Diet Modification as an Adjunct to Treatment for Lymphatic Fistula Following Inguinal Lymphadenectomy: A Case Report

Lymphadenectomy of the groin that includes inguinal and iliac node dissection is an important treatment adjunct in the management of select cases of melanoma. While this procedure can improve overall survival, it is not without morbidity. Postoperative complications can range from mild to severe and occur in upwards of 77% of patients.¹ Most common complications are related to the surgical site and include lymphedema, seroma, surgical site infection, wound dehiscence, lymphocele, hematoma, and chronic wounds.^1,2 Of these complications, most are multifactorial and often overlap. Factors that contribute to complications include nutritional status, chemotherapy and immunotherapy, radiation, steroid use, extent of intraoperative dissection, obesity, and diabetes, as well as other comorbidities.

Obesity is, in particular, a predictor of complicated wound healing for multiple reasons, including anatomical differences, decreased vascularity of adipose tissue, upregulation of proinflammatory cytokines, increased oxidative stress, and micronutrient and macronutrient deficiencies. In obesity, protein malnutrition leads to decreased fibroblast proliferation, decreased angiogenesis, and ultimately, delayed wound healing. Notably, insulin resistance in obesity leads to increased oxidation of amino acids to meet caloric needs, further exacerbating protein malnutrition and delayed wound healing.³ Seroma, lymphocele, and infection all delay healing and can precipitate nonhealing wounds.⁴ The incidence of lymphocele and subsequent lymphatic fistula formation varies widely in the literature and ranges from 5% to 32.5% of patients undergoing therapeutic inguinal lymph node dissection for melanoma and other malignancies.^5-7 Lymphatic fistula is a risk factor for chronic drainage and considerable delay in wound healing.^4-6 The following case documents dietary modification in addition to conservative wound care in the treatment of a lymphatic fistula that developed after right inguinal lymphadenectomy for metastatic melanoma.

An 86-year-old White male presented with a past medical history of peptic ulcer disease, morbid obesity (BMI, 30.9 kg/m²), chronic lower extremity edema, multiple nonmelanoma skin cancers, and melanoma of the back and left leg after curative wide local excisions. The patient had a family history of melanoma (from the father). The patient reported a long-standing history of unprotected sun exposure and had lived in Argentina for 6 years.

In October 2017, the patient noticed a flat, red skin lesion on the medial aspect of the right calf. The lesion was biopsied and initially reported to be benign. The biopsy wound did not heal and continued to weep. The patient was referred to dermatology by the primary care physician in July 2018, and a shave biopsy was performed. Dermatopathologic evaluation demonstrated superficial spreading melanoma with Breslow thickness of 5.6 mm, positive ulceration, Clark level IV (invasion into the reticular dermis), and a mitotic rate of 20/mm². The patient was referred to a surgical oncologist for evaluation. He underwent wide local excision with partial-thickness skin graft coverage and sentinel lymph node biopsy. Pathologic evaluation demonstrated in-transit melanoma metastasis with angiolymphatic invasion with the primary lesion measuring 22 mm in greatest dimension with narrowly negative margins. BRAF V600E/V600K mutation was detected. The patient was diagnosed with American Joint Committee on Cancer tumor, node, metastasis system stage IIIC (pathologic T4b, pathologic N1c, clinical M0) malignant melanoma and referred to a medical oncologist for evaluation. The patient underwent adjuvant immunotherapy with nivolumab.

During a surveillance examination in January 2019, the patient was found to have palpable right inguinal lymphadenopathy. Positron emission tomography demonstrated fluorodeoxyglucose avid right inguinal lymph nodes concerning for metastatic melanoma without evidence of distant disease. After discussion by the multidisciplinary tumor board, the patient underwent right inguinal lymph node dissection with sartorius muscle flap and placement of a JP drain. At final pathologic evaluation, 6 of 10 lymph nodes were positive for metastatic melanoma without extranodal extension. The patient progressed well postoperatively and was discharged on postoperative day 3 with a drain in place. The medical oncologist did not recommend additional adjuvant therapies.

By the 2-week postoperative appointment, the patient had developed worsening right lower extremity lymphedema and partial wound dehiscence at the superior aspect of the wound measuring 1 cm × 1 cm and depth to subcutaneous tissues. The JP drain was removed because the wound was no longer sealed. Prior to removal of the JP drain, output was 100 mL to 150 mL of serous fluid daily. High-volume, serous-appearing fluid drainage continued, with delayed healing of the JP drain removal site and the wound dehiscence site. Drainage was difficult to quantify without a drain in place, but the patient was exchanging dressings 4 or more times daily, and packing was exchanged twice daily. He was referred to the wound clinic for management of nonhealing wounds.

Wounds included a skin defect measuring approximately 1 cm × 1 cm at the superior portion of the incision site, as well as the drain site, which remained open. These were connected by a 10-cm subcutaneous tunnel, which extended to the level of muscle/fascia. Conservative measures—extremity compression stockings, extremity elevation, light activity, supplementation with 500 mg of ascorbic acid (vitamin C) twice daily and a daily over-the-counter multivitamin with minerals, local wound care with placement of a Penrose drain, and daily dressing changes—were trialed. Despite conservative treatment, the wounds slowly increased in size to a maximum diameter of 1.5 cm each and continued high-output serous drainage even after the Penrose drain was removed. At that time, the patient was diagnosed with lymphatic fistula.

One month postoperatively, after no objective improvement, the patient was placed on a high-protein (100 g/day), low-fat diet to target the lymphatic leak; this was in addition to the previously described interventions. No specific parameters were listed for dietary fat intake during chart review, but the patient was given educational materials focused on nutrition optimization. These included examples of snacks and meals, including preference for lean meats and produce and avoidance of red meats and foods containing saturated and trans fats. Omega-3 fatty acids were not excluded with diet modification.

The patient and spouse reported good adherence to the diet. Drainage significantly decreased over the following days, and it completely resolved within 26 days. Wound closure commenced, and the wounds were completely healed after 75 days of diet modification in addition to the previously listed conservative measures.

At the 6-month follow-up appointment, the right lower extremity remained more edematous compared with the left lower extremity, but the edema was manageable with compression and exercise. Extremity circumference and weight measured at follow-up appointments remained stable. Based on subjective questioning at follow-up appointments, as of the time of this writing, lymphedema has not limited the patient’s quality of life and remains quite active.

Inguinal lymphadenectomy for melanoma remains a morbid procedure. Complications include lymphedema, lymphatic leak, and lymphatic fistulas. Factors that contribute to lymphatic leak postoperatively include preexisting comorbidities, surgical technique, infection, immune status, nutrition, and radiation.⁸

A lymphatic fistula developed in this case owing to an ongoing lymphatic leak. Given the comorbidities of obesity and preexisting lower extremity edema, the patient was at an increased risk of developing lymphatic sequela even with meticulous surgical technique. A variety of treatment modalities are available for lymphatic fistula, ranging from conservative wound therapies to more invasive surgical measures. Examples of more invasive approaches on reoperation that have demonstrated mixed results include intranodal glue embolization, sclerosing agents, ligation of lymphatic vessels, lymphatic reconstruction, omental flaps, and negative pressure wound therapy, among other novel therapies. In addition to treatment, multiple intraoperative preventative techniques are available for use at the initial surgery, including energy devices, lymphatic mapping, ligating lymphatic channels, and drains.^4-6,9-11

Historically, lymphatic leak and associated wounds have been managed conservatively in the early postoperative period. Patients with lymphedema are counseled on techniques such as extremity compression and elevation, limb volume tracking, exercise, osteopathic manipulative therapy, and meticulous skin care.^9,12 Enlarging lymphoceles are managed with local drainage, especially if there is concern for infection. Drainage of the lymphocele places patients at increased risk for lymphatic fistula formation, which is difficult to manage in the event of a high-output lymphatic fistula.¹³

There is considerable literature reviewing treatment options for lymphatic leak of the peritoneum and thorax with the propensity for high fluid losses secondary to the anatomy of central lymphatic drainage. Somatostatin analogues, total parenteral nutrition, diuretics, and diet modification are frequently used in the management of high-output lymphatic leaks of the chest and abdomen.⁸ These modalities are not always considered in the management of lymphatic fistulas of the groin and axilla, however, likely owing to the limited research on the topic. Nutrition optimization as well as vitamin and mineral supplementation have been shown to support healing in chronic and postoperative wounds.^14-16 Nutritional status cannot be ignored regardless of the location or cause of the wound.

This is a case study of a single patient. The current report is limited in its ability to quantify the effect of nutritional optimization on the patient’s outcomes. Future randomized controlled studies are needed to better determine the efficacy of nutritional optimization as an adjunct in the treatment of inguinal lymphatic fistulas.

In the current case, diet modification was used in conjunction with conservative wound care to promote resolution of a lymphatic leak in the right groin and subsequent closure of the associated cutaneous fistula. Dietary modification has typically been used in the management of high-output thoracic and abdominal lymphatic leaks, but it is not well-described in the management of lymphatic fistulas of the groin. Nutritional optimization can be used successfully as an adjunct to traditional treatment modalities in the management of inguinal lymphatic fistulas using similar pathophysiology behind the treatment of other types of lymphatic leaks. Chronic wounds associated with lymphatic fistulas are complex and require a multimodal approach to healing. It is recommended that a high-protein, low-fat diet be considered as an adjunct to traditional treatment modalities in such cases.