Regional Metastases Research Articles

Tumor glycolytic heterogeneity improves detection of regional nodal metastasis in patients with lung adenocarcinoma.

The diagnostic performance of 18F-FDG PET for detecting regional lymph node metastasis in resectable lung cancer is variable, and its sensitivity for adenocarcinoma is even lower. We aimed to evaluate the value of 18F-FDG PET-derived features in predicting pathological lymph node metastasis in patients with lung adenocarcinoma. We retrospectively analyzed pretreatment 18F-FDG PET-derived features of 126 lung adenocarcinoma patients who underwent curative surgery. A logistic regression model was used to analyze the association between study variables and pathological regional lymph node status obtained from the curative surgery. Furthermore, Cox regression analysis was used to test the effect of the study variables on survival outcomes, including disease-free survival (DFS) and overall survival (OS). The primary tumor entropy (OR = 1.7, p = 0.014) and visual interpretation of regional nodes via 18F-FDG PET (OR = 2.5, p = 0.026) independently predicted pathological regional lymph node metastasis. The areas under the receiver-operating-characteristic curves were 0.631, 0.671, and 0.711 for visual interpretation, primary tumor entropy, and their combination, respectively. Based on visual interpretation, a primary tumor entropy ≥ 3.0 improved the positive predictive value of positive visual interpretation from 51.2% to 63.0%, whereas an entropy < 3.0 improved the negative predictive value of negative visual interpretation from 75.3% to 82.6%. In cases with positive visual interpretation and low entropy, or negative visual interpretation and high entropy, the nodal metastasis rates were approximately 30%. In the survival analyses, the primary tumor entropy was also independently associated with DFS (HR = 2.7, p = 0.001) and OS (HR = 4.8, p = 0.001). Our preliminary results show that the primary tumor entropy may improve 18F-FDG PET visual interpretation in predicting pathological nodal metastasis in lung adenocarcinoma, and may also show a survival prognostic value. This versatile biomarker may facilitate tailored therapeutic strategies for patients with resectable lung adenocarcinoma.

Ovarian Malignancies Frequency in the Female Population from the Bryansk Region Living in Conditions of Radioactive, Chemical and Combine Contamination (2000-2020).

Background: Radioactive contamination and chemical pollution of the environment can affect the processes of carcinogenesis, including the formation of malignant neoplasms of the ovaries in women. We used the data of official state statistics for 2000–2020 to test the hypothesis about the effect of radioactive contamination (following the Chernobyl disaster) and chemical pollutants on the incidence of ovarian malignancies in the female population of the Bryansk region. Methods: A variety of statistical approaches were used to estimate the incidence of ovarian malignancies, including the Shapiro–Wilk test, Mann–Whitney U test, Spearman’s rank correlation test and linear regression. Results: We did not establish statistically significant differences in the frequency of primary morbidity of women with malignant neoplasms of the ovaries, regardless of the environmental conditions of living. Furthermore, no significant correlations were found between the frequency of primary morbidity of ovarian malignancies, both with the level of contamination by Cesium-137 and Strontium-90, and air pollution with volatile organic compounds, carbon monoxide, sulfur dioxide and nitrogen oxides. A statistically significant increase in the long-term trend in the frequency of ovarian malignant neoplasms was revealed in the areas of chemical pollution (p = 0.02), however, in other territories, no statistically significant regularities were established. The forecast of the frequency of newly diagnosed malignant neoplasms of the ovaries on average in the Bryansk region shows an increase of 12.4% in 2020 in comparison with the real data for 2020, while the largest increase in predicted values is recorded in the territories of radioactive contamination (by 79.6%), and the least in the combined territories (by 6.9%). Conclusions: The results obtained indicate the need for further work to understand the trends in the presence/absence of independent and combined effects of pollutants and the growth of oncogynecological pathology from the perspective of assessing the distant and regional metastasis, histological and immunohistochemical profile of a specific malignant ovarian neoplasm with levels of environmental contamination.

The Impact of Race and Sex on Metastatic Bladder Cancer Survival

ObjectiveTo characterize the epidemiological profile of metastatic bladder cancer (BC) and assess mortality rate with respect to race and gender across the three most common histologies of bladder cancer—Transitional Cell Carcinoma, Adenocarcinoma, and SCC (Squamous Cell Carcinoma). Materials and MethodsThe Surveillance, Epidemiology, and End Results Program database (2000-2017) was queried for all metastatic bladder cancer patients at presentation. Our primary exposure consists of four race/gender combinations. One-way ANOVA and Chi-square tests compared categorical and continuous variables across the exposure variable, respectively. Univariable and multivariable Cox proportional hazards regression analyses were used to examine the association between race/gender combinations and the overall and cancer specific survival adjusting for the other variables. ResultsA total of 312,846 bladder cancer patients, 6337 with distant metastases and 11,446 with regional metastases were evaluated. Black female cancer specific survival in metastatic disease was disproportionally lower compared to all race/gender for Transitional Cell Carcinoma 4.3% (95% CI: 1.6-8.9), SCC 2.6% (95% CI: 0.2-11.8), and Adenocarcinoma 6.4% (0.4%-25%). In regional metastastatic disease, worse cancer specific mortality was associated with identifying as a Black Female (aHR 1.17, P = .023), SCC (aHR 1.8, P <.001), increasing age (aHR 1.3, P <.001), and poorly differentiated grade (aHR 2.01, P <.001). ConclusionBlack females experience excess mortality in overall and cancer oncologic outcomes in metastatic BC. Our findings contribute to the body of research warranting examination of the impact of social determinants of health and provider decisions on BC survivorship and contribute to physician decision making in the treatment and surveillance of bladder cancer.

Anatomical and topographical variations in the distribution of brain metastases based on primary cancer origin and molecular subtypes: a systematic review.

BackgroundWhile it has been suspected that different primary cancers have varying predilections for metastasis in certain brain regions, recent advances in neuroimaging and spatial modeling analytics have facilitated further exploration into this field.MethodsA systematic electronic database search for studies analyzing the distribution of brain metastases (BMs) from any primary systematic cancer published between January 1990 and July 2020 was conducted using PRISMA guidelines.ResultsTwo authors independently reviewed 1957 abstracts, 46 of which underwent full-text analysis. A third author arbitrated both lists; 13 studies met inclusion/exclusion criteria. All were retrospective single- or multi-institution database reviews analyzing over 8227 BMs from 2599 patients with breast (8 studies), lung (7 studies), melanoma (5 studies), gastrointestinal (4 studies), renal (3 studies), and prostate (1 study) cancers. Breast, lung, and colorectal cancers tended to metastasize to more posterior/caudal topographic and vascular neuroanatomical regions, particularly the cerebellum, with notable differences based on subtype and receptor expression. HER-2-positive breast cancers were less likely to arise in the frontal lobes or subcortical region, while ER-positive and PR-positive breast metastases were less likely to arise in the occipital lobe or cerebellum. BM from lung adenocarcinoma tended to arise in the frontal lobes and squamous cell carcinoma in the cerebellum. Melanoma metastasized more to the frontal and temporal lobes.ConclusionThe observed topographical distribution of BM likely develops based on primary cancer type, molecular subtype, and genetic profile. Further studies analyzing this association and relationships to vascular distribution are merited to potentially improve patient treatment and outcomes.

Report of A Case of Papillary Thyroid Carcinoma Following Intracranial Germinoma

Introduction The occurrence of second primary thyroid malignancy should be noticed in survivors of brain germinoma treated by irradiation. Case Report A patient with a history of intracranial germinoma who underwent chemoradiotherapy was referred to our endocrine clinic due to impotency and infertility. The patient received replacement therapy due to hypopituitarism. He returned to us 11 years after brain radiation with enlargement of the thyroid gland. Thyroid ultrasonography showed enlargement with a dominant 62*37 mm solid hypoechoic nodule in the right thyroid lobe. Several lymph nodes at both sides of the neck were seen. Total thyroidectomy revealed PTC with regional metastasis. Conclusion Endocrine disruption must be considered in adult cancer survivors and the importance of long-term follow-up should be emphasized in these patients.

Prognosis of patients operated on for renal cell carcinoma and tumor venous thrombosis: experience of the Urology Clinics, N.N. Blokhin National Medical Research Center of Oncology

Objective: to identify independent risk factors affecting survival of patients with renal cell carcinoma (RCC) and tumor venous thrombosis who have undergone nephrectomy and thrombectomy.Materials and methods. This study included 768 patients with RCC complicated by tumor venous thrombosis who have undergone nephrectomy and thrombectomy. Median age was 58 years (range: 16-82 years); the male to female ratio was 2.3:1. The symptoms of tumor venous thrombosis were identified in 232 patients (30.2 %); laboratory abnormalities at baseline were observed in 456 patients (59.3 %). Grade I and II tumor thrombosis was diagnosed in 456 (59.3 %) and 201 (26.2 %) patients, respectively; grade III and IV thrombosis was found in 171 (22.3 %) and 177 (23.0 %) patients, respectively. One hundred and twenty-nine participants (16.8 %) had infrarenal inferior vena cava thrombosis. Regional metastases were detected in 188 individuals (24.4 %), distant metastases were registered in 274 patients (35.7 %). All patients have undergone surgery: either radical (n = 555; 72.3 %) or cytoreductive (n = 213; 27.7 %). All primary tumors were histologically classified as RCC (G3-4 in 337 cases; 43.9 %). A total of 719 patients (93.6 %) survived the perioperative period; 183 patients with metastasis (23.8 %) received systemic antitumor therapy.Results. The median follow-up was 24 months (range: 1-200 months). The 24-month overall and cancer-specific survival of all patients were 96.9 and 99.7 %, respectively; recurrence-free survival of patients after radical surgery reached 92.9 %. Progression-free survival among those patients who underwent cytoreductive surgery and received first-line therapy/follow-up was 41.7 %. Negative predictive factors of overall survival included hepatomegaly (p = 0.024), ascites (p = 0.033), level IV tumor thrombosis (p &lt;0.0001), infrarenal inferior vena cava thrombosis (p = 0.002), regional metastases (p &lt;0.0001), and cytoreductive surgery (p = 0.012). Depending on the number of risk factors, we have identified 3 prognostic groups: favorable (0 factors), intermediate (1-2 factors), and poor (3-6 factors). Median overall survival differed significantly between the groups and was 128.6 ± 11.8; 40.9 ± 6.7 and 12.3 ± 2.2 months, respectively (p &lt;0.0001 for all).Conclusion. Stratification of patients operated on for RCC and venous tumor thrombosis with their allocation to prognostic groups will ensure the choice of an optimal management strategy.

Quantitative nuclear phenotype signatures predict nodal disease in oral squamous cell carcinoma.

BackgroundEarly-stage oral squamous cell carcinoma (OSCC) patients have a one-in-four risk of regional metastasis (LN+), which is also the most significant prognostic factor for survival. As there are no validated biomarkers for predicting LN+ in early-stage OSCC, elective neck dissection often leads to over-treatment and under-treatment. We present a machine-learning-based model using the quantitative nuclear phenotype of cancer cells from the primary tumor to predict the risk of nodal disease.Methods and findingsTumor specimens were obtained from 35 patients diagnosed with primary OSCC and received surgery with curative intent. Of the 35 patients, 29 had well (G1) or moderately (G2) differentiated tumors, and six had poorly differentiated tumors. From each, two consecutive sections were stained for hematoxylin & eosin and Feulgen-thionin staining. The slides were scanned, and images were processed to curate nuclear morphometric features for each nucleus, measuring nuclear morphology, DNA amount, and chromatin texture/organization. The nuclei (n = 384,041) from 15 G1 and 14 G2 tumors were randomly split into 80% training and 20% test set to build the predictive model by using Random Forest (RF) analysis which give each tumor cell a score, NRS. The area under ROC curve (AUC) was 99.6% and 90.7% for the training and test sets, respectively. At the cutoff score of 0.5 as the median NRS of each region of interest (n = 481), the AUC was 95.1%. We then developed a patient-level model based on the percentage of cells with an NRS ≥ 0.5. The prediction performance showed AUC of 97.7% among the 80% (n = 23 patient) training set and with the cutoff of 61% positive cells achieved 100% sensitivity and 91.7% specificity. When applying the 61% cutoff to the 20% test set patients, the model achieved 100% accuracy.ConclusionsOur findings may have a clinical impact with an easy, accurate, and objective biomarker from routine pathology tissue, providing an unprecedented opportunity to improve neck management decisions in early-stage OSCC patients.

Prognostic factors and long-term survival in oral squamous cell carcinoma

Objective: this study aimed to evaluate long-term survival and prognostic factors in patients with oral squamous cell carcinoma (OSCC) in an economically poor region of Brazil.Methods: the data were obtained from analysis of medical and mortality records of 210 patients with OSCC treated at an oncology hospital providing services to the Brazilian Unified National Health System in a State of northeastern Brazil between January 2006 and December 2008. Sociodemographic and clinical information, treatment performed, recurrence and evolution were collected. Survival curves were estimated by the Kaplan-Meier method and the log rank and Cox regression tests were used to compare the curves.Results: the median survival in the study period was 47.4 months (95% CI = 38.2 - 56.7). The overall survival rates at 5 and 10 years were 29% and 19.8%, respectivelly. Individuals over 60 years of age (HR = 1.70; 95% CI = 1.06 - 2.73), presence of regional metastasis (HR = 2.51; 95% CI = 1.55 - 4.08), presence of recurrence (HR = 3.18; 95% CI = 1.88 - 5.39) and no surgical treatment (HR = 2.10; 95% CI = 1.31 - 3.35) had a worse prognosis.Conclusions: advanced age, presence of regional metastasis, tumor recurrence and non-surgical treatment predict poorer survival in patients diagnosed with OSCC.

Interstitial Brachytherapy for Locally Advanced Tongue Cancer: Analysis of the Long-Term Treatment Results for Survival and Complications

<h3>Purpose/Objective(s)</h3> The purpose of this study was to evaluate the long-term treatment results of interstitial brachytherapy (IBT) in patients with locally advanced tongue cancer. <h3>Materials/Methods</h3> between 1994 and 2015, 60 patients (18 females and 42 males) with locally advanced tongue cancer treated by IBT using Ir-192 sources and Au-198 seeds were analyzed. The median age was 63 years (range, 22–86 years). All histological type was squamous cell carcinoma. T3/T4a/T4b was noted in 51/9/0 patients, respectively. The median depth of invasion was 11 mm (3–27 mm). The growth type was infiltrative/exophytic/superficiality in 54/0/6 patients, respectively. In all cases, no lymph node metastasis was not found at diagnosis. IBT was performed using Ir-192 in 56 patients and Au-198 in 4 patients. Median irradiation doses of Ir-192 and Au-198 were 60 Gy (29–77 Gy) and 68 Gy (64–73 Gy), respectively. External beam radiation therapy (EBRT) was performed before IBT in 41 patients (68%). Median dose of EBRT was 30 Gy (30–50 Gy). Chemotherapy was combined with IBT in 42 patients. <h3>Results</h3> Median follow-up time for survivors was 103 months (36–230 months). CR rate was 98%. The 10-year overall/cause specific survival (OS, CSS) rate was 67/84%, respectively. According to T factors, the 10-year OS/CSS rates for T3 and T4a were 64/85% and 77/77%, respectively. There was no significant difference in OS and CSS between T3 and T4a. The10-year local/regional control rates were 78/72%, respectively. The 75% of the regional metastasis was occurred within 1 year, and more than 90% was within 2 years. The 10-year local control rates for T3 and T4a were 75% and 88%, respectively. The 10-year regional control rates for T3 and T4a were 71% and 77%, respectively. There was no significant difference in local/regional control between T3 and T4a. In the multivariate analysis, significant differences in OS were seen with elderly age, patients having double cancer and having late regional lymph node recurrence. According to CTCAE ver. 5.0, grade 2 soft tissue complications were observed in 33 (55%) patients and grade 2 mandibular complications in 2 (3%) patients. There were no grade 3 or more late complications. <h3>Conclusion</h3> Our 10-year treatment results of IBT for locally advanced tongue cancer showed favorable survival and low occurrence rate in patients with severe late complications.

The 3-Year Outcome of 3D High-Dose-Rate Brachytherapy in Combination With Regional Metastatic Lymph Nodes Intensity-Modulated Radiotherapy in Peripheral Locally Advanced Non-Small Cell Lung Cancer: A Phase I/II Clinical Trial

To determine the safety, late toxicities and locoregional control of three-dimensional(3D) high-dose-rate (HDR) brachytherapy in combination with regional metastatic lymph nodes intensity-modulated radiotherapy (IMRT) in patients with peripheral locally advanced non-small cell lung cancer (LA-NSCLC).Eligible patients with LA-NSCLC were recruited to this prospective, phase I/II clinical study. The primary lung tumors were treated with the CT-guided interstitial HDR brachytherapy, DT:30Gy/F. The IMRT was applied to the regional positive lymph nodes, DT: 60-70Gy/30-33F/ 6-7W. The concurrent chemotherapy regimens include used Etoposide and cisplatin, the sequential chemotherapy consisted of paclitaxel/pemetrexed + cisplatin/carboplatin. The safety analysis included operational complications and toxicity related to radiotherapy and chemotherapy. Clinical evaluation includes short-term efficacy, survival, and quality of life scores.A total of 83 patients were enrolled in this study. There were 56 males and 27 females, with a median age of 65 years (45-80 years). The median follow-up time was 55 months (32-114 months) up to November 2020. The operational complications included mild pneumothorax (16.8%) and minor hemorrhage around the needle (19.3%). The major toxicity was myelosuppression and gastrointestinal reaction during the concurrent chemoradiotherapy and sequential chemotherapy. The clinical symptoms alleviated after symptomatic supportive treatment. The radiotherapy was completed successfully without grade 4 or more serious acute toxicity. Grade 1 late radiation pneumonitis was found by in 5 patients (6.1%), and only showed imaging changes after radiotherapy. There were 61 patients achieved complete remission, 20 patients achieved partial remission, and 2 patients were in stable disease in the primary tumor, the total response rate was 97.6%. There were 55 patients achieved complete remission, 22 patients achieved partial remission, 5 patients were in stable disease and 1 patient with progressive disease in the positive lymph nodes, the total response rate was 92.8%. The 1-,2-,3-year overall survival rates were 90.6%, 70.6% and 62.4%. The 1-,2-,3-year local control rates were 90.0%,81.0% and 54.5%. The 1-,2-,3-year disease-free survival rates were 68.3%,42.2% and 23.9%. The 1-,2-,3-year metastasis-free survival rates were 73.3%, 50.9% and 39.5%. The patient who treated with 3D interstitial high dose rate brachytherapy has a higher life quality score than the baseline level.3D interstitial high dose rate brachytherapy combined with regional positive lymph node intensity-modulated radiotherapy is safe and feasible for the locally advanced peripheral non-small cell lung cancer, with low adverse reactions, increased the survival, and improved the life quality. But it still needs a phase III randomized controlled trial to investigate its clinical utility and promotion, compared to IMRT.

Klatskin Tumor in the Light of ICD-O-3: A Population-Based Clinical Outcome Study Involving 1,144 Patients from the Surveillance, Epidemiology, and End Result (SEER) Database (2001-2012).

IntroductionKlatskin tumors (KTs) occur at the confluence of the right and left extrahepatic ducts and are classified based on their anatomical and histological codes in the International Classification of Diseases for Oncology (ICD-O). The second edition of the ICD-O (ICD-O-2) allocated a distinctive histological code to KT, which also included intrahepatic cholangiocarcinoma (CC). This unclear coding may result in ambiguous reporting of the demographic and clinical features of KT. The current study aimed to investigate the demographic, clinical, and pathological factors affecting the prognosis and survival of KT in the light of the updated third edition of ICD-O, Ninth Revision (ICD-O-3).MethodsData of 1,144 patients with KT from the Surveillance, Epidemiology, and End Result (SEER) database (2001-2012) were extracted. Patients with KT were analyzed for age, sex, race, stage, treatment, and long-term survival. The data were analyzed using chi-square tests, t-tests, and univariate and multivariate analyses. The Kaplan-Meier analysis was used to compare long-term survival between KT and subgroups of all biliary CCs.ResultsOf all biliary CCs, KT comprised 9.35%, with a mean age of diagnosis of 73±13 years, and was more common in men (54.8%) and Caucasian patients (69.5%). Histologically, moderately differentiated tumors were the most common (38.9%) followed by poorly differentiated (35.7%), well-differentiated (23.3%), and undifferentiated tumors (2.2%) (p<0.001). Most tumors in the KT group were 2-4 cm in size (41.5%), while fewer were >4 cm (29.7%) and <2 cm (28.8%) (p<0.001). ICD-O-3 defined most KTs in extrahepatic location (53.5%), while the remainder were in other biliary locations (46.5%) (p<0.001). Most KT patients received no treatment (73%), and for those who were treated, the most frequent modality was radiation (52.7%), followed by surgery (28.1%), and both surgery and radiation (19.2%) (p<0.001). Mean survival time for KT patients treated with surgery was inferior to all CCs of the biliary tree (1.72±2.61 vs. 1.87±2.18 years) (p=0.047). Multivariate analysis identified regional metastasis (OR=2.8; 95% CI=2.6-3.0), distant metastasis (OR=2.1; 95% CI=1.9-2.4), lymph node positivity (OR=1.6; 95% CI=1.4-1.8), Caucasian race (OR=2.0; 95% CI=1.8-2.2), and male sex (OR=1.2; 95% CI=1.1-1.3) were independently associated with increased mortality for KT (p<0.001).ConclusionThe ICD-O-3 has permitted a greater understanding of KT. KT is a rare and lethal biliary malignancy that presents most often in Caucasian men in their seventh decade of life with moderately differentiated histology. Surgical resection does not provide any survival advantage compared to similarly treated biliary CCs. In addition, the combination of surgery and radiation appeared to provide no added survival benefits compared to other treatment modalities for KT.

Features of tumor heterogeneity in regional metastasis of breast cancer

The review looked at the issues of tumor heterogeneity in breast cancer. Tumor heterogeneity is classified according to the main feature demonstrating regional differences within a tumor (for example, heterogeneity of clinical manifestations, histological heterogeneity, heterogeneity of protein expression, etc.) and by tumor regions (differences between primary tumors and metastases, differences between cell clones within a single tumor node, etc.). Temporal heterogeneity is also distinguished, which manifests itself in the clonal evolution of tumor cells. The review covers the heterogeneity in the expression of four biomarkers from the gold standard for immunohistochemical staining of breast cancer: estrogen receptors, progesterone receptors, Her2/neu and Ki67 in primary tumor tissue and regional metastases. According to various studies, discordance in estrogen receptor status of primary tumor cells and metastases was observed with a frequency of 4 to 62%, progesterone receptors from 12 to 54%, Her2/neu from 0 to 24%, Ki67 from 4 to 39%. The results of studies of changes in the expression levels of individual markers in breast cancer metastases, as well as the heterogeneity of surrogate subtypes of tumor tissue in metastasis, are briefly described. Possible reasons for heterogeneity in the expression of key prognostic and predictive markers by primary tumor and metastatic cells, such as artificial factors at the preanalytic and analytic stages of the study, polyclonality of the primary tumor before metastasis, clonal evolution of tumor cells during metastasis, selection of tumor clones under the therapy are highlighted.

Indications and limits of minimally invasive treatment of esophageal gastrointestinal stromal tumor: a narrative review

: Esophageal gastrointestinal stromal tumor (GIST) is a rare neoplasm that arises from interstitial cells of Cajal that typically requires surgical resection due to its potential for aggressive behavior. These tumors can affect any site of the digestive tract, from the esophagus to the rectum. Though they arise from the submucosal layer, they can ulcerate through the mucosa or form pedunculated masses. Esophageal GIST generally has a worse outcome compared to tumors arising in the stomach. The preoperative evaluation includes imaging and endoscopic ultrasound (EUS) to obtain a tissue biopsy. For large, locally advanced, or metastatic tumors, neoadjuvant tyrosine kinase inhibitor therapy should be strongly considered. Tumor genotyping can help identify imatinib non-responders or those requiring a higher dose. Due to the rarity of regional nodal metastasis, surgical options include esophagectomy, tumor enucleation, and submucosal tunneling endoscopic resection (STER). Given a high risk of postoperative morbidity, esophagectomy should be avoided in favor of the less invasive enucleation or endoscopic resection. Thoracoscopic/laparoscopic and robotic-assisted enucleation and STER are minimally invasive operative approaches that appear to be safe with adequate oncologic outcomes based on currently available evidence. Adjuvant therapy should be considered for high-risk tumors, though the optimal duration of therapy remains under investigation.

Molecular and Clinical Implications of Somatostatin Receptor Profile and Somatostatin Analogues Treatment in Oral Cavity Squamous Cell Carcinoma.

Simple SummaryThe treatment of oral squamous cell carcinoma (OSCC) represents a significant problem worldwide. Among cancers with the highest incidence, OSCC renders one of the worst prognoses. Therefore, novel prognostic biomarkers and therapeutic tools to tackle OSCC are urgently needed. Somatostatin-analogues (SSA) are an invaluable therapeutic option in the treatment of several cancers. We aimed to determine the expression levels of all somatostatin-receptors (SSTs) in OSCC, compared to adjacent healthy control tissues, to analyze the relationship of SSTs expression with key clinical and histopathological data, and to explore the direct in vitro effect of different SSAs on OSCC cancer cells. Our findings highlight a potential role of SST2 as a good prognostic biomarker for recurrence and metastasis in OSCC and unveil that SSA exerts antitumoral effects on OSCC cells, providing a relevant clinical conclusion, which should be soon tested for their use in humans.Oral squamous cell carcinoma (OSCC) incidence has increased by 50% over the last decade. Unfortunately, surgery and adjuvant radiotherapy and chemotherapy are still the mainstream modality of treatment, underscoring the need for alternative therapies. Somatostatin-analogues (SSA) are efficacious and safe treatments for a variety of tumors, but the presence of somatostatin-receptors (SSTs) and pharmacological effects of SSA on OSCC are poorly known. In this study, we demonstrated that SST2 and SST3 levels were significantly higher in OSCC, compared to adjacent healthy control tissues. SST2 expression was associated with less regional metastasis and a lower recurrence rate. Moreover, SST2 was elevated in OSCC and associated with histopathological good prognosis factors, such as high peritumoral inflammation, smaller depth of invasion, and expansive vs. infiltrative front of tumor invasion. Importantly, treatment with different SSA (octreotide, lanreotide, and pasireotide) significantly reduced cell-proliferation in OSCC primary cell cultures. Altogether, this study demonstrated that SST2 is overexpressed in OSCC vs. healthy tissues and could represent a novel prognostic biomarker, since its expression is associated with tumors that show better prognostic factors and less recurrent rate. Moreover, our data unveil clear antitumoral effects of SSAs on OSCC, opening new avenues to explore their potential as targeting therapy to OSCC.

Diagnostic Potential of miR-30a and miR-200c in Invasive Breast Ductal Carcinoma

Background: Breast cancer is one of the most common cancers worldwide and is responsible for the death of many people. It is mainly found in women; however, it is rarely observed in men. Nowadays, extensive research has been conducted on the detection, diagnosis, and prognosis of biomarkers of this type of cancer, as well as other types. MicroRNAs play a major role in regulating the onset and progression of breast cancer. To date, many significant increases and decreases in microRNAs levels have been reported during various cancers, and also tumor inhibitory roles have been reported for these small non-coding RNA molecules. Methods: In this study, miR-30a and miR-200c were studied to find new expression patterns in breast cancer patients. For this purpose, a quantitative polymerase chain reaction was used to analyze the relationships between expression levels of miR-30a and miR-200c and several clinical and pathological features of the disease, such as tumor stage, HER2 gene expression, and lymphatic metastasis. Results: Our results showed that the expression of miR-200c and miR-30a in tumor samples was significantly lower than in normal samples (P &lt; 0.01). Also, at higher stages of the disease, the expression of both miRNAs was remarkably reduced (P &lt; 0.01). We also found that the expression of two miRNAs in patients with HER2 gene expression and metastasis in lymphatic regions was significantly lower than in HER2-negative and non-metastatic patients (P &lt; 0.05 and P &lt; 0.01, respectively). Conclusions: We identified the relationship between miR-200c and miR-30a and breast cancer. These findings indicate that these microRNAs can be considered biomarkers in breast cancer.

Medullary Thyroid Cancer: Case Series Reports and Literature Review

Background: Medullary thyroid carcinoma (MTC) is a rare neuro-endocrine tumor that arises from the C-cells of the thyroid. About 20- 25 % of MTC cases may be associated with hereditary syndromes like MEN 2A, MEN 2B and Familial MTC. The survival rate is related mainly to the age of the patient, stage of the disease and completion of the surgical resection.&#x0D; Methods: Retrospective review of 11 patients who were diagnosed with medullary thyroid cancer in our general surgery department during the period from 2011 to 2021. All patients had preoperative assessment including history taking, clinical examination, tumor marker (calcitonin and CEA), thyroid function testing, ultrasonography and FNAC. All patients underwent genetic assessment to exclude any underlying genetic mutation.&#x0D; Results: The mean age of diagnosis was 57.73 ± 16.45 years of age. Three patients were males and eight were females. All patients had total thyroidectomy, central and lateral neck dissection except one patient who had prophylactic thyroidectomy due to familial inherited RET mutation. Two patients had recurrence; both of them had high-stage tumor (T3 and T4) with multiple cervical lymph nodes metastasis. The sensitivity of serum calcitonin for the detection of MTC was about 98%. Patients, who had localized disease and underwent complete surgical resection, had good overall survival rates compared with patients with advanced disease.&#x0D; Conclusion: MTC represent a heterogeneous group of thyroid cancers. The overall survival is better than that of undifferentiated thyroid cancers. Complete resection of the thyroid tumor and any local or regional metastases provides the only cure for patients with MTC. Further researches are still needed to improve our understanding and management of MTC.

Retiform Hemangioendothelioma

Histopathology Histopathological examination is required to confirm the diagnosis of retiform hemangioendothelioma (RH) because RH does not have distinctive clinical features. Histopathological examination reveals arborizing blood vessels in the dermis, extending between the collagen bundles in a reticular fashion and flanked by lymphocytes and hyaline sclerosis. The vessels are lined by monomorphic endothelial cells with scanty cytoplasm and prominent protuberance of the nucleus. The cells can protrude to the vascular lumen like a matchstick or hobnail, and nuclear atypia and mitotic figures are generally absent (Fig. 1).1 Some interspersed lymphocytes can also be seen in and around the blood vessels. Immunohistochemical examination of RH shows positive expression of vascular endothelial cell marker CD34 and weak positive expression of CD31 and FVIII-related antigen.2 This low-grade tumor recurs frequently, but the risk of metastasis is very low.Figure 1: Histopathological features of Retiform Hemangioendothelioma. The epidermis is normal. However, arborizing blood vessels are visible in the dermis. The vessels are lined by monomorphic endothelial cells, and interspersed lymphocytes can be seen in and around the blood vessels. (A) Hematoxylin-eosin, ×100. (B) Hematoxylin-eosin, ×200.Clinical features RH is an extremely rare variant of low-grade angiosarcoma that was first described in 1994 as a distinctive form of angiosarcoma.3 It often occurs in young or middle-aged people and has an unclear pathogenesis. Its main clinical feature is an asymptomatic, slowly growing, well-defined solitary nodular or plaque-like lesion on either the extremities or trunk (Fig. 2).2,4Figure 2: Clinical presentation of Retiform Hemangioendothelioma. Asymptomatic, well-defined, solitary nodular lesion on the lower limb. No abnormality is present in the surrounding skin.The differential diagnoses for RH are angiosarcoma and targetoid hemosiderotic hemangioma. The histopathological features of angiosarcoma are very similar to those of RH. However, angiosarcoma often exhibits nuclear atypia and mitotic figures and the absence of a retiform pattern of blood vessels; additionally, it is more invasive than RH and has a higher risk of recurrence and metastasis. In contrast, targetoid hemosiderotic hemangioma is a superficial and limited lesion, and shoe nail-like vascular endothelial cells can only be seen in some areas.3 These lesions can be identified by histopathologic examination. About 60% of patients with RH develop local recurrence with a tendency for local aggressive behavior. Previous reports have described regional lymph gland metastasis in a single patient and local spread to soft tissue in another patient.5 Only one RH-related death has been reported to date. Surgical excision is the most effective treatment for a circumscribed lesion.6

Inhibition of Hepatic Stellate Cell Activation Suppresses Tumorigenicity of Hepatocellular Carcinoma in Mice

Transdifferentiation (or activation) of hepatic stellate cells (HSCs) to myofibroblasts is a key event in liver fibrosis. Activated HSCs in the tumor microenvironment reportedly promote tumor progression. This study analyzed the effect of an inhibitor of HSC activation, retinol-binding protein–albumin domain III fusion protein (R-III), on protumorigenic functions of HSCs. Although conditioned medium collected from activated HSCs enhanced the migration, invasion, and proliferation of the hepatocellular carcinoma cell line Hepa-1c1c7, this effect was not observed in Hepa-1c1c7 cells treated with conditioned medium from R-III–exposed HSCs. In a subcutaneous tumor model, larger tumors with increased vascular density were formed in mice transplanted with Hepa-1c1c7+HSC than in mice transplanted with Hepa-1c1c7 cells alone. Intriguingly, when Hepa-1c1c7+HSC–transplanted mice were injected intravenously with R-III, a reduction in vascular density and extended tumor necrosis were observed. In an orthotopic tumor model, co-transplantation of HSCs enhanced tumor growth, angiogenesis, and regional metastasis accompanied by increased peritumoral lymphatic vessel density, which was abolished by R-III. In vitro study showed that R-III treatment affected the synthesis of pro-angiogenic and anti-angiogenic factors in activated HSCs, which might be the potential mechanism underlying the R-III effect. These findings suggest that the inhibition of HSC activation abrogates HSC-induced tumor angiogenesis and growth, which represents an attractive therapeutic strategy.

Medullary thyroid carcinoma and pregnancy

Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor of the parafollicular cells of the thyroid gland. The tumor occurs, either sporadically or in a hereditary form, as a component of the type 2 multiple endocrine neoplasia (MEN) syndromes, MEN2A and MEN2B, both with an autosomal dominant transmission. Due to its higher aggressiveness and urgency to treat, it poses a challenge when diagnosed during pregnancy. We performed a literature review searching medical databases as UpToDate and PubMed for relevant information about diagnosis, impact, treatment, and outcome of medullary thyroid carcinoma during pregnancy. Diagnosis of MTC is established by clinical and ultrasound evaluation, followed by a fine needle aspiration biopsy. Further analyses decide whether it is a sporadic or a hereditary disease. Surgery offers the curative solution, but careful postoperative follow-up is needed for the best outcome. The decision for surgery is taken considering the DNA mutation of RET oncogene and pregnancy status. A premature planned delivery is associated with potential complications for the newborn, but it is recommended when maternal status worsens. Conclusions. Complete resection of the thyroid tumor and any local and regional metastases is the only curative solution. Timing of the intervention is extremely important to decrease fetal outcomes. Close follow-up during the postoperative period, by both biochemical and imaging methods, is needed.

Elective neck dissection versus observation in patients with head and neck cutaneous squamous cell carcinoma.

The survival benefit of elective neck dissection (END) for patients with cutaneous squamous cell carcinoma (cSCC) of the head and neck and no evidence of regional metastasis (cN0) has never been reported. The aim of this study was to determine the effect of END on patient survival. The authors included patients with head and neck cSCC who had undergone primary surgery from 1995 to 2017. The primary end point was survival, and the secondary end points were the incidence of occult regional disease and regional disease control. To assess the impact of END on survival, the authors used multivariable Cox proportional hazards models with propensity score and matching techniques for internal validation. A total of 1111 patients presented with no evidence of nodal disease; 173 had END, and 938 were observed. Adjuvant radiotherapy to the neck was administered to 101 patients (9%). END resulted in a 5-year overall survival rate of 52%, whereas the rate was 63% in the observation group (P=.003 [log-rank]). The 5-year disease-free survival rate for patients undergoing END was similar to that for the observation group (73% vs 75%; P=.429). A multivariate regression model showed that the performance of END was not associated with improved rates of overall, disease-specific, or disease-free survival; similarly, among patients with advanced disease (T3-4), those who underwent END did not have improved survival rates. Among patients with cSCC of the head and neck, observation of the neck nodes resulted in noninferior survival rates in comparison with END at the time of primary surgery. Further studies are required to elucidate the role of END in patients with advanced disease.