Low Metastatic Rate Research Articles

Abstract IA025: Using genetically engineered mouse models to study sarcoma metastasis

Abstract Despite aggressive conventional therapy, many patients with high-risk soft-tissue sarcoma develop metastatic disease. To investigate mechanism(s) of sarcoma metastasis, our lab has utilized genetically engineered mouse models. For example, we injected an adenovirus expressing Cre recombinase (adeno-Cre) into the gastrocnemius muscle of LSL-KrasG12D; p53Flox/Flox (KP) mice to initiate high grade undifferentiated pleomorphic sarcomas, and after amputation approximately 40% of the mice develop lung metastasis. Using a genetic approach, we found that miR-182, NEAT-1, and HIF-1a regulate metastasis to the lung. We also performed lineage tracing with complementary fluorescent proteins and CRISPR-generated bar codes to find that lung metastases from KP sarcomas arise from clones with specific gene expression profiles. Although the KP sarcoma model is useful for studying metastasis, one limitation of this model is that there are few non-synonymous mutations to engage the immune system. Therefore, we generated a high mutational load primary mouse model of soft tissue sarcoma by injecting adeno-Cre into the gastrocnemius muscle of p53Flox/Flox mice to delete p53 and also injected 3-methylcholanthrene (MCA) to generate primary p53/MCA undifferentiated pleomorphic sarcomas. In this p53/MCA model, the overall rate of lung metastasis after amputation was surprisingly low (~12%). We hypothesized that the immune system suppressed lung metastasis in this model. However, when we generated p53/MCA sarcomas in Rag2 −/− mice that lack mature B and T cells, we still observed a low rate of lung metastasis after amputation. These data suggest that mutations caused by MCA may have disabled tumor intrinsic factors needed to drive sarcoma metastasis. We are currently performing genome-wide screens in the p53/MCA model to search for genes required for sarcoma metastasis. Citation Format: David G. Kirsch, Rutulkumar Patel, Sophie R. Finkelstein, Joy Ban, Yuning J Tang, Jianguo Huang, Benjamin A. Alman, Yvonne M. Mowery. Using genetically engineered mouse models to study sarcoma metastasis [abstract]. In: Proceedings of the AACR Special Conference: Sarcomas; 2022 May 9-12; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2022;28(18_Suppl):Abstract nr IA025.

Poorly differentiated cluster grade-a vital predictor for lymph node metastasis and oncological outcomes in patients with T1 colorectal cancer: a retrospective study

BackgroundT1 colorectal cancers have a low lymph node metastasis rate and good prognosis. Thus, endoscopic resection is an attractive choice. This study aimed to describe the value of poorly differentiated cluster grade in identifying endoscopically curable T1 colorectal cancers.MethodsWe included 183 T1 colorectal cancer patients who underwent curative resection. Univariate and multivariate logistic regressions were used to identify lymph node metastasis predictors. The Akaike information criterion was used to determine whether poorly differentiated cluster grade was the best predictor. Backward regression was used to screen the variables. Survival analyses were conducted to determine the prognostic predictive power of poorly differentiated cluster grade. Correlations among predictors and concordance between our pathologists were also investigated.ResultsPoorly differentiated cluster grade was an independent predictor for lymph node metastasis (adjusted odds ratio [OR]G 3 = 0.001; 95% confidence interval [95% CI]G 3 = < 0.001, 0.139) in T1 colorectal cancer patients; moreover, it had the best predictive value (AIC = 61.626) among all indicators. It was also screened for inclusion in the predictive model. Accordingly, a high poorly differentiated cluster grade independently indicated shorter overall survival (hazard ratio [HR]G 2 = 4.315; 95% CIG 2 = 1.506, 12.568; HRG 3 = 5.049; 95% CIG 3 = 1.326, 19.222) and disease-free survival (HRG 3 = 6.621; 95% CIG 3 = 1.472, 29.786).ConclusionsPoorly differentiated cluster grade is a vital reference to manage T1 colorectal cancer. It could serve as an indicator to screen endoscopically curable T1 colorectal cancers.

Comparative Metastatic Rates in GEP Class 1A versus 1B Posterior Uveal Melanoma: Results Contrary to Expectations

Purpose: The purpose of this study was to determine whether the metastatic rates in patients with gene expression profile (GEP) class 1A versus 1B posterior uveal malignant melanoma supported or contradicted predictions of very low metastatic rate in GEP 1A cases and moderate rate in GEP 1B cases. Patients/Methods: 164 patients with a cytopathologically confirmed primary posterior uveal malignant melanoma classified by GEP testing as class 1 (100 GEP 1A, 64 GEP 1B) were evaluated. Kaplan-Meier rates of metastasis were computed and plotted for the GEP class 1 subgroups. Median follow-up of patients who were still alive without metastasis on the date of data analysis was 100.5 months for the GEP 1A patients and 97.2 months for the GEP 1B patients. Results: The actuarial 5-year rate of uveal melanoma metastasis was 10.8% (std. error = 3.2%) in the GEP 1A patients versus 0% in the GEP 1B patients, and the actuarial 10-year rate of metastasis was 12.2% (std. error = 3.5%) in the GEP 1A patients versus 2.1% (std. error 2.1%) in the GEP 1B patients. Conclusion: The results of this retrospective single-center study cast doubt on the validity of the prognostic stratification of GEP class 1 posterior uveal malignant melanomas into very low risk (GEP 1A) versus intermediate risk (GEP 1B) of metastasis subgroups provided by the commercially available GEP test.

Crosstalk between Pancreatic Cancer Cells and Cancer-Associated Fibroblasts in the Tumor Microenvironment Mediated by Exosomal MicroRNAs.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant digestive tumors, characterized by a low rate of early diagnosis, strong invasiveness, and early metastasis. The abundant stromal cells, dense extracellular matrix, and lack of blood supply in PDAC limit the penetration of chemotherapeutic drugs, resulting in poor efficacy of the current treatment regimens. Cancer-associated fibroblasts (CAFs) are the major stromal cells in the tumor microenvironment. Tumor cells can secrete exosomes to promote the generation of activated CAFs, meanwhile exosomes secreted by CAFs help promote tumor progression. The aberrant expression of miRNAs in exosomes is involved in the interaction between tumor cells and CAFs, which provides the possibility for the application of exosomal miRNAs in the diagnosis and treatment of PDAC. The current article reviews the mechanism of exosomal miRNAs in the crosstalk between PDAC cells and CAFs in the tumor microenvironment, in order to improve the understanding of TME regulation and provide evidence for designing diagnostic and therapeutic targets against exosome miRNA in human PDAC.

Abstract 5998: Peroxiredoxin IV promotes progression of colorectal cancer

Abstract Peroxiredoxin IV (Prx4) is a multifunction enzyme with a primary antioxidant role of reducing free radicals such as hydrogen peroxide and peroxynitrite. Literature review suggests that Prx4 upregulation in colorectal cancer is associated with higher tumor metastasis and shorter survival of patients. However, the function and mechanisms of Prx4 in cancer development are not well understood. The goal of this study is to validate the oncogenic role of Prx4 and to identify potential mechanisms of invasion and metastasis. Western Blot was performed to compare the expression of Prx4 protein in a normal colon cell line and seven colorectal cancer cell lines. shRNA mediated knockdown of Prx4 was performed in cancer cell lines with higher expression of Prx4. Stable vector control and Prx4 knockdown cells were used to perform Scratch Wound healing assay to compare the rate of migration. Transwell Matrigel invasion assay was performed using the same cell lines with 10% FBS containing-medium as chemoattractant. Vector control and Prx4 knockdown HCT116 cells were orthotopically implanted into the cecum wall of immunodeficient mice and humanely euthanized four weeks later. Prx4 expression is upregulated in colorectal cancer cell lines compared to normal colon cell line NCM356. Stable knockdown of Prx4 in HCT116 and RKO cell lines resulted in a significant decrease in migration and invasion rates of cancer cell lines in vitro compared to vector control. Orthotopic implantation of HCT116 vector control and Prx4 knockdown cells into cecum wall resulted in a lower metastasis rate to the liver and the lungs. We are currently conducting mechanistic studies to determine how the loss of Prx4 leads to a decrease in malignancy of colorectal cancer cell lines. Prx4 promotes colorectal cancer cell invasion and metastasis. Our study suggests Prx4 is a critical oncogenic protein that can be used as a therapeutic target for patients. This work was partially supported by the National Institutes of Health R01CA222596, Molecular Mechanisms of Toxicity Training Grant in Toxicology (T32ES07266), and American Cancer Society RSG-16-213-01-TBE. Citation Format: Pratik Thapa, Hong Jiang, Yanning Hao, Na Ding, Aziza Alshahrani, Yekaterina Zaytseva, Qiou Wei. Peroxiredoxin IV promotes progression of colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5998.

Oncological and Functional Outcomes after Hemicortical Resection and Biological Reconstruction Using Allograft for Parosteal Osteosarcoma of the Distal Femur

Background Parosteal osteosarcoma (PAOS) is a surface osteosarcoma. Treatment options include wide excision and endoprosthetic or allograft. However, due to the low local recurrence and metastasis rate, when it appears in the posterior surface of the distal femur, the lesion can be managed with hemicortical wide resection and biological reconstruction with hemicortical allograft. The purpose of this study is to evaluate the oncological and functional outcomes of patients with parosteal osteosarcoma (PAOS) of the posterior cortex of the distal femur who underwent biological reconstruction after hemicortical resection. Methods Eleven patients who underwent wide tumor resection and defect reconstruction of the posterior surface of the distal femur using hemicortical allograft were retrospectively studied. Local recurrence, metastasis, complications, and the functional outcome using the Musculoskeletal Tumor Society (MSTS) scoring system were evaluated. Results The average postoperative follow-up period was 53.64 months (range, 30 to 84 months). At the latest follow-up, all patients had no evidence of disease without metastases. One patient with local recurrence underwent revision surgery with fibula autograft reconstruction. The mean MSTS score was 93.45 ± 3.56. Conclusions Treatment of patients with PAOS of the posterior aspect of the distal femur with hemicortical resection and allograft reconstruction has satisfactory oncological and functional outcome and low complication rates.

Patients Undergoing Gastric Cancer Surgery with Epidural Combined with General Anesthesia and General Anesthesia

Background: Gastric cancer (GC) is one of the leading causes of mortality and morbidity and adds significantly financial burden to patient and their family on healthcare. The incidence of gastric cancer continues to increase in Bangladesh; therefore there is unmet need of promising treatment modalities. Objective: To investigate the survival of patients undergoing gastric cancer surgery with epidural combined with general anesthesia (EGA) and general anesthesia alone (GA). Methods: A retrospectively observation study was carried out at the Dept. of Anesthesia, National Institute of Cancer Research &amp; Hospital (NICRH), Mohakhali, Dhaka, Bangladesh from June 2021 March 2022. 451 patients with gastric cancer who were scheduled for radical resection. Propensity score matching was performed at a 1:1 ratio between GA (n=75) and EGA (n=75) to reduce selection bias. Univariate and multivariate analyses were used to identify factors significantly correlated with recurrence and/or metastasis and prognosis. The 3-year overall survival rates of patients receiving EGA and GA alone were compared. Results: After the propensity scores were matched, there were 75 patients who underwent EGA and 75 patients who underwent GA. For the entire population, reconstruction type, pN stage, and complications were significantly correlated with prognosis based on multivariate analyses. For patients with a recurrence and/or metastasis, lymphadenectomy and pN stage were shown to be independent prognostic factors by multivariate analysis. Conclusions: In summary, patients might benefit from EGA as a result of better analgesic and anti-inflammatory effects, fewer postoperative complications, higher safety, and a lower rate of metastasis and recurrence is conducive to postoperative recovery in patients with gastric cancer.

Serum Thyroglobulin Measurement Following Surgery Without Radioactive Iodine for Differentiated Thyroid Cancer: A Systematic Review.

Background: The utility of serum thyroglobulin (Tg) measurement following partial thyroidectomy or total/near-total thyroidectomy without radioactive iodine (RAI) for differentiated thyroid cancer is unclear. This systematic review examines the diagnostic accuracy of serum Tg measurement for persistent, recurrent, and/or metastatic cancer in these situations. Methods: Ovid MEDLINE, Embase, and Cochrane Central were searched in October 2021 for studies on Tg measurement following partial thyroidectomy or total/near-total thyroidectomy without or before RAI. Quality assessment was performed, and evidence was synthesized qualitatively. Results: Thirty-seven studies met inclusion criteria. Four studies (N = 561) evaluated serum Tg measurement following partial thyroidectomy, five studies (N = 751) evaluated Tg measurement following total/near-total thyroidectomy without RAI, and 28 studies (N = 7618) evaluated Tg measurement following total or near-total thyroidectomy before RAI administration. Following partial thyroidectomy, Tg measurement was not accurate for diagnosing recurrence or metastasis, or estimates were imprecise. Following total/near-total thyroidectomy without RAI, evidence was limited due to few studies with very low rates of recurrence or metastasis, but indicated that Tg levels were usually stable and low. For Tg measurements before RAI administration, diagnostic accuracy for metastatic disease or persistence varied, although sensitivity appeared high (but specificity low) at a cutoff of >1 to 2.5 ng/mL. However, applicability to patients who do not undergo RAI is uncertain because patients selected for RAI are likely to represent a higher risk group. The evidence was very low quality for all scenarios. All studies had methodological limitations, and there was variability in the Tg thresholds evaluated, patient populations, outcomes assessed, and other factors. Conclusions: Very limited evidence suggests low utility of Tg measurement for identifying recurrent or metastatic disease following partial thyroidectomy. Following total/near-total thyroidectomy, Tg levels using a cutoff of 1-2.5 ng/mL might identify patients at low risk for persistent or metastatic disease. Additional research is needed to clarify the role of Tg measurement in these settings, determine optimal Tg thresholds, and determine appropriate measurement intervals.

Nuclear Location Bias of HCAR1 Drives Cancer Malignancy by Multiple Routes

IntroductionG‐Protein Coupled Receptors (GPCR) are virtually involved in all physiological processes. HCAR1 (GPR81), as a GPCR, is endogenously activated by lactate and has been shown to promote cancer malignancy via higher level of glycolysis due to Warburg effect. Its expression level is highly elevated in many cancers and negatively correlates with patient’s prognosis. However, its mechanism of action is not well understood.On the other hand, nuclear localization of several GPCRs have been described albeit it is unusual feature for them. Additionally, it has been shown that nuclear GPCRs can perform functions distinct from their cell surface counterparts in vivo. Here we demonstrate HCAR1 has a nuclear localization and this localization pattern promotes cancer malignancy by multiple routes.Methods and ResultsWe determined HCAR1 nuclear localization pattern by cell fractionation, immunofluorescence confocal imaging and TEM. Site‐directed mutagenesis showed ICL3 and phosphorylation of C‐terminal domains are required for nuclear localization. We also demonstrated that this localization is ligand independent and there is a pool of nuclear HCAR1 (N‐HCAR1) in the cells. We show N‐HCAR1 induces intra‐nuclear signaling through Gi and Gßγ by WB and ELISA leading to increased phosphorylation of nuclear AKT and ERK resulting in increased cancer cell survival and proliferation. Our ChIP‐sequencing data shows N‐HCAR1 binds to the genes regulating transcription and promoting expression of genes involved in cell migration and we validated this in cellulo proving N‐HCAR1 promotes migration. We identified N‐HCAR1 interactome by Bio‐ID coupled with mass spectrometry and found, it interacts with proteins involved in ribosome biogenesis, translation and DNA damage repair and our experimental data demonstrates that specifically the N‐HCAR1 promotes these three process in cellulo. Additionally, we identified the transcriptomic signature of N‐HCAR1 and showed it regulated a larger gene network than its plasma membrane counterpart. Concordantly, our in vivo tumor xenografts and tail vein injections proves that tumors without N‐HCAR1 have smaller size and tumor mass and lower metastatic rate as well.ConclusionHere we show an unusual localization of a GPCR in the nucleus and provide evidence that N‐HCAR1 specifically promotes various hallmarks of cancer malignancy. The effect of N‐HCAR1 is validate in vivo in tumor xenografts as well. Understanding these mechanisms can provide targets and cues for therapeutic developments.

Circular RNA circMRPS35 regulates progression and autophagy in osteosarcoma cells by recruiting KAT6B to govern FOXO3.

Osteosarcoma serves as frequently occurred bone malignancy that displays low survival rate and high incidence of metastasis. Circular RNAs (circRNAs) have been reported as the crucial molecules in osteosarcoma development. However, the effect of circRNA circMRPS35 on osteosarcoma remains unclear. Here, we aimed to explore the function of circMRPS35 in the regulation of autophagy and progression of osteosarcoma. The colony formation numbers and Edu-positive osteosarcoma cells were repressed by the overexpression of circMRPS35. Meanwhile, the overexpression of circMRPS35 increased the apoptosis rate of osteosarcoma cells. The expression levels of autophagy markers, including LC3 and Beclin1, were enhanced by the overexpression of circMRPS35 in osteosarcoma cells. Mechanically, the depletion of circMRPS35 reduced the enrichment of histone H3 lysine 23 acetylation (H3K23ac) on forkhead box O3 (FOXO3) promoter in osteosarcoma cells. The interaction of circMRPS35 and KAT6B was identified. The knockdown of KAT6B reduced the enrichment of H3K23ac on FOXO3 promoter in osteosarcoma cells. The depletion of circMRPS35 repressed the expression of FOXO3 in the MG63 and MNNG/HOS cells, whereas the overexpression of KAT6B reversed the effect. Significantly, KAT6B promotes apoptosis and autophagy of osteosarcoma cells. The overexpression of circMRPS35 induced the apoptosis and autophagy of osteosarcoma cells, in which the depletion of KAT6B or FOXO3 reversed the effect. The overexpression of circMRPS35 inhibited the tumor growth in vivo , whereas the depletion of KAT6B could reverse the effect in the mice. Therefore, we concluded that circRNA circMRPS35 repressed progression and induced autophagy of osteosarcoma cells.

Hypoxia and anaerobic metabolism relate with immunologically cold breast cancer and poor prognosis.

Hypoxia-Inducible Factor HIF1α and lactate dehydrogenase LDHA drive anaerobic tumor metabolism and define clinical aggressiveness. We investigated their expression in breast cancer and their role in immune response and prognosis of breast cancer. Tissue material from 175 breast cancer patients treated in a prospective study were analyzed with immunohistochemistry for HIF1α and LDH5 expression, in parallel with the tumor-infiltrating lymphocyte TIL-density and tertiary lymphoid structure TLS-density. High LDH5 expression was noted in 48/175 tumors, and this was related to HIF1α overexpression (p < 0.0001), triple-negative TNBC histology (p = 0.01), poor disease-specific survival (p < 0.007), metastasis (p < 0.01), and locoregional recurrence (p = 0.03). High HIF1α expression, noted in 39/175 cases, was linked with low steroid receptor expression (p < 0.05), her2 overexpression (p = 0.01), poor survival (p < 0.04), and high metastasis rates (p < 0.004). High TIL-density in the invading tumor front (TILinv) was linked with low LDH5 and HIF expression (p < 0.0001) and better prognosis (p < 0.02). High TIL-density in inner tumor areas (TILinn) was significantly linked with TNBC. Multivariate analysis showed that PgR-status (p = 0.003, HR 2.99, 95% CI 1.4-6.0), TILinv (p = 0.02, HR 2.31, 95% CI 1.1-4.8), LDH5 (p = 0.01, HR 2.43, 95% CI 1.2-5.0), N-stage (p = 0.04, HR 2.42, 95% CI 1.0-5.8), T-stage (p = 0.04, HR 2.31, 95% CI 1.0-5.1), and her2 status (p = 0.05, HR 2.01, 95% CI 1.0-4.2) were independent variables defining death events. Overexpression of LDH5, an event directly related to HIF1α overexpression, characterizes a third of breast tumors, which is more frequent in TNBC. Both HIF1α and LDH5 define cold breast cancer microenvironment and poor prognosis. A rational is provided to study further whether metabolic manipulations targeting HIF and LDH5 may enhance the antitumor immune response in breast cancer.

The Necessity of Lymph Node Dissection Between Sternocleidomastoid and Sternohyoid Muscles in pN1b Papillary Thyroid Carcinoma

BackgroundThis study aimed to evaluate the association between clinicopathologic variables and metastasis of the lymph node (LN) between the sternocleidomastoid and sternohyoid muscles (LNSS) to clarify the necessity of LNSS dissection in papillary thyroid carcinomas (PTCs).MethodsA total of 219 patients undergoing unilateral or bilateral neck dissection for PTCs were prospectively enrolled. The associations between clinicopathologic variables and LNSS metastasis were evaluated by univariate and multivariate analyses.ResultsLNSS was present in 108 (40.1%) neck dissection samples and in 76 (34.7%) patients. Positive LNSS occurred in 40/269 (14.9%) neck dissection samples and in 20/219 (9.1%) patients. Univariate analysis showed that tumor stage, number of positive nodes in level III, and number of positive nodes in level IV were related to LNSS metastasis. Multivariate analysis confirmed that T3/4 stage tumors and >2 positive LNs in level IV independently increased the risk of LNSS metastasis.ConclusionsThe low rate of LNSS metastasis would deem routine dissection unnecessary; however, LNSS would require excision if advanced stage tumors or level IV LN metastasis were present.

Location of inferior mesentery artery ligation in rectal cancer surgery: how to make decisions based on available evidence

There are still controversies as to the location of ligating the inferior mesenteric artery and the central lymph node dissection during rectal cancer surgery. The reason is that the level of evidence in this area is low. Existing studies are mostly retrospective, analyses or small-sample randomized controlled trials. These results showed no significant differences between high-ligation and low-ligation, in terms of anastomotic leakage and other short-term postoperative complications. Low-ligation seems better for the recovery of postoperative genitourinary function. Due to the low rate of central lymph node metastasis and many other confounding factors that affect the survival rate, it is difficult to conclude the survival benefits of ligation site or central node dissection. It is necessary to carry out some targeted, well-designed, large-scale randomized controlled trials to explain the related issues of inferior mesenteric artery ligation site and extent of central lymphadenectomy.

Progress in neoadjuvant therapy for gastric cancer.

Gastric cancer is one of the most common malignant tumor types in the world and the majority of patients have already reached the advanced stage at the time of initial diagnosis, owing to the subtle symptoms of gastric cancer in the early stage and the low rate of screening in the population. Surgical resection is one of the main treatments for advanced gastric cancer; however, the efficacy of surgery is limited by factors such as low radical resection rate and high distant metastasis rate. A large number of clinical trials have indicated that neoadjuvant therapy (NAT), which consists of neoadjuvant chemotherapy, neoadjuvant chemoradiotherapy and NAT combined with targeted therapy, may improve the therapeutic effect and prognosis of patients to different degrees. However, the benefit of NAT remains controversial due to the heterogeneity of clinical trials and gastric cancer itself. The present review summarizes the main research progress and key breakthrough of NAT for advanced gastric cancer and discusses its prospects.

A Critical Review of the risk factors associated with Canine Squamous Cell Carcinoma development

Squamous cell carcinoma (SCC) is a common neoplastic skin disease that is highly prevalent in tropical countries. As the skin has a variety of cells, overexposure to environmental factors, such as ultraviolet light, can affect this organ, resulting in malignancies, such as cutaneous SCC, hemangioma, and hemangiosarcoma. SCC arises from keratinocytes in the skin and is locally invasive with low metastatic rates, commonly affecting unpigmented skin in sites with high exposure to sunlight, such as ventral regions. SCC has a variable etiology that is not well understood. Therefore, literature review aimed to critically evaluate the risk factors involved in the SCC development.

Сongenital infantile fibrosarcoma with a non-canonical TPM3-NTRK1 fusion transcript: a case report and a literature review

Infantile fibrosarcoma (IFS) is a rare malignant soft tissue tumor characterized by local invasion, a low rate of distant metastasis (1–13%), and manifestation during the first years of life. Overall survival rates range from 89 to 94%, event-free survival rates – from 81 to 84%. Classic IFS is characterized by t(12;15)(p13;q25) translocation resulting in the formation of the ETV6-NTRK3 fusion transcript. However, over the past few years, there have been numerous reports of IFS-like tumors with non-canonical genetic aberrations (BRAF, NTRK1, MET genes) whose prognosis is less predictable. Here we report a rare case of congenital IFS with involvement of subcutaneous fat, indolent course and a non-canonical TPM3-NTRK1 fusion transcript identified in the soft tissue and intradermal tumor components with different histological features. The patient’s parents gave their consent to the use of their child’s data, including photographs, for research purposes and in publications. The literature review explores modern algorithms for the diagnosis and treatment of IFS in children, including the use of new therapies, such as tropomyosin receptor kinase inhibitors, as well as algorithms for detecting NTRK1, NTRK2, NTRK3 gene rearrangements in solid neoplasms in general, and soft tissue tumors in particular.

Risk factors for vertical incomplete resection in endoscopic submucosal dissection of deep invasive submucosal colorectal cancer

Introduction It has been recently reported that deep invasive submucosal (T1b) colorectal cancer (CRC) without other pathological risk factors for lymph node metastasis has a low rate of lymph node metastasis, increasing the possibility of endoscopic submucosal dissection (ESD) in the future. However, ESD for T1b CRC is technically difficult, and some lesions cannot be resected en bloc. This study aimed to identify the risk factors associated with vertical incomplete ESD in T1b CRC. Methods We retrospectively studied 140 pathological T1b CRC lesions that underwent initial ESD at our institution between January 2011 and October 2020, and categorized them into positive vertical margin (PVM) and negative vertical margin (NVM) groups. The risk factors for PVM were examined using univariate and multivariate analyses, and a subgroup analysis for T1b CRC with an obvious depressed surface was performed. Results Multivariate analysis revealed obvious depression (hazard ratio [HR]: 7.4; 95% confidence interval [CI]: 2.47–22.5) and severe fibrosis (HR: 11.4; 95% CI: 3.95–33.0) as significant risk factors for PVM. Length of depressed surface ≥12 mm (HR: 6.19; 95% CI: 1.56 –24.6) was identified as an independent predictor of PVM for T1b CRC with an obvious depression. Conclusion Pathological T1b CRC cases with an obvious depression and severe fibrosis are at a high risk of vertical incomplete ESD.

Measuring the Submucosal Depth of Invasion in Endoscopic Mucosal Resections for Barrett-associated Adenocarcinoma: Practical Issues and Relevance for the Decision for Esophagectomy.

Endoscopic mucosal resection (EMR) has made it possible for Barrett esophagus patients with superficial cancers to be treated without esophagectomy. Recent guidelines recommend measuring depth of invasion (DOI) in submucosal cancers based on reports that in low-risk cancers, submucosal invasion 500 μm or less is associated with low nodal metastasis rates. However, pathologists face challenges in reproducibly measuring DOI. To determine how often DOI measurements could impact treatment and to evaluate reproducibility in measuring submucosal DOI in EMR specimens. Consecutive adenocarcinoma EMR cases were identified, including cases of "low histologic risk" submucosal cancer, as follows: those with negative deep margins, no high-grade histology (G3), and no lymphovascular invasion. Submucosal DOI was measured by 7 pathologists according to guidelines. Of 213 cancer EMR cases, 46 were submucosa invasive and 6 cases were low histologic risk submucosal cancers for which measurement could impact decision-making. Of these low histologic risk cases, 3 were categorized as superficial, indicating that measurement would be a clinically actionable decision point in only 1.4% of adenocarcinoma EMRs. Interobserver agreement for in-depth categorization between 7 pathologists was moderate (κ = 0.42), and the range of measurements spanned the 500-μm relevant threshold in 40 of 55 measured samples (72.7%). While therapeutic decisions would rarely have depended on DOI measurements alone in our cohort, interobserver variability raises concerns about their use as a sole factor on which to offer patients conservative therapy. Responsibly reporting and clinically using submucosal DOI measurements will require practical experience troubleshooting common histologic artifacts, as well as multidisciplinary awareness of the impact of variable specimen-handling practices.

Dermatofibrosarcoma Protuberans- A Case Report

Dermatofibrosarcoma Protuberans (DFSP) is an uncommon soft tissue tumor that involves the dermis, subcutaneous fat, and in rare cases, muscle and fascia. It represents less than 0.1% of all tumors, but is considered to be the most common skin sarcoma. We present one such case where histopathology and immunohistochemistry helped clinch the diagnosis .DFSP has a high rate of recurrence but a low rate of metastasis. Wide surgical excision is the cornerstone of treatment for DFSP.

VEGF Expression, Cellular Infiltration, and Intratumoral Collagen Levels after Electroporation-Based Treatment of Dogs with Cutaneous Squamous Cell Carcinoma.

Canine cutaneous squamous cell carcinoma (SCC) is the most common type of skin cancer in tropical countries and is generally associated with exposure to solar ultraviolet light. It has a low metastatic rate, and local treatments, such as electrochemotherapy (ECT), promote long-term control or even complete remission. This study aimed to evaluate pre- and post-ECT treatment expression levels of vascular endothelial growth factor (VEGF) and CD31, cellular infiltration, and intratumoral collagen levels in dogs with cutaneous SCC. A prospective nonrandomized clinical study was performed using dogs with spontaneous SCC treated with ECT. Eighteen lesions from 11 dogs were included in the study. The expression levels of VEGF and CD31; cellular infiltration; and intratumoral collagen levels, as determined by Masson’s trichrome staining, were not significantly different from pre-treatment measurements on day 21 (p > 0.05). However, among cellular infiltration, the mixed subtype was correlated with better overall survival time when compared to lymphoplasmacytic and neutrophilic infiltration (p < 0.05). In conclusion, ECT had no effect on VEGF expression, cellular infiltration, or intratumoral collagen levels in dogs with cutaneous SCC at the time of evaluation, suggesting that early and late post-ECT-treatment phases should be considered.