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<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">Front. Med.</journal-id>
<journal-title-group>
<journal-title>Frontiers in Medicine</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Med.</abbrev-journal-title>
</journal-title-group>
<issn pub-type="epub">2296-858X</issn>
<publisher>
<publisher-name>Frontiers Media S.A.</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.3389/fmed.2026.1777158</article-id>
<article-version article-version-type="Version of Record" vocab="NISO-RP-8-2008"/>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Case Report</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Case Report: Rare case of primary rectal adenocarcinoma presenting as a smooth submucosal elevation: endoscopic submucosal excavation and 4&#x202F;years and 11&#x202F;months follow-up</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Kong</surname>
<given-names>Qing-li</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<uri xlink:href="https://loop.frontiersin.org/people/2297668"/>
<role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="conceptualization" vocab-term-identifier="https://credit.niso.org/contributor-roles/conceptualization/">Conceptualization</role>
<role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="Data curation" vocab-term-identifier="https://credit.niso.org/contributor-roles/data-curation/">Data curation</role>
<role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="Formal analysis" vocab-term-identifier="https://credit.niso.org/contributor-roles/formal-analysis/">Formal analysis</role>
<role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="investigation" vocab-term-identifier="https://credit.niso.org/contributor-roles/investigation/">Investigation</role>
<role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="methodology" vocab-term-identifier="https://credit.niso.org/contributor-roles/methodology/">Methodology</role>
<role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="Project administration" vocab-term-identifier="https://credit.niso.org/contributor-roles/project-administration/">Project administration</role>
<role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="Writing &#x2013; original draft" vocab-term-identifier="https://credit.niso.org/contributor-roles/writing-original-draft/">Writing &#x2013; original draft</role>
<role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="Writing &#x2013; review &#x0026; editing" vocab-term-identifier="https://credit.niso.org/contributor-roles/writing-review-editing/">Writing &#x2013; review &#x0026; editing</role>
</contrib>
<contrib contrib-type="author" corresp="yes">
<name>
<surname>Zhang</surname>
<given-names>Yao-wen</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
<xref ref-type="corresp" rid="c001"><sup>&#x002A;</sup></xref>
<uri xlink:href="https://loop.frontiersin.org/people/3092465"/>
<role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="conceptualization" vocab-term-identifier="https://credit.niso.org/contributor-roles/conceptualization/">Conceptualization</role>
<role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="methodology" vocab-term-identifier="https://credit.niso.org/contributor-roles/methodology/">Methodology</role>
<role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="Writing &#x2013; review &#x0026; editing" vocab-term-identifier="https://credit.niso.org/contributor-roles/writing-review-editing/">Writing &#x2013; review &#x0026; editing</role>
</contrib>
<contrib contrib-type="author" corresp="yes">
<name>
<surname>Fan</surname>
<given-names>Huan-qing</given-names>
</name>
<xref ref-type="aff" rid="aff3"><sup>3</sup></xref>
<xref ref-type="corresp" rid="c001"><sup>&#x002A;</sup></xref>
</contrib>
</contrib-group>
<aff id="aff1"><label>1</label><institution>Phase I Clinical Trial Laboratory, Affiliated Hospital of Jining Medical University</institution>, <city>Jining</city>, <country country="cn">China</country></aff>
<aff id="aff2"><label>2</label><institution>Department of Endoscopy, Affiliated Hospital of Jining Medical University</institution>, <city>Jining</city>, <country country="cn">China</country></aff>
<aff id="aff3"><label>3</label><institution>Department of Rehabilitation Medicine, Affiliated Hospital of Jining Medical University</institution>, <city>Jining</city>, <country country="cn">China</country></aff>
<author-notes>
<corresp id="c001"><label>&#x002A;</label>Correspondence: Yao-wen Zhang, <email xlink:href="mailto:228zhangyaowen228@163.com">228zhangyaowen228@163.com</email>; Huan-qing Fan, <email xlink:href="mailto:fanhuanqing5917@163.com">fanhuanqing5917@163.com</email></corresp>
</author-notes>
<pub-date publication-format="electronic" date-type="pub" iso-8601-date="2026-03-02">
<day>02</day>
<month>03</month>
<year>2026</year>
</pub-date>
<pub-date publication-format="electronic" date-type="collection">
<year>2026</year>
</pub-date>
<volume>13</volume>
<elocation-id>1777158</elocation-id>
<history>
<date date-type="received">
<day>29</day>
<month>12</month>
<year>2025</year>
</date>
<date date-type="rev-recd">
<day>13</day>
<month>02</month>
<year>2026</year>
</date>
<date date-type="accepted">
<day>20</day>
<month>02</month>
<year>2026</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright &#x00A9; 2026 Kong, Zhang and Fan.</copyright-statement>
<copyright-year>2026</copyright-year>
<copyright-holder>Kong, Zhang and Fan</copyright-holder>
<license>
<ali:license_ref start_date="2026-03-02">https://creativecommons.org/licenses/by/4.0/</ali:license_ref>
<license-p>This is an open-access article distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="https://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License (CC BY)</ext-link>. The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</license-p>
</license>
</permissions>
<abstract>
<p>Primary adenocarcinoma of the rectum presenting as a smooth submucosal elevation is clinically rare. Due to its insidious symptoms and diagnostic challenges in imaging differentiation, the malignant risk is easily overlooked. We report a 64-year-old female patient who was incidentally found to have a 0.9&#x202F;cm diameter submucosal elevation in the rectum (15&#x202F;cm from the anus) during physical examination. Endoscopic ultrasonography (EUS) revealed a hypoechoic mass originating from the muscularis mucosae. Based on intraoperative ultrasound examination, a preliminary diagnosis of rectal neuroendocrine tumor (NET) is made. The lesion was completely resected via endoscopic submucosal excavation (ESE), and postoperative pathology confirmed adenocarcinoma with negative resection margins. The patient had an uneventful postoperative recovery and was followed up for 4&#x202F;years and 11&#x202F;months, nearly 5&#x202F;years without tumor recurrence, metastasis, or impairment of intestinal function, maintaining a good quality of life. This case highlights the necessity of vigilant evaluation for smooth submucosal rectal lesions to avoid missed diagnosis of malignancy. As an advanced minimally invasive endoscopic technique, ESE enables complete resection of submucosal lesions with the advantages of minimal trauma, rapid recovery, preserved intestinal function, and favorable long-term safety, providing valuable clinical experience for the management of similar rare cases.</p>
</abstract>
<kwd-group>
<kwd>clinical cure</kwd>
<kwd>endoscopic submucosal excavation (ESE)</kwd>
<kwd>primary adenocarcinoma</kwd>
<kwd>smooth surface</kwd>
<kwd>submucosal elevation</kwd>
</kwd-group>
<funding-group>
<award-group id="gs1">
<funding-source id="sp1">
<institution-wrap>
<institution>Key Research and Development Program of Jining</institution>
</institution-wrap>
</funding-source>
<award-id rid="sp1">2025YXNS062</award-id>
</award-group>
<funding-statement>The author(s) declared that financial support was received for this work and/or its publication. This study was supported by the Key Research and Development Program of Jining (Grant No. 2025YXNS062). This played an important role in data analysis and manuscript writing.</funding-statement>
</funding-group>
<counts>
<fig-count count="4"/>
<table-count count="0"/>
<equation-count count="0"/>
<ref-count count="15"/>
<page-count count="5"/>
<word-count count="3037"/>
</counts>
<custom-meta-group>
<custom-meta>
<meta-name>section-at-acceptance</meta-name>
<meta-value>Gastroenterology</meta-value>
</custom-meta>
</custom-meta-group>
</article-meta>
</front>
<body>
<sec sec-type="intro" id="sec1">
<label>1</label>
<title>Introduction</title>
<p>Most rectal neuroendocrine tumors are early-stage, small-sized, and superficial lesions. Primary rectal adenocarcinoma typically presents as mucosal roughness, erosion, ulceration, or cauliflower-like protrusion, whereas adenocarcinoma manifesting as a smooth submucosal elevation is extremely uncommon (<xref ref-type="bibr" rid="ref1">1</xref>). Owing to its submucosal location and intact overlying mucosa, this subtype typically lacks obvious clinical symptoms in the early stage and is often detected incidentally during routine physical examinations or workups for other diseases (<xref ref-type="bibr" rid="ref2">2</xref>). The patient in this case was asymptomatic, and the lesion was identified solely through a routine check-up. In clinical practice, most patients with similar lesions are managed with observational follow-up (<xref ref-type="bibr" rid="ref3">3</xref>). However, based on our clinical experience, further pathological examination is imperative to confirm the diagnosis and avoid overlooking malignant risks simply due to the &#x201C;smooth surface&#x201D; of the lesion. For such patients, endoscopic submucosal excavation (ESE) is recommended, as this procedure not only enables definitive diagnosis but also achieves endoscopic treatment. Notably, through long-term follow-up, we report for the first time that this patient has achieved clinical cure, highlighting the potential of ESE as an effective therapeutic strategy for this specific subtype of rectal adenocarcinoma.</p>
</sec>
<sec id="sec2">
<label>2</label>
<title>Case description</title>
<p>A 64-year-old female was admitted to our hospital with a 10-day history of &#x201C;discovered rectal submucosal elevation.&#x201D; Routine laboratory tests upon admission showed no abnormalities. On March 11, 2021, she underwent ESE for the rectal elevation and polypectomy under anesthesia. Colonoscopy revealed the endoscope reached 5&#x202F;cm from the terminal ileum, with normal ileal mucosa, ileocecal valve, and appendix orifice. During withdrawal, a 0.4&#x202F;cm hyperemic mucosal elevation in the ascending colon was ablated by argon plasma coagulation (APC). Six scattered mucosal elevations (0.2&#x2013;0.5&#x202F;cm in diameter), some with hyperemia, were detected in the sigmoid colon and rectum, all treated with APC; one local wound was closed with a metal clip. A 0.9&#x202F;cm smooth submucosal elevation was found in the rectum (15&#x202F;cm from the anus). EUS showed a 9.5&#x202F;mm&#x202F;&#x00D7;&#x202F;3.4&#x202F;mm hypoechoic mass in the muscularis mucosae with clear borders and homogeneous internal echoes. Intraoperative diagnosis was rectal NET and multiple colorectal polyps. Treatment procedure: Submucosal injection was performed around the rectal lesion, followed by marginal pre-incision with a dual-knife. The lesion was completely excised by repeated submucosal injection and stepwise dissection, and the specimen was sent for pathological examination. Hemostasis was achieved at the wound, which was closed with 7 metal clips (Nanjing MicroPort Science &#x0026; Technology Co., Ltd., soft tissue clip, model ROCC-D-26-195, batch number 200119238) (<xref ref-type="fig" rid="fig1">Figure 1</xref>). The patient recovered uneventfully. The postoperative pathology report was shown in <xref ref-type="fig" rid="fig2">Figure 2</xref>. During 4&#x202F;years and 11&#x202F;months, nearly 5&#x202F;years follow-up, the patient had no tumor recurrence or metastasis (<xref ref-type="fig" rid="fig3">Figure 3</xref>), with normal defecation and good quality of life (see <xref ref-type="fig" rid="fig4">Figure 4</xref>).</p>
<fig position="float" id="fig1">
<label>Figure 1</label>
<caption>
<p><bold>(A)</bold> The rectal protruding lesion showed a smooth surface under white light endoscopy. <bold>(B)</bold> No obvious large abnormal blood vessels were observed under narrow-band imaging (NBI). <bold>(C)</bold> Mini-probe endoscopic ultrasound (EUS) revealed a hypoechoic mass located in the muscularis mucosae, with clear borders, uniform internal echo, and a size of approximately 9.5&#x202F;mm&#x202F;&#x00D7;&#x202F;3.4 mm. <bold>(D)</bold> The area around the protruding lesion was marked. <bold>(E)</bold> The mucosal layer was circumferentially incised at a distance of about 5 mm from the lesion. <bold>(F)</bold> After complete resection of the lesion, the muscularis propria was fully exposed at the wound site. <bold>(G)</bold> The wound was closed using multiple metal clips (Micro-Tech, ROCC-D-26-195). <bold>(H)</bold> The completely resected mass was obtained from the submucosal plane.</p>
</caption>
<graphic xlink:href="fmed-13-1777158-g001.tif" mimetype="image" mime-subtype="tiff">
<alt-text content-type="machine-generated">Panel A shows a smooth, raised lesion in an endoscopic view. Panel B depicts a biopsy tool sampling the lesion. Panel C provides an ultrasound image with a green arrow indicating the lesion. Panel D shows the lesion with multiple cauterized biopsy marks. Panel E demonstrates the lesion surrounded by blue dye after submucosal injection. Panel F depicts the tissue following partial removal. Panel G shows several metallic surgical clips closing the wound. Panel H presents the excised lesion extracted from the gastrointestinal tract.</alt-text>
</graphic>
</fig>
<fig position="float" id="fig2">
<label>Figure 2</label>
<caption>
<p><bold>(A)</bold> HE staining, 40&#x00D7;. The long line indicates that the cancerous tissue is located 1.97&#x202F;mm in the submucosa. The short line indicates that the cancerous tissue is 0.75 mm away from the basal resection margin. <bold>(B)</bold> IHC (InVision two-step method), CDX-2(+), 40&#x00D7;. <bold>(C)</bold> IHC (InVision two-step method), SATB-2(+), 40&#x00D7;. Pathological diagnosis: Adenocarcinoma (moderately to poorly differentiated) is identified in the submucosal hyperplastic lymphoid tissue of the rectum. Immunohistochemically, the tumor cells show diffuse strong positivity for CDX-2, CK20, and SATB-2, suggesting an intestinal origin. Tumor budding is graded as G1. No definite lymphovascular tumor emboli or perineural invasion is identified. No carcinoma is found at the lateral and basal resection margins. Immunohistochemistry: Tumor cells: CK(+), CK20(+), CDX-2(+), SATB2(+), CD56(&#x2212;), CgA(&#x2212;), Syn(&#x2212;), P53 (wild-type), Ki-67 (+, &#x003E;75%).</p>
</caption>
<graphic xlink:href="fmed-13-1777158-g002.tif" mimetype="image" mime-subtype="tiff">
<alt-text content-type="machine-generated">Panel A shows a histological section stained with hematoxylin and eosin, including two red measurement lines. Panel B and panel C display adjacent tissue sections with immunohistochemical staining, highlighting brown-stained regions within glandular structures.</alt-text>
</graphic>
</fig>
<fig position="float" id="fig3">
<label>Figure 3</label>
<caption>
<p><bold>(A)</bold> Follow-up colonoscopy showed smooth and unremarkable mucosa. <bold>(B&#x2013;D)</bold> Follow-up chest computed tomography (CT) and abdominal CT revealed no signs of recurrence or metastasis.</p>
</caption>
<graphic xlink:href="fmed-13-1777158-g003.tif" mimetype="image" mime-subtype="tiff">
<alt-text content-type="machine-generated">Panel A shows an endoscopic view of the lower gastrointestinal tract. Panel B displays a CT scan of the lungs in a transverse section. Panel C depicts an abdominal CT scan at the upper abdomen level, and panel D shows an abdominal CT scan at a lower level, both in transverse sections for diagnostic evaluation.</alt-text>
</graphic>
</fig>
<fig position="float" id="fig4">
<label>Figure 4</label>
<caption>
<p>Adenocarcinoma was identified in the hyperplastic submucosal lymphoid tissue of the resected rectal specimen.</p>
</caption>
<graphic xlink:href="fmed-13-1777158-g004.tif" mimetype="image" mime-subtype="tiff">
<alt-text content-type="machine-generated">Histology slide under light microscopy showing a section of tissue with glandular structures and dense clusters of purple-stained cells on a pink background, likely representing a pathological sample.</alt-text>
</graphic>
</fig>
</sec>
<sec sec-type="discussion" id="sec3">
<label>3</label>
<title>Discussion</title>
<p>Traditionally, surgical resection was the mainstay of treatment for rectal submucosal lesions, but it is associated with large trauma, slow recovery, and potential impairment of intestinal function (<xref ref-type="bibr" rid="ref4">4</xref>, <xref ref-type="bibr" rid="ref5">5</xref>). With the advancement of endoscopic technology, ESE has become an important therapeutic option for submucosal lesions originating from the muscularis propria. Its feasibility and advantages in this case are demonstrated as follows: &#x2460; Complete lesion resection: Through submucosal injection, incision, and dissection, ESE allows for en bloc resection of lesions arising from the muscularis propria under direct vision. Postoperative pathology confirmed negative resection margins with no residual tumor, achieving curative resection. &#x2461; Minimally invasive with rapid recovery: ESE is performed via natural orifices without laparotomy or laparoscopy, resulting in minimal intraoperative bleeding. The patient was discharged 3&#x202F;days postoperatively, significantly shortening hospital stay and reducing medical costs. &#x2462; Preservation of intestinal function: ESE only removes the lesion and a small amount of surrounding mucosa and submucosa without damaging the normal intestinal wall structure (<xref ref-type="bibr" rid="ref6 ref7 ref8 ref9 ref10">6&#x2013;10</xref>). Postoperatively, the patient had normal defecation without intestinal dysfunction such as abdominal pain or bloating, maintaining a good quality of life. The 4&#x202F;years and 11&#x202F;months, nearly 5&#x202F;years follow-up showed no tumor recurrence or long-term complications such as intestinal perforation or stricture, confirming the long-term safety and efficacy of ESE in treating such lesions. Early colorectal cancer generally refers to histologically confirmed tumors with a maximum invasion depth not exceeding the superficial submucosa (1/3, sm1), and without other high-risk histological features, including poor differentiation, lymphatic or vascular invasion, and high-grade tumor budding (<xref ref-type="bibr" rid="ref11">11</xref>). Precise and standardized histological risk assessment is required before and after endoscopic treatment to identify the presence of these high-risk features. In patients with two or more high-risk factors, the risk of lymph node metastasis exceeds 10%, and the curative effect of endoscopic resection is insufficient; therefore, additional surgery is recommended. For patients with a single controllable high-risk factor&#x2014;such as isolated deep submucosal invasion (sm2 stage) without other high-risk features [well-differentiated, no lymphovascular invasion (LVI), G1 tumor budding], combined with a lesion diameter &#x2264;20&#x202F;mm and a superficial location (e.g., mid-to-lower rectum)&#x2014;endoscopic treatment can be the first choice, accompanied by rigorous follow-up (<xref ref-type="bibr" rid="ref12">12</xref>). Chen et al. (<xref ref-type="bibr" rid="ref13">13</xref>) reported that poor histological grade and LVI are independent risk factors for lymph node metastasis. Their study indicated that the coexistence of poor histological grade and LVI may exert a synergistic effect, as patients with both high-risk factors exhibited significantly reduced survival rates. In contrast, a cohort study by Gijsbers et al. (<xref ref-type="bibr" rid="ref14">14</xref>) identified tumor budding as a strong risk factor for lymph node metastasis. The author also emphasized that clinical treatment strategies should balance the risk of tumor recurrence against the risk of treatment-related complications. In addition, patients undergoing endoscopic treatment require comprehensive oncological follow-up to enable early detection and intervention of tumor recurrence. The goals of endoscopic treatment include complete resection confirmed by endoscopic evaluation, R0 resection with negative lateral and vertical margins, and curative resection without the aforementioned high-risk features (poor differentiation, lymphatic or vascular invasion, high-grade tumor budding) (<xref ref-type="bibr" rid="ref15">15</xref>). Consistent with previous reports, our case exhibited G1 tumor budding, with no perineural or vascular invasion, and was negative for the above high-risk factors. Notably, the tumor in this case originated in the submucosa, which is distinct from tumors invading into the submucosa. After multidisciplinary team discussion and in accordance with the patient&#x2019;s preference, a supplementary PET-CT scan performed within 3&#x202F;months postoperatively showed no abnormal findings. Subsequent repeated PET-CT scans revealed no evidence of recurrence or metastasis, and regular follow-up contrast-enhanced chest and abdominal CT scans also showed no signs of recurrence or metastasis. Furthermore, telephone follow-up regarding the patient&#x2019;s dietary and bowel habits indicated no discomfort. Although no similar cases have been reported in the literature, we adopted the management strategy for early invasive colorectal cancer, achieving complete resection, negative endoscopic margins, precise histological risk assessment, and close follow-up, which ensured the patient&#x2019;s high-quality survival. In this case of smooth submucosal elevation-type primary rectal adenocarcinoma, EUS clarified the lesion origin and nature, and ESE achieved complete resection with negative margins. The patient had an uneventful recovery without severe complications, no tumor recurrence during 4&#x202F;years and 11&#x202F;months, nearly 5&#x202F;years follow-up, and maintained a good quality of life. This case confirms that for early-stage, non-metastatic smooth submucosal rectal adenocarcinoma, ESE is a safe and effective minimally invasive treatment option, providing important clinical evidence for the management of similar rare lesions.</p>
<sec id="sec4">
<label>3.1</label>
<title>Patient perspective</title>
<p>The patient was discharged on the 3rd postoperative day without experiencing any adverse symptoms such as bleeding. She expressed sincere gratitude to the medical team, commenting that she was fortunate to have followed the physicians&#x2019; recommendation to undergo endoscopic submucosal excavation (ESE). Up to the present follow-up, no abnormalities have been identified, and her bowel habits as well as daily routines have remained consistent with the preoperative state, free of any discomfort. She also conveyed a reminder to patients with analogous conditions: early detection, timely diagnosis, and prompt treatment are the cornerstones of achieving an optimal prognosis.</p>
</sec>
</sec>
</body>
<back>
<sec sec-type="data-availability" id="sec5">
<title>Data availability statement</title>
<p>The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding authors.</p>
</sec>
<sec sec-type="ethics-statement" id="sec6">
<title>Ethics statement</title>
<p>The studies involving humans were approved by Medical Ethics Committee of the Affiliated Hospital of Jining Medical University. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.</p>
</sec>
<sec sec-type="author-contributions" id="sec7">
<title>Author contributions</title>
<p>Q-lK: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Writing &#x2013; original draft, Writing &#x2013; review &#x0026; editing. Y-wZ: Conceptualization, Methodology, Writing &#x2013; review &#x0026; editing. H-qF: Conceptualization, Formal analysis, Methodology, Writing &#x2013; original draft.</p>
</sec>
<sec sec-type="COI-statement" id="sec8">
<title>Conflict of interest</title>
<p>The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</p>
</sec>
<sec sec-type="ai-statement" id="sec9">
<title>Generative AI statement</title>
<p>The author(s) declared that Generative AI was not used in the creation of this manuscript.</p>
<p>Any alternative text (alt text) provided alongside figures in this article has been generated by Frontiers with the support of artificial intelligence and reasonable efforts have been made to ensure accuracy, including review by the authors wherever possible. If you identify any issues, please contact us.</p>
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<title>Publisher&#x2019;s note</title>
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</sec>
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<fn-group>
<fn fn-type="custom" custom-type="edited-by" id="fn0001"><p>Edited by: <ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/1062079/overview">Monica Trif</ext-link>, Centre for Innovative Process Engineering, Germany</p></fn>
<fn fn-type="custom" custom-type="reviewed-by" id="fn0002"><p>Reviewed by: <ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/3358436/overview">Daibo Kojima</ext-link>, Fukuoka University Chikushi Hospital, Japan</p>
<p><ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/3359700/overview">Luis Joaqu&#x00ED;n Garc&#x00ED;a Fl&#x00F3;rez</ext-link>, Central University Hospital of Asturias, Spain</p></fn>
</fn-group>
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</article>