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Perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal tumor. Some papers have reported that colonoscopy could be used to treat PEComa with a predominantly pedunculated polyp, whereas surgical intervention is often required for cases with submucosal-type tumors. These findings suggest that the morphology of PEComa changes dramatically with disease progression. Because of the rapid progression of PEComa, endoscopic treatment remains challenging, and early-stage PEComa morphology is not well understood. A 64-year-old man presented to our hospital for a follow-up colonoscopy after undergoing multiple polypectomies. He had a medical history of colorectal adenoma and prostate cancer. A 4-mm pale blue elevated but not pedunculated lesion was observed in the transverse colon, an area where he had not had polyps previously. Since no epithelial change was observed, the presence of a submucosal tumor, such as a gastrointestinal stromal tumor, was suspected. Cold snare polypectomy was performed, and the lesion was completely resected. Histological evaluation using hematoxylin and eosin staining identified that the submucosal tumor included thickened vascular walls and adipose tissue. Although fragmented due to significant degeneration, spindle-shaped cells staining positive for smooth muscle actin were observed within and surrounding the unstructured hyalinized tissue with calcifications. Based on these findings, the lesion was diagnosed as angiomyolipoma, a subtype of PEComa. Complete resection was confirmed by histopathology. To our knowledge, this PEComa is the smallest of any PEComa reported in the literature. Our finding provides valuable insights into the very early stage of colorectal PEComas.
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Objective: The population-based colorectal cancer screening guidelines in Japan recommend an annual fecal immunochemical test (FIT). However, there is no consensus on the need for annual FIT screening for patients who recently performed a total colonoscopy (TCS). Therefore, we evaluated the repeated TCS results for patients with positive FIT after a recent TCS to assess the necessity of an annual FIT. Methods: We reviewed patients with positive FIT in opportunistic screening from April 2017 to March 2022. The patients were divided into two groups: those who had undergone TCS within the previous 5 years (previous TCS group) and those who had not (non-previous TCS group). We compared the detection rates of advanced neoplasia and colorectal cancer between the two groups. Results: Of 671 patients, 151 had received TCS within 5 years and 520 had not. The detection rates of advanced neoplasia in the previous TCS and non-previous TCS groups were 4.6% and 12.1%, respectively (p < 0.01), and the colorectal cancer detection rates were 0.7% and 1.5%, respectively (no significant difference). The adenoma detection rates were 33.8% in the previous TCS group and 40.0% in the non-previous TCS group (no significant difference). Conclusions: Only a few patients were diagnosed with advanced neoplasia among the patients with FIT positive after a recent TCS. For patients with adenomatous lesions on previous TCS, repeated TCS should be performed according to the surveillance program without an annual FIT. The need for an annual FIT for patients without adenomatous lesions on previous TCS should be prospectively assessed in the future.
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PURPOSE: This study aimed to elucidate the predictive role of an oxidative stress-related genes (OSRGs) model in colon cancer. MATERIALS AND METHODS: First, OSRGs that were differentially expressed between tumor and normal tissues were identified using The Cancer Genome Atlas (TCGA)-(Colorectal Adenocarcinoma) COAD dataset. Then, Lasso COX regression was performed to develop an optimal prognostic model patients were stratified into high- and low-risk groups based on the expression patterns of these genes. The model's validity was confirmed through Kaplan-Meier survival curves and receiver operating characteristic curve (ROC) analysis. Additionally, enrichment analyses were performed using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) to uncover underlying mechanisms. RESULTS: A totally of 115 differentially expressed OSRGs were identified within the TCGA cohort, with 17 significantly linked to overall survival. These 17 genes were used to formulate a prognostic model that differentiated patients into distinct risk groups, with the high-risk group demonstrating a notably inferior overall survival rate. The risk score, when integrated with clinical and pathological data, emerged as an independent prognostic indicator of colon cancer. Further analyses revealed that the disparity in prognostic outcomes between risk groups could be attributed to the reactive oxygen species pathway and the p53 signaling pathway. CONCLUSION: A new prediction model was established based on OSRGs. CYP19A1, NOL3 and UCN were found to be highly expressed in tumor tissues and substantial clinical predictive significance. These findings offer new insights into the role of oxidative stress in colon cancer.
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Thrombosis is the primary cause of death in patients with cancer. Resveratrol inhibits platelet activation, a crucial pathophysiological basis of thrombosis, in healthy individuals. However, its effects and mechanisms of action in patients with colon cancer remain unknown. Here, we investigated the effect of resveratrol on platelet adhesion and aggregation in patients with colon cancer. Through numerous in vitro and in vivo analyses, including flow cytometry, western blotting, ELISA, and immunofluorescence and colon cancer rat models, we demonstrated that resveratrol reduced thrombosis in patients with colon cancer by inhibiting the phosphorylation of the MAPK and activating the cyclic-GMP/vasodilator-stimulated phosphoprotein pathway. These findings demonstrate the potential of resveratrol in reducing thrombosis in patients with colon cancer and could be used to develop novel therapeutic strategies for this condition.
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BACKGROUND: Clinical care pathways help guide and provide structure to clinicians and providers to improve healthcare delivery and quality. The Quality Improvement and Patient Safety Committee (QIPS) of the American Society for Metabolic and Bariatric Surgery (ASMBS) has previously published care pathways for the performance of laparoscopic sleeve gastrectomy (LSG) and pre-operative care of patients undergoing Roux-en-Y gastric bypass (RYGB). OBJECTIVE: This current RYGB care pathway was created to address intraoperative care, defined as care occurring on the day of surgery from the preoperative holding area, through the operating room, and into the postanesthesia care unit (PACU). METHODS: PubMed queries were performed from January 2001 to December 2019 and reviewed according to Level of Evidence regarding specific key questions developed by the committee. RESULTS: Evidence-based recommendations are made for care of patients undergoing RYGB including the pre-operative holding area, intra-operative management and performance of RYGB, and concurrent procedures. CONCLUSIONS: This document may provide guidance based on recent evidence to bariatric surgeons and providers for the intra-operative care for minimally invasive RYGB.
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Lung and colon cancers are leading contributors to cancer-related fatalities globally, distinguished by unique histopathological traits discernible through medical imaging. Effective classification of these cancers is critical for accurate diagnosis and treatment. This study addresses critical challenges in the diagnostic imaging of lung and colon cancers, which are among the leading causes of cancer-related deaths worldwide. Recognizing the limitations of existing diagnostic methods, which often suffer from overfitting and poor generalizability, our research introduces a novel deep learning framework that synergistically combines the Xception and MobileNet architectures. This innovative ensemble model aims to enhance feature extraction, improve model robustness, and reduce overfitting.Our methodology involves training the hybrid model on a comprehensive dataset of histopathological images, followed by validation against a balanced test set. The results demonstrate an impressive classification accuracy of 99.44%, with perfect precision and recall in identifying certain cancerous and non-cancerous tissues, marking a significant improvement over traditional approach.The practical implications of these findings are profound. By integrating Gradient-weighted Class Activation Mapping (Grad-CAM), the model offers enhanced interpretability, allowing clinicians to visualize the diagnostic reasoning process. This transparency is vital for clinical acceptance and enables more personalized, accurate treatment planning. Our study not only pushes the boundaries of medical imaging technology but also sets the stage for future research aimed at expanding these techniques to other types of cancer diagnostics.
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Neoplasias do Colo , Aprendizado Profundo , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/classificação , Neoplasias do Colo/diagnóstico por imagem , Neoplasias do Colo/classificação , Inteligência ArtificialRESUMO
Colorectal cancer (CRC) represents a significant global healthcare burden, with a particularly concerning rising incidence among younger adults. This trend may highlight potential links between diet, gut microbiome, and CRC risk. Novel therapeutic options have been increasingly based on the understanding of molecular mechanisms and pathways. The PI3K/AKT/mTOR pathway, a crucial cell growth regulator, offers a promising target for CRC therapy. mTOR, a key component within this pathway, controls cell growth, survival, and metabolism. Understanding the specific roles of defensins, particularly human ß-Defensin 1 (HBD-1), in CRC is crucial. HBD-1 exhibits potent antimicrobial activity and may influence CRC development. Deciphering defensin expression patterns in CRC holds the promise of improved understanding of tumorigenesis, which may pave the way for improved diagnostics and therapies. This article reviews recent advances in understanding regarding how HBD-1 influences CRC initiation and progression, highlighting the molecular mechanisms by which it impacts CRC. Further, we describe the interaction between defensins and mTOR pathway in CRC.
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(1) Background: Adenosquamous carcinoma (ASC) is a rare subtype of colon cancer. Its rarity makes characterization challenging, although colonic ASC is believed to present at more advanced stages and have worse outcomes versus adenocarcinoma. This study aims to characterize the clinicopathological characteristics and clinical outcomes of colonic ASC. (2) Methods: This is a single-center, retrospective review of patients diagnosed with colonic ASC from 2000 to 2020. Data extracted included patient demographics, staging at diagnosis, tumor clinicopathologic and genetic characteristics, and clinical outcomes. (3) Results: Among 61,126 patients with colorectal cancer, 13 (0.02%) had colonic ASC, with a mean age at diagnosis of 48.7 years. The cecum/ascending colon was the most common primary site (6/13, 46.2%), and all except one patient was diagnosed with Stage III or IV disease. Among the eight patients with mismatch repair genetics available, only one was mismatch repair deficient. Eleven patients (84.6%) underwent surgery, and 11 likewise received some form of chemotherapy. Recurrence occurred in 7 of 13 patients (53.8%), and the overall five-year survival rate was 38.5%. The median survival rate was 39.4 months overall (30.5 months for Stage III, 23.7 months for Stage IV). (4) Conclusions: Overall, colonic ASC is rare, and this cohort of colonic ASC patients demonstrated advanced stage at diagnosis, frequent recurrence, and poor overall survival. Additional research remains to compare these characteristics with those of comparably staged adenocarcinoma and to develop specific management recommendations.
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Background: Drug resistance is the primary obstacle to advanced tumor therapy and the key risk factor for tumor recurrence and death. 5-Fluorouracil (5-FU) chemotherapy is the most common chemotherapy for individuals with colorectal cancer, despite numerous options. Methods: The Gene Expression Omnibus database was utilized to extract expression profile data of HCT-8 human colorectal cancer wild-type cells and their 5-FU-induced drug resistance cell line. These data were used to identify 5-FU resistance-related differentially expressed genes (5FRRDEGs), which intersected with the colorectal adenocarcinoma (COAD) transcriptome data provided by the Cancer Genome Atlas Program database. A prognostic signature containing five 5FRRDEGs (GOLGA8A, KLC3, TIGD1, NBPF1, and SERPINE1) was established after conducting a Cox regression analysis. We conducted nomogram development, drug sensitivity analysis, tumor immune microenvironment analysis, and mutation analysis to assess the therapeutic value of the prognostic qualities. Results: We identified 166 5FRRDEGs in patients with COAD. Subsequently, we created a prognostic model consisting of five 5FRRDEGs using Cox regression analysis. The patients with COAD were divided into different risk groups by risk score; the high-risk group demonstrated a worse prognosis than the low-risk group. Conclusion: In summary, the 5FRRDEG-based prognostic model is an effective tool for targeted therapy and chemotherapy in patients with COAD. It can accurately predict the survival prognosis of these patients as well as to provide the direction for exploring the resistance mechanism underlying COAD.
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Objectives: Fibroleukin (FGA) and NOTCH3 are vital in both exercise-induced muscle adaptation and colon adenocarcinoma (COAD) progression. This study aims to elucidate the roles of FGA and NOTCH3 in phenotypic variations of striated muscle induced by exercise and in COAD development. Additionally, it seeks to evaluate the prognostic significance of these proteins. Methods: Gene Set Variation Analysis (GSVA) and protein-protein interaction (PPI) network analysis were employed to identify differentially expressed genes (DEGs). Molecular docking studies were conducted to assess the binding affinities of 39 compounds to the NOTCH3 protein. In vitro assays, including mobileular viability, gene expression, and apoptosis assays, were performed to evaluate the effects of glycerophosphoinositol on FGA and NOTCH3 expression. Additionally, copy number variation (CNV), methylation status, and survival analyses were conducted across multiple cancers types. Results: The NOTCH signaling pathway was consistently upregulated in exercise-induced muscle samples. High NOTCH3 expression was associated with poor prognosis in COAD, extracellular matrix organization, immune infiltration, and activation of the PI3K-Akt pathway. Molecular docking identified gamma-Glu-Trp, gamma-Glutamyltyrosine, and 17-Deoxycortisol as strong binders to NOTCH3. Glycerophosphoinositol treatment modulated FGA and NOTCH3 expression, influencing cell proliferation and apoptosis. CNV and methylation analyses revealed specific changes in FGA and NOTCH3 across 20 cancers types. Survival analyses showed strong associations between FGA/NOTCH3 expression and survival metrics, with negative correlations for FGA and positive correlations for NOTCH3. Conclusion: FGA and NOTCH3 play significant roles in exercise-induced muscle adaptation and colon cancer progression. The expression profiles and interactions of these proteins provide promising prognostic markers and therapeutic targets. These findings offer valuable insights into the post-translational modifications (PTMs) in human cancer, highlighting novel pharmacological and therapeutic opportunities.
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Oligosaccharides have been widely used as prebiotics in the food industry, however their properties have been examined in vitro, without considering hydrolysis in the human digestive tract, especially in the small intestine. Here, we hypothesized that the prebiotic effects and utilization efficiency of ingested oligosaccharides would be altered in the colon, as their structures are partially hydrolyzed during digestion. Different types of oligosaccharides were partially degraded during simulated digestion, and digestible monosaccharides were released from the initial substrates. The growth of some probiotic strains responded to the presence of digestible/absorbable mono- and disaccharides (components of the prebiotic oligosaccharides), but not to that of the oligosaccharides themselves. These findings regarding oligosaccharide degradation in the gastrointestinal tract can be used to achieve greater experimental accuracy when examining the effects of prebiotics on gut flora via in vitro studies (e.g., on fecal fermentation or microbial growth rates). Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01474-z.
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The incidence of ulcerative colitis (UC) is rapidly rising worldwide. Oral drug delivery system is a promising approach for treating UC, but it often fails to accumulate to the inflammatory lesions, thus, it is impressive to develop a colon-targeted oral delivery system for preventing systemic toxicity and maintaining UC therapeutics. Here, a negative-charged PLGA nanoparticle system was designed to encapsulate celastrol (Cel), and then chitosan and mannose were coated on the surface of the nanoparticles (MC@Cel-NPs) to endow these nanoparticles with the mucosal adsorption and macrophage targeting abilities. MC@Cel-NPs demonstrate excellent resist decomposition ability against the strong acidic gastrointestinal environment, and accumulates in the specific inflammatory sites through the affinity of electrostatic reaction. After releasing the payload, MC@Cel-NPs could remarkably alleviate the colon inflammation, which was evidenced by the decrease in pro-inflammatory cytokines TNF-α, IL-1ß, and IL-6 in both blood and colon sections, and scavenging reactive oxygen species (ROS) in colon cells, including macrophage, neutrophil, T cell, and B cell. This nanoparticle system provided a new approach for treating UC through a Chinese herbal ingredient-related oral delivery manner.
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Colonoscopy has proven efficacy for both screening and diagnostic purposes. Although the risk of complications during colonoscopy is low, it is not negligible. As such, we present the case of a 72-year-old male patient who presented with abdominal pain and positive peritoneal signs post-colonoscopy. He was found to have anemia and acute on chronic kidney disease. An abdominal CT scan found evidence of hemoperitoneum. Subsequently, he underwent a diagnostic laparoscopy converted into an open exploratory laparotomy to identify the source of bleeding, an avulsed mesocolon. A review of the literature regarding colonoscopy and associated complications is discussed, highlighting the importance of risk stratification to better treat patients and prognosticate outcomes.
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Studies in rodents suggest that inulin supplements may be carcinogenic. We present a case implicating that this risk extends to humans. A healthy male from a family lacking history of cancer had his first cancer-screening colonoscopy at age 56. No intestinal polyps/abnormalities were detected. A second colonoscopy, performed 7 years later, revealed a tumor in the cecum, with evidence of metastasis to lymph nodes. The only known change in patient's lifestyle during that seven-year period was the addition of 4g of inulin powder as a daily supplement during the last 2 years. Such inulin consumption is a plausible contributor to his disease.
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Hemangiomas in the gastrointestinal tract are extremely rare, benign vascular tumors, known for their associated complication of bleeding. They are usually difficult to diagnose, despite the characteristic definition of radiolucent phleboliths on radiology and purplish, tannish brown nodule or polyp on endoscopy. Surgical resection is the treatment of choice. We describe a rare case of sigmoid colon cavernous hemangioma in a 49-year-old male who underwent colonoscopy for lower abdominal pain and revealed a large pedunculated polyp in the sigmoid colon measuring 1.7 cm in diameter. The hemangioma was completely resected endoscopically via hot snare with a favorable outcome.
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Background: Otopetrin 2 (OTOP2) is a conserved ion channel protein that regulates cell signaling, growth, and development. Although the role of OTOP2 in tumor suppression has been reported in several studies of colon adenocarcinoma (COAD), characterized its immunomodulatory effects on tumors. Methods: We conducted a thorough analysis of OTOP2 expression and its association with clinicopathological characteristics, immune-related pathways, and immune-related molecules in individuals with COAD using data from The Cancer Genome Atlas (TCGA) and confirmed the findings with tissue microarrays (TMAs). We conducted in vitro assays to demonstrate the tumor suppressive effect of OTOP2 in COAD cells. Results: OTOP2 expression was abnormal in multiple types of tumors and was significantly downregulated in patients with COAD (P<0.001). Moreover, the presence of OTOP2 was linked to enhanced survival in individuals diagnosed with COAD. In vitro experiments showed that OTOP2 suppressed cell proliferation, migration, invasion, and adhesion. Gene set enrichment analysis of the TCGA database indicated that OTOP2 was positively correlated with antigen presentation pathways and T cell responses. The immunophenoscore (IPS) indicated a positive correlation between OTOP2 expression and MHC molecule expression (P<0.001) as well as between OTOP2 expression and the number of effector cells (P<0.01). Immunohistochemical analysis of the TMAs revealed strong associations between OTOP2 expression and MHC-I, TAP1, and TAP2 expression, and between OTOP2 expression and CD8+ T cell infiltration in COAD patients. Conclusion: In summary, our research emphasizes the role of OTOP2 as a tumor suppressor, suggesting its use as a prognostic indicator and predictor of response to immunotherapy in COAD patients.
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Background: The impact of tumor size on the survival and chemotherapy reponse of early-stage colon cancer remains unclear. Our study explored the effect of tumor size on overall survival (OS) and postoperative chemotherapy efficacy in patients with stage I/II colon cancer. Methods: Stage I/II colon cancer patients from the Surveillance, Epidemiology and End Results (SEER) database and a China center were extracted as two cohorts respectively. X-tile program was adopted to acquire optimal cutoff points of tumor size (16mm and 49mm). Harrell's concordance index (c-index) and time-dependent receiver operating characteristic curve (ROC) were used to indicate discrimination ability of prognostic factors. Results: Overall, 104,908 and 168 stage I/II postoperative colon cancer patients from SEER database and a China center were eligible, respectively. Kaplan-Meier analysis showed that large tumor size was associated with poor OS in two cohorts. The effect of tumor size on OS gradually decreased as the T stage increased both before PSM (c-index 0.535 for T1N0M0 and 0.506 for T4N0M0, p<0.05) and after PSM (c-index 0.543 for T1N0M0, p<0.05; c-index 0.543 for T4N0M0, p>0.05). Stratified analyses showed that chemotherapy improved the OS rate by 9.5% (chemotherapy vs. non-chemotherapy: 83.5% vs. 73.0%) or 12.8% (chemotherapy vs. non-chemotherapy: 85.7% vs. 72.9%) before and after PSM in T2N0M0 patients with tumor size >49 mm, but not in T1N0M0. The survival benefit provided by chemotherapy for T2N0M0 patients with large tumor was also validated in the Chinese cohort. Conclusions: Large tumor size was a risk factor for stage I/II colon cancer, especially for T1N0M0. Tumor size could serve as a complementary factor guiding postoperative chemotherapy for T2N0M0 patients.
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Endoscopic colorectal stenting has gained momentum over the last two decades as a viable alternative to surgical intervention in a subgroup of patients with colorectal disease. Stenting can be used as a temporizing bridge to surgical intervention or as a definitive treatment measure. Patient selection and the technical expertise of the endoscopist are of paramount importance to optimize the clinical outcome. Technical skills in therapeutic endoscopy and the choice of proper equipment including the consumables are required for the conduct of a safe and successful procedure. In this article, we share the lessons learned from a two-decade journey of the senior author with therapeutic endoscopy.
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Colorectal cancer is the third most common cancer among men and the second among women. In the United States alone, there are 150,000 cases diagnosed each year. Colonoscopy remains the best method for identifying, evaluating, and intervening on patients with precancerous lesions. Multiple guidelines and techniques are available to assist the endoscopist with accurate diagnosis of these lesions. These include the Paris, Narrow-Band Imaging (NBI) International Colorectal Endoscopic (NICE), Japan NBI Expert Team (JNET), Kudo, Hiroshima, and Shudo classifications which utilize techniques such as chromoendoscopy, narrow-band imaging, and endocytoscopy to evaluate pit pattern and surface morphology. Utilization of these tools can help the endoscopist predict the cytology of a colonic lesion and select the most appropriate method for resection while maximizing organ preservation.
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BACKGROUND: Surgical standardization for transverse colon cancers (TCC) has not been established, and the oncologic benefit of central vessel ligation (CVL) are still unclear. This study aimed to evaluate the oncologic safety of TCC surgery without CVL of the middle colic artery (MCA). METHODS: This is a single-center, retrospective, observational, comparative study. The clinical, surgical, and pathological characteristics of the patients who underwent radical surgery for non-metastatic TCC between January 2012 and December 2020 were investigated, and the characteristic and oncologic outcomes of No CVL and CVL groups were compared. RESULTS: The number of No CVL and CVL groups was 47 (44.3%) and 59 (55.7%), respectively. There was no statistically significant difference between the two groups in surgical complications, stage, mean number of retrieved lymph nodes (LN) (24.12 vs. 22.36 p = 0.464), mean number of metastatic LN (1.53 vs. 0.74, p = 0.163), mean proximal margin (19.2 cm vs. 16.7 cm, p = 0.139), mean distal margin (9.6 cm vs. 9.9 cm, p = 0.753), adjuvant chemotherapy, total recurrence rate (6.4 vs. 11.9%, p = 0.507), lymphatic recurrence rate (0.0% vs. 5.1%, p = 0.253), and local recurrence rate (2.1 vs. 1.7%, p = 0.984). Furthermore, there was no statistically significant difference of 5-year disease-free survival (DFS) and overall survival (OS) in stage II (DFS: 94.4 vs. 91.3%, p = 0.685, OS: 94.1 vs. 95.5%, p = 0.838) and stage III (DFS: 88.5 vs. 68.4%, p = 0.253, OS: 100.0% vs. 79.7, p = 0.328). CONCLUSION: TCC surgery without CVL of the MCA showed comparable surgical and oncologic outcomes compared to surgery with CVL. Therefore, preservation of a branch of the MCA may be considered a safe option, when combined with adequate lymph node dissection, if necessary. A large, prospective, and controlled study will be necessary to provide solid evidence of the oncologic safety of this procedure.