Assessing the Efficacy of Imiquimod Use in Patients With Persistent Locally Advanced Melanoma In Situ

BACKGROUND: The standard of care when treating melanoma in situ (MMIS) is an excision with at least 5 mm surgical margins.1 Some studies have suggested up to 9 mm margins to maximize local recurrence-free survival.2 This retrospective review aims to assess the efficacy of imiquimod as a topical treatment for persistently positive MMIS at the margins of prior excisions or where surgery is not an option. METHODS: Retrospective study conducted at Moffitt Cancer Center between 2019 and 2021 with patients aged > 18 years with MMIS at the margins of excision of an invasive melanoma or MMIS. Included patients were not ideal candidates for primary or additional surgical resection due to non-feasibility of surgery because of comorbidity or cosmetically sensitive location and/or the need for repeated skin grafting, or due to patient's refusal. Patients received imiquimod on protocol for 16 weeks and were monitored for treatment response and side effects. Following completion of the treatment, scouting biopsies were performed to assess histological response, and dermoscopy was used to determine the clinical disease status. RESULTS: Ten patients completed 16 weeks of imiquimod. Seven (75%) had a median of 2 surgical resections, and 3 refused surgery despite discussion that surgery was standard of care. Seven were deemed free of disease on post-imiquimod treatment scouting biopsies, while 2 were found to be clinically free of disease following confocal microscopy, indicating a tumor clearance rate of 90% with imiquimod treatment. One patient was found to have persistent residual disease following 2 rounds of imiquimod and was taken for an additional surgical excision after which they were deemed free of disease. Median follow-up duration from the onset of imiquimod therapy to the last clinic visit was 18 months, without any recurrences to date. CONCLUSION: Imiquimod appears to demonstrate an encouraging tumor clearance among patients with persistent MMIS after surgery where further surgical resection may not be feasible. Although long-term durability has not been demonstrated in this study, a 90% tumor clearance rate is promising. J Drugs Dermatol. 2023;22(5): doi:10.36849/JDD.6987.

Adaptation to tonic heat in healthy subjects and patients with sensory polyneuropathy.

Background Adaptation to a constant sensory stimulus involves many sites along the path of sensory volleys towards perception. The evaluation of such phenomenon may be of clinical interest. We studied adaptation to a constant temperature stimulus in healthy subjects to set normative data and in patients with sensory polyneuropathy (SPN), as proof of concept. Methods Twenty-six healthy subjects and 26 patients with SPN in the context of chemotherapy treatment with oxaliplatin for colon cancer were instructed to express through an electronic VAS system (eVAS); the level of sensation felt when a thermode set at either 39º, 41º, 43º, 45º or 47º was applied to their ventral forearm. Results The eVAS recordings showed typically an abrupt onset that slowed to approach maximum sensation and continued with a slow decrease indicating adaptation. The time to respond (TR), the velocity of the initial response (VR), the maximum sensation (MA), the time to reach MA (MAt), the onset of adaptation (AO) and the decrease in the sensation level with respect to MA at 30 s after stimulus application (SL30), were dependent on the temperature level in all subjects. However, patients showed significantly delayed TR, slowed VR, decreased MA, delayed AO and reduced SL30, with respect to healthy subjects. Differences were more pronounced at low-temperature levels, with absent AO in 25 patients versus 2 healthy subjects at temperatures of 39º and 41ºC. Conclusion The study of adaptation to a constant temperature stimulus can furnish valuable data for the assessment of patients with SPN. SIGNIFICANCE: We studied perceptual changes in the intensity of thermoalgesic sensation during 30 s of constant temperature stimulation after an abrupt initial contact in healthy subjects and patients with sensory polyneuropathy. Patients showed delayed time to respond, decreased maximal sensation and reduced adaptation with respect to healthy subjects. Differences were more pronounced at low and intermediate temperatures (39ºC to 43ºC). The method is of easy implementation and shows clinically relevant abnormalities in patients with sensory polyneuropathy.

The role of pretreatment percutaneous endoscopic gastrostomy in facilitating therapy of head and neck cancer and optimizing the body mass index of the obese patient.

BACKGROUND: Chemoradiation of head and neck cancer induces severe dysphagia and malnutrition, which may lead to interruptions in therapy and reduction in its efficacy. Percutaneous endoscopic gastrostomy (PEG) feedings bypass the oropharynx, allowing administration of nutrients and medications into the stomach, thus preventing malnutrition, dehydration, and treatment interruption. METHODS: Medical records of 161 patients treated for head and neck cancer who had PEGs placed prior to chemoradiation and 2 PEGs placed during chemoradiation were reviewed from the date of PEG placement throughout treatment and utilization. The objective was to determine the contribution of pretreatment PEGs to the therapy of patients with head and neck cancer and to optimize their body mass index. RESULTS: Severe chemoradiation-induced dysphagia developed in 160 patients (98%), necessitating PEG utilization for feeding and hydration. PEGs were used for a mean 251 +/- 317 days. Significant complications related to PEG placement and utilization were infrequent. PEG feeding allowed chemoradiation to continue without interruption in 93% of patients. Individualized feeding regimens optimized body mass index in obese and overweight patients with a decline from 33.0 +/- 3.4 to 28.4 +/- 4.8 kg/m(2) (P < .001) and 27.3 +/- 1.5 to 24.6 +/- 2.7 kg/m(2) (P < .001), respectively. Radiation-induced strictures developed in 12% of patients, requiring endoscopic dilatation. CONCLUSIONS: Enteral feeding through prechemoradiation-placed PEGs is an effective and safe method for nutrition and hydration of patients with head and neck cancer undergoing chemoradiation. PEGs allowed chemoradiation to proceed with minimal interruptions despite severe dysphagia, which excluded oral intake for prolonged periods.

Thermoalgesic stimuli induce prepulse inhibition of the blink reflex and affect conscious perception in healthy humans.

All sensory stimuli produce transient excitability changes in various central nervous system circuits. One example is prepulse inhibition (PPI), which is the inhibition generated by a preceding weak stimulus (prepulse) over the reflex response to a subsequent suprathreshold stimulus. The PPI is a ubiquitous phenomenon, common to many different sensory modalities. However, it has not yet been studied with thermoalgesic stimuli. These stimuli take a relatively long time to reach their peak, which implies some uncertainty in the exact timing of prepulse effects with respect to stimulus onset. In 20 healthy volunteers, we determined when thermoalgesic stimuli cause PPI of the blink reflex and measured conscious awareness (AW) of thermoalgesic stimulus perception using the Libet's clock. In this way, we determined the temporal relationship between AW and PPI. In a second experiment, we investigated whether prepulse effects on blink reflex also involved a change in conscious perception of the supraorbital nerve stimulus. Our results show that thermoalgesic stimuli generate PPI of the blink reflex long before subjects were consciously aware of the stimulus, confirming the already-known principle that conscious perception is not required for PPI to take place, and that prepulse stimuli induce a change in the time of conscious perception of prepulse and pulse stimuli, in such a way that AW of both stimuli tended to become closer to each other.

Clinical utility of contact heat evoked potentials (CHEPs) in a case of mentalis nerve lesion.

OBJECTIVE: Nociceptive evoked potentials are still infrequently used in electrodiagnostic studies of single patients. We report a case in which the results of contact heat evoked potentials (CHEPs) provided unique information for the diagnosis. METHODS: After biopsy for a local cementoma, a 21-year-old woman presented with neuropathic pain in the distribution of her left mentalis nerve. A CT scan showed a well circumscribed lesion near the mentalis nerve groove. We examined brainstem reflexes and evoked potentials conveyed through the mentalis nerve. RESULTS: Blink reflex responses recorded from the orbicularis oculi, jaw jerk and masseteric silent period recorded from the masseter muscles and long latency evoked potentials recorded from Cz to electrical stimulation of the mentalis nerve were all within normal values, with no differences between sides. However, CHEPs, recorded from Cz to thermoalgesic stimulation of the left mentalis area were decreased to approximately 1/3 their size in comparison to stimulation to the unaffected side. CONCLUSION: While the patient reported symptoms and had neuroimaging signs of mentalis neuropathy, the sole electrophysiological abnormality identified was that of CHEPs, which specifically test small, unmyelinated fibers. SIGNIFICANCE: Nociceptive evoked potentials can provide unique information on damage of small nerve fibers in specific cases.