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JAK Inhibitors

Surgical and Non-Medical Dermatology

ANTISEPTIC TECHNIQUES​

  • When evaluation surgical site infections for patients receiving abdominal and cardiac surgeries, there was no difference in outcomes between povidone iodine in alcohol and chlorhexidine gluconate in alcohol. 38884982

Post-op water exposure 

  • There was no difference in culture-proven post-op infections when comparing early (6 hour) water exposure and delayed (48hr).  Also no difference in bruising or bleeding. 39004350

BLOOD THINNER MANAGEMENT AND CUTANEOUS SURGERY

​​​AAD Guidelines​​

Trager MH, Gordon ER, Humphreys TR, Samie FH. Part 1: Management of Antithrombotic Medications in Dermatologic Surgery. J Am Acad Dermatol. Published online May 10, 2024. PMID: 38735483.

  • Warfarin

    • Check INR 2-3 days prior to surgery.  May procede if INR <3.5 (with or without patient on aspirin).​

  • DOAC (Direct Oral Acting Anticoagulants): rivaroxaban, apixaban, edoxaban, dabigatran​

    • Continue

      • Notably, the S3 (German) guidelines recommend stopping 24 hours prior to surgery and continuing no sooner than 1 hour before surgery. 25819254​

    • if post-op bleeding occurs, discontinue DOAC for 2 half-lives

  • Aspirin ​

    • Continue for high risk patients (history of cerebrovascular disease, cardiac surgery, unstable angina, or coronary stenting).​

    • For patients on aspirin prophylactically, may consider cessation 7-10 days prior, resume 7 days after. 

  • Clopidogrel​

    • Continue, but may consider holding if risk of hemorrhage outweighs thromboembolic risk​

  • Clopidogrel + Warfarin​

    • Consider switching to monotherapy​

  • Clopidogrel + aspirin

    • ​Continue for high risk patients (history of cerebrovascular disease, cardiac surgery, unstable angina, or coronary stenting).

    • However, consider monotherapy when feasible

  • Other anti-platelet therapies: prasugrel, ticagrelor, dipyridamole

    • Analagous to approach to aspirin/clopidogrel

  • Thrombin inhibitors: heparin, fondaparinux

    • Usually used for more acute scenarios, so consider postponing surgery until transitioned to alternate therapy.

  • Bruton tyrosine kinase inhibitors: ibrutinib, acalabrutinib​​​​​

    • bleeding with ibrutinib >> acalabrutinib

    • Discontinuation can lead to resistance of the underlying condition and should be done with caution and in collaboration with the prescribing physician.​​​

  • Supplements

    • ​vitamin E, fish oil, feverfew, garlic, ginger, gingko, ginseng, and glucosamine; herbal tea

    • may be prudent to d/c prior to surgery​

Literature

Callahan S, Goldsberry A, Kim G, Yoo S. The management of antithrombotic medication in skin surgery. Dermatol Surg. 2012. PMID: 22734794.

  • Literature review including: aspirin, clopidogrel, ticlopidine, prasugrel, warfarin, heparins, lepirudin, argatroban, dabigatran, fondaparinux, rivaroxaban.

  • No reports of life threatening hemorrhage from continued antithrombotic medications.

  • Potentially fatal cardiovascular events after cessation are recognized.  

​

Cook-Norris RH, Michaels JD, Weaver AL, et al. Complications of cutaneous surgery in patients taking clopidogrel-containing anticoagulation. J Am Acad Dermatol. 2011. PMID: 21514003.

  • Review of patients getting Mohs at Mayo Rochester taking clopidogrel.

  • Continuing clopidogrel was associated with increased risks of severe nonlife-threatening complications. 

    • Most common complication was flap or graft necrosis. ​

  • No patients who stopped clopidogrel had a thrombotic complication, but 1 patient who modified the regimen did. ​

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Assessment of Bleeding Risk / Thromboembolic Risk

​Procedures with Greater Risk of Postoperative Bleeding

  • Surgeries involving multiple layers below subcutaneous fat (fascia, muscle, cartilage, or bone)

  • Large surgical defects (>4cm) or closures with a large graft/flap

  • Interventions with limited visual access to the surgical field

Risk Category for Thromboembolism

High

  • Mechanical heart valve with caged ball or tilting disc valve

  • Atrial fibrillation with high CHADS2 score of 5-6 or CHA2DS2VASc >/=7 VTE within the past 3 months

  • Severe thrombophilia (deficiency in protein C, protein S, or antithrombin)

  • Antiphospholipid antibodies

  • Active cancer with associated VTE risks

  • Drug eluting stent within 12 months Bare metal stent within 30 days

Moderate

  • Mechanical heart valve with bileaflet AVR with major risk factors for stroke

  • Atrial fibrillation with high CHADS2 score of 3-4 or CHA2DS2VASc 5 or 6

  • VTE within the past 3-12 months

  • Recurrent VTE

  • Nonsevere thrombophilia 

Low

  • Bileaflet AVR without major risk factors for stroke

  • Atrial fibrillation with high CHADS2 score of 0-2 or CHA2DS2VASc 1-4

  • VTE over 12 months ago and no other risk factors

  • Coronary artery disease without stent

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ELECTROSURGICAL METHODS​

  • A good table summarizing electrosurgical methods can be found here: 31318829 (Table).

Common Devices Encountered in Dermatologic Surgery Patients (31318829)

Pacemakers and Implantable Cardiac Defibrillators

  • Modern pacemakers are less affected by electromagnetic interference, but interference can still occur.

  • Electrocautery or bipolar forceps are preferred. 

  • Monoterminal modalities are usually safe in patients with defibrillators and when used 5cm from pacemakers.  

  • If using biterminal modalities, place dispersive electrode away from the device so vector does not encompass the device. 

  • Use 5-10s bursts (1s or less may be prudent if operating directly near the device) at lowest possible setting with 10s in between to allow device to function appropriately. 

  • If surgery is being performed close to the device, consult cardiologist. 

Deep Brain Stimulators​

  • DBS may be turned off if tremor doesn't interfere with surgery. 

  • Electrocautery or bipolar forceps are preferred.

  • If monopolar necessary, use a dispersive plate and position so that the pulse generator or the lead wire are not located between the plate and surgical site.

Cochlear Implants

  • Electrocautery is preferred.

  • Avoid monoterminal electrosurgery in the head and neck region.

  • Biterminal electrosurgery should not be used within 1-2cm of implant.

  • Conservative recommendation is to use electrocautery, or biterminal electrosurgery only below the clavicles. 

Nerve Stimulators

  • Best to temporarily turn them off if possible.  If this isn't feasible, using electrocautery, or biterminal modalities (preferably bipolar forceps), with the plate positioned so that current passes as far away from the nerve stimulator as possible. 

​

HAIPENG SCARLESS TECHNIQUE

  • A "scar-free" technique for removing epidermal cysts utilizing a punch to make a small opening, extraction, and subsequent introduction of slcerosing agents and packing is described as the trademarked "Haipeng Scarless Technique". It is a feasible option, but it requires multiple sessions and is more time consuming than traditional excision, without an objective cosmetic comparison to conventional excision. 

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MOHS SURGERY​

Bleeding

  • Topical or subcutaneous injection of tranexamic acid may be a safe and effective agent to help control bleeding. 39235116​

Cosmetic Sequelae

Erythema and Telangiectasias

  • Subsequent to facial flap repairs, vascular changes including redness and blood vessel growth may occur.  The nose seems at particularly increased risk. 39048093

Literature

Surgical delays may be associated with tumor growth...

 

Lee J, Forrester VJ, Novicoff WM, Guffey DJ, Russell MA. Surgical delays of less than 1 year in Mohs surgery associated with tumor growth in moderately- and poorly-differentiated squamous cell carcinomas but not lower-grade squamous cell carcinomas or basal cell carcinomas: A retrospective analysis. J Am Acad Dermatol. 2022. PMID: 34499990.

SUMMARY: Compared size of tumor at time of biopsy with post-Mohs surgical defect size (which they used as surrogate for the tumor size after the time delay between biopsy and Mohs surgery).  They concluded that mod- and poorly-differentiated SCCs demonstrated a significant correlation between delay and growth of tumor, about 2-3mm per month of delay, but that SCCis, well-differentiated SCC, and BCCs did not show a correlation. 

 

There are a lot of issues with this study and broadly speaking I don't think I would use it to guide clinical care, particularly because they didn't demonstrated that these delays and the concomitant tumor growth resulted in quantifiably poorer outcomes.  Some critiques I would provide are:

- they controlled for tumor size as a categorical variable (> or < 2cm) but not a continuous variable.  

- they did not comment on how retraction of the skin around a defect that occurs after resection of a mohs layer leads to defects that are inherently larger than the specimen that is removed. 

- they didn't control for location beyond H, M, L (retraction of skin around defects is different based on location)

- they didn't discuss how early treatment may lead to larger defects given the propensity to take bigger initial stages when a fresh scar is present versus potentially smaller margins when the area is allowed to heal fully before Mohs surgery​

Histopathology

Artifacts

  • Suture, tattoo, monsels, fillers, electrocautery, etc., here. 

Malig​nant Adnexal Tumors

  • There is some data that MMS may improve survival compared to WLE when used to treat MATs, but this is based on SEER data and a lot of important details are lacking, like baseline staging or disease extent.  Local recurrence rates are also not provided in SEER data. 39258783

Histopath Artifacts

PROPHYLACTIC ANTIBIOTICS​

Minimal Benefit, but also Small Risk of Severe AEs​

Adverse events after empiric antibiotic administration in dermatologic surgery: A global, propensity-matched, retrospective cohort study. J Am Acad Dermatol. 2024. PMID: 38266681.

  • ​Included 957,609 patients undergoing cutaneous neoplasm excisions or Mohs micrographic surgery. Compared patients receiving ppx (138,168, or 14%) with those who did not.

  • Most common antibiotics: cephalexin (43%), clindamycin (14%), and doxycycline (12%).

  • Adverse Events: overall 1.8%; renal abnormalities (31%), hepatic abnormalities (17%), and diarrhea (12%). 

    • Absolute risk increase of 0.312% for AEs, with severe AEs comprising only a small fraction of these. 

    • Surgical Site Infections: Overall 0.1% rate.  PPx did not significantly reduce the risk of SSIs within 1 month.

SUPERFICIAL XRT and ELECTRONIC BRACHYTHERAPY (eBx)​

Overview of Modalities

Superficial X-ray Therapy (SXRT)

  • Technology: Uses traditional X-rays to treat superficial cancers like certain types of BCC and SCC.

  • Mechanism: Emits low-energy radiation that penetrates just a few millimeters into the skin.

    • ​Photon radiation, typically in the range of 50-150 kVp (kilovoltage peak)

  • Application: Performed with standard radiotherapy equipment in dermatology or radiation oncology settings.

GentleCure/eBx (image-guided SRT)

  • Technology: A specific application of electronic brachytherapy. (SRT is just a more broad term for SXRT that includes more modern advances like ultrasound guidance).

  • Mechanism: Delivers low-energy radiation directly to the lesion using a handheld device, often designed for convenience in outpatient settings.

    • ​photon radiation (often in the 50-70 kVp range)

  • Key Feature: It is marketed for its ease of use, portability, and ability to minimize radiation exposure to surrounding healthy tissues.

Comparison of SXRT and eBX

Similarities

  • Both use low-energy radiation for noninvasive treatment of superficial cancers.

  • They are alternatives for patients who cannot or do not want to undergo surgery, such as Mohs micrographic surgery.

  • Both focus radiation on the skin's surface to minimize deeper tissue impact.

Key Differences

  • Radiation Source: GentleCure uses electronic brachytherapy with a compact X-ray source, while SXRT relies on traditional radiotherapy equipment.

  • Delivery: GentleCure is marketed as a more patient- and provider-friendly option with potential for in-office treatment, whereas SXRT may require more extensive setup.

  • Branding: GentleCure is a proprietary brand that focuses on patient accessibility and education around the treatment.​

External Beam Radiotherapy (XRT)​

  • Uses higher energy radiation (4-25 megavolts) with deeper potential penetration. 1 MV = 1,000 kVp so XRT delivers 1-2 orders of magnitude more energy. 

Effectiveness/Application​

  • My impressions to date (January 2025) are the following: although SRT seems to have a viable application, there are 2 major limitations, 1 practical and 1 evidenced-based.  From a practical standpoint, the administration of treatment over extended period of time - treatment on 2-5 days per week for potentially 4 weeks or more - makes it infeasible for many patients.  From an evidence-based standpoint, the attrition rate of patients available for follow up (often over half the patients initially included aren't available for follow up at 2 years) makes conclusions about its absolute recurrence rate difficult. 

*Superficial X-ray in the treatment of nonaggressive basal and squamous cell carcinoma in the elderly: A 22-year retrospective analysis. J Am Acad Dermatol. 2024. PMID: 38224912.

Background

  • This study in my opinion provides the best estimated of recurrence rates of all the studies listed here, although the protocol was hypofractionated which is different than other protocols.   

  • Cancers treated: nodular and superficial BCC; invasive and in situ SCC (high risk cancers were excluded on a histological basis). 

  • Looked at hypofractionated SRT: "We administered an average dose of 35.7 Gy over 5.47 fractions, while most treatment protocols utilize 40 to 45 Gy over 10 to 15 fractions".

Results

  • All Tumors (2yr, 5yr, 10yr recurrence rates): 2.2%, 6.0%, 10.5%.

    • BCC: 2.8%, 6.9%, 12.4%.

    • SCC: 2.0%, 5.8%, 9.9%.

  • Average follow up was 48.4mo (SD 40.3mo).​

  • Tumors on the nose and scalp exhibited higher recurrence rates

  • Size did not influence recurrence rate, but larger tumors were not as commonly treated with SXRT

  • SCC and SCCis were grouped together, BCC subtypes were grouped together

Image-Guided Superficial Radiation Therapy for Basal and Squamous Cell Carcinomas Produces Excellent Freedom from Recurrence Independent of Risk Factors. J Clin Med. 2024. PMID: 39407895.

Background

  • Included tumors: BCC (49.5%), SCC (26.4%), SCCis (23.2%), mixed subtypes (1.0%). 

  • Locations treated: Head and Neck 63.7% (16.4% on nose), extremities 20.6%, trunk 4.1%.

  • Excluded cancers: AJCC stage 3 tumors with deep invasion, cortical erosion, or PNI;  AJCC stage 4 tumors.

    • Did not seem to exclude infiltrative BCC or other high risk histologic subtype. ​

    • using AJCC staging for BCC is a bit odd

  • Demographics: Median age 74.9 years (IQR 68.2-81.7).​

  • Radiation protocol: treatment 2-4 times per week for ~20 fractions; each treatment takes less than a minute, treated within a 10-15min visit.

Results

  • Overall treatment success rate was 99.73%: out of 19,988 lesions treated, 54 recurrences.  

  • Recurrence rates did not vary much based on tumor subtype, location, or stage.

  • Recurrent tumors (in supplemental data) were BCC (59.3%), SCC (35.2%), SCCis (5.6%).  Extremities (18.5%), ear (16.7%), and nose (14.8%) were the most common sites of recurrence.

    • ​They did not specify the proportion of tumors available for the 6 year analysis that were BCC, SCC, and SCCis to see if recurrence rates were affected by tumor subtype.  

Limitations​

  • Major: they did not note the average follow up time.  Based on figure 1, only 40% of cases did not have available data at year 2.  This could result in MAJOR differences in recurrence rates.  

Freedom from Recurrence across Age in Non-Melanoma Skin Cancer Treated with Image-Guided Superficial Radiation Therapy. Geriatrics (Basel). 2024. PMID: 39311239.

Background

Image guidance improves freedom from recurrence in superficial radiation therapy for non-melanoma skin cancer. medRxiv. https://doi.org/10.1101/2022.09.29.22280478

Background

  • Included cancers: BCC 48%, SCC 31.4%, SCCis 20.6%.

  • Locations treated: 66% head and neck, 44% trunk and extremities.

  • Excluded cancers: AJCC stage II or higher

  • Demographics: median age 74y (IQR 67-80)

  • Treatment protocol: 7 x 5Gy fractions, 30 x 2Gry fractions. (usually a single fraction per day, 2-5 days per week)

Results

  • Overall treatment success was 99.3% at 2 years: BCC 98.9%, SCC 99.2%, SCCis 100%.

  • Median follow up 26.3mo (IQR 10-38.4 mo).

Limitations​

  • Major: only 58% of cases were available for 2 year follow up. ​

The Treatment of Non-Melanoma Skin Cancer with Image-Guided Superficial Radiation Therapy: An Analysis of 2917 Invasive and In Situ Keratinocytic Carcinoma Lesions. Oncol Ther. 2021. PMID: 33547631.

Background

  • Included cancers: 2917 total cancers, 48.2% BCC, 31.5% SCC, and 20.7% SCCis.

    • No info on BCC subtype​

  • Locations treated: 58% head and neck.

  • Excluded cancers: AJCC stage III and IV

  • Demographics: Mean age 73.2yo (SD +/- 10.93 years)

  • Treatment protocol: 20 fractions over several weeks, 3-5 days per week

Results

  • Overall treatment success was 99.3% (BCC 99.4%, SCC 99.1%, and SCCIS 99.5%)

  • Median follow up 1.2 years, range 0-4.25 years

  • Side effects: 74.6% overall side effect rate

    • ​Mild (grade 1-2): 78.9% (includes erythema, hyperpigmentation, dryness, and mild edema)

    • Moderate (grade 3): 20.2% (includes confluent moist desquamation or pitting edema)

    • Severe (grade 4): 0.9% (includes ulceration, hemorrhage, or necrosis)

Limitations​

  • Major: only 55% of patients had follow up for 1 year or more.

Updated Results of 3,050 Non-melanoma Skin Cancer (NMSC) Lesions in 1725 Patients Treated with High Resolution Dermal Ultrasound-Guided Superficial Radiotherapy, A Multi-institutional Study. medRxiv 2023.04.18.23288760;  doi: https://doi.org/10.1101/2023.04.18.23288760.

Background

  • This is an updated report from 33547631 with more patients and longer average follow up.  The proportion of BCC, SCC, and SCCis are very similar, as are the locations treated.  

Results

  • Overall treatment success was 99.2% (BCC 99.0%, SCC 99.2%, and SCCIS 99.8%)

  • Mean follow up was 2.1 years (IQR 9.45-38.43 mo)

    • only 53% of lesions were available for 2 year follow-up​

Limitations​

  • Major: again, large amount of patients without 2 year data.  its less clear in this study if these patients were just lost to follow up (no data) or just didn't have enough time between when the tumor was treated and study enrollment.

Local control comparison of early-stage non-melanoma skin Cancer (NMSC) treated by superficial radiotherapy (SRT) and external beam radiotherapy (XRT) with and without dermal image guidance: a meta-analysis. Discov Oncol. 2022. PMID: 36414760.

Background

  • Main goal was to compare image-guided vs non image-guided SRT (and XRT).

  • Used data from this study by Maloney but also includes data beyond that.  

  • Treatment protocol (IGSRT):

    • Total Dose: ~5184–5219 cGy

    • Number of Fractions: 20 fractions delivered 3-4 times per week.

    • Treatment Duration: 6–7 weeks on average.

  • Treatment protocol (SRT):​ similar, slightly more fractions/longer duration​​

Results

  • Overall cure rate:

    • US-SRT: 99.1% – 98.9%

    • Traditional SRT/XRT: 91% – 96.9%​

Limitations​

  • Major: surprisingly, they don't specifically present or discuss the different follow up times between treatment groups and the possible limitations.  It is possible that SRT treatment groups had longer follow up periods. 

High resolution dermal ultrasound (US) combined with superficial radiation therapy (SRT) versus non-image guided SRT or external beam radiotherapy (XRT) in early-stage epithelial cancer: a comparison of studies. BMC Cancer. 2023. PMID: 36707774.

Background

  • Nearly identical study to 36414760 (same first author) but with different statistical methods. 

Limitations​

  • Major: The follow-up period for traditional non-image-guided SRT/XRT was consistently longer than for IGSRT.

    • In three of the four comparator studies (Lovett, Locke, Silverman), the mean follow-up was 5 years—which is more than double the 2.1-year mean follow-up for the IGSRT studies used (Yu 2021 & Moloney 2022).

    • In the fourth study (Cognetta, 2012), the mean follow-up was still longer at 2.6 years (compared to 2.1 years for IGSRT).

    • They assert that most recurrences in early-stage NMSC occur within 4-12 months, but don't provide direct evidence from their own data to confirm this pattern held equally for the IGSRT and traditional SRT groups they examined. 

    • Despite providing citations supporting the claim of most recurrences happening in 4-12 months, they don't support this claim. 

Image-guided superficial radiation therapy has superior 2-year recurrence probability to Mohs micrographic surgery. Clin Transl Radiat Oncol. 2023. PMID: 37781716.

  • This study was not new data on effectiveness of IGSRT but used data from 33547631 and unpublished data from here.  They claim 2-year recurrence rates are lower for IGSRT, but the way the data and methodology is presented make it very hard to verify.  For one, it appears follow up for Mohs treated patients is much longer and therefore the confidence in the (absolutely) low recurrence rate is high.

  • The methodology of this study is quite confusing.  They do not present a lot of data from the cohorts they analyzed, specifically follow up periods which are necessary to compare the two outcomes (IGSRT vs Mohs surgery). 

Analysis of image-guided superficial radiation therapy (IGSRT) on the treatment of early-stage non-melanoma skin cancer (NMSC) in the outpatient dermatology setting. J Cancer Res Clin Oncol. 2023. PMID: 36725752.

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External Medicine

 Conceived 2016

DISCLAIMER: This website is a collection of primary literature and the opinions of the website creators on that literature.  It is not intended to be used for the practice of medicine or the delivery of medical care in the absence of other appropriate credentials (like a medical degree).  Discuss any information with your doctor before pursuing treatments mentioned on this site.  

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