Part three: Aye, Aye. AI?

I wonder whether we should use the term 'augmented intelligence' rather than 'artificial intelligence'. I say this because at this moment in our evolution, artificial intelligence (AI) always begins with human intelligence. In this blog, I want to examine how we can begin with human subjectivity and use that to drive the objectivity of AI and come up with a new and original paradigm.

The example used in this post focuses on advice given for an appropriate disease-free interval between the excision of a patient's malignant melanoma (MM) followed by cosmetic surgery. The patient needs to be given this information as part of their holistic care. The oncologists need to know this information in order to educate and inform other professionals. However, the cosmetic surgeons are in a very difficult bind – ethically and professionally they need to know what risks any cosmetic procedures could cause an individual patient; they need to know this information because it is a critical part of cancer / patient management.

What is the professional duty of care for a surgeon who is not involved in the treatment of cancer; who is not involved in the general care of a patient, but has the skills and training to perform a cosmetic procedure upon that patient?

This situation arose in the context of a medical legal case in Australia. A patient who had had an MM removed subsequently underwent a significant cosmetic procedure which then resulted in a number of complications with delayed wound healing. During the prolonged period of healing, the patient also experienced considerable pain and discomfort with severe anxiety and stress.

The local experts were focused on the cosmetic procedure, the competences of the operator and aspects of patient management. Whilst I took these on board, I was also somewhat alarmed at the short interval (six months) between excision of the tumour and undergoing a significant cosmetic procedure. Talking informally with former colleagues in the UK, I understand there are no best practice guidelines with regard to a disease-free interval before undertaking cosmetic surgery on a patient – there are no NICE guidelines and there are no guidelines within the plastic surgery or the dermatological literature that I can find.

I have asked leading experts in both fields for their views on this matter and there was no clear consensus. Comments ranged from “Use common sense,” “wait at least twelve months for a thin lesion and longer for a thicker lesion,” and “wait two years at least.” I also contacted the Macmillan Nurses who confirmed that they also did not have formal guidelines. So, it appears that we have a clinical situation that is real and has potentially serious implications, and, there are no guidelines regarding how such patients should be best managed. This could be a situation where AI might be able to help, and it is in this context that I want to compare ChatGPT and DeepSeek. First of all, I will establish some facts, then I would like to explore how the AI program extrapolates from those facts and begins the declarative deliberation on potentially useful clinical guidelines.

1. Is malignant melanoma intimately associated with the immune system?
2. Does a significant surgical intervention depress the bodies immunity?
3. Do you know of any clinical guidelines regarding the appropriate disease-free interval between the primary excision of a malignant melanoma and a significant, non-medically indicated surgical event (essentially a cosmetic procedure)?
4. Do you think that there should be such guidelines?

I asked the questions and did not engage in follow-up dialogue. I do note that such qualifiers as 'intimately' and 'significantly' can alter the response. We do this when using human intelligence to refine and modify communication. One wonders what training has been undertaken on the significance of adjectival modifiers but that is a topic for another day. I will summarise the responses for those not wanting to delve into the details. The complete responses are appended.

1. Is malignant melanoma intimately associated with the immune system?

Both ChatGPT and DeepSeek responded in the affirmative and justify this response by looking at various key points. The lists were not identical (DeepSeek: 7 points; ChatGPT: 5 points) but both highlight the use of immunotherapy.

2. Does a significant surgical intervention depress the bodies immunity?

Again, both programs were in agreement and both offered a range of justifications ranging from pain and anaesthesia to blood loss and trauma. Both began by referencing the surgical stress response. DeepSeek again gave more examples than ChatGPT. Neither expressly focused on the type of surgery, which is of course relevant to our concerns.

3. Do you know of any clinical guidelines regarding the appropriate disease-free interval between the primary excision of a malignant melanoma and a significant, non-medically indicated surgical event (essentially a cosmetic procedure)?

This is obviously a more complex question, and the responses were rather different. Both agree that there are no current universal standards of care. Both indicate the benefits of guidelines and both actually preempting the final question proposed guidelines linking disease-free interval to the stage of the disease. Again neither considered the extent and nature of the proposed cosmetic surgical intervention.

4. Do you think that there should be such guidelines?

Both programs agree that there should be guidelines and both make similar suggestions, linking stage of disease to disease free interval before a cosmetic intervention. DeepSeek does suggest ways forward in terms of constructing clinical guidelines and this is a very important consideration. It recognises the need to include all stakeholders including the patient advocacy groups. I like the DeepSeek conclusion, which I include in full:

Formal clinical guidelines would provide a structured, evidence-based approach to managing patients who have undergone melanoma treatment and are considering elective surgery. This would enhance patient safety, standardize care, and support informed decision-making. Given the increasing prevalence of melanoma and the growing interest in cosmetic procedures, such guidelines are both timely and necessary.

Several points come up in discussing these findings. In this simple exercise, DeepSeek has contributed more information and has taken the answers further by anticipating relevant questions. Both have functioned extremely well and I think there is now an indisputable case for establishing some relevant guidelines for this currently neglected aspect of clinical practice.

What is needed now is to develop a consensus view on the 'stress impact' of different cosmetic interventions. That could well be done using AI.

A final word at this stage is that I am now changing my view on the nature of cosmetic surgery and cosmetic surgeons. I have been consistent in my view that qualifications do not guarantee competence, and I say this in regard to the specialty of plastic surgery and the practice of cosmetic surgery. On the other hand, I have suggested that a procedure-trained cosmetic surgeon may well perform better (surgery) than a specialty-trained plastic surgeon. Whilst that may be the case, we have to recognise the importance of holistic care. In the patient who is a cancer survivor, a more important and relevant question than how to perform a procedure is whether to perform a procedure. As such, I am now inclined more than ever before to explore a general surgical foundation course which leads into a specialty of cosmetic surgery with procedure-based training.

At this time, I think the profession has an urgent responsibility to establish formal guidelines regarding the safe undertaking of cosmetic surgery in cancer survivors. The training of cosmetic surgeons and establishing a specialty of cosmetic surgery is a matter for another day.

As always, these blogs are my opinion and I am very happy to be challenged or corrected.

Question 1: Is malignant melanoma intimately associated with the immune system?

ChatGPT said: Yes, malignant melanoma is intimately associated with the immune system. This relationship is evident in several ways:

1. Immune Surveillance and Evasion: The immune system plays a crucial role in detecting and eliminating abnormal melanocytes before they become malignant. However, melanoma can evade immune detection by expressing immune checkpoint proteins like PD-L1 and CTLA-4, which suppress T-cell responses.
2. Immunotherapy Response: Melanoma is one of the most responsive cancers to immune checkpoint inhibitors (e.g., nivolumab, pembrolizumab, and ipilimumab), which restore T-cell activity and enhance the immune system’s ability to fight the cancer.
3. Tumor Microenvironment: The immune system’s interaction with melanoma occurs within the tumor microenvironment, where tumor-associated macrophages, regulatory T cells (Tregs), and myeloid-derived suppressor cells (MDSCs) can either promote or suppress tumor progression.
4. Inflammation and Mutational Load: Melanoma has a high mutational burden, especially when linked to UV radiation. This generates neoantigens that can trigger an immune response, making the cancer highly immunogenic.
5. Role of Cytokines: Immune signaling molecules such as interferons (e.g., IFN-γ) and interleukins (e.g., IL-2) influence melanoma progression and response to therapy.

Because of this deep immune involvement, melanoma has become a prime target for cancer immunotherapy research and treatment strategies. Would you like details on specific immunotherapies or the mechanisms of immune evasion?

Question 2: Does significant surgical intervention depress the body's immune system?

ChatGPT said: Yes, significant surgical intervention can temporarily depress the body's immune system. This immune suppression is influenced by several factors:

1. Surgical Stress Response: Major surgery triggers a stress response, leading to increased levels of cortisol and catecholamines (e.g., adrenaline, noradrenaline), which suppress immune function by reducing lymphocyte proliferation and cytokine production.
2. Inflammatory and Anti-inflammatory Balance: Surgery induces an acute inflammatory response with pro-inflammatory cytokines (IL-6, TNF-α, IL-1β). This is followed by a compensatory anti-inflammatory response (IL-10, TGF-β), which can suppress immune activity, particularly T-cell function.
3. Lymphocyte and Natural Killer (NK) Cell Suppression: Studies show that surgery reduces CD4+ T cells, CD8+ T cells, and NK cell activity, impairing the body's ability to fight infections and cancer cells.
4. Anesthesia Effects: General anesthesia, particularly with opioids and volatile anesthetics, has been linked to immune modulation, reducing NK cell function and increasing susceptibility to infections and tumor recurrence.
5. Blood Loss and Transfusions: Significant blood loss and perioperative blood transfusions can induce immunosuppression, partly due to transfusion-related immunomodulation (TRIM), which affects T-cell and dendritic cell function.
6. Postoperative Infections and Wound Healing: A suppressed immune system post-surgery can increase susceptibility to infections and delay wound healing.

This immunosuppression is usually transient, lasting from a few days to weeks, depending on factors like the extent of surgery, patient's age, and underlying health conditions. Minimally invasive techniques (e.g., laparoscopic or robotic surgery) and strategies like regional anesthesia may help reduce the degree of immune suppression.

Question 3: Do you know of any clinical guidelines regarding the appropriate disease-free interval between the primary excision of a malignant melanoma and the subsequent significant non-medically intubated surgical intervention, essentially cosmetic procedures?

ChatGPT said: There are no universally standardized clinical guidelines specifically addressing the optimal disease-free interval between primary excision of malignant melanoma and subsequent elective cosmetic surgery (such as facelifts, abdominoplasty, or breast augmentation). However, recommendations can be inferred from oncology and surgical best practices:

Key Considerations for Timing Elective Surgery After Melanoma Excision

1. Melanoma Stage and Recurrence Risk: (1) Thin melanoma (Stage IA–IB, ≤1mm thickness, no ulceration): Lower recurrence risk, but follow-up for at least 1–2 years is often recommended before elective cosmetic procedures. (2) Intermediate-thickness melanoma (Stage II, 1–4mm thickness): Higher recurrence risk, requiring at least 2–3 years of disease-free survival before elective surgery. (3) Advanced melanoma (Stage III–IV, nodal or metastatic involvement): High recurrence risk; elective surgery is typically discouraged unless disease-free for at least 5 years.
2. Follow-up Surveillance: (1) Regular dermatologic and oncologic follow-up is critical before elective surgery to ensure no recurrence. (2) Imaging (e.g., CT, PET-CT, MRI) may be necessary for higher-stage melanoma before proceeding with surgery.
3. Surgical and Immunologic Considerations: (1) Surgical stress-induced immunosuppression post-elective procedures could theoretically increase the risk of recurrence in high-risk patients. (2) Lymphedema risk if melanoma was excised from areas with nodal dissection (e.g., axilla, groin).
4. Adjuvant Therapy Effects: If the patient underwent checkpoint inhibitors (e.g., nivolumab, pembrolizumab) or BRAF/MEK inhibitors, elective surgery should ideally be deferred until therapy completion and immune recovery.

General Consensus from Clinical Experience & Expert Opinion

• For Stage I melanoma: At least 1–2 years disease-free before elective surgery.
• For Stage II melanoma: At least 2–3 years disease-free.
• For Stage III+ melanoma: Ideally 5 years disease-free before elective surgery.

Question 4: Do you think that clinical guidelines should be available for this situation?

ChatGPT said: Yes, clinical guidelines for the appropriate disease-free interval between melanoma excision and elective (non-medically necessary) surgery would be valuable. While oncologic guidelines focus on recurrence risk, surveillance, and adjuvant therapy, there is a gray area regarding timing elective cosmetic or reconstructive surgery, which could be addressed systematically.

Why Guidelines Would Be Beneficial

1. Risk Stratification: A formal guideline could help categorize patients by melanoma stage and recurrence risk, providing clear recommendations on when elective procedures are reasonably safe.
2. Patient Safety: Surgery-induced immune suppression could theoretically influence melanoma recurrence risk, making evidence-based recommendations essential.
3. Surgeon Guidance: Plastic and reconstructive surgeons would benefit from a standardized reference to avoid performing elective procedures too soon after melanoma treatment.
4. Legal & Ethical Considerations: A defined disease-free interval could protect both patients and surgeons by reducing medicolegal risks associated with recurrence post-elective surgery.
5. Multidisciplinary Consensus: Collaboration between oncologists, dermatologists, plastic surgeons, and immunologists could lead to practical guidelines based on current evidence.

Potential Structure of Such Guidelines:

• Melanoma stage-based recommendations (e.g., 1 year for Stage I, 2–3 years for Stage II, 5 years for Stage III–IV)
• Consideration of adjuvant therapy status
• Preoperative oncologic clearance requirements (e.g., PET-CT for Stage II+)
• Discussion of immune modulation and surgical stress effects

Current Gap in Literature: While guidelines exist for oncologic follow-up and reconstructive surgery after melanoma excision, there's no widely accepted framework for elective aesthetic procedures post-melanoma treatment. Given the increasing use of immune checkpoint inhibitors and evolving understanding of surgical stress and immunosuppression, this area warrants further research and formal recommendations.

Question 1: Is malignant melanoma intimately associated with the immune system?

DeepSeek said:

1. Yes, malignant melanoma is intimately associated with the immune system. Here are some key points that highlight this relationship:
   Immune Surveillance : The immune system plays a crucial role in identifying and destroying cancer cells, including melanoma cells. Immune surveillance involves the detection of abnormal cells by immune cells such as T cells, natural killer (NK) cells, and dendritic cells.
2. Tumor Microenvironment : Melanoma often creates an immunosuppressive tumor microenvironment. This includes the recruitment of regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), and the secretion of cytokines like IL-10 and TGF-β, which inhibit effective anti-tumor immune responses.
3. Immunotherapy : Melanoma is one of the cancers most responsive to immunotherapy. Treatments such as immune checkpoint inhibitors (e.g., anti-PD-1, anti-CTLA-4 antibodies) have shown significant success in treating melanoma by enhancing the immune system's ability to attack cancer cells.
4. Tumor Antigens : Melanoma cells often express specific antigens (e.g., MART-1, gp100, tyrosinase) that can be recognized by the immune system. These antigens can be targeted by immune therapies, including vaccines and adoptive cell transfer (ACT) therapies.
5. Inflammation and Immune Response : Chronic inflammation can contribute to melanoma development and progression. Conversely, acute inflammatory responses can sometimes help in controlling tumor growth. The balance between pro-inflammatory and anti-inflammatory signals is critical in the context of melanoma.
6. Genetic Mutations and Immune Evasion : Melanoma cells frequently acquire mutations that help them evade immune detection. For example, mutations in the BRAF gene are common in melanoma and can influence the tumor's interaction with the immune system.
7. Biomarkers : Immune-related biomarkers, such as PD-L1 expression, tumor-infiltrating lymphocytes (TILs), and mutational burden, are used to predict response to immunotherapy in melanoma patients.

Understanding the complex interplay between melanoma and the immune system has led to the development of innovative treatments that harness the body's immune response to combat this aggressive form of cancer. 

Question 2: Does significant surgical intervention depression the bodies immunity?

DeepSeek said: Yes, significant surgical intervention can depress the body's immunity, at least temporarily. Surgery, especially major procedures, can induce a stress response and cause various physiological changes that may impair immune function. Here are some key points to consider:

1. Surgical Stress Response: Surgery triggers a systemic stress response, leading to the release of stress hormones like cortisol and catecholamines. Elevated levels of these hormones can suppress immune function by reducing the activity of immune cells such as T cells, NK cells, and macrophages.
2. Inflammatory Response : Surgery causes tissue damage and inflammation, which can lead to the release of pro-inflammatory cytokines (e.g., IL-6, TNF-α). While acute inflammation is a normal part of the healing process, excessive or prolonged inflammation can impair immune function and increase susceptibility to infections.
3. Anesthesia : Anesthetic agents used during surgery can also affect immune function. Some anesthetics have been shown to suppress the activity of immune cells, including neutrophils and lymphocytes, potentially increasing the risk of postoperative infections.
4. Pain and Analgesia : Postoperative pain and the use of analgesic medications, particularly opioids, can further impact immune function. Opioids have been shown to have immunosuppressive effects, including reducing the activity of NK cells and altering cytokine production.
5. Nutritional Status : Major surgery can affect nutritional status, either directly (e.g., gastrointestinal surgeries) or indirectly (e.g., reduced appetite, nausea). Poor nutrition can compromise immune function, as adequate intake of vitamins, minerals, and proteins is essential for maintaining a robust immune system.
6. Immune Cell Function : Studies have shown that surgical intervention can lead to a temporary reduction in the number and function of various immune cells, including T cells, B cells, and dendritic cells. This immunosuppression can last for days to weeks, depending on the extent of the surgery and the patient's overall health.
7. Risk of Infections : The combination of these factors increases the risk of postoperative infections, including surgical site infections, pneumonia, and urinary tract infections. Patients undergoing major surgery are often monitored closely for signs of infection and may receive prophylactic antibiotics to reduce this risk.
8. Recovery and Rehabilitation : The body's immune function typically recovers as the patient heals and the stress response subsides. Adequate rest, nutrition, and appropriate medical care can support immune recovery and reduce the risk of complications.

In summary, while significant surgical intervention can temporarily depress the body's immunity, this effect is usually transient. Proper preoperative, intraoperative, and postoperative care can help mitigate the impact on immune function and promote a smoother recovery. 

Question 3: Do you know of any clinical guidelines regarding the appropriate disease-free interval between the primary excision of a malignant melanoma and the subsequent significant non-medically intubated surgical intervention, essentially cosmetic procedures?

DeepSeek said: The appropriate disease-free interval between the primary excision of a malignant melanoma and elective (cosmetic) surgery is not strictly defined in clinical guidelines, as it depends on several factors, including the stage of the melanoma, the risk of recurrence, and the patient's overall health. However, there are some general principles and recommendations that can guide decision-making:

Key Considerations:

1. Melanoma Stage and Risk of Recurrence: (1) For early-stage melanoma  (e.g., Stage 0 or Stage I), where the risk of recurrence is low, a shorter disease-free interval (e.g., 6–12 months) may be considered sufficient before elective surgery. (2) For  higher-risk melanoma  (e.g., Stage II or III), where the risk of recurrence is higher, a longer disease-free interval (e.g., 2–5 years) is typically recommended before undergoing elective procedures.
2. Follow-Up and Surveillance: (1) Patients should complete the recommended follow-up schedule for melanoma surveillance, which often includes regular skin exams, imaging, and possibly blood tests, depending on the stage. (2) Elective surgery should only be considered if there is no evidence of recurrence or metastasis during follow-up.
3. Individualized Decision-Making: The decision should be made in consultation with the patient's dermatologist, oncologist, and surgeon, taking into account the patient's specific risk factors, such as tumor thickness, ulceration, mitotic rate, and genetic markers (e.g., BRAF mutation status).
4. Immunosuppression Concerns: Elective surgery can temporarily suppress the immune system, which may theoretically increase the risk of melanoma recurrence. This risk should be weighed against the benefits of the cosmetic procedure.
5. Psychological and Quality-of-Life Factors: If the cosmetic procedure is important for the patient's psychological well-being or quality of life, this should be considered in the decision-making process.

General Recommendations:

• Low-risk melanoma (Stage 0–I) : A disease-free interval of  6–12 months  may be reasonable, provided there is no evidence of recurrence during follow-up.
• Intermediate-risk melanoma (Stage II) : A disease-free interval of  1–2 years  is often recommended.
• High-risk melanoma (Stage III) : A disease-free interval of  2–5 years  is typically advised, as the risk of recurrence is higher in the first few years after diagnosis.

Clinical Guidelines: 

• While there are no specific guidelines addressing the exact timing of elective surgery after melanoma excision, the following resources provide general principles for melanoma management and follow-up:
• National Comprehensive Cancer Network (NCCN) Guidelines for Melanoma : These guidelines outline follow-up schedules based on melanoma stage and risk factors.
• American Academy of Dermatology (AAD) Guidelines : These provide recommendations for melanoma surveillance and management.
• European Society for Medical Oncology (ESMO) Guidelines : These also offer guidance on melanoma follow-up and recurrence risk.

Conclusion: The decision to proceed with elective cosmetic surgery after melanoma excision should be individualized and based on the patient's melanoma stage, risk of recurrence, and overall health. A multidisciplinary approach involving dermatologists, oncologists, and surgeons is essential to ensure patient safety and optimal outcomes. Always consult the most recent clinical guidelines and the patient's medical team for personalized recommendations.

Question 4: Do you think there should be such formal clinical guidelines?

DeepSeek said: Yes, I believe there should be formal clinical guidelines regarding the appropriate disease-free interval between the primary excision of a malignant melanoma and elective (cosmetic) surgery. Such guidelines would provide several benefits:

Reasons for Formal Guidelines:

1. Standardization of Care: Formal guidelines would help standardize the approach to managing patients who have undergone melanoma treatment and are considering elective surgery. This would reduce variability in practice and ensure that all patients receive evidence-based care.
2. Risk Stratification: Guidelines could provide clear recommendations based on melanoma stage, risk of recurrence, and other prognostic factors. This would help clinicians and patients make informed decisions about the timing of elective procedures.
3. Patient Safety: Elective surgery can temporarily suppress the immune system and potentially increase the risk of melanoma recurrence. Guidelines would help minimize this risk by recommending appropriate disease-free intervals based on the latest evidence.
4. Multidisciplinary Collaboration: Guidelines would encourage collaboration between dermatologists, oncologists, surgeons, and other healthcare providers, ensuring that all aspects of the patient's care are considered.
5. Patient Education and Counseling: Clear guidelines would help clinicians educate patients about the risks and benefits of elective surgery after melanoma treatment. This would empower patients to make informed decisions about their care.
6. Medicolegal Protection: Formal guidelines would provide a reference point for clinicians, reducing the risk of medicolegal issues related to the timing of elective surgery after melanoma treatment.

Potential Components of Guidelines:

1. Disease-Free Intervals: Recommendations for minimum disease-free intervals based on melanoma stage (e.g., 6–12 months for Stage 0–I, 1–2 years for Stage II, 2–5 years for Stage III).
2. Follow-Up and Surveillance: Requirements for completing a specified period of melanoma surveillance (e.g., regular skin exams, imaging, blood tests) before considering elective surgery.
3. Risk Assessment: Criteria for assessing individual patient risk factors, such as tumor thickness, ulceration, mitotic rate, and genetic markers.
4. Immunosuppression Considerations: Guidance on minimizing the impact of elective surgery on immune function and melanoma recurrence risk.
5. Psychological and Quality-of-Life Factors: Consideration of the patient's psychological well-being and quality of life in the decision-making process.
6. Multidisciplinary Review: Recommendations for involving a multidisciplinary team (e.g., dermatologist, oncologist, surgeon) in the decision-making process.

Development of Guidelines: The development of such guidelines should involve input from key stakeholders, including:

• Dermatologists and Oncologists : Experts in melanoma management and recurrence risk.
• Surgeons : Experts in elective and cosmetic surgery.
• Immunologists : Experts in the impact of surgery on immune function.
• Patient Advocacy Groups : To ensure that patient perspectives and quality-of-life considerations are included.

Conclusion: Formal clinical guidelines would provide a structured, evidence-based approach to managing patients who have undergone melanoma treatment and are considering elective surgery. This would enhance patient safety, standardize care, and support informed decision-making. Given the increasing prevalence of melanoma and the growing interest in cosmetic procedures, such guidelines are both timely and necessary.