Plasma Cytokine Analysis in Patients with Advanced Extremity Melanoma Undergoing Isolated Limb Infusion

Background

Preprocedure clinical and pathologic factors have failed to consistently differentiate complete response (CR) from progressive disease (PD) in patients after isolated limb infusion (ILI) with melphalan for unresectable in-transit extremity melanoma.

Methods

Multiplex immunobead assay technology (Milliplex MAP Human Cytokine/Chemokine Magnetic Bead Panel, Millipore Corp., Billerica, MA; and Magpix analytical test instrument, Luminex Corp., Austin, TX) was performed on pre-ILI plasma to determine concentrations of selected cytokines (MIP-1α, IL-1Rα, IP-10, IL-1β, IL-1α, MCP-1, IL-6, IL-17, EGF, IL-12p40, VEGF, GM-CSF, and MIP-1β) on a subset of patients (n = 180) who experienced CR (n = 23) or PD (n = 24) after ILI. Plasma from normal donors (n = 12) was also evaluated.

Results

Of 180 ILIs performed, 28 % (95 % confidence interval 22–35, n = 50) experienced a CR, 14 % (n = 25) experienced a partial response, 11 % (n = 21) had stable disease, 34 % (n = 61) had PD, and 13 % (n = 23) were not evaluable for response. Tumor characteristics and pharmacokinetics appeared similar between CR (n = 23) and PD (n = 24) patients who underwent cytokine analysis. Although there were no differences in cytokine levels between CR and PD patients, there were differences between the melanoma patients and controls. MIP-1α, IL-1Rα, IL-1β, IL-1α, IL-17, EGF, IL-12p40, VEGF, GM-CSF, and MIP-1β were significantly higher in normal controls compared to melanoma patients, while IP-10 was lower (p < 0.001) in controls compared to melanoma patients.

Conclusions

Patients with unresectable in-transit melanoma appear to have markedly decreased levels of immune activating cytokines compared to normal healthy controls. This further supports a potential role for immune-targeted therapies and immune monitoring in patients with regionally advanced melanoma.     

Combined Analysis of Phase III Trials Evaluating [99mTc]Tilmanocept and Vital Blue Dye for Identification of Sentinel Lymph Nodes in Clinically Node-Negative Cutaneous Melanoma

Background

[^99mTc]Tilmanocept is a CD206 receptor-targeted radiopharmaceutical designed for sentinel lymph node (SLN) identification. Two nearly identical nonrandomized phase III trials compared [^99mTc]tilmanocept to vital blue dye.

Methods

Patients received [^99mTc]tilmanocept and blue dye. SLNs identified intraoperatively as radioactive and/or blue were excised and histologically examined. The primary end point, concordance, was the proportion of blue nodes detected by [^99mTc]tilmanocept; 90 % concordance was the prespecified minimum concordance level. Reverse concordance, the proportion of radioactive nodes detected by blue dye, was also calculated. The prospective statistical plan combined the data from both trials.

Results

Fifteen centers contributed 154 melanoma patients who were injected with both agents and were intraoperatively evaluated. Intraoperatively, 232 of 235 blue nodes were detected by [^99mTc]tilmanocept, for 98.7 % concordance (p < 0.001). [^99mTc]Tilmanocept detected 364 nodes, for 63.7 % reverse concordance (232 of 364 nodes). [^99mTc]Tilmanocept detected at least one node in more patients (n = 150) than blue dye (n = 138, p = 0.002). In 135 of 138 patients with at least one blue node, all blue nodes were radioactive. Melanoma was identified in the SLNs of 22.1 % of patients; all 45 melanoma-positive SLNs were detected by [^99mTc]tilmanocept, whereas blue dye detected only 36 (80 %) of 45 (p = 0.004). No positive SLNs were detected exclusively by blue dye. Four of 34 node-positive patients were identified only by [^99mTc]tilmanocept, so 4 (2.6 %) of 154 patients were correctly staged only by [^99mTc]tilmanocept. No serious adverse events were attributed to [^99mTc]tilmanocept.

Conclusions

[^99mTc]Tilmanocept met the prespecified concordance primary end point, identifying 98.7 % of blue nodes. It identified more SLNs in more patients, and identified more melanoma-containing nodes than blue dye.     

A Collision of Diseases: Chronic Lymphocytic Leukemia Discovered During Lymph Node Biopsy for Melanoma

Background

In the United States in 2012, there were 16,060 new cases of chronic lymphocytic leukemia (CLL). Often CLL is clinically occult and first detected during pathologic evaluation of the sentinel lymph node biopsy (SLNB). We reviewed our experience of patients with the coexisting diagnosis of melanoma and CLL.

Methods

An institutional review board-approved review was performed on patients with CLL and melanoma treated from 1995 to 2009 at Moffitt Cancer Center and compared with the incidence of melanoma and CLL in our tumor registry patients with breast, prostate, lung, and colon cancer.

Results

Fifty-two patients (44 males; median age, 71 years [range, 46–88]) were identified with concurrent diagnoses of melanoma and CLL. Twenty-two patients (42 %) had CLL on SLNB for their melanoma. Thirty-two patients (62 %) were diagnosed with melanoma before CLL. Concomitant or prior cancer diagnoses included nonmelanoma skin cancers (N = 29), prostate (N = 6), colorectal (N = 2), and Merkel cell carcinoma (N = 2). Five of 20 patients (25 %) had metastatic melanoma found at the time of SLNB. Patients with melanoma had a tenfold increase of CLL diagnosis compared with colorectal cancer patients, an eightfold increase compared to prostate cancer patients, and a fourfold increase compared with breast cancer patients.

Conclusions

We have confirmed an increased association of CLL and melanoma. This may be related to an underlying immunologic defect; however, there has been scant investigation into this phenomenon. Surgeons and pathologists should understand this occurrence and recognize that not all grossly enlarged or abnormal sentinel lymph nodes in melanoma patients represent melanoma.     

Current surgical instrument labeling techniques may increase the risk of unintentionally retained foreign objects: a hypothesis

Background

Marking of surgical instruments is essential to ensure their proper identification after sterile processing. The National Quality Forum defines unintentionally retained foreign objects in a surgical patient as a serious reportable event also called "never event."

Presentation of the hypothesis

We hypothesize that established practices of surgical instrument identification using unkempt tape labels and plastic tags may expose patients to "never events" from retained disintegrating labels.

Testing of the hypothesis

We demonstrate the near miss of a "never event" during a surgical case in which the breakage of an instrument label remained initially unwitnessed. A fragment of the plastic label was accidentally found in the wound upon closing. Further clinical testing of the occurrence of this "never event" appears not feasible. As the name implies a patient should never be exposed to the risk of fragmenting labels.

Implication of the hypothesis

Current practice does not mandate verifying intact instrument markers as part of the instrument count. The clinical confirmation of our hypothesis mandates a change in perioperative practice: Mechanical labels need to undergo routine inspection and maintenance. The perioperative count must not only verify the quantity of surgical instruments but also the intactness of labels to ensure that no part of an instrument is left behind. Proactive maintenance of taped and dipped labels should be performed routinely. The implementation of newer labeling technologies - such as laser engraved codes - appears to eliminate risks seen in traditional mechanical labels.This article reviews current instrument marking technologies, highlights shortcomings and recommends safe instrument handling and marking practices implementing newer available technologies.

     

Surgical treatment of obstruction of the nasolacrimal ducts in patients with anatomical endonasal variants

The presence of anatomical endonasal variants (concha bullosa, nasal septal deviation, or hypertrophic turbinates) may cause more complications in patients with epiphora who have external dacryocystorhinostomy (DCR). The purpose of this study was to assess the results of surgical placement of a stent in 28 patients. They were randomised into two groups and had either DCR or placement of a Song's polyurethane stent. They were followed up for 18 months. Twenty-six patients had a good result. The success rate was 13/14 for those who had DCR and 13/14 for those who had a stent. Operating time was significantly less for placing a stent (mean (SD) 15 (2) minutes) compared with 40 (3) minutes for DCR (p<0.01). Placement of a polyurethane stent is an effective and short procedure for nasolacrimal obstruction, which is suitable for patients with unusual intranasal conditions.     

Somatic underpinnings of perceived empathy: The importance of psychotherapy training

Abstract

This study investigated the somatic underpinning of empathy using an interpersonal physiology approach. Thirty-nine dyads were formed by a “pseudo-patient” and a “listener” (a therapist, a psychologist, or a non-therapist). Dyadic physiological concordance in electrodermal responses and listeners' empathy were evaluated during simulations of clinical sessions. A significant positive correlation between empathy as perceived by pseudo-patients and physiological concordance was found, providing empirical evidence of a somatic underpinning of empathy. Moreover, therapists showed higher levels of physiological concordance and empathy, confirming the importance of psychotherapy training in managing clinical interactions.     

Short- and long-term motor outcome of STN-DBS in Parkinson’s Disease: focus on sex differences

Neurological Sciences - Subthalamic nucleus deep brain stimulation (STN-DBS) is an established treatment for patients with Parkinson’s disease (PD) with motor complications; the contribution...     

Efficacy of Crocus sativus L. on reduction of cadmium‐induced toxicity on spermatogenesis in adult rats

Cadmium is a toxic heavy metal element, which probably cause infertility by impairment in spermatogenesis. The present work aimed (i) to study the toxic effect of cadmium on spermatogenesis in rat, as well as (ii) the protective effect of Crocus sativus L. on cadmium‐intoxicated rats. Cadmium chloride was administered intraperitoneally during 16 days at intervals of 48 h between subsequent treatments. Crocus sativus L. was pre‐treated in both of control and cadmium‐injected rats. Animals were sacrificed on day 17 after the first treatment. The left cauda epididymis was removed and immediately immersed into Hank's balanced salt solution for the evaluation of sperm count and viability, and left testis was fixed in 10% formalin for histological evaluation. Following contamination with cadmium, a decrease was observed in the number and viability of cauda epididymis sperm, which were increased by Crocus sativus L. pre‐treatment (P < 0.05). In addition, cadmium decreased both cell proliferation and Johnsen Scores in the seminiferous tubules, which were reversed by Crocus sativus pre‐treatment (P < 0.05). Furthermore, cadmium‐induced decrease in the amount of free serum testosterone as well as an increase in lipid peroxidation activity in the testicular tissue was reversed by Crocus sativus L. (P < 0.05). These findings may support the concept that Crocus sativus L. can improve the cadmium toxicity on spermatogenesis.