Lateral Femoral Cutaneous Nerve Radiofrequency Ablation for Long-term Control of Refractory Meralgia Paresthetica.

BACKGROUND: Meralgia paresthetica is a term used to describe a clinical pain syndrome related to the compression or irritation of the lateral femoral cutaneous nerve (LFCN). The LFCN is a pure sensory nerve that is susceptible to compression injury. The most common compression locations are: as it courses from the lumbosacral plexus, through the abdominal cavity, under the inguinal ligament, and into the subcutaneous tissue of the thigh. METHODS: This case series is a retrospective single-center review of six patients with medically intractable meralgia paresthetica who were treated with radiofrequency ablation. To be considered for radiofrequency ablation, the patient must have been unsuccessful with medical management alone for more than two months and have a clinical diagnosis of meralgia paresthetica. Temporary relief of pain of 50% or greater was considered a positive result. Average pain scores were measured pre- and postprocedure, along with one-, two-, three-, and six-month intervals postoperation. RESULTS: All patients demonstrated immediate relief in self-reported pain scores, averaging a 75.5% reduction in pain. At the one-, two-, three-, and six-month follow-ups, patients averaged a reduction of 60.0%, 58.0%, 51.4%, and 40.5%, respectively. Both the postop and one-month follow-up pain scores were lower, statistically significantly so (P < 0.05), whereas the two-, three-, and six-month follow-ups were not statistically different from pretreatment scores. CONCLUSIONS: Although our study was small, radiofrequency ablation showed a clear reduction in average pain scores in a subset of patients who had failed standard medical therapy with a reduction in pain at one-month follow-up with relief of symptoms sometimes lasting longer than 12 months.

Transplantation of mouse HSCs genetically modified to express a CD4-restricted TCR results in long-term immunity that destroys tumors and initiates spontaneous autoimmunity.

The development of effective cancer immunotherapies has been consistently hampered by several factors, including an inability to instigate long-term effective functional antitumor immunity. This is particularly true for immunotherapies that focus on the adoptive transfer of activated or genetically modified mature CD8+ T cells. In this study, we sought to alter and enhance long-term host immunity by genetically modifying, then transplanting, mouse HSCs. We first cloned a previously identified tumor-reactive HLA-DR4-restricted CD4+ TCR specific for the melanocyte differentiation antigen tyrosinase-related protein 1 (Tyrp1), then constructed both a high-expression lentivirus vector and a TCR-transgenic mouse expressing the genes encoding this TCR. Using these tools, we demonstrated that both mouse and human HSCs established durable, high-efficiency TCR gene transfer following long-term transplantation into lethally irradiated mice transgenic for HLA-DR4. Recipients of genetically modified mouse HSCs developed spontaneous autoimmune vitiligo that was associated with the presence of a Th1-polarized memory effector CD4+ T cell population that expressed the Tyrp1-specific TCR. Most importantly, large numbers of CD4+ T cells expressing the Tyrp1-specific TCR were detected in secondary HLA-DR4-transgenic transplant recipients, and these mice were able to destroy subcutaneously administered melanoma cells without the aid of vaccination, immune modulation, or cytokine administration. These results demonstrate the creation of what we believe to be a novel translational model of durable lentiviral gene transfer that results in long-term effective immunity.

High-avidity autoreactive CD4+ T cells induce host CTL, overcome T(regs) and mediate tumor destruction.

Despite progress made over the past 25 years, existing immunotherapies have limited clinical effectiveness in patients with cancer. Immune tolerance consistently blunts the generated immune response, and the largely solitary focus on CD8+ T cell immunity has proven ineffective in the absence of CD4+ T cell help. To address these twin-tier deficiencies, we developed a translational model of melanoma immunotherapy focused on the exploitation of high-avidity CD4+ T cells that become generated in germline antigen-deficient mice. We had previously identified a tyrosinase-related protein-1 specific HLA-DRB1*0401-restricted epitope. Using this epitope in conjunction with a newly described tyrosinase-related protein-1 germline-knockout, we demonstrate that endogenous tyrosinase-related protein-1 expression alters the functionality of the autoreactive T cell repertoire. More importantly, we show, by using major histocompatibility complex-mismatched combinations, that CD4+ T cells derived from the self-antigen deficient host indirectly triggers the eradication of established B16 lung metastases. We demonstrate that the treatment effect is mediated entirely by endogenous CD8+ T cells and is not affected by the depletion of host regulatory T cells. These findings suggest that high-avidity CD4+ T cells can overcome endogenous conditions and mediate their antitumor effects exclusively through the elicitation of CD8+ T cell immunity.

Pathologic characteristics of exophytic renal masses.

OBJECTIVE: Pathologic grade is an important prognostic factor for renal-cell carcinoma (RCC). The objective of this study was to determine if there is any association of radiologic characteristics with pathologic grade and type of small renal tumors. PATIENTS AND METHODS: We retrospectively reviewed the records of 500 patients who underwent extirpative renal surgery. Fifty-one patients met the inclusion criteria of solitary RCC <6 cm and adequate radiologic imaging available for review. The axial images with the largest area of tumor growing into the kidney were evaluated by a single radiologist to determine the percent of tumor that was exophytic. RESULTS: Nine patients had tumors that were >67% exophytic, and 42 patients had tumors <67% exophytic. There is a statistically significant difference in the mean Fuhrman grade for these 2 groups (1.78 v 2.25, P < 0.01). The distribution of histologic subtype was as follows: 34 patients with clear cell, 15 with papillary, and one each with chromophobe and unclassified tumors. Papillary RCC comprised 78% (7 of 9) of tumors that were >67% exophytic and 15% (3 of 20) that were <33% exophytic. The relative risk of a >67% exophytic tumor being papillary v nonpapillary is 4.1. CONCLUSIONS: Exophytic renal tumors are more likely to be of lower pathologic grade and of the papillary RCC subtype when compared with endophytic renal tumors. A larger prospective study is required to confirm these findings and determine the implications. This information may be useful when small tumors are being considered for watchful waiting or ablative therapies.