Nicolás Droppelmann

High-risk cutaneous squamous cell carcinoma and the emerging role of sentinel lymph node biopsy: A literature review

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer in the world. A minority of patients will be given a diagnosis of a high-risk cSCC (HRcSCC) and a proportion of these will have a poor outcome. HRcSCC is characterized by an increase in aggressiveness manifested as locoregional recurrence, and occasionally death. The utility of sentinel lymph node biopsy in this group of patients is unclear without high-level evidence or clear-cut recommendations. If clinicians accept a cutoff threshold of 10% risk of harboring occult nodal metastasis, then a selected group of patients with HRcSCC may benefit from sentinel lymph node biopsy. We performed a review of the currently available evidence, in the form of systematic reviews, meta-analysis, trials, and case series and analyzed the features that define a HRcSCC and the feasibility of performing sentinel lymph node biopsy in this group of patients.

Neck Sonography and Suppressed Thyroglobulin Have High Sensitivity for Identifying Recurrent/Persistent Disease in Patients With Low‐risk Thyroid Cancer Treated With Total Thyroidectomy and Radioactive Iodine Ablation, Making Stimulated Thyroglobulin Unnecessary

Follow‐up of patients with low‐risk differentiated thyroid cancer treated with total thyroidectomy and radioiodine requires neck sonography and thyroglobulin (Tg). The need to stimulate Tg is controversial. The goal of this study was to compare the diagnostic performances of sonography plus suppressed or stimulated Tg in low‐risk thyroid cancer.

Radioactive Iodine Administration Is Associated with Persistent Related Symptoms in Patients with Differentiated Thyroid Cancer

Context. Radioiodine (RAI) administration has adverse effects in patients treated for thyroid cancer (DTC), but there is scarce information regarding their intensity and duration. Objective. To evaluate frequency and intensity of early and late RAI-related symptoms in patients with DTC. Design. Observational prospective study. Patients. DTC patients who underwent thyroidectomy, with or without RAI. Measurements. Patients answered 2 surveys: (1) from 0 to 6 months and (2) between 6 and 18 months after initial treatment. Results. 110 patients answered the first survey and 61 both. Nearly 80 percent received RAI. Among early symptoms, periorbital edema, excessive tearing, salivary gland disturbances, dry mouth, taste disorders, and nausea were more frequent and intense among RAI patients. Regarding late symptoms, periorbital edema, salivary gland pain and swelling, and dry mouth were more frequent and intense in RAI patients. Frequency and intensity of adverse effects were not different between low and high RAI doses (50 versus ≥100 mCi). Conclusion. RAI-related symptoms are frequent and usually persist after 6 months of administration, even when low doses are given. This finding must be considered when deciding RAI administration, especially in low risk patients, among whom RAI benefit is controversial.

Differential expression profile of CXCR3 splicing variants is associated with thyroid neoplasia. Potential role in papillary thyroid carcinoma oncogenesis

Papillary thyroid cancer (PTC) is the most prevalent endocrine neoplasia. The increased incidence of PTC in patients with thyroiditis and the frequent immune infiltrate found in PTC suggest that inflammation might be a risk factor for PTC development. The CXCR3-ligand system is involved in thyroid inflammation and CXCR3 has been found upregulated in many tumors, suggesting its pro-tumorigenic role under the inflammatory microenvironment. CXCR3 ligands (CXCL4, CXCL9, CXCL10 and CXCL11) trigger antagonistic responses partly due to the presence of two splice variants, CXCR3A and CXCR3B. Whereas CXCR3A promotes cell proliferation, CXCR3B induces apoptosis. However, the relation between CXCR3 variant expression with chronic inflammation and PTC development remains unknown. Here, we characterized the expression pattern of CXCR3 variants and their ligands in benign tumors and PTC. We found that CXCR3A and CXCL10 mRNA levels were increased in non-metastatic PTC when compared to non-neoplastic tissue. This increment was also observed in a PTC epithelial cell line (TPC-1). Although elevated protein levels of both isoforms were detected in benign and malignant tumors, the CXCR3A expression remained greater than CXCR3B and promoted proliferation in Nthy-ori-3-1 cells. In non-metastatic PTC, inflammation was conditioning for the CXCR3 ligands increased availability. Consistently, CXCL10 was strongly induced by interferon gamma in normal and tumor thyrocytes. Our results suggest that persistent inflammation upregulates CXCL10 expression favoring tumor development via enhanced CXCR3A-CXCL10 signaling. These findings may help to further understand the contribution of inflammation as a risk factor in PTC development and set the basis for potential therapeutic studies.

Riesgo de recurrencia en cáncer diferenciado de tiroides: escala MINSAL

BACKGROUND Differentiated thyroid cancer (DTC) is generally associated with a favorable prognosis. Its treatment requires surgery, selective use of radioiodine and levothyroxine, and its intensity must be adjusted to the initial risks of mortality and recurrence. AIM To validate the risk of recurrence classification developed by the Chilean Ministry of Health in 2013 (MINSAL 2013), and compare it with the American Thyroid Association (ATA) 2009 and 2015 classifications. MATERIAL AND METHODS Retrospective study of 362 patients with DTC aged 44.3 ± 13.4 years (84% women), treated with total thyroidectomy, selective radioiodine ablation and levothyroxine and followed for a median of 4.2 years (range 2.0-7.8). Risk of recurrence was estimated with MINSAL 2013, ATA 2009 and ATA 2015 classifications, and risk of mortality with 7th and 8th American Joint Committee on Cancer (AJCC)/TNM systems. Clinical data obtained during follow-up were used to detect structural and biochemical persistence/recurrence. RESULTS A mean dose of 104 ± 48 mCi radioiodine was received by 91% of patients. MINSAL 2013 classified 148 (41%), 144 (40%), 67 (19%) and 3 (1%) patients as very low, low, intermediate and high risk of recurrence, respectively. Forty-five (12.4%) patients had persistence or recurrence during follow-up: 33 structural and 12 biochemical. Rates of persistence/recurrence on each category of MINSAL 2013 were 4.1%, 7.6%, 37.3% and 100%, respectively (p < 0.01). Areas under Receiver Operating Characteristic curves for persistence or recurrence of MINSAL 2013, ATA 2009 and ATA 2015 were 0.77 vs 0.73 vs 0.72, respectively. CONCLUSIONS MINSAL 2013 classifies appropriately DTC patients and estimates correctly their risk of persistence or recurrence.

Papillary thyroid microcarcinoma: characteristics at presentation, and evaluation of clinical and histological features associated with a worse prognosis in a Latin American cohort

Objective We aimed to describe the presentation of papillary microcarcinoma (PTMC) and identify the clinical and histological features associated with persistence/recurrence in a Latin American cohort. Subjects and methods Retrospective study of PTMC patients who underwent total thyroidectomy, with or without radioactive iodine (RAI), and who were followed for at least 2 years. Risk of recurrence was estimated with ATA 2009 and 2015 classifications, and risk of mortality with 7th and 8th AJCC/TNM systems. Clinical data obtained during follow-up were used to detect structural and biochemical persistence/recurrence. Results We included 209 patients, predominantly female (90%), 44.5 ± 12.6 years old, 183 (88%) received RAI (90.4 ± 44.2 mCi), followed-up for a median of 4.4 years (range 2.0-7.8). The 7th and 8th AJCC/TNM system classified 89% and 95.2% of the patients as stage I, respectively. ATA 2009 and ATA 2015 classified 70.8% and 78.5% of the patients as low risk, respectively. Fifteen (7%) patients had persistence/recurrence during follow-up. In multivariate analysis, only lymph node metastasis was associated with persistence/recurrence (coefficient beta 4.0, p = 0.016; 95% CI 1.3-12.9). There were no PTMC related deaths. Conclusions Our series found no mortality and low rate of persistence/recurrence associated with PTMC. Lymph node metastasis was the only feature associated with recurrence in multivariate analysis. The updated ATA 2015 and 8th AJCC/TNM systems classified more PTMCs than previous classifications as low risk of recurrence and mortality, respectively.

Entendiendo las terapias actuales en melanoma metastásico

Cutaneous melanoma is a highly aggressive tumor developing from melanocytes, its incidence is increasing, and prognosis in advanced stages is daunting. New therapies have been approved during the recent years with unprecedented results, including inhibitors of MAPK/ERK pathway and immune checkpoint blockade (anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) as ipilimumab, anti-programmed cell death protein 1 (PD-L1) as pembrolizumab and anti-programmed cell death protein 1 ligand (PD-L1), among many others). The aim of this paper is to review currently available metastatic melanoma therapies focusing mainly on new therapies that have demonstrated effectiveness, after several decades of little progress in the treatment of this disease.