Perspective Chapter: Palliative Surgery in Pediatric Cancer

Abstract

Childhood can cer survival rates have lately improved (from 54% in 1980 to an actual 80%), and palliative care has taken on a larger role in the management of oncological kids, with many clinicians involved (including oncologists, radiologists, and surgeons). Palliative surgery has evolved from “noncurative” treatments to a variety of surgeries used to relieve organ dysfunction and provide the best possible quality of life in all aspects of life (clinical, psychological, and social).

1. Introduction

Palliative surgical oncology, which is widely developed in adult care, is a new issue in children, whose treatment should include not only the patients but also their relatives.

Palliative care is defined by the World Health Organization (WHO) as “an approach that improves the quality of life of patients and their families facing the problem of life-threatening illness through the prevention and relief of suffering through early identification and impeccable assessment and treatment of pain and other physical, psychosocial, and spiritual problems” [1]. This statement emphasizes the need of treating oncological children comprehensively.

2. The application of palliative care in pediatric patients

The word “palliative” comes from the Latin terms “pallium” (which represents the dress or overcoat of ancient Roma) and “palliation” (which means “to cloak or cover”); in medicine, the concept of cloaking or covering has been employed not to “hide” but to “protect” the person, in a vision of protective care [2].

Pediatric oncology represents a huge success in the story of medicine, with an overall survival rate of 80%. Recently, many progress has been made in pediatric palliative protocols, incorporating multidisciplinary support in physical, emotional, spiritual, mental, social, and financial aspects, highlighting the significance of comprehensive palliative care teams and management programs [3, 4]. Recent medical advances in South Africa have demonstrated that effective multidisciplinary palliative care involving children’s families and communities can be implemented successfully even in resource-limited settings, usually through voluntary and unstructured forms of activities and participations [5, 6, 7].

The Wayne State University School of Medicine established the first hospital-based palliative care consult service in the United States in 1985 at Detroit Receiving Hospital; Dr. Declan Walsh established the first palliative medicine program in the United States in 1987 at the Cleveland Clinic Cleveland, Ohio: it was the first wide-ranging integrated program designated as a WHO international demonstration project and accredited by the European Society of Medical Oncology. Following it, several other programs were established, including the Palliative Care Program at the Medical College of Wisconsin (1993), the Pain and Palliative Care Service at Memorial Sloan-Kettering Cancer Center (1996), and The Lilian and Benjamin Hertzberg Palliative Care Institute at Mount Sinai School of Medicine (1997). Since then, there has been a considerable increase in the number of hospital-based palliative care programs, which now number over 1400. Currently, 80% of US hospitals with more than 300 beds have a palliative care program [8].

Palliative care was not available for children for many decades, and only a few pediatric patients have recently benefited from a dedicated palliative care service [3, 9]. It can be used in a variety of fields, including:

• Clinical: monitoring of symptoms and signs, balancing relief of adverse events with avoidance of unnecessary hospitalizations without compromising the quality of life;

• Psychological: patient and family support, clear communication, dealing with emotional issues (understanding, acceptance, anger, self-confidence, etc). The care plan should encourage personality development, the preservation of daily routines, the achievement of targets, and the setting of realistic future goals;

• Social: providing opportunities for entertainment, allowing the child to remain an active school participant and an age-appropriate socially functional community member, and promoting spiritual and religious fulfillment.

The role of surgery in palliative care is to achieve the best quality of life for cancer patients for as long as possible; surgeons may participate in oncological management in a variety of ways, including obtaining correct and representative biopsies to confirm histological diagnosis, positioning central venous catheters for short- or long-term use and nutritional devices, and performing curative or tumor-debulking surgeries (reducing symptoms caused by tumor compression on adjacent structures) [10]. Furthermore, based on clinical aspects and tumor peculiarities, each patient must have a unique, tailored management plan. “How far is too far?”, “What is far enough?”, and “How far is not far enough?” are among the numerous questions that remain for surgical management of palliative care patients. Ethical conflict is vital, especially when choosing on tumor debulking and removal of malignant metastases in palliative patients: each decision must be founded on the child’s and family’s values and rights, as well as the beliefs, duties, and rights of all parties involved [11].

Moreover, Kassam A. et al. found that adolescents and young adults with cancer (particularly hematological disorders) have a greater rate of intensive care at the end-of-life stage than adults in a recent publication (40.6% vs. 22.4%) [12]. Oncological kids die in hospitals over half of the time (and nearly half of them in intensive care units), compared to only 25% of adults who die in hospitals. Furthermore, pediatric patients dying of oncological disease usually suffer greatly in their final weeks of life: according to parental reports, 89% of these children have at least one debilitating symptom, particularly weariness, discomfort, or dyspnea, till the end of their lives [13, 14].

These findings may reflect professionals’ discomfort and lack of experience with advanced care planning discussions, deferred conversations about end-of-life (in order to protect younger patients), and caregiver pressure to continue treatments (even if they are ineffective) at the end of their child’s life [15, 16]. It may be challenging for the surgeon to pick the appropriate care for their patients in this highly emotional and demanding scenario.

The American College of Surgeons [17] issued a statement on the values of palliative care in August 2005, which was based on the following principles:

1. Respect the dignity and autonomy of patients, patients’ surrogates, and caregivers;

2. Honor the right of the competent patient or surrogate to choose among treatments, including those that may or may not prolong life;

3. Communicate effectively and empathically with patients, their families, and caregivers;

4. Identify the primary goals of care from the patient’s perspective and address how the surgeon’s care can achieve the patient’s objectives;

5. Strive to alleviate pain and other burdensome physical and nonphysical symptoms;

6. Recognize, assess, discuss, and offer access to services for psychological, social, and spiritual issues;

7. Provide access to therapeutic support, encompassing the spectrum from life-prolonging treatments through hospice care, when they can realistically be expected to improve the quality of life as perceived by the patient;

8. Recognize the physician’s responsibility to discourage treatments that are unlikely to achieve the patient’s goals and encourage patients and families to consider hospice care when the prognosis for survival is likely to be less than half a year;

9. Arrange for continuity of care by the patient’s primary and/or specialist physician, alleviating the sense of abandonment patients may feel when “curative” therapies are no longer useful;

10. Maintain a collegial and supportive attitude toward others entrusted with care of the patient.

Pain, bleeding, intestinal or urinary obstruction, malnutrition, lack of vascular access, fluid collections, intracranial hypertension, respiratory distress, infections, and selective intra-tumoral therapies are just a few of the conditions that may necessitate surgical intervention in oncological patients.

2.1 Pain

Pain is one of the most pressing concerns for children with cancer, as it has a significant impact on their quality of life [18]. It is one of the most concerning and widespread symptoms, with prevalence rates ranging from 24–60% of patients during chemotherapy and 62–86% in advanced-stage cancer, indicating that the problem has yet to be solved [13, 19]. Furthermore, according to a recent meta-analysis, more than one-third of patients with pain describe it as moderate to severe (VAS >4), and while many authors distinguish between cancers with a high risk of pain (bone, pancreas, and esophagus) and cancers with a low risk of pain (lymphoma, leukemia, and soft tissue), no significant correlation has been found between pain prevalence and cancer type. There were no changes in the prevalence of pain between senior and younger patients [20].

Aside from physical concerns, a variety of variables might influence how you feel. Pain management is important in palliative care because cancer pain is multifactorial and can present with a variety of other symptoms. It should include pharmacological, medical, biopsychosocial, and even surgical approaches (such as debulking procedures to reduce tumoral compression/stimulation of nerves or ganglions). To study each clinical case and establish a customized “pain-relieving” strategy, a multidisciplinary surgical team (e.g. surgeons, anesthesiologists, radiologist, interventionist, and nursing staff) is required [21].

WHO developed a “Three-Step Analgesic Ladder” to demonstrate proper analgesic use in adult patients [22], with three levels:

1. Simple analgesics (acetaminophen [paracetamol] and nonsteroidal anti-inflammatory drugs);

2. Minor opioids (codeine and tramadol);

3. Major opioids (morphine, diamorphine, and fentanyl).

In pediatrics, however, it is recommended to use analgesics in two steps, depending on the degree of the pain: paracetamol and ibuprofen should be used first for children with light pain; in patients with moderate to severe pain, an opioid may be considered [23].

Analgesics from the following step up should be added or substituted as the pain intensity increases and the current analgesics are no longer sufficient. Adjuvant therapies, such as anticonvulsant medication for neuropathic pain, should be added at all stages.

The authors of a recent multicenter study based in the United Kingdom found that patients dying of solid tumors are more likely to receive high doses of opioids; this circumstance could be related to the biology of these neoplasms, which can compress nerves or metastasize to bone in the late stages, causing pain: in fact, pain was more common in children with solid tumors (98.4%) than in others (87%) [24].

Other instruments that can aid in the pain management of cancer patients include:

• Intrathecal therapy: individuals with refractory cancer pain or unbearable side effects may benefit from intrathecal morphine sulfate delivery via an implanted patient-activated delivery system [25, 26, 27];

• Epidural analgesic administration: As previously documented by many authors (such as Plancarte R. in 1991 and Portas M. in 1998) [28, 29], epidural opioid injection should be investigated in children with intractable body pain to minimize discomfort and improve long-term analgesia [30, 31, 32];

• Peripheral nerve block: neurolytic plexus blockage (i.e. celiac or brachial plexus) may be conducted on children with malignancies whose pain is inadequately controlled with oral medications or who have uncontrollable adverse effects (such as opiod toxicity), as stated by several authors [33]. According to Chambers W.A [34], about 8–10% of patients may benefit from a peripheral nerve block, and about 2% from a central neuraxial block; additionally, some patients may benefit from a simple peripheral block relieving just one component of their pain [33].

• Cryoablation and radiofrequency: these procedures are routinely investigated for malignant painful lesions in the axial/appendicular skeleton and in a variety of soft tissue. They are less commonly employed in pediatric palliative care [35]. According to Ferrer-Mileo L.et al. systematic’s review [36], they may reduce mean pain scores and the demand for opioids, therefore enhancing the quality of life.

• Cordotomy: Cordotomy was first described in 1912, and it was performed by interrupting the spinothalamic route many layers above the painful location with an open surgical procedure. This procedure, which has now evolved into a minimally invasive percutaneous image-guided needle cordotomy, is an effective and selective surgical treatment for intractable cancer pain; it consists in inserting a needle in the upper cervical spinal cord at the C1–C2 level under CT guidance in order to reach the antero-lateral quadrant of the opposite side. Electrical stimulation is used to check for coverage of painful body locations and current-induced paresthesias. Percutaneous cordotomy complications, such as hemiparesis and dysesthesia, have become extremely rare, and mortality is nearly nonexistent. However, no reports of application in the pediatric population have been made, most likely due to the need for active participation in the process to ensure proper needle positioning during intraoperative stimulation [37, 38, 39].

• Neuromodulation procedures: recentlyvarious stimulating devices have been developed, even if it is yet unknown the exact mechanism producing the antalgic impact of electrical stimulation: possibilities include activation of GABAergic neurons and recruitment of multimodality transmitting sensory pathways [40]. Anesthesiologists can readily place these devices percutaneously in the epidural space, and they can be used at various levels of the neurological system. Electrodes for peripheral nerves are also available, but they usually necessitate an open surgical operation. Because stimulation intensity and frequency are modifiable factors, all of these methods have the advantage of reversibility and personalization of treatment. Infection risk, high expenses, and the invasiveness of surgical procedures are all major drawbacks [41].

• Midline myelotomy: this procedure could be used as a substitute for a cordotomy, which can be done openly (via a laminotomy) or by a percutaneous needle method. Interrupting the crossing of spinothalamic fibers in the midline allows for the control of bilateral pain, making it the usual method for both bilateral and visceral pain [37].

Despite all of the various therapies to oncological pain, a number of studies have found that 40–70% of patients had insufficient pain control [42, 43]. The Agency for Health Care Policy and Research’s “First Barriers National Clinical Practice Guidelines on Cancer Pain” [44] clearly describes and categorizes the barriers to proper cancer pain treatment into three groups:

1. System barriers: Low priority given to cancer pain treatment, legal and regulatory barriers to the use of opioids for cancer pain (due to concerns about opioid abuse and addiction) [45], insufficient or late start of palliative care program, high cost of opioids, and challenges with treatment availability or access.

2. Professional barriers: Failure to follow guidelines and lack of medical education, analgesia level based on prognosis rather than pain severity, fear of patient addiction and analgesic tolerance, lack of proactive questioning about the symptom, insufficient experience with pain management.

3. Patient barriers: Reluctance to disclose pain, recognition of increased levels of pain suggesting disease progression, fear of being labeled as “bad patient,” fear of addiction, tolerance, and opioid adverse effects.

Based on WHO standards, two metrics for evaluating analgesic adequacy have been created:

• Morphine Consumption Data: because morphine is the medicine of choice for the management of severe cancer pain, it is a common indication of how well cancer pain is handled on a national and worldwide basis [46];

• Pain Management Index (PMI) [47]: when the patient’s reported level of pain and the necessary prescribed analgesics are in agreement, pain management is termed adequate. The patient describes the pain using a numerical rating scale from 0 to 10 and the symptom is then classified into four categories:

1. No pain;

2. Mild pain [1, 2, 3, 4];

3. Moderate pain [5, 6];

4. Severe pain [7, 8, 9, 10].

The analgesic drug prescribed is similarly classified at one of four levels:

1. No analgesics;

2. Non-opioid analgesics;

3. Weak opioids

4. Strong opioids.

The PMI is calculated by subtracting the pain level from the analgesic level. Scores will range from −3 to 3: negative scores are an indicator of undertreatment, while a score of 0 is considered acceptable as a minimal level of treatment.

2.2 Bleeding

Bleeding can be a life-threatening complication in pediatric oncology patients, necessitating rapid blood transfusions and/or definitive hemorrhage control (by surgery, embolization, or devascularization) [48]. Bleeding was recorded in 12.7% of the investigated population (particularly in hematological patients) in the UK Children’s Cancer Study Group/Pediatric Oncology Nurses Forum Survey of 2006 [49], but only a handful of them required surgical operations. Selective arterial embolization (SAE) may be a safer and more successful method of treating acute hemorrhages in children with cancer than surgery, which can be too intrusive and carry a high risk of morbidity and mortality in patients with severe illnesses [50].

2.3 Bowel obstruction

In oncological children, bowel blockage normally progresses over time, although it can also be abrupt. Symptoms are connected to irregular intestinal transit (abdominal distension, bilious/fecaloid vomiting, and dehydration) and can quickly affect the patient’s clinical state and the quality of life [51]. Bowel obstruction can be caused by a variety of factors, including tumor growth compressing the gut, intra-luminally blocking masses, radiotherapy side effects, past surgery complications, or harsh medical treatment creating intestinal stenosis or occlusion. The goal of treatment should be to relieve abdominal distention, clear the blockage (restore bowel continuity and/or bypass the “obstacle”), and avoid consequences (dyselectrolytemia, bacterial overgrowth, and perforation) as well as respiratory distress (caused by increase of intra-abdominal pressure) [52]. Even while an intestinal stoma can be a source of additional trauma for oncological children and their parents, it can also help to improve the quality of life by providing a viable option for nutritional needs (through gastrostomy), bolus or continuous enteral feedings. Although most patients tolerate bolus feeding, intolerance can manifest itself in the form of vomiting, severe abdominal distension, excessive gastric residuals, or diarrhea. If this is the case, continual feedings are required, especially in patients who are at high risk of aspiration or have poor absorption [53].

2.4 Urinary obstruction

Urinary obstruction occurs in nearly 10% of adults with advanced primary or metastatic intra-abdominal cancer, according to recent literature; no data on this issue has been documented in the pediatric population. Pelvic neuroblastoma, vesical or prostatic rhabdomyosarcoma, abdominal Burkitt lymphoma, non-Hodgkin lymphoma, retroperitoneal germ cell tumors, diffuse desmoplastic tumor, and peritoneal metastatic disease are the most common cancers that can cause urinary obstruction in children. Furthermore, periureteral fibrosis, a long-term side effect of chemo and radiation therapy, may exacerbate the situation. Urinary blockage can be influenced by a variety of factors, including: tumor development caused by recurrent, metachronous, or metastatic disease; tumor blockage caused by extraluminal carcinomatosis or bulk; tumor intramural growth; tumor direct adhesion or kinking. Urinary blockage symptoms include abdominal pain, oliguria/anuria, ascites increasing hydronephrosis, and a high serum creatinine level. It denotes a situation that necessitates immediate urine relief or diversion (depending on the degree of obstruction) using:

• Open urinary diversion: Surgical alternatives include laparotomy for tumor debulking and/or urinary tract resection with anastomosis or stoma and suprapubic cystostomy for individuals with a favorable prognosis, good performance level, and a single site of obstruction.

• Retrograde ureteral stent: In individuals with a short life expectancy, a percutaneous nephrostomy tube, such as an internal double J nephro-ureteric stent (double J) or an internal/external nephroureteral stent (NUS), is advised [54].

• Nephrostomy tube: In patients who are not candidates for surgery, a percutaneous nephrostomy should considered.

There are currently few data on the true occurrence of this complication in intra-abdominal malignancies, resulting in a lack of therapy guidelines [55, 56]. Even in these circumstances, a multidisciplinary team of specialists is needed, including pediatric surgeons, urologists, radiologists, interventionists, and medical oncologists.

2.5 Malnutrition

Malnutrition is an unfavorable side effect of cancer treatment. Weight loss happens in 41.3% of children with cancer, and nutritional supplementation is required in some cases. In many circumstances, nutritional needs are met by administering total parenteral nutrition (TPN) through central venous catheters; in other cases, enteral feeding via a nasogastric/orogastric tube or gastrostomy/jejunostomy is an option [57, 58].

2.6 Vascular access

Vascular access is a major concern in the treatment of children with cancer [59, 60, 61, 62]. Vascular access can be divided into two categories:

• Peripheral: intravenous fluids, medicine, blood product delivery, and blood collection are all indications for peripheral vascular lines.

• Central: TPN, chemotherapy, long-term medication, emergency access, critical care monitoring, dialysis, and extracorporeal membrane oxygenation are all done with them (ECMO). The involvement of the surgeon in their insertion is critical, but so is flawless management by competent experts.

2.7 Fluid collections

Persistent ascites is uncommon in children and is usually caused by past surgery or congenital lymphatic system problems. To minimize abdominal distension, diaphragm raising, and respiratory difficulty, refractory ascites may necessitate surgical interventions. Fluid accumulation in other organ systems (chest, heart, liver, etc.) can lead to organ dysfunction, failure, and, in the worst-case scenario, multi-organ failure.

When medical treatments (bed rest, diet changes, drugs, and fluid restriction) fail, surgical options include fluid drainage or shunting (paracentesis, pleurocentesis, cardiocentesis, chest drains, perito-venous shunt, transjugular intrahepatic portosystemic shunt—TIPS), and even organ transplantation [63]. Every procedure must be incorporated in a wider vision of palliative care, balancing between the best therapy and the quality of life of the kid.

While ultrasound-guided paracentesis is normally reserved for patients who are toward the end of their lives [64], cuffed tunneled peritoneal catheters can be used for long-term external drainage in patients who have a longer life expectancy. A peritoneal catheter joined to a subcutaneous port or completely implanted peritoneovenous (PVS) shunting (such as the Denver shunt) may be used as an alternate instrument for intermittent aspiration in rare cases [65].

Malignant pleural effusion is also a major issue in cancer children’s palliative care. The most common treatments for treating oncological children with life-threatening pleural effusions are repeated thoracentesis, pleurodesis, or insertion of pleural drainage [66, 67].

2.8 Intracranial hypertension

Solid organ tumors account for around 30% of all malignancies in children, with brain tumors being the most frequent. Intracranial hypertension is the most aggressive indicator of central nervous system (CNS) neoplasms, and it can produce neurological symptoms such as seizures, worsening levels of awareness, and debilitation [68]. Shunting (ventriculo-peritoneal or ventriculo-atrial shunting) to reduce intracranial pressure can improve the quality of life, and drainage to reduce pressure (EVD-external ventricular drain) can be performed if shunting is contraindicated. These surgical operations must be proposed with caution, taking into account all parties involved in the child’s palliative care plan. Each surgical intervention in a successful palliative care plan should strike a balance between proper pain and symptom control and avoiding unnecessary extension of suffering [69].

2.9 Respiratory complications

Almost 11% of advanced tumors in children cause upper respiratory tract compression [70]; in these circumstances, a tracheostomy should be performed to alleviate child discomfort, allow more effective airway suctioning and simpler movement, and simplify the capacity to speak and feed orally. Caregivers and patients should always be included in the surgical planning process to ensure the best stoma management and an acceptable quality of life, free of prejudice, and prejudice [71, 72].

2.10 Infections

Infections should be managed using the same principles as palliative care for children with cancer. Infections must be treated aggressively in order to eliminate the cause of infection (e.g. debridement, abscess drainage, and wound care). Blood cultures are required if central line-associated bloodstream infections (CLABSI) are suspected, and if confirmed, a decision on whether to remove, replace, or leave the line in place should be made [73].

2.11 Selective intra-tumoral/intra-lesional therapies

The surgical team in the palliative care program for children with cancer should not overlook this issue. The intra-arteriolar chemo-infusion by super-selective catheterization of the involved area in retinoblastoma is a well-known example [74]; transcatheter selective arterial chemoembolization (TACE) as adjuvant preoperative treatment for unresectable or chemoresistant hepatoblastoma is another one [75].

3. Conclusion

The following are the main principles of surgical palliative care in pediatric cancer patients:

• Respect the patient’s life, health, and autonomy;

• Maximize the benefit to the patient while minimizing the harm;

• Always act professionally, fairly, rationally, and honestly;

• Each patient must have a tailored care plan that adheres to the principles discussed.

Success in surgical palliative care for oncological children includes assisting the child and their families in living as well as possible and then, at the end of life, helping the patient in dying quietly.

“Death isn’t a medical failure, it’s a biological certainty. But poorly managed death IS a medical failure.” (Dr. Kathryn Mannix).