Electrochemotherapy as a Trigger to Overcome Primary Resistance to Anti-PD-1 Treatment: A Case Report of Melanoma of the Scalp.

BACKGROUND: Immunotherapy with immune checkpoint inhibitors is one of the main therapies for advanced melanoma. Nevertheless, albeit remarkable, immunotherapy results are still unsatisfactory as more than half of patients progress, and resistance to treatment still has a dramatic impact on clinical outcomes. Local treatments such as radiotherapy or electrochemotherapy (ECT), in addition to local control with palliative intent, have been shown to release tumoral neoantigens that can stimulate a robust systemic antitumor immune response. CASE PRESENTATION: We report the case of a patient with multiple nodular melanoma lesions of the scalp initially treated with local ECT. Soon after the procedure, multiple new lesions appeared close to the treated ones, therefore the patient started a systemic treatment with the anti-PD-1 nivolumab. The lesions of the scalp did not respond to immunotherapy, presenting a loco-regional spreading. To control the bleeding and painful lesions, we performed a second ECT, while continuing systemic immunotherapy. The treated lesions responded to the second procedure, while the other lesions continued progressing in number and dimension. Unexpectedly, after 2 months from the second ECT, the patient presented a progressive shrinkage of both treated and untreated lesions until complete remission. Concomitantly, he developed immune-related adverse events including grade 4 thyroid toxicity, grade 2 vitiligo-like depigmentation and grade 2 pemphigoid. At present, after 18 months from the first ECT and 14 months from the starting of anti-PD-1 immunotherapy, the patient is in good clinical condition and complete remission of disease still persists. CONCLUSION: This case highlights the potential role of ECT in increasing tumor immunogenicity and consequently in inducing a powerful immune response overcoming primary resistance to checkpoint inhibitor immunotherapy.

Minimally-invasive treatments for benign thyroid nodules: a Delphi-based consensus statement from the Italian minimally-invasive treatments of the thyroid (MITT) group.

Benign thyroid nodules are a common clinical occurrence and usually do not require treatment unless symptomatic. During the last years, ultrasound-guided minimally invasive treatments (MIT) gained an increasing role in the management of nodules causing local symptoms. In February 2018, the Italian MIT Thyroid Group was founded to create a permanent cooperation between Italian and international physicians dedicated to clinical research and assistance on MIT for thyroid nodules. The group drafted this list of statements based on literature review and consensus opinion of interdisciplinary experts to facilitate the diffusion and the appropriate use of MIT of thyroid nodules in clinical practice. (#1) Predominantly cystic/cystic symptomatic nodules should first undergo US-guided aspiration; ethanol injection should be performed if relapsing (level of evidence [LoE]: ethanol is superior to simple aspiration = 2); (#2) In symptomatic cystic nodules, thermal ablation is an option when symptoms persist after ethanol ablation (LoE = 4); (#3) Double cytological benignity confirmation is needed before thermal ablation (LoE = 2); (#4) Single cytological sample is adequate in ultrasound low risk (EU-TIRADS ≤3) and in autonomously functioning nodules (LoE = 2); (#5) Thermal ablation may be proposed as first-line treatment for solid, symptomatic, nonfunctioning, benign nodules (LoE = 2); (#6) Thermal ablation may be used for dominant lesions in nonfunctioning multinodular goiter in patients refusing/not eligible for surgery (LoE = 5); (#7) Clinical and ultrasound follow-up is appropriate after thermal ablation (LoE = 2); (#8) Nodule re-treatment can be considered when symptoms relapse or partially resolve (LoE = 2); (#9) In case of nodule regrowth, a new cytological assessment is suggested before second ablation (LoE = 5); (#10) Thermal ablation is an option for autonomously functioning nodules in patients refusing/not eligible for radioiodine or surgery (LoE = 2); (#11) Small autonomously functioning nodules can be treated with thermal ablation when thyroid tissue sparing is a priority and ≥80% nodule volume ablation is expected (LoE = 3).

Zenker Diverticulum: A Potential Pitfall in Thyroid Ultrasound Evaluation: A Case Report and Systematic Review of Literature.

BACKGROUND AND OBJECTIVE: Zenker Diverticulum (ZD) can sometimes be misinterpreted as a thyroid nodule both at clinical evaluation and at Ultrasound (US). CASE PRESENTATION: We reported the case of a 46-years-old woman complaining of a lump in the anterior left aspect of the neck. Following clinical examination and US evaluation, a thyroid nodule was initially diagnosed and the patient was referred to our institution to be submitted to a fine-needle aspiration cytology. Management and Outcome: A ZD was suspected by US and diagnosed by gastrografin esophagram, thus an endoscopic diverticulotomy was requested. CONCLUSION: A correct US evaluation can be crucial for the appropriate management of a neck mass.

A comparison of laser with radiofrequency ablation for the treatment of benign thyroid nodules: a propensity score matching analysis.

PURPOSE: To compare technique efficacy and safety of laser ablation (LA) and radiofrequency ablation (RFA) in treatment of benign thyroid nodules. MATERIALS AND METHODS: Institutional review board approval was obtained, and patients' consent was waived. 601 nodules were treated from May 2009 to December 2014 at eight centres, 449 (309 females, age 57 ± 14 years) with LA and 152 (107 females, age 57 ± 14 years) with RFA. A matched cohort composed of 138 patients from each group was selected after adjustment with propensity score matching. Factors influencing volume reduction at 6 and 12 months and complications were evaluated. RESULTS: No significant differences were observed in the baseline characteristics between groups after propensity score matching adjustment. Mean nodule reduction at 6 and 12 months was -67 ± 19% vs. -57 ± 21% (p < 0.001) - 70 ± 19% vs. -62 ± 22% (p = 0.001) in LA group and in RFA group, respectively. Nodules with volume >30 mL had significantly higher percentage volume reduction at 6 and 12 months (-69 ± 19 vs. -50 ± 21, p = 0.001) and (-73 ± 18 vs. -54 ± 23 8, p = 0.001) in the LA group than in the RFA group, respectively. In both groups, operator's skills affected the results. Major complications occurred in 4 cases in each group (p = 0.116) Conclusions: LA and RFA showed nearly similar outcome but LA was slightly more effective than RFA in large nodules. Operator's skills could be crucial in determining the extent of nodule volume reduction regardless of the used technique.

Thyroglobulin Determination in Fine Needle Aspiration Biopsy Washout of Suspicious Lymph Nodes in Thyroid Carcinoma Follow up.

BACKGROUND: Differentiated thyroid carcinomas (DTCs) account for about 1% of all human malignancies. Cervical lymph nodes metastases and recurrences in the thyroid bed frequently occur. Furthermore, about 10-15% of patients develop distant metastases. Therefore, patients must undergo life-long follow-up. OBJECTIVE: The aim of this study was to evaluate the usefulness of Thyroglobulin measurement in FNAB washout (FNAB-Tg) in the detection of local metastasis in patients affected by or evaluated for thyroid cancer. MATERIALS AND METHODS: In a 3-year period, a total of 83 consecutive patients coming to our attention at the Ear-Nose-Throat (ENT) Outpatients Service of the National Cancer Research Center &quot;Istituto Tumori Giovanni Paolo II&quot; of Bari, Italy, because of the finding of one or more cervical lymph node(s), were enrolled in the study. After collection of the cytological specimen, the needle used for performing FNAB was then washed in 1 ml of normal saline. 89 FNAB washouts were collected from the same number of lymph nodes and subsequently investigated for Thyroglobulin levels using a sequential chemiluminescent-immunometric assay. RESULTS: Comparing the cytological or, when performed, histological diagnoses with the results of FNAB-Tg, we found that in 24 cases of lymph node metastases from PTC (19 lymph nodes from patients at the first diagnoses and 5 lymph nodes from PTC patients in follow up) the mean level of Thyroglobulin was 1840.11 ng/ml; range: <0,2 to 11440 ng/ml. In the group of PTC patients (27 lymph nodes) with lymph nodes negative for metastatic involvement at cytology (i.e. no lymph node recurrence at follow-up), as well as in the cases of subjects without PTC and submitted to FNAB because of the appearance of lymph node(s) classified as reactive at cytology (37 lymph nodes), FNAB-Tg was lower than or equal to 0.2 ng/ml. As expected, the Thyroglobulin level was not detectable (< 0.2 ng/ml) also in a lymph node FNAB from a case of anaplastic thyroid carcinoma. CONCLUSION: In our study, FNAB-Tg was not detectable in all node negative patients showing, when considering together all the lymph node metastases, a 96% sensitivity and 100% specificity.

Ultrasound-guided percutaneous laser ablation in treating symptomatic solid benign thyroid nodules: Our experience in 45 patients.

BACKGROUND: Laser ablation may be useful in debulking of benign thyroid nodules. METHODS: In order to retrospectively evaluate the effectiveness and safety of laser ablation, 45 patients with benign solid thyroid nodules, with a fluid component ≤20%, were included in our series between October 2009 and January 2011. All reported pressure and/or cosmetic complaints. Nd:YAG laser at 1064 nm was used, with a fix-power (3W), changing the application time. All patients were evaluated at baseline, 6 months, and 12 months and any complications were recorded. RESULTS: Mean nodule volume reduction decreased from 24.2 mL ± 19.4 to 4.5 ± 5.2 at 12 months (p < .001). Mean nodule volume reduction was 84% ± 13. Cosmetic signs were completely resolved in 87%, reduced in 9%, unchanged in 2%, and pressure symptoms were resolved in 88%. One patient experienced transient dysphonia. CONCLUSION: Ultrasound-guided laser ablation is an effective tool for treatment of symptomatic benign thyroid nodules in patients not eligible for surgery.

Microvessel density, mast cell density and thymidine phosphorylase expression in oral squamous carcinoma.

To elucidate the role of angiogenesis in the carcinogenesis and progression of oral cancer, we investigated microvessel density (mVd), mast cell density (mCd) and thymidine phosphorylase (TP) expression in a series of 50 patients with T1-3 N0-1 M0 oral squamous carcinoma (OSC) and 21 patients with non-dysplastic oral leukoplakia (NDOLP). Paraffin-embedded pathological tissue was utilised for the immunohistochemical analysis of mVd and TP expression. Toluidine blue histochemical method was employed for mast cell identification. OSC and NDOLP were not significantly different with respect to mVd (mVd mean value +/- SD: 30+/-17 and 27+/-18, respectively) and mCd characteristics (mCd mean value +/- SD: 8+/-6 and 7+/-6 units, respectively). Conversely, tumour epithelia showed some degree of TP immunostaining in 100% of cases compared with 76% in NDOLP samples (p< or =0.001 by Fisher's test). A good correlation was found between mVd and mCd in both NDOLP (c.c. 0.632; p=0.002) and OSC (c.c. 0.496; p=0.000) tissue, whereas no association between TP expression and mVd or between mCd and TP status was evident. At a median follow-up of 18 months, patients with high mVd tumours showed a greater probability of survival than those with low mVd (75 and 40%, respectively; p=0.04 log-rank test). Our results suggest that the development of oral cancer epithelia is associated with a significant increase in TP expression. Conversely, the clinical outcome of OSC seems inversely related specifically to mVd.

Fluorescence in situ hybridization analysis of HER-2/neu in brushings of normal oral mucosa.

Oncogene alterations have been clearly demonstrated to be related to the carcinogenesis and progression of oral squamous cell carcinoma (OSCC). However, the analysis of these alterations for screening and early diagnostic purposes generally requires invasive techniques for surgical removal of pathological epithelium. The aim of the present study was to assess the feasibility of fluorescence in situ hybridization (FISH) analysis of HER-2/neu amplification in oral mucosa brushings and to compare the HER-2/neu status with the history and smoking and drinking habits of healthy subjects. Cells obtained by centrifugation of oral brushings from 21 subjects (overall no. of cells: 5125) were suspended in physiological saline and fixed onto two slides for cytological evaluation and FISH analysis (dual-target, dual-color fluorescence assay) of the HER-2/neu gene and CEP17 centromere. A mean of 89.8% of the cells showed two HER-2/neu signals and a mean of 94% had two CEP17 signals at fluorescent microscopy. Finally, a mean of 96% of cells with HER-2/neu / CEP17 had a ratio equal to 1. No association between smoking and drinking habits, age and the HER-2/neu and CEP17 characteristics evaluated by FISH was found.