14.5 mo(+/-2.1),and progression-free survival was 10.9 mo(+/-2.3).After 4 mo of treatment,78.3%of patients remained clinically stable or even showed improvement in WHO PS.Grade 3 adverse events occurred in 17.2%of patients,none had grade 4 adverse events,and no patients ceased nivolumab due to adverse events.CONCLUSION Nivolumab monotherapy is a good treatment choice in frail patients with HCC who are ineligible for the standard of care or other validated systemic treatments.

Androgen-related disorders and hormone therapy for patients with keloids

Keloids are a fibroproliferative disorder of the skin and can cause physical discomfort and psychological burden.Apart from local factors such as skin tension and infection,increasing evidence has suggested that systemic endocrine factors also contribute to the emergence and development of keloids.Hormone disorders have long been suspected to be a risk factor;however,previous studies have mainly focused on the role of female hormones and neglected the critical role of male hormones.As we reviewed the published literature addressing sex steroids in pathological scars,we speculated that androgens(i.e.,male hormones)could become actively involved through sebum-associated hypersensitivity reactions and acne-derived skin lesions,resulting in persistent cutaneous inflammation.This hypothesis was also supported by previous in vitro studies,in which elevated androgen levels and androgenic receptors were detected in keloid tissues.Moreover,relief of pain and pruritus has been observed in patients with keloids who accidently received anti-androgen treatment for other irrelevant indications.Thus,we propose that androgen-related disorders are critical in the pathogenesis of keloids,and systemic treatment targeting sex hormones may provide long-term benefits for predisposed patients with multiple keloids.