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11 pages, 386 KiB  
Article
Predicting the Unexpected: Clinicopathological Insights into Skip Metastasis in Papillary Thyroid Carcinoma
by Ibrahim Burak Bahcecioglu, Adile Begum Bahcecioglu, Sevket Baris Morkavuk, Yasin Hatipoglu, Sumeyra Guler, Mujdat Turan, Gokhan Giray Akgul, Nese Ersoz Gulcelik and Mehmet Ali Gulcelik
J. Clin. Med. 2025, 14(12), 4255; https://doi.org/10.3390/jcm14124255 - 15 Jun 2025
Viewed by 437
Abstract
Background/Objectives: Papillary thyroid carcinoma (PTC) accounts for the majority of thyroid cancers, with lymph node metastasis, including skip metastasis (SM), playing a crucial role in guiding prognosis and therapeutic planning. SM, characterized by lateral lymph node spread in the absence of central compartment [...] Read more.
Background/Objectives: Papillary thyroid carcinoma (PTC) accounts for the majority of thyroid cancers, with lymph node metastasis, including skip metastasis (SM), playing a crucial role in guiding prognosis and therapeutic planning. SM, characterized by lateral lymph node spread in the absence of central compartment involvement, has been observed in PTC with a wide range of reported frequencies. The identification of risk factors for SM is crucial for preoperative evaluation and surgical planning. This research aims to explore the clinicopathological features and potential risk factors linked to SM in patients with PTC, while also offering valuable insights for preoperative risk evaluation. Methods: A retrospective cohort study was conducted on 81 PTC patients who underwent central and lateral cervical lymph node dissection (LND) in our center. Clinical, demographic, and pathological data, including age, sex, tumor size, location, subtype, extrathyroidal extension, lymphovascular invasion, and the number of lymph node metastases were analyzed. Clinicopathological characteristics were analyzed between SM-positive and SM-negative patient groups using suitable statistical methods. Additionally, a regression analysis was performed to identify the risk factors for SM. Results: Of the 81 patients, 17.3% (n = 14) were diagnosed with skip metastasis (SM). The SM-positive group had a significantly higher age (p = 0.006), smaller tumor size (p < 0.001), and higher rates of extrathyroidal extension (p = 0.006). The proportion of female patients was elevated in the SM-positive group, but this observation did not achieve statistical significance (p = 0.128). Tumors located in the upper pole were more common in the SM-positive group (p = 0.016). Multivariate analysis revealed that female sex, older age, and tumor location in the upper pole were significant risk factors for SM (p = 0.031, p = 0.004, and p = 0.017, respectively), while a lower number of lateral lymph node metastases was significantly associated with SM (p = 0.010). Additionally, an age over 43.5 years predicted SM with a sensitivity of 78.6% and a specificity of 72.7%. Conclusions: Skip metastasis is not uncommon in PTC and may be associated with older age, female sex, upper pole tumor location, and fewer lateral lymph node metastases. Recognizing these factors during preoperative assessment may aid in anticipating atypical lymphatic spread patterns and optimizing surgical strategies. Full article
(This article belongs to the Section Endocrinology & Metabolism)
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3 pages, 481 KiB  
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Tumor Cavitation with Anlotinib Treatment in Lung Adenocarcinoma
by Jie Huang and Xueqin Chen
Diagnostics 2025, 15(10), 1280; https://doi.org/10.3390/diagnostics15101280 - 18 May 2025
Viewed by 584
Abstract
Tumor cavitation is distinguished by the emergence of central necrosis and cavity formation within the tumor mass, which indicates a notable outcome of anti-angiogenic therapies. This case describes a 52-year-old Chinese female with advanced EGFR-mutated lung adenocarcinoma (Exon 19 deletion), which was metastatic [...] Read more.
Tumor cavitation is distinguished by the emergence of central necrosis and cavity formation within the tumor mass, which indicates a notable outcome of anti-angiogenic therapies. This case describes a 52-year-old Chinese female with advanced EGFR-mutated lung adenocarcinoma (Exon 19 deletion), which was metastatic to bilateral lungs, brain, and right adrenal gland, who exhibited a radiographic response to combination therapy with the third-generation EGFR tyrosine kinase inhibitor (TKI) aumolertinib and the anti-angiogenic agent anlotinib. The patient achieved near-complete cavitation of almost all bilateral lung nodules, manifesting as distinctive “bullet hole” lesions on the chest CT. Despite this initial response, disease progression occurred two months later with new liver metastases, culminating in the patient’s death. This case underscores the potential efficacy of EGFR TKIs and anti-angiogenic agents in inducing unique tumor microenvironment modifications, while highlighting the transient nature of such responses and the critical need to address resistance mechanisms. Tumor cavitation may serve as a radiographic marker of anti-angiogenic activity but does not preclude metastatic spread, necessitating vigilant monitoring even in the setting of favorable imaging changes. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
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10 pages, 674 KiB  
Article
Colonic Polyp Study: Differences in Adenoma Characteristics Based on Colonoscopy History over 5-Year Follow-Up Period
by Sang Hyun Park, Kwang Il Hong, Hyun Chul Park, Young Sun Kim, Gene Hyun Bok, Kyung Ho Kim, Dong Suk Shin, Jae Yong Han, Young Kwan Kim, Yeun Jong Choi, Soo Hoon Eun, Byung Hoon Lim, Kyeong Kun Kwack and The Korean Society of Digestive Endoscopy Polyp Study
J. Clin. Med. 2025, 14(1), 194; https://doi.org/10.3390/jcm14010194 - 31 Dec 2024
Cited by 1 | Viewed by 1860
Abstract
Background: Timely detection and removal of colonic adenomas are critical for preventing colorectal cancer. Methods: This study analyzed differences in colonic adenoma characteristics based on colonoscopy history by reviewing the medical records of 14,029 patients who underwent colonoscopy between January and [...] Read more.
Background: Timely detection and removal of colonic adenomas are critical for preventing colorectal cancer. Methods: This study analyzed differences in colonic adenoma characteristics based on colonoscopy history by reviewing the medical records of 14,029 patients who underwent colonoscopy between January and June 2020 across 40 primary medical institutions in Korea. Results: Adenoma and advanced neoplasia characteristics varied significantly with colonoscopy history (p < 0.05). In the first-time colonoscopy group, adenomas were more frequent in the sigmoid colon (S-colon) and rectum, with Is features and non-granular laterally spreading tumors. Advanced neoplasia was also more common in the S-colon and rectum, with Is and advanced-type features. In the <5-year group, adenomas were predominantly found in the transverse colon (T-colon) and descending colon (D-colon), with IIa and IIb features. Advanced neoplasia in this group was more frequent in the cecum and T-colon, with IIa and IIb features and laterally spreading tumors. In the ≥5-year group, adenomas were more commonly located in the ascending colon (A-colon) and cecum, with Ip features, while advanced neoplasia was more frequent in the A-colon and D-colon, also with Ip features. Conclusions: Although every segment of the colorectum should be carefully observed regardless of colonoscopy history, these findings suggest that prioritizing specific colonic segments for examination based on colonoscopy history may improve adenoma detection rates and reduce the incidence of colorectal cancer. However, further large-scale, prospective studies are needed to confirm these findings and support their application in clinical practice. Full article
(This article belongs to the Special Issue Updates in Digestive Diseases and Endoscopy)
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13 pages, 1577 KiB  
Article
Endoscopic Surveillance after (Procto)Colectomy with Gastrointestinal Reconstruction in Patients with Familial Adenomatous Polyposis (FAP)—Principles, Goals and Practical Aspects Based on 12 Years of Observation
by Jarosław Cwaliński, Wiktoria Zasada, Hanna Cholerzyńska, Wiktoria Andrzejewska, Hanna Michalak, Tomasz Banasiewicz and Jacek Paszkowski
Life 2024, 14(8), 1000; https://doi.org/10.3390/life14081000 - 12 Aug 2024
Cited by 1 | Viewed by 1545
Abstract
(1) Background: Familial adenomatous polyposis (FAP) is a hereditary condition characterized by the development of numerous adenomas in the large intestine, often necessitating colectomy due to an elevated risk of colorectal cancer. Despite surgical intervention, adenomas frequently recur, underscoring the importance of ongoing [...] Read more.
(1) Background: Familial adenomatous polyposis (FAP) is a hereditary condition characterized by the development of numerous adenomas in the large intestine, often necessitating colectomy due to an elevated risk of colorectal cancer. Despite surgical intervention, adenomas frequently recur, underscoring the importance of ongoing surveillance. This study evaluates the outcomes of a 12-year endoscopic follow-up after colectomy and gastrointestinal reconstruction for FAP. (2) Methods: A retrospective analysis was conducted on 41 FAP patients who underwent at least one postoperative endoscopic examination. Assessments of the pouch or rectum were performed every 12–18 months following ileorectal anastomosis and every 18–24 months after ileal pouch–anal anastomosis. Follow-up biopsies were assessed using the adopted Spigelman classification. (3) Results: Postoperative pathology revealed invasive colorectal cancer in three patients. Abdominoperineal resection was performed in two cases due to secondary invasive carcinoma, and one T1 tumor was radically removed with ESD. One patient underwent radical pouch excision following a nodal pelvic recurrence of rectal cancer. Over a 12-year observation period, the mean Spigelman score increased by 2 points, and the proportion of patients with low-grade polypoid lesions decreased. The quantity or size of polyps increased in 24 patients, decreased in 8 patients, and remained stable in 9 patients. In four patients, granular, laterally spreading tumors were discovered in the rectal stump. (4) Conclusions: Regular endoscopic surveillance in FAP patients facilitates early identification of neoplastic and inflammatory changes. The downstaging potential highlights the effectiveness of early interventions. While the Spigelman classification assessed polyps well, it did not predict cancer occurrence. A notable number of patients had invasive cancer at the time of surgery, underscoring the importance of early surgical qualification, which is particularly crucial for identifying upstaging or secondary cancer. Full article
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15 pages, 21658 KiB  
Review
Rationale for Using High-Frequency Ultrasound as a Routine Examination in Skin Cancer Surgery: A Practical Approach
by Diana Crisan, Evelyne Tarnowietzki, Lukas Bernhard, Melina Möller, Karin Scharffetter-Kochanek, Maria Crisan and Lars Alexander Schneider
J. Clin. Med. 2024, 13(7), 2152; https://doi.org/10.3390/jcm13072152 - 8 Apr 2024
Cited by 2 | Viewed by 2890
Abstract
Ultrasound and high-frequency ultrasound assessment of melanoma and non-melanoma skin cancer in the pre-therapeutical setting is becoming increasingly popular in the field of dermatosurgery and dermatooncology, as it can provide clinicians with relevant, ”in vivo“ parameters regarding tumor lateral and depth extension as [...] Read more.
Ultrasound and high-frequency ultrasound assessment of melanoma and non-melanoma skin cancer in the pre-therapeutical setting is becoming increasingly popular in the field of dermatosurgery and dermatooncology, as it can provide clinicians with relevant, ”in vivo“ parameters regarding tumor lateral and depth extension as well as potential locoregional spread, cancelling the need of more extensive imaging methods and avoiding a delay in diagnosis. Furthermore, preoperative sonography and color Doppler can aid in orienting the clinical diagnosis, being able in numerous situations to differentiate between benign and malignant lesions, which require a different therapeutic approach. This preoperative knowledge is of paramount importance for planning an individualized treatment regimen. Using sonography at the time of diagnosis, important surgical complications, such as neurovascular damage, can be avoided by performing a preoperative neurovascular mapping. Furthermore, sonography can help reduce the number of surgical steps by identifying the lesions’ extent prior to surgery, but it can also spare unnecessary surgical interventions in cases of locally advanced lesions, which infiltrate the bone or already present with locoregional metastases, which usually require modern radiooncological therapies in accordance to European guidelines. With this review, we intend to summarize the current indications of sonography in the field of skin cancer surgery, which can help us improve the therapeutic attitude toward our patients and enhance patient counseling. In the era of modern systemic radiooncological therapies, sonography can help better select patients who qualify for surgical procedures or require systemic treatments due to tumoral extension. Full article
(This article belongs to the Section Dermatology)
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12 pages, 1928 KiB  
Review
Updates on the Management of Ampullary Neoplastic Lesions
by Roberta Maselli, Roberto de Sire, Alessandro Fugazza, Marco Spadaccini, Matteo Colombo, Antonio Capogreco, Torsten Beyna and Alessandro Repici
Diagnostics 2023, 13(19), 3138; https://doi.org/10.3390/diagnostics13193138 - 6 Oct 2023
Cited by 1 | Viewed by 2999
Abstract
Ampullary neoplastic lesions (ANLs) represent a rare cancer, accounting for about 0.6–0.8% of all gastrointestinal malignancies, and about 6–17% of periampullary tumors. They can be sporadic or occur in the setting of a hereditary predisposition syndrome, mainly familial adenomatous polyposis (FAP). Usually, noninvasive [...] Read more.
Ampullary neoplastic lesions (ANLs) represent a rare cancer, accounting for about 0.6–0.8% of all gastrointestinal malignancies, and about 6–17% of periampullary tumors. They can be sporadic or occur in the setting of a hereditary predisposition syndrome, mainly familial adenomatous polyposis (FAP). Usually, noninvasive ANLs are asymptomatic and detected accidentally during esophagogastroduodenoscopy (EGD). When symptomatic, ANLs can manifest differently with jaundice, pain, pancreatitis, cholangitis, and melaena. Endoscopy with a side-viewing duodenoscopy, endoscopic ultrasound (EUS), and magnetic resonance cholangiopancreatography (MRCP) play a crucial role in the ANL evaluation, providing an accurate assessment of the size, location, and characteristics of the lesions, including the staging of the depth of tumor invasion into the surrounding tissues and the involvement of local lymph nodes. Endoscopic papillectomy (EP) has been recognized as an effective treatment for ANLs in selected patients, providing an alternative to traditional surgical methods. Originally, EP was recommended for benign lesions and patients unfit for surgery. However, advancements in endoscopic techniques have broadened its indications to comprise early ampullary carcinoma, giant laterally spreading lesions, and ANLs with intraductal extension. In this paper, we review the existing evidence on endoscopic diagnosis and treatment of ampullary neoplastic lesions. Full article
(This article belongs to the Special Issue Advances in Endoscopic Diagnosis and Tissue Resection Techniques)
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9 pages, 399 KiB  
Article
Risk of Residual Neoplasia after a Local-Risk Resection of Colorectal Lesions by Endoscopic Submucosal Dissection: A Multinational Study
by João Santos-Antunes, Mathieu Pioche, Felipe Ramos-Zabala, Paolo Cecinato, Francisco Gallego, Pedro Barreiro, André Mascarenhas, Sandro Sferrazza, Frieder Berr, Andrej Wagner, Arnaud Lemmers, Mariana Figueiredo Ferreira, Eduardo Albéniz, Hugo Uchima, Ricardo Küttner-Magalhães, Carlos Fernandes, Rui Morais, Sunil Gupta, Daniel Martinho-Dias, Isabel Faria-Ramos, Margarida Marques, Michael J. Bourke and Guilherme Macedoadd Show full author list remove Hide full author list
J. Clin. Med. 2023, 12(16), 5356; https://doi.org/10.3390/jcm12165356 - 17 Aug 2023
Cited by 5 | Viewed by 1533
Abstract
Endoscopic submucosal dissection (ESD) in colorectal lesions is demanding, and a significant rate of non-curative procedures is expected. We aimed to assess the rate of residual lesion after a piecemeal ESD resection, or after an en bloc resection but with positive horizontal margins [...] Read more.
Endoscopic submucosal dissection (ESD) in colorectal lesions is demanding, and a significant rate of non-curative procedures is expected. We aimed to assess the rate of residual lesion after a piecemeal ESD resection, or after an en bloc resection but with positive horizontal margins (local-risk resection—LocRR), for colorectal benign neoplasia. A retrospective multicenter analysis of consecutive colorectal ESDs was performed. Patients with LocRR ESDs for the treatment of benign colorectal lesions with at least one follow-up endoscopy were included. A cohort of en bloc resected lesions, with negative margins, was used as the control. A total of 2255 colorectal ESDs were reviewed; 352 of the ESDs were “non-curative”. Among them, 209 were LocRR: 133 high-grade dysplasia and 76 low-grade dysplasia. Ten cases were excluded due to missing data. A total of 146 consecutive curative resections were retrieved for comparison. Compared to the “curative group”, LocRRs were observed in lengthier procedures, with larger lesions, and in non-granular LSTs. Recurrence was higher in the LocRR group (16/199, 8% vs. 1/146, 0.7%; p = 0.002). However, statistical significance was lost when considering only en bloc resections with positive horizontal margins (p = 0.068). In conclusion, a higher rate of residual lesion was found after a piecemeal ESD resection, but not after an en bloc resection with positive horizontal margins. Full article
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18 pages, 2285 KiB  
Review
Endoscopic Submucosal Dissection, Endoscopic Mucosal Resection, and Transanal Minimally Invasive Surgery for the Management of Rectal and Anorectal Lesions: A Narrative Review
by Pedro Moreira, Pedro Marílio Cardoso, Guilherme Macedo and João Santos-Antunes
J. Clin. Med. 2023, 12(14), 4777; https://doi.org/10.3390/jcm12144777 - 19 Jul 2023
Cited by 12 | Viewed by 4718
Abstract
Endoscopic submucosal dissection (ESD), endoscopic mucosal resection (EMR), and transanal minimally invasive surgery (TAMIS) are modern techniques that now play a crucial role in the treatment of colorectal lesions. ESD is a minimally invasive endoscopic procedure that allows for the resection of lesions [...] Read more.
Endoscopic submucosal dissection (ESD), endoscopic mucosal resection (EMR), and transanal minimally invasive surgery (TAMIS) are modern techniques that now play a crucial role in the treatment of colorectal lesions. ESD is a minimally invasive endoscopic procedure that allows for the resection of lesions of any size in a single piece, with clear advantages regarding oncological outcomes and recurrences. However, it is a complex technique, requiring high endoscopic skills, expertise, and specialized training, with higher rates of adverse events expected compared with EMR. EMR is another endoscopic technique used to remove superficial gastrointestinal tumors, particularly those that are limited to the mucosal layer. It is a faster and more accessible procedure, with fewer adverse events, although it only allows for an en-bloc resection of lesions measuring 15–20 mm. TAMIS is a minimally invasive surgical technique used to remove rectal tumors, involving the insertion of a single-port device through the anus, allowing for a better visualization and removal of the tumor with minimal disruption. This article reviews the current applications and evidence regarding these techniques, in search for the most adequate treatment for the removal of lesions in the rectum and anorectal junction, as these locations possess distinct characteristics that demand a more specific approach. Full article
(This article belongs to the Special Issue Advances in Minimally Invasive Gastrointestinal Surgery)
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13 pages, 642 KiB  
Article
Hereditary Gastric Cancer: Single-Gene or Multigene Panel Testing? A Mono-Institutional Experience
by Mariarosaria Calvello, Monica Marabelli, Sara Gandini, Elena Marino, Loris Bernard, Matteo Dal Molin, Giulia Di Cola, Cristina Zanzottera, Giovanni Corso, Nicola Fazio, Lorenzo Gervaso, Uberto Fumagalli Romario, Massimo Barberis, Aliana Guerrieri-Gonzaga, Lucio Bertario, Davide Serrano and Bernardo Bonanni
Genes 2023, 14(5), 1077; https://doi.org/10.3390/genes14051077 - 13 May 2023
Cited by 6 | Viewed by 2774
Abstract
Gastric cancer (GC) has long been a ‘Cinderella’ among hereditary cancers. Until recently, single-gene testing (SGT) was the only approach to identify high-risk individuals. With the spread of multigene panel testing (MGPT), a debate arose on the involvement of other genes, particularly those [...] Read more.
Gastric cancer (GC) has long been a ‘Cinderella’ among hereditary cancers. Until recently, single-gene testing (SGT) was the only approach to identify high-risk individuals. With the spread of multigene panel testing (MGPT), a debate arose on the involvement of other genes, particularly those pertaining to homologous recombination (HR) repair. We report our mono-institutional experience in genetic counseling and SGT for 54 GC patients, with the detection of nine pathogenic variants (PVs) (9/54:16.7%). Seven out of fifty (14%) patients who underwent SGT for unknown mutations were carriers of a PV in CDH1 (n = 3), BRCA2 (n = 2), BRCA1 (n = 1), and MSH2 (n = 1), while one patient (2%) carried two variants of unknown significance (VUSs). CDH1 and MSH2 emerged as genes involved in early-onset diffuse and later-onset intestinal GCs, respectively. We additionally conducted MGPT on 37 patients, identifying five PVs (13.5%), including three (3/5:60%) in an HR gene (BRCA2, ATM, RAD51D) and at least one VUS in 13 patients (35.1%). Comparing PV carriers and non-carriers, we observed a statistically significant difference in PVs between patients with and without family history of GC (p-value: 0.045) or Lynch-related tumors (p-value: 0.036). Genetic counseling remains central to GC risk assessment. MGPT appeared advantageous in patients with unspecific phenotypes, although it led to challenging results. Full article
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10 pages, 921 KiB  
Systematic Review
Precision Surgery of Colorectal Liver Metastases in the Current Era: A Systematic Review
by Dimitrios Papaconstantinou, Nikolaos Pararas, Anastasia Pikouli, Constantinos Nastos, Anestis Charalampopoulos, Dionysios Dellaportas, George Bagias and Emmanouil Pikoulis
Cancers 2023, 15(7), 2083; https://doi.org/10.3390/cancers15072083 - 31 Mar 2023
Cited by 2 | Viewed by 1985
Abstract
Liver resection for colorectal liver metastases (CRLM) is widely considered the treatment with the highest curative potential. However, not all patients derive the same oncological benefit, underlining the need for better patient stratification and treatment allocation. In this context, we performed a systematic [...] Read more.
Liver resection for colorectal liver metastases (CRLM) is widely considered the treatment with the highest curative potential. However, not all patients derive the same oncological benefit, underlining the need for better patient stratification and treatment allocation. In this context, we performed a systematic review of the literature to determine the role of RAS status in selecting the optimal surgical strategy. Evidence comparing anatomical with non-anatomical resections depending on RAS mutational status was scarce and conflicting, with two studies reporting superiority in mutated RAS (mutRAS) patients and two studies reporting equivalent outcomes. The rate of incomplete microscopic resection (R1) was found to be increased among mutRAS patients, possibly due to higher micrometastatic spread lateral to the primary lesion. The impact of R1 resection margins was evaluated separately for mutRAS and wild-type patients in three studies, of which, two indicated an additive detriment to long-term survival in the former group. In the current era of precision surgery, RAS status can be utilized to predict the efficacy of liver resection in the treatment of CRLM, avoiding a potentially morbid operation in patients with adverse tumor profiles. Full article
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22 pages, 4429 KiB  
Article
MicroRNA-155 and Disease-Related Immunohistochemical Parameters in Cutaneous Melanoma
by Manal S. Fawzy, Afaf T. Ibrahiem, Naglaa A. Bayomy, Amin K. Makhdoom, Khalid S. Alanazi, Abdulaziz M. Alanazi, Abdulaziz M. Mukhlef and Eman A. Toraih
Diagnostics 2023, 13(6), 1205; https://doi.org/10.3390/diagnostics13061205 - 22 Mar 2023
Cited by 11 | Viewed by 2721
Abstract
Cutaneous melanoma is a severe and life-threatening form of skin cancer with growing incidences. While novel interventions have improved prognoses for these patients, early diagnosis of targeted treatment remains the most effective approach. MicroRNAs have grown to good use as potential biomarkers for [...] Read more.
Cutaneous melanoma is a severe and life-threatening form of skin cancer with growing incidences. While novel interventions have improved prognoses for these patients, early diagnosis of targeted treatment remains the most effective approach. MicroRNAs have grown to good use as potential biomarkers for early detection and as targets for treatment. miR-155 is well-studied for its role in tumor cell survival and proliferation in various tissues, although its role in melanoma remains controversial. In silico data analysis was performed in the dbDEMC v.3 to identify differentially expressed miRNA. We validated gene targets in melanoma using TarBase v8.0 and miRPath v3.0 and determined protein-protein interactions of the target genes. One hundred forty patients (age range 21–90 years) with cutaneous melanoma who underwent resection were included. Molecular assessment using Real-Time RT-qPCR, clinicopathological associations, and a literature review for the different roles of miR-155 in melanoma were performed. Analysis of the dbDEMC reveals controversial findings. While there is evidence of upregulation of miR-155 in primary and metastatic melanoma samples, others suggest decreased expression in later-stage melanoma and cases with brain metastasis. miR-155 has been overexpressed in prior cases of melanoma and precancerous lesions, and it was found to be dysregulated when compared to benign nevi. While miR-155 expression was associated with favorable outcomes in some studies, others showed an association with metastasis. Patients with high levels of miR-155 also noted reduction after receiving anti-PD-1 treatment, correlated with more prolonged overall survival. In our patient’s cohort, 22.9% relapsed during treatment, and 45% developed recurrence, associated with factors such as lymph node infiltration, high mitotic index, and positive staining for CD117. Although overall analysis revealed miR-155 downregulation in melanoma specimens compared to non-cancer tissues, increased expression of miR-155 was associated with cases of superficial spreading melanoma subtype (p = 0.005) and any melanoma with a high mitotic rate (p = 0.010). The analysis did not identify optimum cutoff values to predict relapse, recurrence, or mortality. In conclusion, miR-155 could have, in part, a potential prognostic utility in cutaneous melanoma. Further mechanistic studies are required to unravel the multifunctional role of miR-155 in melanoma. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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22 pages, 3232 KiB  
Article
Phenotypic Plasticity in Circulating Tumor Cells Is Associated with Poor Response to Therapy in Metastatic Breast Cancer Patients
by Evan N. Cohen, Gitanjali Jayachandran, Hui Gao, Phillip Peabody, Heather B. McBride, Franklin D. Alvarez, Megumi Kai, Juhee Song, Yu Shen, Jie S. Willey, Bora Lim, Vicente Valero, Naoto T. Ueno and James M. Reuben
Cancers 2023, 15(5), 1616; https://doi.org/10.3390/cancers15051616 - 6 Mar 2023
Cited by 9 | Viewed by 4214
Abstract
Circulating tumor cells (CTCs) are indicators of metastatic spread and progression. In a longitudinal, single-center trial of patients with metastatic breast cancer starting a new line of treatment, a microcavity array was used to enrich CTCs from 184 patients at up to 9 [...] Read more.
Circulating tumor cells (CTCs) are indicators of metastatic spread and progression. In a longitudinal, single-center trial of patients with metastatic breast cancer starting a new line of treatment, a microcavity array was used to enrich CTCs from 184 patients at up to 9 timepoints at 3-month intervals. CTCs were analyzed in parallel samples from the same blood draw by imaging and by gene expression profiling to capture CTC phenotypic plasticity. Enumeration of CTCs by image analysis relying primarily on epithelial markers from samples obtained before therapy or at 3-month follow-up identified the patients at the highest risk of progression. CTC counts decreased with therapy, and progressors had higher CTC counts than non-progressors. CTC count was prognostic primarily at the start of therapy in univariate and multivariate analyses but had less prognostic utility at 6 months to 1 year later. In contrast, gene expression, including both epithelial and mesenchymal markers, identified high-risk patients after 6–9 months of treatment, and progressors had a shift towards mesenchymal CTC gene expression on therapy. Cross-sectional analysis showed higher CTC-related gene expression in progressors 6–15 months after baseline. Furthermore, patients with higher CTC counts and CTC gene expression experienced more progression events. Longitudinal time-dependent multivariate analysis indicated that CTC count, triple-negative status, and CTC expression of FGFR1 significantly correlated with inferior progression-free survival while CTC count and triple-negative status correlated with inferior overall survival. This highlights the utility of protein-agnostic CTC enrichment and multimodality analysis to capture the heterogeneity of CTCs. Full article
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15 pages, 673 KiB  
Perspective
Stereotactic Body Radiotherapy and Immunotherapy for Older Patients with Oligometastases: A Proposed Paradigm by the International Geriatric Radiotherapy Group
by Nam P. Nguyen, Ahmed Ali, Vincent Vinh-Hung, Olena Gorobets, Alexander Chi, Thandeka Mazibuko, Natália Migliore, Maria Vasileiou, David Lehrman, Mohammad Mohammadianpanah, Seyed Alireza Javadinia, Gokoulakrichenane Loganadane, Trinanjan Basu, Satya Bose, Ulf Karlsson and Huan Giap
Cancers 2023, 15(1), 244; https://doi.org/10.3390/cancers15010244 - 30 Dec 2022
Cited by 7 | Viewed by 3330
Abstract
The standard of care for metastatic disease is systemic therapy. A unique subset of patients with limited metastatic disease defined as distant involvement of five anatomic sites or less (oligometastases) have a better chance of remission or improved survival and may benefit from [...] Read more.
The standard of care for metastatic disease is systemic therapy. A unique subset of patients with limited metastatic disease defined as distant involvement of five anatomic sites or less (oligometastases) have a better chance of remission or improved survival and may benefit from local treatments such as surgery or stereotactic body radiotherapy (SBRT). However, to prevent further spread of disease, systemic treatment such as chemotherapy, targeted therapy, and hormonal therapy may be required. Older patients (70 years old or above) or physiologically frail younger patients with multiple co-morbidities may not be able to tolerate the conventional chemotherapy due to its toxicity. In addition, those with a good performance status may not receive optimal chemotherapy due to concern about toxicity. Recently, immunotherapy with checkpoint inhibitors (CPI) has become a promising approach only in the management of program death ligand 1 (PD-L1)-positive tumors. Thus, a treatment method that elicits induction of PD-L1 production by tumor cells may allow all patients with oligometastases to benefit from immunotherapy. In vitro studies have demonstrated that high dose of radiotherapy may induce formation of PD-L1 in various tumors as a defense mechanism against inflammatory T cells. Clinical studies also corroborated those observations. Thus, SBRT, with its high precision to minimize damage to normal organs, may be a potential treatment of choice for older patients with oligometastases due to its synergy with immunotherapy. We propose a protocol combining SBRT to achieve a minimum radiobiologic equivalent dose around 59.5 Gy to all tumor sites if feasible, followed four to six weeks later by CPI for those cancer patients with oligometastases. All patients will be screened with frailty screening questionnaires to identify individuals at high risk for toxicity. The patients will be managed with an interdisciplinary team which includes oncologists, geriatricians, nurses, nutritionists, patient navigators, and social workers to manage all aspects of geriatric patient care. The use of telemedicine by the team may facilitate patient monitoring during treatment and follow-up. Preliminary data on toxicity, local control, survival, and progression-free survival may be obtained and serve as a template for future prospective studies. Full article
(This article belongs to the Special Issue Oligometastatic Disease)
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12 pages, 325 KiB  
Article
Factors Predicting Malignant Occurrence and Polyp Recurrence after the Endoscopic Resection of Large Colorectal Polyps: A Single Center Experience
by Olga Mandic, Igor Jovanovic, Mirjana Cvetkovic, Jasmina Maksimovic, Tijana Radonjic, Maja Popovic, Novica Nikolic and Marija Brankovic
Medicina 2022, 58(10), 1440; https://doi.org/10.3390/medicina58101440 - 13 Oct 2022
Cited by 4 | Viewed by 3543
Abstract
Background: The aim of this study was to identify risk factors contributing to the malignancy of colorectal polyps, as well as risk factors for recurrence after the successful endoscopic mucosal resection of large colorectal polyps in a referral center. Materials and Methods: [...] Read more.
Background: The aim of this study was to identify risk factors contributing to the malignancy of colorectal polyps, as well as risk factors for recurrence after the successful endoscopic mucosal resection of large colorectal polyps in a referral center. Materials and Methods: This retrospective cohort study was performed in patients diagnosed with large (≥20 mm diameter) colorectal polyps and treated in the period from January 2014 to December 2019 at the University Hospital Medical Center Bezanijska Kosa, Belgrade, Serbia. Based on the endoscopic evaluation and classification of polyps, the following procedures were performed: en bloc resection, piecemeal resection or surgical treatment. Results: A total of 472 patients with large colorectal polyps were included in the study. The majority of the study population were male (62.9%), with a mean age of 65.7 ± 10.8 years. The majority of patients had one polyp (73.7%) less than 40 mm in size (74.6%) sessile morphology (46.4%), type IIA polyps (88.2%) or polyps localized in the descending colon (52.5%). The accessibility of the polyp was complicated in 17.4% of patients. En bloc resection was successfully performed in 61.0% of the patients, while the rate of piecemeal resection was 26.1%. Due to incomplete endoscopic resection, surgery was performed in 5.1% of the patients, while 7.8% of the patients were referred to surgery directly. Hematochezia (p = 0.001), type IIB polyps (p < 0.001) and complicated polyp accessibility (p = 0.002) were significant independent predictors of carcinoma presence in a multivariate logistic regression analysis. Out of the 472 patients enrolled in the study, 364 were followed after endoscopic resection for colorectal polyp recurrence, which was observed in 30 patients (8.2%) during follow-up. Piecemeal resection (p = 0.048) and incomplete resection success (p = 0.013) were significant independent predictors of polyp recurrence in the multivariate logistic regression analysis. Conclusions: Whenever an endoscopist encounters a complex colorectal lesion (i.e., a polyp with complicated accessibility), polyp size > 40 mm, the Laterally Spreading Tumor nongranular (LST-NG) morphological type, type IIB polyps or the presence of hematochezia, malignancy risk should be considered before making the decision to either resect, refer to an advanced endoscopist or perform surgery. Full article
(This article belongs to the Special Issue Digestive Endoscopy: Inside the Evidence and Outside)
19 pages, 8171 KiB  
Article
Infra-Temporal and Pterygo-Palatine Fossae Tumors: A Frontier in Endoscopic Endonasal Surgery—Description of the Surgical Anatomy of the Approach and Report of Illustrative Cases
by Matteo Zoli, Giacomo Sollini, Fulvio Zaccagna, Viscardo Paolo Fabbri, Lorenzo Cirignotta, Arianna Rustici, Federica Guaraldi, Sofia Asioli, Caterina Tonon, Ernesto Pasquini and Diego Mazzatenta
Int. J. Environ. Res. Public Health 2022, 19(11), 6413; https://doi.org/10.3390/ijerph19116413 - 25 May 2022
Cited by 4 | Viewed by 6064
Abstract
Infratemporal and pterygopalatine fossae (ITF and PPF) represent two complex paramedian skull base areas, which can be defined as jewelry boxes, containing a large number of neurovascular and osteomuscular structures of primary importance. They are in close communication with many craniofacial areas, such [...] Read more.
Infratemporal and pterygopalatine fossae (ITF and PPF) represent two complex paramedian skull base areas, which can be defined as jewelry boxes, containing a large number of neurovascular and osteomuscular structures of primary importance. They are in close communication with many craniofacial areas, such as nasal/paranasal sinuses, orbit, middle cranial fossa, and oral cavities. Therefore, they can be involved by tumoral, infective or inflammatory lesions spreading from these spaces. Moreover, they can be the primary site of the development of some primitive tumors. For the deep-seated location of ITF and PPF lesions and their close relationship with the surrounding functional neuro-vascular structures, their surgery represents a challenge. In the last decades, the introduction of the endoscope in skull base surgery has favored the development of an innovative anterior endonasal approach for ITF and PPF tumors: the transmaxillary-pterygoid, which gives a direct and straightforward route for these areas. It has demonstrated that it is effective and safe for the treatment of a large number of benign and malignant neoplasms, located in these fossae, avoiding extensive bone drilling, soft tissue demolition, possibly unaesthetic scars, and reducing the risk of neurological deficits. However, some limits, especially for vascular tumors or lesions with lateral extension, are still present. Based on the experience of our multidisciplinary team, we present our operative technique, surgical indications, and pre- and post-operative management protocol for patients with ITF and PPF tumors. Full article
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