Abstract

Background. The prevalence of cancer is growing daily. Oral cancer, which is primarily triggered by tobacco use, can have detrimental effects on facial appearance. Despite significant advances in the molecular underpinnings of cancer, surgery, chemotherapy and radiotherapy have become standard cancer treatment methods. These treatments remove the tumor but can significantly alter patient’s appearance, which can impact their physical and mental wellbeing. The soft tissue augmentation technique of autologous fat grafting (AFG), commonly referred to as lipofilling, is frequently used in cosmetic and reconstructive surgery to promote facial rejuvenation and body form remodeling. The advantages of AFG include its biocompatibility, low immunogenicity and allergenicity, as well as its capability to heal wounds.

Objectives. To explore the advantages of and patient satisfaction with the AFG technique as a potential facial restoration procedure in oral cancer patients.

Materials and methods. We examined the effects of facial AFG in cosmetic surgery patients and investigated the prevalence of postoperative problems. Patient satisfaction and potential complications after autologous fat filling in different areas of the facial space were investigated using clinical evaluations, patient-reported outcomes and photographic assessments.

Results. All of the patients were satisfied with the results in terms of improved facial shape, skin glossiness, skin elasticity, ptosis, and facial expressions. More than 80% of the patients and surgeons reported overall satisfaction.

Conclusions. Based on these findings, we hypothesize that the AFG approach may be beneficial as a reconstructive therapy for patients with oral cancer following treatment. This technique will improve the patient’s physical appearance, confidence and mental wellbeing.

Key words: reconstructive surgery, oral cancer, autologous fat grafting, fat fillers, lipofilling

Background

Cancer is one of the leading causes of death worldwide and was responsible for approx. 10 million deaths in 2020.¹ Oral cancer is the 6^th most common type of cancer and has a high incidence in South Asia.² Oral cancer is caused by various physical, chemical and biological carcinogens, which have drastically hampered prophylactic measures. To prevent metastasis and disease progression, chemotherapy, radiotherapy and surgery are commonly employed. Even though these treatments are effective, they can cause tissue damage, aesthetic defects, irregularities, atrophic skin, scars, and so on.³ These side effects can significantly alter patient’s appearance and have an impact on their physical and mental wellbeing.

A common soft tissue augmentation procedure used in cosmetic and reconstructive surgery to achieve body shape remodeling and facial rejuvenation is autologous fat grafting (AFG), commonly referred to as lipofilling.^{4, 5} The AFG is known for its benignity, reliability, predictability, and biocompatibility, and is an affordable technique used to improve tissue deformities and for reconstruction. Fat cell grafts are considered the closest acceptable autologous soft tissue, and these cells can be easily harvested with low donor-recipient morbidity, immunogenicity and allergenicity. In addition, these cells promote wound healing due to the presence of cytokine profiles and certain extracellular matrices.^{6, 7}

Moscatello et al.⁸ showed that an increase in the important surface area of the recipient bed’s troubled fat lobules led to improved fat survival after infusion. Li et al. examined facial fat filling under the anatomical structure of the facial fat chamber.⁹ They proposed that injecting a small amount of fat into the subcutaneous layer was enough to make the transition between the zygomatic arch and the buccal and mandibular regions look natural, which provided a personalized approach based on the facial fat compartment theory.^{10, 11} The aforementioned technique overcomes the disadvantages of other grafting cosmetic surgery techniques and artificial materials, such as prostheses, hyaluronic acid and botulinum toxin type A.¹²

The current study aims to evaluate the feasibility of utilizing the AFG technique to improve facial aesthetics in oral cancer patients after cancer treatment. We compared the impact of autologous fat in the face area before and after the surgery, as well as the occurrence of postoperative problems. After the autologous fat filling in various areas of the facial space, patient satisfaction and potential problems were examined further.

Objectives

The aim of this research was to explore the advantages of utilizing the AFG technique as a potential facial restoration procedure in oral cancer patients to promote physical and mental health after treatment.

Materials and methods

Ethical approval

This study was approved by the Institutional Review Board at Shandong Provincial Hospital, Jinan, China (approval No. SDPH202139002), and was performed in accordance with the guidelines of Good Clinical Practice and the Declaration of Helsinki. Written informed consent was obtained from all patients after explaining the limitations, benefits and realistic surgical outcomes. Preoperative images were also obtained.

Inclusion and exclusion criteria

A total of 52 patients who underwent AFG for facial rejuvenation between January 2016 and December 2020 were enrolled in the study, and were prospectively followed up at 3, 6, 8, 12, 24, and 36 months after the procedure. The inclusion criterion was age ≥18 years. Patients who had a positive pregnancy test or were breastfeeding were excluded from the study. Other exclusion criteria were current infection at the treatment site and systemic diseases (such as diabetes, hypertension, iatrogenic coagulation disorders, disorders of lipid metabolism, and history of connective tissue disorders). Preoperative laboratory tests, including a complete blood routine, comprehensive metabolic panel and prothrombin time/partial thromboplastin time, were performed to assess current health status of the patients.

Surgical procedure

Donor site and marking

Considering the availability of accessible adipose tissue and the individual facial features of each patient, the outer thighs (saddlebags) were mainly selected as the donor site. However, the lower abdomen, inner thighs, periumbilical region, and buttocks were occasionally used. Preoperative marking of the surgical site was done with the patient standing before administering general anesthesia.

Tumescence and fat harvesting

Harvesting and subsequent fat injection were performed using a previously published method.⁵ A tumescent solution (500 mL) containing normal saline, 0.5 mL of 0.1% epinephrine (1:100,000) and 10 mL of 2% lidocaine was administered through a multi-hole infiltration cannula (Wells Johnson, Tucson, USA; diameter: 1.5 mm). In addition, 15 mL of 2% lidocaine was injected as a local anesthetic. The entire procedure was carried out with extreme caution. The tumescent solution was injected gently from one site to another until maximum vasoconstriction was achieved at the fat donor site. After waiting for 10 min, a 10-milli­liter Luer-Lock syringe (Sigma-Aldrich, St. Louis, USA) connected to a liposuction needle with a blunt 3-millimeter tip was used to extract the adipose tissue under negative pressure, minimizing potential oxidation and injury to the adipose tissue.

Fat purification

After collection, the fat was allowed to stand to eliminate excess water and blood. For this procedure, the 10-milliliter syringe that was utilized for fat harvesting was used. Then, the syringe was capped and centrifuged at 3000 rpm for 3 min, resulting in a separation of the fat grafts into 3 distinct layers: oil in the upper layer, intact adipose aspirates in the middle layer and cell debris in the lower layer.⁶ Finally, the deep portion of the middle layer was collected in a 1-milliliter syringe, capped and stored in an upright position until subsequent use.

Fat implantation

A disposable 18-gauge needle was used to treat the temporal, frontal and orbital facial regions (at the forehead, upper anterior space of masseter muscles, corner regions of the mouth, zygomatic arch, and areas surrounding the eye). Before fat grafting, all patients (regardless of the anesthetic modality) were injected with the tumescent fluid (same composition as described above) to fill the facial spaces. The surgeon decided on the graft volume after considering individual characteristics of a patient. An injecting cannula was used to transfer fat from a 1-milliliter syringe to the recipient’s facial site. Special attention was paid to homogenously deposit the fat. Finally, oral antibiotics were administered to the injected area of the face to avoid microbial infection.

Aesthetic outcome evaluation

At the end of each follow-up visit, aesthetic improvement was evaluated by the operating surgeon. A 4-point Likert scale was used to assess the results, with 1 = excellent (for utterly satisfactory results), 2 = good (for substantially satisfactory results), 3 = fair (for somewhat satisfactory results), and 4 = poor (for unsatisfactory results). Patient satisfaction was measured using a questionnaire based on 5 evaluation indicators: correction of facial expressions, alleviation of facial droop, improvement of fine facial lines, and naturalness of facial expression, with each given a score out of 20. A score over 90 points was considered excellent, 81–90 was considered good, 70–80 was considered moderate, and ≤70 was considered poor. The degree to which patients were satisfied with their surgical outcomes was derived based on the following formula (Equation 1):

(1)

Regular postoperative care was administered for the first 7 days after the surgery. In addition, the injected fat volume, follow-up period, observed complications, treatment site, and patient satisfaction scores were recorded.

Results

In the present study, most of the participants were female (female-to-male ratio: 16:1). Several facial regions, including the superior temporal space, anterior zygomatic space and buccal clearance, were used as filling sites. The patients’ age ranged from 28 to 62 years, with a mean age of 41.6 ±9.2 years. The mean follow-up period was 18.3 months (range: 6–36 months, excluding a 28-year-old female patient who was followed up for 40 months). Table 1 summarizes the quantity of fat that was injected into each site (range: 5–20 mL), which was based upon the facial morphology and the desired corrections. The anterior zygomatic, upper anterior masseter, superior temporal, and frontal reticular tissues were the most frequent injection locations. The frontal reticular tissue received the maximum fat volume (20 mL).

During follow-up visits, cosmetic evaluation of preoperative and postoperative photographs showed 100% patient satisfaction in terms of improved facial contours, skin glossiness, skin elasticity, ptosis, and facial expressions. More than 80% of both patients and surgeons reported feeling generally satisfied, as shown in Table 2. Figure 1 illustrates 4 representative cases of cosmetic improvement achieved after 6, 12 and 36 months of follow-up. Standardization and facial portion analysis through meticulous photography are critical steps in assessing the postoperative results of fat grafting, and are typically achieved through 2D photography.¹³ The 2D imaging was used to evaluate the aesthetic results of the surgery, which showed a high level of satisfaction among patients and surgeons.

Discussion

In this study, although we could not estimate the amount of fat retained at each facial site and only knew the total amount of fat grafted, the atrophy corrections for different facial compartments were significant and lasted for the entire follow-up period. Despite this, 9 patients underwent additional fat grafting sessions to correct asymmetries, likely due to differences in graft vascularization, delaying the healing of the initial graft.

As the human body ages, numerous facial changes occur. Gravity causes face soft tissue to descend, forming unattractive folds and shadows (e.g., nasolabial folds, tear troughs, marionette lines) that contribute to an aged appearance. In addition, as patients age, their facial volume decreases due to a combination of skin thinning, muscular atrophy, fat volume loss, and bone thinning.¹³ While gravity-related changes are traditionally treated with resuspension procedures such as face lifting, brow lifting, midface lifting, and neck lifting, the loss of facial volume is treated with a variety of filler materials, which in some cases may produce results comparable to surgical lifting. Due to their effectiveness, fat grafting and dermal filler injections have recently gained popularity as supplementary facial rejuvenation treatments.¹⁴ Fat grafting requires a comprehensive knowledge of facial anatomy and the interactions between various structures and fascial planes in order to obtain satisfactory results and reduce complications.¹⁵

In the past, a number of dermal fillers have been tested with varying degrees of success. However, fat fillers have gradually become a cheaper and more effective replacement for augmenting soft tissue for cosmetic indications.¹⁶ Other than being employed either as a standalone technique or as an adjunct to other facelift surgeries, AFG has also been used in breast reconstruction, periocular facial rejuvenation, and for the correction of congenital deformities (Parry–Romberg syndrome, Poland syndrome, Dupuytren’s and Raynaud’s diseases, and pectus excavatum), treatment of burn scars, hand rejuvenation, augmentation rhinoplasty, and breast and gluteal augmentation.^{17, 18}

Clinical observation studies have demonstrated long-term differences in the outcomes of fat implantation at various anatomical facial region planes.¹⁶ In addition, it has been shown that the quantity of the fat graft is connected with the volume of adipose tissue in the patients. Lipomodelling increases the volume of body regions. Moreover, the presence of mesenchymal stem cells in the adipose tissue plays a crucial role in repairing tissue deformities.¹⁹

The harvested fat, which is often extracted from the flank, inner thigh or abdomen, is injected into the recipient locations only after careful planning. It is crucial to identify the proper position and depth of the fat compartments that will receive the grafts. The primary fat compartments of the face are separated by the superficial musculoaponeurotic system into the superficial and deep fat spaces.²⁰ Each of these regions can be further subdivided within the same plane, and the identification of suitable recipient sites requires substantial skill. The superficial fat space is comprised of the nasolabial fat pad, superior, inferior and lateral orbital fat pads, temporal and forehead fat pads, jowl fat pad, and medial, middle and lateral cheek fat pads. The medial and lateral suborbicularis oculi fat pads, the suborbicularis oris fat pad, the deep medial and lateral cheek fat pads, and the buccal fat pad make up the deep fat space.²¹ Understanding these subdivisions enables injectors to choose ideal areas for fat transfer and to determine the necessary volume and the most effective injection procedures and equipment.

The AFG for facial rejuvenation improves facial volume and revitalizes skin by enhancing its tone and texture. Despite the fact that fat grafting is typically utilized for cosmetic purposes, it is a significant, minimally invasive technique that can be used for a number of reconstructive indications.

Age-related facial alterations that can be treated with AFG include forehead hollowing, sagging cheeks, thinning lips, deep rhytides (especially on the forehead and glabella), temporal depressions, supraorbital depressions, deformities of the tear trough, a deep nasojugal groove, malar bags, nasolabial creases, marionette lines, poor jawline contour or jowls, and a receding chin. In addition to facial aging, AFG can be performed alone or in conjunction with facial rejuvenation to address a number of additional issues.²² Those include nasal contour anomalies, scars, burns, radiation dermatitis, human immunodeficiency virus-associated lipodystrophy, facial deformities (congenital, acquired or traumatic), facial asymmetry, and flap augmentation.

In many cases, fat grafting may not be the most effective technique for rejuvenation and may even be dangerous, especially if general anesthesia is used. The AFG may be contraindicated when there is a significant probability of fat volume instability, such as in cases of targeted weight loss or continuous weight increase, or if the patient has a history of complete or partial resorption of previously grafted fat. Patients receiving fat injections for breast reconstruction or recontouring should also be informed that the injected fat may produce nodules or calcifications that may seem malignant on subsequent imaging.

Patients with local, regional or systemic disorders that impede blood flow or wound healing are also susceptible to complications and unsatisfactory outcomes. Examples include significant burn scarring, radiation therapy, keloid scarring, coagulopathies, the necessity for immunosuppressant drugs, and other metabolic or chronic disorders.

Previously, Li et al. proposed a fat grafting method based on a compartment distribution model, delineating functional zones from transitional zones for the distribution of fat in different anatomical recipient sites.⁹ In this study, the authors advocated grafting fat tissue deep into the tissue layer for the premaxillary area and into the subcutaneous layer for the nasal labial groove, brow tail and temporal region. When fat grafts were implanted in the frontal region or the cheek area, the sub-galea layer and below the zygomatic arches were preferred locations. Similarly, other researchers have explored different strategies to graft fat cells in various facial layers (single or multiple planes) for more satisfactory patient outcomes. While lipofilling is generally considered a safe procedure, several publications have reported various sequelae, ranging from minor skin irregularities, asymmetries and prolonged edema to devastating complications, such as systemic infections, bleeding, graft hypertrophy, fat necrosis, fat embolism, and cerebral infarction, resulting from the intravascular injection, improper intraoperative disinfection and liposuction contamination.^{12, 13, 14, 15, 16, 17}

Despite thorough collection, processing and grafting processes, fat grafting is associated with various complications. The most commonly observed sequelae are bruising, edema, ecchymosis, overcorrection due to the transfer of extra fat, and undercorrection caused by inadequate fat transfer or high resorption of the grafted fat. Other complications include pyogenic granulomas or cellulitis due to infection and/or persistent inflammation. Bleeding, scar tissue bunching or palpable abnormalities may be caused by superficially placed injections. Further problems may include contour abnormalities and the presence of nodules or calcifications. Pain at the donor site may also result from insufficient anesthesia. In addition, deformities caused by excessive or uneven fat harvesting or violations of an adhesion zone may occur. Blindness may also result from ocular artery occlusion, stroke from internal carotid artery occlusion or fat emboli.

In the current study, swelling and edema were the most common patient complaints, which is an expected outcome of the normal postoperative course. However, 2 patients developed complications, including a bulged superior orbital septum (adjusted using fat aspiration after 6 months) and a soft tumor deep into the right cheek (corrected by graft manipulation). No other complications (e.g., donor site hematoma, nerve or vascular injury, necrosis, calcification, or surgical site infections) were observed.

Autologous fat joining is thus an integral tool that can be used by plastic surgeons for facial rejuvenation. Notwithstanding its volumizing impacts and skin rejuvenation, facial fat joining is an optimal filler due to its long lifespan, low cost, compatibility with living tissue, low incidence of complications, and high fulfillment rates.^{23, 24} A more comprehensive understanding of facial maturing mechanisms, including fat decay and ptosis of the distinctive facial compartments, has permitted fat joining to be regarded as a potential procedure for facial restoration.^{25, 26}

Limitations

This study included participants with a female-to-male ratio of 16:1. As the number of male participants was limited, we were unable to determine the male satisfaction level with the AFG technique. In future studies, more male oral cancer patients should be recruited to ensure a female-to-male ratio of 1:1. In addition, the patients’ age ranged from 28 to 62 years, which excluded teenagers. Adolescents may show different satisfaction levels or recover faster than adults and the elderly. Future studies should divide the participants into smaller age groups (e.g., 18–27 years old, 28–37 years old, etc.). As only Asian patients were involved in this study, the results may not be representative of other races.

Conclusions

We investigated the impact of autologous fat injections into the facial area in cosmetic surgery patients and examined the prevalence of postoperative problems. In addition, patient satisfaction and complications after autologous fat filling in different areas of the facial spaces were investigated through clinical evaluations, patient-reported outcomes and photographic assessments.

Autologous fat filling in the facial spaces positively affected facial rejuvenation and improved aesthetics. This technique is a safe and effective surgical procedure, worthy of clinical application. In addition to these effects, the presence of stem cells in the adipose tissue can provide additional support for tissue repair. Thus, the AFG technique may offer significant advantages for oral cancer patients to improve their facial appearance after surgery. The present study provides insights into the use of the AFG technique as a cheap and effective surgical procedure to improve deformities, irregularities, facial lines, and depressions, thereby enhancing the quality of life and the physical and mental health of oral cancer patients.