Holistic Treatment Incorporating Moist Wound Healing for Postoperative Radiation-Induced Perineal Ulcer in Rectal Malignancy: A Case Report

Abstract

Introduction

Radiation-induced perineal ulcers are often refractory to conventional dry exposure therapies. This article reports a case of extensive radiation-induced ulceration successfully managed using a moist wound healing protocol.

Case Presentation

A 67-year-old male developed progressive perianal, scrotal, and penile ulceration following radiotherapy for rectal carcinoma. Four weeks of conventional dry exposure therapy proved ineffective. Upon admission, the patient was transitioned to a holistic treatment incorporating moist wound healing. This approach resulted in complete reepithelialization of the lesions within 1 week.

Conclusion

This case demonstrates the limitations of dry healing protocols for radiation-induced cutaneous injuries. The application of moist wound healing principles provided rapid efficacy. This offers a valuable clinical strategy for managing refractory perineal radiation ulcers.

Introduction

Radiation-induced skin ulcers, a common complication of radiotherapy for malignancies, exhibit a positive correlation between incidence rates and cumulative radiation doses. Irreversible damage to the epidermal stem cell pool and persistent disruption of dermal microvascular architecture caused by ionizing radiation typically manifest as clinically refractory lesions. Particularly in anatomically specialized regions such as the perineum, the synergistic effects of continuous mechanical stress and persistent microbial colonization risks frequently compromise the efficacy of conventional dry healing protocols [1, 2].

Although dry wound management provides mechanical protection through eschar formation in current clinical practice, the resultant wound dehydration reduces epidermal growth factor receptor (EGFR) phosphorylation levels and exacerbates post-radiotherapy microvascular occlusion [3, 4]. In contrast, the moist wound healing theory has been validated to enhance integrin-mediated keratinocyte migratory activity by maintaining an optimally hydrated wound microenvironment and stimulating angiogenesis via modulation of the PI3K/AKT signaling pathway [5]. Notably, existing research on perineal radiation ulcers has predominantly focused on isolated interventions, with limited systematic clinical evidence supporting comprehensive moist wound healing protocols for this specific ulcer subtype.

Case History/Examination

A 67-year-old male presented with the chief complaints of “postoperative rectal carcinoma with 3-month chemotherapy history and 1-month progressive perineal ulceration.” Five months prior to admission, the patient underwent painless gastrointestinal endoscopy, which revealed a rectal mass, with a subsequent biopsy confirming malignant neoplasia. Three months before presentation, the patient underwent endoscopic submucosal dissection for rectal tumor resection, followed by 22 fractions of radiotherapy administered over 1 month. One month before admission, the patient developed erythema, tenderness, and progressive skin ulceration with purulent discharge in the perineal region along with symptoms of frequent and urgent urination. Initial management at an external institution involved a dry wound healing protocol consisting of the following steps: the ulcer was cleansed with sterile normal saline irrigation (without antiseptic solutions, such as povidone-iodine), followed by exposure to an infrared lamp to evaporate residual moisture and maintain a dry wound bed. Subsequently, the area was covered with sterile dry gauze dressing, allowing direct contact with the wound surface while protecting it from clothing. Concurrently, the patient received systemic third-generation cephalosporins. This protocol proved ineffective after 1 month, resulting in ulcer progression from the perianal area to the scrotum and the penile shaft. No other significant comorbidities were noted.

Diagnosis/Treatment

Physical Examination

Physical examination on admission revealed the following vital signs: temperature, 36.5°C; pulse, 75 bpm; respiratory rate, 20 breaths/min; and blood pressure, 115/67 mm Hg; height: 160 cm; weight: 50 kg. The patient exhibited normal development, adequate nutritional status, and clear consciousness during assisted ambulation. Jaundice was not observed in the skin or sclera. No palpable superficial lymphadenopathy. Cardiac examination revealed regular rhythm without murmurs or cardiomegaly. The lungs were clear to bilateral auscultation, with no adventitious breath sounds. The abdomen was soft and non-distended with no tenderness, rebound tenderness, or hepatosplenomegaly. No lower extremity edema. The physiological reflexes were intact, and no pathological reflexes were observed.

Specialized examination revealed circumferential perianal ulceration (approximately 12 cm in diameter, Fig. 1) and scrotal (5 × 3 cm), penile (4 × 2 cm), and bilateral inguinal (8 cm in diameter, Fig. 2) skin erosions. The lesions exhibited creamy purulent exudate with dusky erythematous bases and erythema of the surrounding tissue.

Fig. 1.

Acute radiation-induced perianal ulceration. Clinical photograph demonstrating circumferential ulceration (yellow arrowheads) with erythematous base and peripheral epithelial denudation surrounding the anal verge. Lesions presented 4 weeks following endoscopic submucosal dissection (ESD) for rectal tumor with adjuvant radical radiation therapy.

Fig. 2.

Severe radiation dermatitis in genital region. Panoramic view of confluent ulcerations involving the scrotum (S), penile shaft (P), and bilateral inguinal folds (I), characterized by serosanguinous exudate and pseudomembrane formation (yellow arrowheads). Lesions presented 4 weeks following endoscopic submucosal dissection (ESD) for rectal tumor with adjuvant radical radiation therapy.

Laboratory Examinations

Laboratory investigations revealed no significant abnormalities in complete blood count, C-reactive protein, procalcitonin, coagulation profile, hepatic and renal function panels, electrolytes, or male-specific tumor markers. Diagnostic imaging studies demonstrated an unremarkable abdominal ultrasound and a normal electrocardiogram.

Treatment

Local Wound Management: The affected area was disinfected with 0.02% nitrofurazone solution. Bovine basic fibroblast growth factor gel (21,000 IU) was generously applied to ulcerated regions, whereas triamcinolone acetonide combined with econazole cream was thickly administered to the surrounding erythematous skin. The wound bed was then covered with two layers of petrolatum-impregnated gauze to maintain a moist environment, followed by a sterile gauze dressing secured with an adhesive tape.

Adjuvant Therapies: Intravenous vitamin C infusion, oral administration of rabeprazole (a proton pump inhibitor), and lornoxicam (a nonsteroidal anti-inflammatory drug) were initiated. Nutritional guidance emphasizes a high-protein diet. Clinical protocols included regular blood glucose monitoring, scheduled repositioning with postural percussion to prevent pulmonary complications, and systematic pressure ulcer risk assessment using the Braden Scale.

Results

Following 1 week of moist wound healing protocol implementation, the wound demonstrated substantial epithelial regeneration with near-complete reepithelialization.

Discussion

Radiation-induced cutaneous ulcers, as frequent complications of oncological radiotherapy, exhibit a distinct stage-dependent pathophysiological progression. During the initial radiotherapy phase (weeks 1–4), ionizing radiation induces G2/M phase cell cycle arrest through DNA double-strand breaks in epidermal basal cells, concurrently impairing mitochondrial oxidative phosphorylation chains with a >50% reduction in ATP synthesis [6–8]. The microcirculatory system demonstrates dual injury mechanisms: aberrant E-selectin overexpression in endothelial cells triggers leukocyte-endothelial adhesion cascades, culminating in dermal microvascular occlusion [9], while suppressing PDGFR-β receptor expression synergizes with hypoxia-induced reactive oxygen species (ROS) storms, exacerbating ischemic-hypoxic pathology [10].

In chronic phases, persistent activation of the TGF-β1/Smad2/3 signaling pathway (a key regulator of fibrogenesis) drives the pathological transdifferentiation of fibroblasts into myofibroblasts [11]. This precipitates dynamic extracellular matrix dysregulation, characterized by abnormal type I collagen deposition and disordered collagen fiber cross-linking/alignment in the dermis, ultimately diminishing skin elasticity [12, 13]. Notably, radiation-induced ROS selectively impair mitochondrial function in Schwann cells, inducing progressive degeneration of type C unmyelinated nerve fibers. This neuropathic process lowers substance P release thresholds and perpetuates refractory burning pain, which significantly compromises patients' quality of life [14].

The refractory healing properties of radiation-induced ulcers originate from the synergistic interplay between multiple pathological mechanisms. The ulcer core region demonstrates significantly reduced microvascular density and oxygen partial pressure compared with healthy tissues, resulting in a >60% decrease in keratinocyte migration velocity [1]. At the molecular level, sulfonation modification of the critical Cys797 residue within the tyrosine kinase domain of the EGFR [15], coupled with oxidative damage to the fibroblast growth factor receptor [16], collectively inhibits activation of the PI3K/AKT and MAPK signaling pathways [5]. This molecular blockade persists despite exogenous growth factor administration, resulting in therapeutic resistance [17, 18]. From a microbiological perspective, dense biofilms formed by pathogens such as Staphylococcus aureus reduce antimicrobial penetration efficiency [2], consequently elevating post-debridement recurrence rates. Clinical studies have confirmed that radiation-induced ulcers exhibit significantly prolonged mean healing time compared to conventional traumatic ulcers, with higher 5-year cumulative recurrence rates [19], and demonstrate a strong positive correlation with radiotherapy dosage [20].

The unique anatomical architecture of the perineal region exacerbates the progression of radiation-induced ulcers via synergistic pathological mechanisms. The resting skin tension in this area is markedly higher than that in other anatomical sites, with persistent mechanical stress from daily activities that predisposes the neoepidermis to recurrent tearing. The local humid microenvironment induces excessive stratum corneum hydration [21, 22], whereas abnormally elevated matrix metalloproteinase-9 activity accelerates extracellular matrix degradation, establishing a negative regulatory loop for epidermal regeneration [23]. These factors are further compounded by fecal contamination and shear forces generated by sphincter motility, which persistently disrupt granulation tissue remodeling.

At the immunoregulatory level, post-radiotherapy depletion of Langerhans cells coincides with diminished neutrophil phagocytic activity under elevated wound pH conditions [24], collectively culminating in the collapse of local immune surveillance systems. These interrelated mechanisms ultimately form a self-reinforcing pathological triad comprising mechanical insult, microbial colonization, and regenerative failure [25].

The management of radiation-induced skin ulcers requires the precise modulation of the wound microenvironment and pathological mechanisms. Moist wound healing, achieved through occlusive dressings that maintain appropriate humidity, enhances keratinocyte migration rates [26]. This process is closely associated with strengthened EGFR phosphorylation following integrin α6β4-laminin binding, which synergistically activates the PI3K/Akt pathway to drive cytoskeletal reorganization [3].

In contrast, traditional dry healing protocols, particularly those employing povidone-iodine disinfection combined with gauze dressing during the early stages of perineal ulcers, induce dense eschar formation through wound exudate evaporation. Histological observations revealed sub-eschar accumulation of fibrin and necrotic tissue debris, forcing keratinocytes to adopt a “drilling” mechanism to penetrate this physical barrier, with migration efficiency reduced to less than one-third of the normal levels [4, 27].

More critically, this mechanical obstruction synergizes with radiation-induced microvascular occlusion, resulting in a sub-eschar oxygen partial pressure decline [28]. The compounding effects of microenvironmental deterioration and impaired vascular perfusion significantly impede epithelial regeneration. This case involved a 67-year-old male patient with rectal cancer who developed severe, progressive radiation-induced ulcers involving the perianal region, scrotum, and penis following radiotherapy, which had failed to respond to a conventional dry healing protocol.

Successful resolution within 1 week was achieved through an integrated regimen centered on the principle of moist wound healing. This approach fundamentally alters the wound microenvironment by maintaining optimal humidity with an occlusive dressing, which prevents eschar formation and creates a conductive milieu for cellular activity. The therapeutic effect was synergistically enhanced by combining topical regenerative agents (basic fibroblast growth factor gel) to promote angiogenesis and collagen synthesis and systemic nutritional support to correct catabolic derangements.

This outcome demonstrates that moist wound healing is not merely a supportive measure but also a critical therapeutic strategy that can effectively reverse radiation-induced tissue damage. Its efficacy stems from a tripartite synergistic mechanism that modulates the wound oxygen gradient, eradicates pathogens, and activates endogenous regenerative signaling pathways. This integrated approach is particularly advantageous for complex wounds in specialized anatomical regions, such as the perineum, where sustained mechanical stress and contamination risk necessitate a dynamic and multifaceted healing strategy.

Limitations

As a single-center case report, this case provides preliminary evidence for the feasibility of a holistic treatment approach that integrates moist wound healing for managing radiation-induced skin ulcers. However, constrained by limited sample representativeness and relatively short follow-up duration, the definitive therapeutic efficacy and mechanistic underpinnings still require verification through multicenter cohort studies. Although the current findings cannot establish high-grade evidence-based recommendations, comprehensive documentation of therapeutic procedures provides valuable clinical insights into the application of moist wound healing strategies for radiation-induced dermatological injuries.

Conclusions

This case demonstrates that holistic treatment integrating moist wound healing exhibits definitive therapeutic efficacy for perianal radiation-induced skin ulcers and provides a clinically generalizable therapeutic strategy for managing radiation-induced dermatological injuries.

Statement of Ethics

The study was conducted in accordance with the relevant guidelines of the Declaration of Helsinki and the regulations in ethics approval, accordance, and consent to participate. This study protocol was reviewed and approved by the Ethics Committee of Chengdu Seventh People’s Hospital (Affiliated Cancer Hospital of Chengdu Medical College), Approval No. 2025-CDQY-046. The study was conducted in accordance with the relevant guidelines of the Declaration of Helsinki and the regulations in ethics approval, accordance, and consent to participate. Written informed consent was obtained from all the patients. Patient anonymity was also guaranteed. Written informed consent for publication of this case report and any accompanying images was obtained from the patient. The CARE Checklist has been completed by the authors for this case report, attached as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000550713).

Conflict of Interest Statement

The authors declare no conflicts of interest.

Funding Sources

This research received no specific grants from any funding agency in the public, commercial, or not-for-profit sectors.

Author Contributions

Guikuan Nie: conceptualization, data curation, writing – original draft, supervision, and project administration (corresponding author). Yahong Zhang: writing – original draft. Xichuan Wu and Yan Luo: data collection, formal analysis, and writing – review and editing. Huiyong Song: investigation and resources. Hao Li and Qiyang He: data curation. Qinping Wu and Rongmeng Chen: resources and writing – review and editing.

Funding Statement

This research received no specific grants from any funding agency in the public, commercial, or not-for-profit sectors.

Data Availability Statement

The data that support the findings of this study are not publicly available due to patient privacy but are available from the corresponding author upon reasonable request.