Infections

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Warts

Communicable Diseases

Papillomavirus Infections

Virus Diseases

DNA Virus Infections

Skin Diseases

Skin Diseases, Viral

Tumor Virus Infections

Skin Diseases, Infectious

Pharmaceutical Solutions

All Drugs and Chemicals

In group-A 30 patients were given topical 5%-potassium hydroxide solution on affected area once at night upto 4 weeks

in group-B 30 patients treated with cotton bud method of cryotherapy with liquid nitrogen once every two weeks. Patients were reassessed at every two weeks and final assessment was done at 12th week.

. In group-A 30 patients were given topical 5% potassium hydroxide solution on affected area once at night for upto 4 weeks

5%potassium hydroxide

in group-B 30 patients treated with cotton bud method of cryotherapy with liquid nitrogen once every two weeks. Patients were reassessed at every two weeks. The treatment carried out upto 12 weeks or until complete recovery from warts.

Liquid nitrogen

ABSTRACT Objective: To study the efficacy while comparing Potassium hydroxide 5% with liquid nitrogen in treatment of plane warts.

Study design: Randomized-controlled trial (RCT), (Double-blind). Study setting and duration: Dept dermatology, CMH-Abbottabad, Nov-2022 / April-2023.

Methodology: The sample size of 60 patients (children and adults aged 4 to 30 years) was calculated using Openepi app sample size RCT calculator, after informed consent by using non-probability consecutive sampling technique. Patients randomly assigned into two groups i.e. In group-A 30 patients were given topical 5%-potassium hydroxide solution on affected area once at night upto 4 weeks and in group-B 30 patients treated with cotton bud method of cryotherapy with liquid nitrogen once every two weeks. Patients were reassessed at every two weeks and final assessment was done at 12th week whereas followed up for 3 months to monitor recurrence. Demographic information and frequency percentages were calculated for qualitative variables by using SPSS26. To determine statistical significance taking p-value \<0.05 as significant, and χ2-square test was used.

Comparison of Topical 5%Potassium Hydroxide vs Liquid Nitrogen in the Treatment of Plane Warts

Comparative Efficacy of Topical 5%Potassium Hydroxide vs Liquid Nitrogen in the Treatment of Plane Warts

Combined Military Hospital Abbottabad

Principal investigator

EndWarts® FREEZE were treated to 11 patients with wart at soft keratin

EndWarts® FREEZE were treated to 11 patients with wart at hard keratin

Liquid nitrogen were treated to 11 patients with wart at soft keratin

Liquid nitrogen were treated to 11 patients with wart at hard keratin

EndWarts® FREEZE is an alternative home cryotherapy device. Patients don't have to go to the hospital to receive treatment for their wart.

EndWarts® FREEZE

Liquid nitrogen is a conventional cryotherapy treatment for cutaneous wart performed by physician at the hospital.

Charussri Leeyaphan, Assoc. Prof.

This study aimed to study cost-effectiveness of EndWarts® FREEZE for wart treatment, compared to conventional liquid nitrogen cryotherapy

Cutaneous warts, caused by Human papilloma virus (HPV), are common skin disease. The prevalence reported in primary school children are 2-20%, and even higher in adults. Non-intact skin are prone to the infection, with all parts of the body can be affected. Even warts are not malignant, they can cause lack of confidence or affected patients' quality of life.

Nowadays there are many treatment methods for warts, such as topical application with salicylic acid and electrical cauterization. Cryotherapy with liquid nitrogen has been the therapy of choice due to its clinical effectiveness, which reported for 6-65%. Treatment mechanism in cryotherapy relies on in-depth freezing of infected keratocyte.

EndWarts® FREEZE is alternative home treatment cryotherapy device containing nitrous oxide. Recent clinical study found that it delivers significant result with good tolerability, and is user friendly. As for our knowledge, no study has been reported about cost-effectiveness of this device, so this study was designed to demonstrate the efficacy of this product in cutaneous warts.

Cost-effectiveness of EndWarts® FREEZE - an Alternative Home Cryotherapy Device for Wart Treatment

Cost-effectiveness of EndWarts® FREEZE for Wart Treatment: A Randomized, Controlled, Investigator-Blinded, Comparative Study

Compared patient satisfaction after treatment of EndWarts® FREEZE. Patient who received EndWarts® FREEZE treatment is required to answer the questionnaire after 12-week treatment (or before 12 week if the patient's wart is cured completely). The questionnaire included questions about the opinion of the product, such as effectiveness for wart treatment, portability, user-friendly, safety, and overall satisfaction. Score from each aspect of satisfaction will be calculated with descriptive statistics.

Compared side effect after treatment with EndWarts® FREEZE and liquid nitrogen. Every patient is required to record his/her side effects after each treatment, such as tingling sensation, burn or scar, hypo/hyperpigmentation, pain, pickling feeling, and report them to the physician at the next follow-up visit (Week 4, week 8, week 12). Number of patients with each side effect are recorded and described with descriptive statistics.

Evaluate cost-effectiveness of EndWarts® FREEZE for wart treatment compared with conventional liquid nitrogen therapy. Transportation fee to the hospital, medical and doctor fee are recorded to sum up the costs of treatment at every visit. Every patient is also required to have his/her wart examined by the same physician at each visit with the use of dermoscope to evaluate the result of wart treatment (worse, the same, partial response, complete response). Moreover, wart size is measured for its diameter and height, then photographed at each visit to recorded the change after treatment. Cure rates will be shown according to type of intervention received, with the use of chi-square test.

Compared patient's Dermatology quality of life index (DLQI) between treatment of EndWarts® FREEZE and liquid nitrogen. DLQI is recorded before the treatment start and after 12-week treatment (or before 12 week if the patient's wart is cured completely). Change in DLQI will be shown with descriptive statistics.

Mahidol University

Neoplasms

Wounds and Injuries

Papilloma

Hyperthermia

Fever

Neoplasms, Squamous Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Controllable infrared bioeffect system at 44±2℃ for 30 mins on target lesion, at days of 1, 2, 3, 15, 16, 23, 30.

Common warts, plantar warts, and condyloma acuminata

Liquid nitrogen crytotherapy at days 1, 15, 30.

As an active comparator, for patients with cutaneous warts, liquid nitrogen crytherapy is applied

liquid nitrogen

As an experimental arm, for patients with cutaneous warts

controllable infrared bioeffect system

Xinghua Gao

Local hyperthermia at 44℃ can promote some alterations of immulogical indicators. The procedure is convenient in clinic, has high tolerance with less trauma and less pain. Based on domestic and abroad clinical practice, the investigators observed initially that local hyperthermia brought great benefits to cutaneous warts. In comparison with liquid nitrogen, the safety and efficacy of controllable infrared bioeffect system to treat skin disease has been evaluated. This proved it could be used in treatment of skin warts, and clinical trial met the requirements of Standards for quality control of clinical trials on medical devices, and can be used in product registration and declaration.

Mild local Hyperthermia with a certain temperature range has been successfully used in the treatment of some diseases. It has been utilised in the treatment of some neoplasm, fungal and HPV infections. Investigators' study found that local hyperthermia at 44°C could cleared HPV in more than half of the patients with plantar warts. Investigators also note the fact that in patients with multiple lesions, the clearance of the target lesion is commonly followed by clearance of other distant lesions, a phenomenon suggesting that local hyperthermia could aid in establishing a specific immune response to eliminate HPV.So the purpose of the study is to evaluate the safety and efficacy of controllable infrared bioeffect system to treat cutaneous warts. This trial was designed into two groups, one was experimental group (thermal therapy group), the other one was control group (liquid nitrogen cryotherapy group). The ratio of participants was 1:1 in experiment group and control group. The main evaluation indicator was the recovery rate after 4 months of initial treatment.

Infrared Bioeffect System for the Treatment of Cutaneous Warts

Evaluation of Controllable Infrared Bioeffect Effect for the Treatment of Cutaneous Warts After 3 Months: a Multicenter, Randomized, Open Label Controlled Trial

to evaluate the clearance rate in different treatment groups 3 months after treatment

to evaluate the recovery rate of target lession in different treatment groups 3 months after treatment

to evaluate the recovery rate of non-target lession in different treatment groups 3 months after treatment

to evaluate the score of VAS (0 score represents no pain; 10 score represents sharp pain) in different treatment groups 3 months after treatment

to evaluate the clearance rate of virus in different treatment groups 3 months after treatment

First Hospital of China Medical University

Professor

Digestive System Diseases

Rare Diseases

Carcinoma

Carcinoma, Squamous Cell

Adenocarcinoma

Esophageal Neoplasms

Esophageal Squamous Cell Carcinoma

Gastrointestinal Neoplasms

Digestive System Neoplasms

Head and Neck Neoplasms

Gastrointestinal Diseases

Esophageal Diseases

Esophageal Cancer

Liquid nitrogen spray cryotherapy with the truFreeze device

Low-pressure liquid nitrogen is sprayed through an upper endoscope on the diseased esophageal tissue to freeze and destroy it. The upper endoscope enables direct visualization of mucosal freeze during spray of the liquid nitrogen onto the mucosa and avoids the need for direct contact with the tissues. The target area is frozen and thawed for several consecutive cycles. The treated tissue becomes necrotic and sloughs, with new, healthy tissue regenerating in its place.

Bruce D Greenwald, MD

The goal of this study is to evaluate the safety and efficacy of endoscopic spray cryotherapy using the CSA Medical, Inc. truFreeze System for patients with previously untreated early-stage cancer (T1a, N0, M0) who are ineligible or refuse conventional therapy including surgery, chemotherapy, radiation therapy, and endoscopic resection.

It is hypothesized that one of the two following outcomes will occur:

1. Complete response to therapy: complete tumor eradication confirmed through histologic examination of biopsy specimens from the targeted esophageal tissue site;
2. Stable disease: tumor remission is not attained, but disease progression is halted.

Background

Endoscopic modalities have been reported to be effective in definitive treatment of early stage esophageal cancer. A study comparing endoscopic treatment to surgery in early esophageal cancer using the SEER (Surveillance Epidemiology and End Results) database showed no difference in the relative hazard of death from esophageal cancer between the two groups. The primary endoscopic therapies used in this study were endoscopic mucosal resection (EMR) and photodynamic therapy (PDT). Estimated 1 and 3 year survival in this study were 92% and 75% in the endoscopic arm and 92% and 82% in the surgical arm. EMR, endoscopic excision of superficial cancer, has also been shown to be highly effective in mucosal tumors in single center studies. "Low-risk" lesions, defined as flat or raised mucosal tumors 2 cm or less that are well-or moderately-differentiated without lymphovascular invasion, demonstrate complete response was seen in 96.6% of patients with 5 year survival of 84%. However, "high-risk lesions," defined as greater than 2 cm, poorly-differentiated, flat-ulcerated, or invading into the submucosa, have a complete remission rate of only 59%.

Endoscopic resection is not possible in all mucosal cancers. Some cancers are not visible endoscopically but detected only by endoscopic biopsy. In other cases, the EMR cannot be done due to scarring from previous resection or other therapy, especially external beam radiation. Management of these cases is problematic. PDT using porfimer sodium has been extensively studied for Barrett's esophagus with high-grade dysplasia, however studies of PDT for early stage esophageal cancer are limited. In a recent single site study using PDT and EMR for mucosal cancers, overall survival was comparable to a group treated with esophagectomy at the same center, with estimated 1 and 3 year survival of 98% and 95%. PDT was used in 43% in combination with EMR in the endoscopic treatment group. Recurrent carcinoma was detected in 16% of endoscopically treated patients. All recurrences were intramucosal cancers, with all but one managed by EMR. Overall, endoscopic treatment was well-tolerated. However, side effects of PDT are common and include photosensitivity, esophageal stricture, chest pain, nausea, vomiting, and fever. In the U.S., PDT is no longer commonly used in the esophagus due to availability of alternative treatment modalities with less cost and side effects.

Endoscopic spray cryotherapy with liquid nitrogen has emerged as an alternative treatment in stage I esophageal cancer in those not suitable for other therapies. A recent retrospective review at 10 U.S. centers assessed outcomes in seventy-nine patients. Patients included those with esophageal carcinoma who failed, refused, or were ineligible for conventional therapy including chemotherapy, radiation, combination chemotherapy and radiation, esophagectomy, and endoscopic mucosal resection. The majority of patients (76%) had tumor stage T1N0M0 with mean tumor length of 4 cm. All patients were treated with liquid nitrogen spray cryotherapy, and forty-nine patients completed treatment. Complete response of luminal disease occurred in 61.2%, including 18 of 24 (75%) with mucosal cancer. Follow-up averaged 10.6 to 11.5 months, and no serious adverse events were reported. Longer term follow-up was reported recently in abstract form. Complete response was seen in 92% of patients with mucosal cancer with median follow-up of 28 months and overall estimated survival at 1 and 3 years of 98% and 92% respectively.

Published studies have demonstrated spray cryotherapy to be safe and well-tolerated, with low overall complication rates. Tolerance of the procedure is very good. All procedures are performed on an outpatient basis. Primary side effects include chest pain, dysphagia, and odynophagia, reported in about half of all procedures. Mean duration of symptoms was 3.6 days, and many patients had no side effects after treatment. Serious adverse events were rare. Gastric perforation occurred in one patient with Marfan's syndrome. Benign esophageal stricture was reported in 13% of patients treated for cancer, with previous esophageal narrowing noted in 9/10. In combination with its relative cost-effectiveness and minimal invasiveness, endoscopic spray cryotherapy is an appealing option for those with stage I esophageal cancer who are ineligible or refuse conventional therapies.

Study Device: truFreezeTM System, CSA Medical Inc., Baltimore, MD

Study Objective: The objective of this study is to evaluate the safety and efficacy of endoscopic spray cryotherapy using the CSA Medical, Inc. truFreeze™ System for patients with early-stage esophageal cancer (T1a, N0, M0) who are ineligible or refuse conventional therapy including surgery, chemotherapy, radiation therapy, and endoscopic resection.

Study Design: Multi-center phase II study.

Study Population: Patients with early-stage esophageal cancer (stage T1aN0M0)

Study Duration: It is estimated that enrollment will take approximately two years. Each subject will remain in the study for up to one-year of treatment and for three years post-treatment. It is expected to take five years to collect all required data for this study.

Sample size: 40

Treatment

Participant receives liquid nitrogen spray cryotherapy every 4 - 8 weeks x no more than 8 cycles. Those with complete response to therapy will proceed to surveillance. Those with stable or responding disease will continue with cryotherapy. Those with progression of disease will discontinue protocol. For responding or stable disease after 8 cycles, continue treatment beyond 8 cycles until tumor progression or unacceptable toxicity. Discontinue protocol therapy for disease progression or unacceptable toxicity.

Follow-Up Evaluations and Data Collection

Patients will return for surveillance EGD (esophagogastroduodenoscopy) procedures with biopsies at 3, 6, 9, 12, 18, 24, 30, and 36 months (± 4 weeks) after the last cryotherapy treatment. An estimate of tumor size and response compared to baseline will be made at each endoscopy. Biopsies will be performed using large capacity forceps. In the area where tumor was present, biopsies will be taken every 1 cm in each quadrant. Directed biopsies will be performed in any areas that appear suspicious for cancer.

CT scan of the chest, abdomen, and pelvis (with oral and intravenous contrast if possible) will be performed every 6 months during the follow-up period. Full body PET/CT may also be performed instead of CT scanning.

Endoscopic ultrasound will be performed 6 months after treatment completion to assess for lymphadenopathy.

At the conclusion of this protocol, regardless of the outcome, patients will continue to require periodic surveillance endoscopies for re-emergence of esophageal cancer consistent with the standard surveillance guidelines. This monitoring will be performed at the investigator's site unless otherwise desired by the patient.

Spray Cryotherapy for Esophageal Cancer (ICE-CANCER)

A Phase II, Multi-Center Study of Interventional Spray Cryotherapy for Early-Stage Esophageal Cancer (ICE-CANCER)

The primary endpoint is to determine the response rate to spray cryotherapy.

It is hypothesized that one of the two following outcomes will occur:

1. Complete response to therapy: complete tumor eradication confirmed through histologic examination of biopsy specimens from the targeted esophageal tissue site;
2. Stable disease: tumor remission is not attained, but disease progression is halted.

Number of participants with adverse events; Number of adverse events within the study

University of Maryland, Baltimore

Professor of Medicine

Treated with liquid nitrogen spray cryotherapy

Treatment

Liquid nitrogen spray cryotherapy with the truFreeze device

Liquid nitrogen spray cryotherapy with the truFreeze device: Low-pressure liquid nitrogen is sprayed through an upper endoscope on the diseased esophageal tissue to freeze and destroy it. The upper endoscope enables direct visualization of mucosal freeze during spray of the liquid nitrogen onto the mucosa and avoids the need for direct contact with the tissues. The target area is frozen and thawed for several consecutive cycles. The treated tissue becomes necrotic and sloughs, with new, healthy tissue regenerating in its place.

Cryotherapy

Age, Categorical

Sex: Female, Male

Race and Ethnicity were not collected from any participant.

Race and Ethnicity Not Collected

Dr. Bruce Greenwald

subject withdrawn before outcome measures could be assessed

Response Rate to Therapy

Disease-free Survival at 12 Months After Treatment

Cancer Recurrence Rate at 12 Months After Treatment

Estimate Overall Survival

Estimate Progression-free Survival in Those Who do Not Achieve Complete Pathologic Response

Number of Treatment Sessions Needed for Complete Response in Subjects in Whom the Primary Endpoint is Attained;

subject withdrawn from study before outcomes measures could be assessed

Safety of Spray Cryotherapy in This Setting;

Overall Study

Antineoplastic Agents

Antirheumatic Agents

Dermatologic Agents

Reproductive Control Agents

Micronutrients

Hematinics

Vitamins

Methotrexate

Antimetabolites

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Immunosuppressive Agents

Immunologic Factors

Folinic Acid

Folate

Vitamin B9

patients who will receive topical methotrexate hydrogel 1% coupled with microneedling

Microneedling will be performed on each wart for a maximum 5 lesions per patient using dermapen (Ostar rechargeable dermapen, OB-DG 03N, Ostar Beauty Sci-Tech Co, Beijing, China) supplied with 12 needles arranged in rows. The penetration depth was adjusted at 2-mm, endpoint was pinpoint bleeding and the dermapen will be held by the hand in a vertical direction on the wart. Then topical methotrexate 1% gel will be applied on the lesions every session.

topical methotrexate hydrogel 1% coupled with microneedling.

The wart is frozen for 10 to 30 seconds until a 1- to 2-mm ice ball halo surrounds the targeted area.

The sessions were performed every 2 week until complete clearance for a maximum of six sessions.

Eman R Mohamed, Professor

Heba H Sayed, Lecturer

Khulood F Alhakami, M.B.B.CH

To study the clinical efficacy of the topically applied MTX hydrogel preparation combined with microneedling to increase drug delivery and efficacy in comparison with cryotherapy in treatment of warts.

Warts are benign proliferation of skin and mucosa caused by the human papilloma virus (HPV). Currently, over 170 HPV types have been identified. Certain HPV types tend to infect skin at anatomical sites, for an example, palmoplantar warts are usually caused by Serotypes 1, 2, and 4; however, warts of any HPV type may occur at any site. Warts are transmitted by direct or indirect contact, and predisposing factors include disruption to the normal epithelial barrier.

There are several modalities for treatment of warts including cryotherapy, electrocoagulation, topical salicylic acid, topical 5-fluorouracil, and laser surgery. All these treatment options can be painful, time-consuming, and/or expensive, and none is considered the gold standard.

Treatments for warts have also included intralesional injections of tuberculin purified protein derivative (PPD), measles, mumps, and rubella vaccine (MMR), and Candida albicans antigen (candidin). This treatment approach is known as intralesional immunotherapy as it is thought that these modalities activate the immune system to recognize the virus, leading to wart clearance

. MTX as an antimetabolite and antifolate drug is a time-tested effective treatment extensively used orally or parenteral in various autoimmune disorders like psoriasis, psoriatic arthritis, alopecia areata, lupus erythematosus, and rheumatoid arthritis in low to moderate doses with good efficacy, safety, and tolerability on a long-term basis

MTX is appropriate for rapidly growing tumors since it inhibits DNA synthesis in actively dividing cells. MTX is a folic acid analog that binds to the dihydrofolate reductase, blocking the formation of tetrahydrofolate and preventing the synthesis of the purine nucleotide thymidine .

Antiviral effect of MTX was observed in the treatment of Zika virus infected cells explaining the antiviral effect of MTX through inhibition of dihydrofolate reductase ..

A literature review shows that intralesional MTX has been successfully used for several indications with no complications reported.

Unlike systemic MXT, topical preparations of the drug, that was adapted for the treatment of localized lesions, showed nonsignificant related hepatotoxic and hematologic adverse effects .

Previous studies used intralesional MTX injection in the treatment of viral warts with different concentrations and revealed that intralesional MTX was less effective in treating plantar warts .

Since MTX is used for various diseases via different routes of administration, the development of novel drug delivery systems to improve its pharmacokinetic properties and targetability is a necessary step for future investigations .

Controlling the burst release and the introduction of new routes of administration would be possible if the drug could be formulated using different delivery systems. Among various drug delivery systems proposed for MTX delivery, great attention has been directed to hydrogels due to their unique and attractive characteristics .

Microneedling is a fine needle that penetrates the skin to induce micro-injuries leading to production of collagen fibers and release of growth factors .

Microneedling has been used as an adjuvant therapy helping a drug delivery and also used in treatment of various dermatologic diseases .

In this study, the investigators chose the hydrogel formulation at a concentration of 1%w/v as a topical MTX form coupled with microneedling to increase the efficacy of methotrexate in treatment of warts. Hydrogel used will be optimized for biocompatibility, consistency and chemical compatibility with methotrexate.

Efficacy and Safety of Topical Methotrexate Gel 1% Coupled With Microneedling in Treatment of Warts

Efficacy and Safety of Topical Methotrexate Gel 1% Coupled With Microneedling in Treatment of Warts : A Prospective Controlled Randomized Trial

Proportion of participants with total remission of wart(s) at the end of the intervention in the two arms of the clinical trial assessed by the investigator and photographic evaluation .

Complete response: responders who show 100% improvement (disappearance of all warts and return to normal skin markings).

Number of subjects achieving partial resolution of treated wart(s) at the end of the intervention in the two arms of the clinical trial assessed by the investigator, photographic evaluation and The following grading system :

Marked response: responders who show 76 to 99% decrease in number and/or decrease in apparent size, as assessed by a clinician and photographic evaluation also known as near-complete response.

Moderate response: partial responders show 25 to 75% improvement. No or minimal response: less than 25% decrease in size/numbers of all warts. the stud

Proportion of participants that developed a serious side effect in the two arms during the clinical trial.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Comparison of Topical 5%Potassium Hydroxide vs Liquid Nitrogen in the Treatment of Plane Warts	NCT05895071	Plan Warts	5%potassium hyd... Liquid nitrogen	4 Years - 30 Years	Combined Military Hospital Abbottabad
Cost-effectiveness of EndWarts® FREEZE - an Alternative Home Cryotherapy Device for Wart Treatment	NCT04781244	Cryotherapy Eff... Warts	EndWarts® FREEZ... Liquid nitrogen	18 Years -	Mahidol University
Infrared Bioeffect System for the Treatment of Cutaneous Warts	NCT03734003	Cutaneous Warts Human Papilloma...	liquid nitrogen controllable in...	18 Years - 70 Years	First Hospital of China Medical University
Cost-effectiveness of EndWarts® FREEZE - an Alternative Home Cryotherapy Device for Wart Treatment	NCT04781244	Cryotherapy Eff... Warts	EndWarts® FREEZ... Liquid nitrogen	18 Years -	Mahidol University
Spray Cryotherapy for Esophageal Cancer (ICE-CANCER)	NCT01868139	Esophageal Canc...	Liquid nitrogen...	18 Years -	University of Maryland, Baltimore
Efficacy and Safety of Topical Methotrexate Gel 1% Coupled With Microneedling in Treatment of Warts	NCT05300009	Warts	topical methotr... Liquid nitrogen	18 Years - 60 Years	Assiut University
Spray Cryotherapy for Esophageal Cancer (ICE-CANCER)	NCT01868139	Esophageal Canc...	Liquid nitrogen...	18 Years -	University of Maryland, Baltimore

Spots Global Cancer Trial Database for liquid nitrogen