A Study On The Congruence and Proximity Of The Sling And Clasp Fibres At The Cardio-Esophageal Junction Of The Stomach

A Study On The Congruence and Proximity Of The Sling And Clasp Fibres At The Cardio-Esophageal Junction Of The Stomach | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article A Study On The Congruence and Proximity Of The Sling And Clasp Fibres At The Cardio-Esophageal Junction Of The Stomach Mrudula Chandrupatla, Surraj Susai This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-2886782/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 26 Sep, 2023 Read the published version in Surgical and Radiologic Anatomy → Version 1 posted 8 You are reading this latest preprint version Abstract Background and Aim: The cardio-esophageal sphincter that is located in close longitudinal proximity to the origin of the lesser curvature of the stomach has a unique pattern of external muscle fibres whose inner oblique layer would normally form an elongated sling and the middle partially circular layer would form a projecting clasp into the already existing muscular sling of the former congruently, which would result in the formation of an anatomical sphincter in that area that would normally be devoid of the external longitudinal muscle layer coat. Certain authors have disagreed with the notion of this standard literature and have proposed that the clasp and sling fibres need not necessarily be congruent and may even remain independent of each other with partial contributions from the longitudinal muscle layers as well that may arise tangentially in different populations, which may in turn contribute to reflux esophagitis in that population. Hence, the clasp and sling fibre muscular patterns were observed in six formalin-embalmed cadavers at the department of anatomy in a tertiary care institute as part of routine dissections in series, and the findings were then reported. Findings : At the junction of the lesser curvature of the stomach with the oesophagus, all 6 cadavers showed a longitudinal sling pattern as opposed to the conventional oblique sling. The circular muscle layer was found to be merged with the outer longitudinal muscle layer to form the sling that pulled away from the clasp, resulting in a loss of congruency for the same. The clasp fibres, however, were found to be contributed by the inner oblique muscle layer. The conventional perpendicular or tangential merging of the clasp with the sling was not observed; instead, an obtuse, blunt angular merging of the clasp with the sling was observed. Discussion - The deviation of the sling from the clasp could indicate a lack of a proper fit between them at the cardioesophageal sphincter. The lack of robustness in the attachment of the clasp to the sling may possibly contribute to the diminished taut pull of the clasp in this subset of the population. These would be significant determinants for a predisposition to reflux esophagitis and Barrett's oesophagus. Fibres Cardia Sphincter Muscle Bend Figures Figure 1 Figure 2 Figure 3 Introduction Of the three sphincters that are present from the beginning of the oesophagus till the end of the stomach, the cardio-esophageal one, being a true sphincter, is unique not only with regards to its anatomy but also with regards to the high manometric pressure differences that exist within itself, owing to the individual alterations in pressure between the lower end of the oesophagus and the cardiac region of the stomach in their live toned states, which makes it a functional sphincter too, unlike its other two counterparts, wherein the gastro-duodenal one is a purely physiological sphincter and the upper esophageal one is a sole anatomical sphincter[ 1 – 3 ]. This is more-so-ever evidenced by the fact that the cardio-esophageal sphincter (a.k.a. gastro-esophageal sphincter) has both an intrinsic and an extrinsic component, wherein the intrinsic component is formed by the external muscle fibres of the oesophagus and the extrinsic component is formed by the altercations in pressure differences between the two hollow viscera (viz., the stomach and the oesophagus), attributed in part to the diaphragm(2–4) This is in contrast to the other two sphincters, wherein such a differentiation between the internal and external moieties within the same sphincter does not exist [ 1 – 4 ]. Hence this cardio-esophageal sphincter (CES) has gained considerable attention over the past few years with regards to its muscular fibre orientation, particularly to that of its intrinsic component, wherein a lot of research is going on to decipher the exact orientation of muscle fibres in this region, and so this present cadaveric study was done focusing on the structural fibre aspects of the intrinsic component of this sphincter. Also, in the recent past, this CES located at the cardiac end of the stomach had gained considerable attention among the scientific community not only with regards to the discernment of its internal muscular structural orientation but also for the intriguing reason that for a long time scientists were of the opinion that this intrinsic component of the CES, was possibly attributed to only by the inner circular external muscle fibres of the oesophagus that might have also extended onto the cardiac end of the stomach wall and would then have formed a ringed heap of tissue at that junction between the cardiac end of the stomach and the lower esophageal end, thereby having contributed to the formation of a sphincter[ 3 , 4 ]. However, in the recent past, surgeons and researchers had found with some uncertainty that the intrinsic component of the sphincter was contributed to only by the inner oblique and middle circular muscular layers of the muscularis externa of the cardiac end of the stomach, and they had also found that the formerly mentioned inner circular muscle layers of the oesophagus had minimal or no role to play in the contribution towards this sphincter [ 4 , 5 ]. Contrary to these findings, however, certain other researchers had proven that the esophageal circular muscles might as well track down as a continuity with the circular muscles of the stomach and would possibly form a certain portion of the sphincter as a clasp that may perpendicularly fit into the innermost oblique muscles of the stomach that would normally form a sling with negligible contributions from the esophageal bulk per se [ 3 , 5 ]. However, certain other researchers had refuted each of the above findings and had justifiably argued in support of the uncertainty of the exact muscle fibre orientation in this region and had hypothesised that the intrinsic component had minimal or no role to play in the sphincteric mechanisms of the CES, though this notion had received huge blowback from the scientific community [ 4 , 6 ]. Hence, this cadaveric case study was done to also find out the exact orientation of external muscle fibres of the cardiac end of the stomach at the level of this sphincter, which would have implications with regards to reflux esophagitis and Barrett’s oesophagus. Methodology This cadaveric case study was done on six formalin-fixed cadavers as part of routine dissections and demonstrations to first-year undergraduate medical students at the department of anatomy of a tertiary care institute after obtaining consent from the ethics committee of this national-level institute. The abdomens of the cadavers were opened, and the cardiac ends of their stomachs were dissected along the lesser curvature to look at the level of the cardio-esophageal sphincter and the muscle fibre orientation at the pertaining cardiac wall of the concerned stomach. The abdominal walls as well as the peritonia were opened and reflected as per the procedural steps given in Cunningham’s dissection manual [ 7 ]. A fresh, sharp scalpel blade of size 24 fitted to the Bard-Parker scalpel holder was used to incise the skin of a cadaver as well as for removing the extra-peritoneal pad of fat and also for incising the lesser curvature near the cardiac end of the stomach, whereas a blunt forceps was used to tease away the fascia and the fat along with a curved scissor. Cadavers with traumatic lacerations to the stomach were excluded from the study. Only freshly embalmed cadavers within two days of their receipt were included in the study. 37 percent formalin was used to embalm the cadavers after procuring adequate case records and consent from the relatives of the deceased. Observations and results At the level of the junction between the lesser curvature of the cardiac end of the stomach and the lower end of the oesophagus, five of the six cadavers showed a sling pattern formed by the outer longitudinal muscle fibres of the muscularis externa of the former but not the latter (Fig. 1 , Fig. 2 , Table 1 ), as opposed to the conventionally held view that the inner oblique fibres of the stomach would normally form a sling [ 1 – 3 ]. The clasp fibres, on the other hand, were found to receive contributions from the inner oblique muscle layer in this study (Fig. 1 , Fig. 2 , Table 1 ), as opposed to the circular fibres, which as per the conventional view would normally form them [ 1 – 3 ]. The middle circular muscle layer that would normally form the clasp was rather found to be merged with the outer longitudinal muscle layer to form the sling that pulled away from the underlying clasp, resulting in a loss of congruency for the same (Fig. 1 ). In one of the cadavers, the inner circular fibres from the lower oesophagus were found to be extending onto the cardiac end of the stomach in both the sling and the clasp (Table 1 ). As opposed to the conventional perpendicular or tangential merging of the clasp with the sling [ 1 – 3 ], an acute blunt angular merging of the clasp with the sling was observed in these five cadavers (Table 2 ). The sixth cadaver, on the other hand, showed a relatively perpendicular merging of the clasp with the sling; however, its clasp was contributed by a blend of circular as well as oblique fibres, in contrast to the observations made in the other five of them (Table 2 ). The findings are tabulated below in Table 1 and Table 2 . Table 1 – Orientation of muscle fibres at the level of the cardio-esophageal sphincter Serial order of cadaver Muscle* fibres forming the Sling Muscle fibres forming the Clasp Cadaver 1 Outer longitudinal + middle circular Inner oblique Cadaver 2 Outer longitudinal + middle circular Inner oblique Cadaver 3 Outer longitudinal + middle circular + inner circular of oesophagus extending on to the stomach Inner oblique + inner circular from oesophagus extending on to the stomach Cadaver 4 Outer longitudinal + middle circular Inner oblique Cadaver 5 Outer longitudinal + middle circular Inner oblique Cadaver 6 Outer longitudinal only middle circular + inner oblique * muscularis externa of cardiac end of stomach only As evidenced in Table 1 , the outer longitudinal muscle layer formed the sling and the inner oblique muscle layer formed the clasp in all 6 cadavers. Five of the six cadavers showed the middle circular muscle layers having contributed to the sling, and one of them had also received contributions from the inner circular muscle fibres of the oesophagus as well that swept on to the cardiac end, forming both the sling and the clasp. The sling of the last cadaver, however, had no contributions either from the middle circular layer of the cardia or from any of the muscle layers of the oesophagus, though its clasp was found to contain the middle circular fibres. Table 2 – Angular deviation of the sling from the clasp and its comparison with the distance between the sling and the clasp Serial order of cadaver Distance ( cm ) between the Sling and the Clasp Angular deviation ( degrees ) of the sling from the Clasp P value Cadaver 1 1.5 60 0 0.0014 Cadaver 2 1.7 80 0 Cadaver 3 0.8 30 0 Cadaver 4 1.5 50 0 Cadaver 5 1.4 45 0 Cadaver 6 2.0 90 0 As evidenced in Table 2 , the comparison between the ‘sling to clasp’ distance and the angular deviation of the former with the latter was significant. From this table, it is revealed that as the distance between the sling and the clasp decreased, the angular deviation decreased too, and vice versa. In the last cadaver’s CES, however, the distance between the sling and the clasp was greater, wherein the sling was constituted to be made of the outer longitudinal layer only (Table 1 ) and had a perpendicular deviation of itself from the clasp, which could imply the role played by its thinness, thereby leading itself to an exerted pull away from the clasp. Discussion As shown in literature[ 1 – 3 ], the fibres of the muscularis externa of the cardiac end of the stomach, located at the level of the gastro-esophageal sphincter, in close vertical proximity and continuity with the origins of the lesser curvature of the stomach, exhibit a unique pattern, wherein, the inner oblique layers of the stomach usually elongate to form a sling as also their middle partially circular counterpart that would normally projecte a clasp like pattern into the former, bestowing the sling with a congruent fit that would culminate in the formation of a distinct internal anatomical sphincter by means of the latter, in the concerned area of the clasp, which would normally be devoid of any external longitudinal muscle layer [ 1 – 3 ]. However, certain authors have disagreed with this standard view and had postulated an alternative school of thought, wherein, they hypothesize that the fibres of the clasp as well as those of the sling need not necessarily be congruent and may even remain independent of each other with or without paltry contributions from the longitudinal muscle layers of the stomach that may have arisen haphazardly in a tangential manner at different locations within the sphincter having varied consistently between population groups, which in-turn might have contributed to the associations of reflux esophagitis and other relevant disorders related to gastro-esophageal reflux within the same in that subset of the population[ 3 – 6 ]. In this cadaveric case study however, it had been observed that the longitudinal muscular layer of the externa, at the cardiac lesser curvature, did play a pivotal role in forming the intrinsic component of the sphincter (Table 1 ), thereby having alluded to the alternatively hypothesized view of thought[ 3 – 6 ], as it had contributed to the sling, by way of which it had contradicted the patterns observed in previous studies that were the harbingers of the classical school of thought[ 1 – 3 ]. This could possibly imply that the sling being more vertically reinforced in this group of cadavers, could possibly mitigate the pressure differences within the internal strata of the muscularis externa of the cardiac lesser curvature, which in-turn could disrupt the angulations between the clasp and the sling, as a result of the possible tangential drifts between them, thereby leading to a defective extrinsic sphincteric mechanism in totality, owed in part to the inherent intrinsic sphincteric derangements at that level of the cardia concerned. Also, in this case study, at the level of the junction between the oesophagus and the stomach, the inner oblique fibres of the muscularis externa of the stomach, which were conventionally regarded as the formative muscle fibres of the sling [ 3 – 4 , 8 – 10 ], were found to be constituting the clasp instead. Nevertheless, they were also found to be inclined bluntly towards the sling, as it would be imperative to understand that they lacked the stability that was consistent with the longitudinally oriented sling fortress that comprised of the other two muscle groups, with the rare exception of one distinct cadaver that showed contributions coming in from the inner circular swarm of muscle fibres of the preceding oesophagus that swept onto its succeeding counterpart, this cadaver being the only exception for the same. This could possibly explain the "pulling away" of the sling from the clasp and could also denote a loss of congruency and fitting of these fibres at the level of the cardio-esophageal sphincter, and this might also have implications for the plausible associations of diseases specifically related to heartburn in these tussled states of defectively congruent slings with their clasps [ 10 – 12 ]. Moreover, the blunt angular cling of the clasp with the sling due to the acute angular deviations of the latter with the former (Table 2 ) could also have contributed to the reduced tightness of the clasp in this subset of the population. Hence, the authors would like to opine that these factors might have a primal role as determinants for a predisposition to reflux esophagitis and/or Barrett's oesophagus [ 6 , 8 ], and larger multicentric clinical studies need to be done to substantiate further evidence for the same, keeping cadaveric studies such as these as a base for further related research. Based on the observations of this study and also by drawing parallels with the evidence from available literature [ 2 , 3 , 7 ], the authors would like to propose two supposed models that may exist within the CES for a congruent fit between the sling and the clasp fibres. These would be the "lock and key" model and the "purse-string" model (Fig. 3 ). The "lock and key’ model is based on the observations in this study, wherein the sling fibres deviate at an acute angle from the longitudinal sling, thereby causing the sling to behave like a key for the existing clasp lock, thereby rendering the CES with a congruent fit (Fig. 3 ). The effectiveness of the key would depend upon the degree of angulation of the sling from the clasp. Considering the tangential deviations of the sling from the clasp as seen in literature [ 4 – 6 ], rather than the acute angular deviations as noted in this study (Table 2 ), a "purse-string" model might exist, as opined by the authors in this study, wherein the sling would serve as a string to tighten the purse comprised of the clasp fibres (Fig. 3 ). Future implications of this research study The models of congruency (Fig. 3 ) as proposed by the researchers in this study might be aptly tested and justified by surgeons while conducting endoscopic studies in live patients for similar futuristic research, thereby deriving corroborated evidence for the same. The relationships between the extrinsic and intrinsic derangements of the CES [ 1 , 3 , 11 ] and those of the other two sphincters of the oesophagus and the stomach might well be appreciated during their peristaltic movements by conducting dye antigen-based immune-histochemical studies in the future. Limitations – Since this study has been done on formalin-embalmed cadavers, it is possible that the values of distance between the sling and clasp fibres as well as the angulations between them may not necessarily reflect their consistency in the live state owing to the stiffening caused in cadavers due to formalin fixation. Also, ethnic and geographic variations in the patterns of the sling and clasp might exist between populations groups too [ 3 , 9 , 10 ], warranting future researchers to be aware of these while conducting multicentric studies to substantiate the findings of the same before extrapolating the results to the general larger population. Conclusion/s This cadaveric case study has not only revealed startling insights into the congruency of the longitudinal muscle fibre layers of the externa at the level of the CES, but also on their tightness and tightly packed states with respect to the other muscular fibre layers of the externa of the concerned region as a whole. Also, this study revealed that the longitudinal muscle fibres of the lesser curvature of the cardiac end of the stomach did strongly contribute to the formation of the CES, as opposed to the previously held classical school of thought (1–3). The role played by the esophageal muscles in the contribution of this sphincter couldn’t be undermined. Moreover, the middle circular and the inner oblique muscles at the cardiac end of the stomach did not have fixed roles either in forming the sling or the clasp. Abbreviations CES C ardio- E sophageal S phincter cm centimeter Declarations Ethics approval - The authors would like to affirm that they have obtained a proper ethics approval from the institutional research committee cum ethics review board for this study. The ethics approval for this study was obtained only after an internal review meeting held within the department of the researchers followed by an external review meeting held by representatives outside the department and institution where the researchers work. The allotted ethics approval number for this study was AIIMS/BBN/IEC/MAR/2023/273. The cadavers that were procured for this study were obtained either as a result of willful donation of bodies of the deceased through their self-attested will prior to their death or through a proper informed written consent from the relatives of the deceased in accordance with the guidelines that were laid down by the ethics board, wherein the consent to publish the findings related to dissection of cadavers was also obtained. Competing interests - The authors would like to declare that they have no competing interests with other researchers to the best of their knowledge as far as this study is concerned. Author contributions - Mrudula Chandrupatla - planning, implementation and supervision of research Surraj Susai - execution of research work, data collection, analysis and interpretation of results Funding - The authors would like to declare that they have not received any intramural or extramural financial support / grants / funds for this study. Availability of data and materials - The materials that were used by the researchers to embalm the cadavers as well as to dissect the cadavers were already in use before the start of this study and had been purchased earlier by the establishment section of the institute prior to the start of this research and they were not procured as a result of funding/ grants and neither did the researchers of this study apply for any grants nor did they receive any monetary support to purchase the materials related to this study. The data pertaining to the profile of the deceased persons who had donated their bodies for dissection were to be kept confidential within the records of the institute as per the mandate issued by the ethics board. References Farré R, Aulí M, Lecea B, Estrada O, Suñol X, Clavé P. Mechanisms controlling function in the clasp and sling regions of porcine lower oesophageal sphincter. Br J Surg. 2007 Nov;94(11):1427-36. doi: 10.1002/bjs.5831. PMID: 17542040. Liu JF, Sun J, Drew PA. Characterization of excitatory and inhibitory motor neurons to the human gastric clasp and sling fibers. Can J Physiol Pharmacol. 2011 Sep;89(9):617-22. doi: 10.1139/y11-059. Epub 2011 Aug 17. PMID: 21846301. Tian ZQ, Liu JF, Wang GY, Li BQ, Wang FS, Wang QZ, Cao FM, Zhang YF. Responses of human clasp and sling fibers to neuromimetics. J Gastroenterol Hepatol. 2004 Apr;19(4):440-7. doi: 10.1111/j.1440-1746.2003.03307.x. PMID: 15012783. Miller L, Clavé P, Farré R, Lecea B, Ruggieri MR, Ouyang A, Regan J, McMahon BP. Physiology of the upper segment, body, and lower segment of the esophagus. Ann N Y Acad Sci. 2013 Oct;1300:261-277. doi: 10.1111/nyas.12250. Erratum in: Ann N Y Acad Sci. 2014 Sep;1325:269. Erratum in: Ann N Y Acad Sci. 2014 Sep;1325(1):269. PMID: 24117648; PMCID: PMC3889860. Liu JF, Gao LP, Wen SW, Lu HL, Zhang J, Sun J, Zhang SW, Wang QZ. Responses of human sling and clasp fibers to cholecystokinin (CCK) and gastrin through CCK receptors. J Gastroenterol Hepatol. 2008 Oct;23(10):1608-12. doi: 10.1111/j.1440-1746.2008.05327.x. Epub 2008 Apr 28. PMID: 18444993. Liu JF, Lu HL, Wen SW, Wu RF. Effects of acetylcholine on sling and clasp fibers of the human lower esophageal sphincter. J Gastroenterol Hepatol. 2011 Aug;26(8):1309-17. doi: 10.1111/j.1440-1746.2011.06731.x. PMID: 21443668. Romanes G J, Koshi R. Cunningham’s Manual Of Practical Anatomy, Vol 2.16 th -ed.USA:Oxford Univ Press;2017:106-120 Vegesna AK, Braverman AS, Miller LS, Tallarida RJ, Tiwana MI, Khayyam U, Ruggieri MR Sr. Comparison of human and porcine gastric clasp and sling fiber contraction by M2 and M3 muscarinic receptors. Am J Physiol Gastrointest Liver Physiol. 2010 Apr;298(4):G530-4. doi: 10.1152/ajpgi.00129.2009. Epub 2010 Feb 4. PMID: 20133950; PMCID: PMC2853305. Code CF, Fyke FE, Jr, Schlegel JF. The gastroesophageal sphincter in healthy human beings. Gastroenterologia 86: 135–150, 1956 [ PubMed ] [ Google Scholar ] Lerche W. The Esophagus and Pharynx in Action. A Study of Structure in Relation to Function Springfield, IL: Charles C. Thomas, 1950 [ Google Scholar ] Liebermann-Meffert D, Allgower M, Schmid P, Blum AL. Muscular equivalent of the lower esophageal sphincter. Gastroenterology 76: 31–38, 1979 [ PubMed ] [ Google Scholar ] Brown DR, Timmermans JP. Lessons from the porcine enteric nervous system. Neurogastroenterol Motil 16, Suppl 1: 50–54, 2004 [ PubMed ] [ Google Scholar ] Additional Declarations No competing interests reported. Supplementary Files ackss.docx Cite Share Download PDF Status: Published Journal Publication published 26 Sep, 2023 Read the published version in Surgical and Radiologic Anatomy → Version 1 posted Editorial decision: Major revision 12 Aug, 2023 Reviewers agreed at journal 09 Aug, 2023 Reviews received at journal 09 Aug, 2023 Reviewers agreed at journal 18 Jun, 2023 Reviewers invited by journal 09 May, 2023 Editor assigned by journal 09 May, 2023 Submission checks completed at journal 05 May, 2023 First submitted to journal 02 May, 2023 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-2886782","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":197701119,"identity":"06e16ed4-1cdc-4531-9019-52796c101643","order_by":0,"name":"Mrudula Chandrupatla","email":"","orcid":"","institution":"All India Institute of Medical Sciences, Bibinagar, Hyderabad Metropolitan Region, Telangana, India 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19:55:39","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":6628,"visible":true,"origin":"","legend":"","description":"","filename":"ackss.docx","url":"https://assets-eu.researchsquare.com/files/rs-2886782/v1/1d7e5dd5e2ae8e42f6fb0a33.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eA Study On The Congruence and Proximity Of The Sling And Clasp Fibres At The Cardio-Esophageal Junction Of The Stomach\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eOf the three sphincters that are present from the beginning of the oesophagus till the end of the stomach, the cardio-esophageal one, being a true sphincter, is unique not only with regards to its anatomy but also with regards to the high manometric pressure differences that exist within itself, owing to the individual alterations in pressure between the lower end of the oesophagus and the cardiac region of the stomach in their live toned states, which makes it a functional sphincter too, unlike its other two counterparts, wherein the gastro-duodenal one is a purely physiological sphincter and the upper esophageal one is a sole anatomical sphincter[\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e–\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. This is more-so-ever evidenced by the fact that the cardio-esophageal sphincter (a.k.a. gastro-esophageal sphincter) has both an intrinsic and an extrinsic component, wherein the intrinsic component is formed by the external muscle fibres of the oesophagus and the extrinsic component is formed by the altercations in pressure differences between the two hollow viscera (viz., the stomach and the oesophagus), attributed in part to the diaphragm(2–4) This is in contrast to the other two sphincters, wherein such a differentiation between the internal and external moieties within the same sphincter does not exist [\u003cspan additionalcitationids=\"CR2 CR3\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e–\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Hence this cardio-esophageal sphincter (CES) has gained considerable attention over the past few years with regards to its muscular fibre orientation, particularly to that of its intrinsic component, wherein a lot of research is going on to decipher the exact orientation of muscle fibres in this region, and so this present cadaveric study was done focusing on the structural fibre aspects of the intrinsic component of this sphincter. Also, in the recent past, this CES located at the cardiac end of the stomach had gained considerable attention among the scientific community not only with regards to the discernment of its internal muscular structural orientation but also for the intriguing reason that for a long time scientists were of the opinion that this intrinsic component of the CES, was possibly attributed to only by the inner circular external muscle fibres of the oesophagus that might have also extended onto the cardiac end of the stomach wall and would then have formed a ringed heap of tissue at that junction between the cardiac end of the stomach and the lower esophageal end, thereby having contributed to the formation of a sphincter[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. However, in the recent past, surgeons and researchers had found with some uncertainty that the intrinsic component of the sphincter was contributed to only by the inner oblique and middle circular muscular layers of the muscularis externa of the cardiac end of the stomach, and they had also found that the formerly mentioned inner circular muscle layers of the oesophagus had minimal or no role to play in the contribution towards this sphincter [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Contrary to these findings, however, certain other researchers had proven that the esophageal circular muscles might as well track down as a continuity with the circular muscles of the stomach and would possibly form a certain portion of the sphincter as a clasp that may perpendicularly fit into the innermost oblique muscles of the stomach that would normally form a sling with negligible contributions from the esophageal bulk per se [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. However, certain other researchers had refuted each of the above findings and had justifiably argued in support of the uncertainty of the exact muscle fibre orientation in this region and had hypothesised that the intrinsic component had minimal or no role to play in the sphincteric mechanisms of the CES, though this notion had received huge blowback from the scientific community [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Hence, this cadaveric case study was done to also find out the exact orientation of external muscle fibres of the cardiac end of the stomach at the level of this sphincter, which would have implications with regards to reflux esophagitis and Barrett’s oesophagus.\u003c/p\u003e "},{"header":"Methodology","content":"\u003cp\u003eThis cadaveric case study was done on six formalin-fixed cadavers as part of routine dissections and demonstrations to first-year undergraduate medical students at the department of anatomy of a tertiary care institute after obtaining consent from the ethics committee of this national-level institute. The abdomens of the cadavers were opened, and the cardiac ends of their stomachs were dissected along the lesser curvature to look at the level of the cardio-esophageal sphincter and the muscle fibre orientation at the pertaining cardiac wall of the concerned stomach. The abdominal walls as well as the peritonia were opened and reflected as per the procedural steps given in Cunningham’s dissection manual [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. A fresh, sharp scalpel blade of size 24 fitted to the Bard-Parker scalpel holder was used to incise the skin of a cadaver as well as for removing the extra-peritoneal pad of fat and also for incising the lesser curvature near the cardiac end of the stomach, whereas a blunt forceps was used to tease away the fascia and the fat along with a curved scissor. Cadavers with traumatic lacerations to the stomach were excluded from the study. Only freshly embalmed cadavers within two days of their receipt were included in the study. 37 percent formalin was used to embalm the cadavers after procuring adequate case records and consent from the relatives of the deceased.\u003c/p\u003e"},{"header":"Observations and results","content":"\u003cp\u003eAt the level of the junction between the lesser curvature of the cardiac end of the stomach and the lower end of the oesophagus, five of the six cadavers showed a sling pattern formed by the outer longitudinal muscle fibres of the muscularis externa of the former but not the latter (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e), as opposed to the conventionally held view that the inner oblique fibres of the stomach would normally form a sling [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. The clasp fibres, on the other hand, were found to receive contributions from the inner oblique muscle layer in this study (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e), as opposed to the circular fibres, which as per the conventional view would normally form them [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. The middle circular muscle layer that would normally form the clasp was rather found to be merged with the outer longitudinal muscle layer to form the sling that pulled away from the underlying clasp, resulting in a loss of congruency for the same (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). In one of the cadavers, the inner circular fibres from the lower oesophagus were found to be extending onto the cardiac end of the stomach in both the sling and the clasp (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). As opposed to the conventional perpendicular or tangential merging of the clasp with the sling [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], an acute blunt angular merging of the clasp with the sling was observed in these five cadavers (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The sixth cadaver, on the other hand, showed a relatively perpendicular merging of the clasp with the sling; however, its clasp was contributed by a blend of circular as well as oblique fibres, in contrast to the observations made in the other five of them (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The findings are tabulated below in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e and Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003e\u0026ndash; Orientation of muscle fibres at the level of the cardio-esophageal sphincter\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eSerial order of cadaver\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eMuscle* fibres forming the Sling\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eMuscle fibres forming the Clasp\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCadaver 1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOuter longitudinal\u0026thinsp;+\u0026thinsp;middle circular\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eInner oblique\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCadaver 2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOuter longitudinal\u0026thinsp;+\u0026thinsp;middle circular\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eInner oblique\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCadaver 3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOuter longitudinal\u0026thinsp;+\u0026thinsp;middle circular\u0026thinsp;+\u0026thinsp;inner circular of oesophagus extending on to the stomach\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eInner oblique\u0026thinsp;+\u0026thinsp;inner circular from oesophagus extending on to the stomach\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCadaver 4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOuter longitudinal\u0026thinsp;+\u0026thinsp;middle circular\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eInner oblique\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCadaver 5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOuter longitudinal\u0026thinsp;+\u0026thinsp;middle circular\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eInner oblique\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCadaver 6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOuter longitudinal only\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003emiddle circular\u0026thinsp;+\u0026thinsp;inner oblique\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003e\u003cb\u003e*\u003c/b\u003e\u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003emuscularis externa of cardiac end of stomach only\u003c/span\u003e\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAs evidenced in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, the outer longitudinal muscle layer formed the sling and the inner oblique muscle layer formed the clasp in all 6 cadavers. Five of the six cadavers showed the middle circular muscle layers having contributed to the sling, and one of them had also received contributions from the inner circular muscle fibres of the oesophagus as well that swept on to the cardiac end, forming both the sling and the clasp. The sling of the last cadaver, however, had no contributions either from the middle circular layer of the cardia or from any of the muscle layers of the oesophagus, though its clasp was found to contain the middle circular fibres.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003e\u0026ndash; Angular deviation of the sling from the clasp and its comparison with the distance between the sling and the clasp\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eSerial order of cadaver\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eDistance (\u003c/em\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003ecm\u003c/span\u003e\u003cem\u003e) between the Sling and the Clasp\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eAngular deviation (\u003c/em\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003edegrees\u003c/span\u003e\u003cem\u003e) of the sling from the Clasp\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCadaver 1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e60\u003csup\u003e0\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\" morerows=\"5\" rowspan=\"6\"\u003e \u003cp\u003e0.0014\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCadaver 2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e80\u003csup\u003e0\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCadaver 3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e30\u003csup\u003e0\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCadaver 4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e50\u003csup\u003e0\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCadaver 5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e45\u003csup\u003e0\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCadaver 6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e90\u003csup\u003e0\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAs evidenced in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, the comparison between the \u0026lsquo;sling to clasp\u0026rsquo; distance and the angular deviation of the former with the latter was significant. From this table, it is revealed that as the distance between the sling and the clasp decreased, the angular deviation decreased too, and vice versa. In the last cadaver\u0026rsquo;s CES, however, the distance between the sling and the clasp was greater, wherein the sling was constituted to be made of the outer longitudinal layer only (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) and had a perpendicular deviation of itself from the clasp, which could imply the role played by its thinness, thereby leading itself to an exerted pull away from the clasp.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eAs shown in literature[\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], the fibres of the muscularis externa of the cardiac end of the stomach, located at the level of the gastro-esophageal sphincter, in close vertical proximity and continuity with the origins of the lesser curvature of the stomach, exhibit a unique pattern, wherein, the inner oblique layers of the stomach usually elongate to form a sling as also their middle partially circular counterpart that would normally projecte a clasp like pattern into the former, bestowing the sling with a congruent fit that would culminate in the formation of a distinct internal anatomical sphincter by means of the latter, in the concerned area of the clasp, which would normally be devoid of any external longitudinal muscle layer [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. However, certain authors have disagreed with this standard view and had postulated an alternative school of thought, wherein, they hypothesize that the fibres of the clasp as well as those of the sling need not necessarily be congruent and may even remain independent of each other with or without paltry contributions from the longitudinal muscle layers of the stomach that may have arisen haphazardly in a tangential manner at different locations within the sphincter having varied consistently between population groups, which in-turn might have contributed to the associations of reflux esophagitis and other relevant disorders related to gastro-esophageal reflux within the same in that subset of the population[\u003cspan additionalcitationids=\"CR4 CR5\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. In this cadaveric case study however, it had been observed that the longitudinal muscular layer of the externa, at the cardiac lesser curvature, did play a pivotal role in forming the intrinsic component of the sphincter (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e), thereby having alluded to the alternatively hypothesized view of thought[\u003cspan additionalcitationids=\"CR4 CR5\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], as it had contributed to the sling, by way of which it had contradicted the patterns observed in previous studies that were the harbingers of the classical school of thought[\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. This could possibly imply that the sling being more vertically reinforced in this group of cadavers, could possibly mitigate the pressure differences within the internal strata of the muscularis externa of the cardiac lesser curvature, which in-turn could disrupt the angulations between the clasp and the sling, as a result of the possible tangential drifts between them, thereby leading to a defective extrinsic sphincteric mechanism in totality, owed in part to the inherent intrinsic sphincteric derangements at that level of the cardia concerned.\u003c/p\u003e \u003cp\u003eAlso, in this case study, at the level of the junction between the oesophagus and the stomach, the inner oblique fibres of the muscularis externa of the stomach, which were conventionally regarded as the formative muscle fibres of the sling [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan additionalcitationids=\"CR9\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], were found to be constituting the clasp instead. Nevertheless, they were also found to be inclined bluntly towards the sling, as it would be imperative to understand that they lacked the stability that was consistent with the longitudinally oriented sling fortress that comprised of the other two muscle groups, with the rare exception of one distinct cadaver that showed contributions coming in from the inner circular swarm of muscle fibres of the preceding oesophagus that swept onto its succeeding counterpart, this cadaver being the only exception for the same. This could possibly explain the \"pulling away\" of the sling from the clasp and could also denote a loss of congruency and fitting of these fibres at the level of the cardio-esophageal sphincter, and this might also have implications for the plausible associations of diseases specifically related to heartburn in these tussled states of defectively congruent slings with their clasps [\u003cspan additionalcitationids=\"CR11\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Moreover, the blunt angular cling of the clasp with the sling due to the acute angular deviations of the latter with the former (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e) could also have contributed to the reduced tightness of the clasp in this subset of the population. Hence, the authors would like to opine that these factors might have a primal role as determinants for a predisposition to reflux esophagitis and/or Barrett's oesophagus [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], and larger multicentric clinical studies need to be done to substantiate further evidence for the same, keeping cadaveric studies such as these as a base for further related research.\u003c/p\u003e \u003cp\u003eBased on the observations of this study and also by drawing parallels with the evidence from available literature [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], the authors would like to propose two supposed models that may exist within the CES for a congruent fit between the sling and the clasp fibres. These would be the \"lock and key\" model and the \"purse-string\" model (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). The \"lock and key\u0026rsquo; model is based on the observations in this study, wherein the sling fibres deviate at an acute angle from the longitudinal sling, thereby causing the sling to behave like a key for the existing clasp lock, thereby rendering the CES with a congruent fit (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). The effectiveness of the key would depend upon the degree of angulation of the sling from the clasp. Considering the tangential deviations of the sling from the clasp as seen in literature [\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], rather than the acute angular deviations as noted in this study (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e), a \"purse-string\" model might exist, as opined by the authors in this study, wherein the sling would serve as a string to tighten the purse comprised of the clasp fibres (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e\n\u003ch3\u003eFuture implications of this research study\u003c/h3\u003e\n\u003cp\u003eThe models of congruency (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e) as proposed by the researchers in this study might be aptly tested and justified by surgeons while conducting endoscopic studies in live patients for similar futuristic research, thereby deriving corroborated evidence for the same. The relationships between the extrinsic and intrinsic derangements of the CES [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] and those of the other two sphincters of the oesophagus and the stomach might well be appreciated during their peristaltic movements by conducting dye antigen-based immune-histochemical studies in the future.\u003c/p\u003e \u003cp\u003e \u003cb\u003eLimitations\u003c/b\u003e \u0026ndash;\u003c/p\u003e \u003cp\u003eSince this study has been done on formalin-embalmed cadavers, it is possible that the values of distance between the sling and clasp fibres as well as the angulations between them may not necessarily reflect their consistency in the live state owing to the stiffening caused in cadavers due to formalin fixation. Also, ethnic and geographic variations in the patterns of the sling and clasp might exist between populations groups too [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], warranting future researchers to be aware of these while conducting multicentric studies to substantiate the findings of the same before extrapolating the results to the general larger population.\u003c/p\u003e"},{"header":"Conclusion/s","content":"\u003cp\u003eThis cadaveric case study has not only revealed startling insights into the congruency of the longitudinal muscle fibre layers of the externa at the level of the CES, but also on their tightness and tightly packed states with respect to the other muscular fibre layers of the externa of the concerned region as a whole. Also, this study revealed that the longitudinal muscle fibres of the lesser curvature of the cardiac end of the stomach did strongly contribute to the formation of the CES, as opposed to the previously held classical school of thought (1\u0026ndash;3). The role played by the esophageal muscles in the contribution of this sphincter couldn\u0026rsquo;t be undermined. Moreover, the middle circular and the inner oblique muscles at the cardiac end of the stomach did not have fixed roles either in forming the sling or the clasp.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eCES\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003e \u003cb\u003eC\u003c/b\u003eardio-\u003cb\u003eE\u003c/b\u003esophageal \u003cb\u003eS\u003c/b\u003ephincter\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003ecm\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ecentimeter\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval\u003c/strong\u003e -\u003c/p\u003e\u003cp\u003eThe authors would like to affirm that they have obtained a proper ethics approval from the institutional research committee cum ethics review board for this study. The ethics approval for this study was obtained only after an internal review meeting held within the department of the researchers followed by an external review meeting held by representatives outside the department and institution where the researchers work. The allotted ethics approval number for this study was AIIMS/BBN/IEC/MAR/2023/273. The cadavers that were procured for this study were obtained either as a result of willful donation of bodies of the deceased through their self-attested will prior to their death or through a proper informed written consent from the relatives of the deceased in accordance with the guidelines that were laid down by the ethics board, wherein the consent to publish the findings related to dissection of cadavers was also obtained.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e -\u003c/p\u003e\u003cp\u003eThe authors would like to declare that they have no competing interests with other researchers to the best of their knowledge as far as this study is concerned.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e -\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMrudula Chandrupatla\u003c/strong\u003e - planning, implementation and supervision of research\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eSurraj Susai\u003c/strong\u003e - execution of research work, data collection, analysis and interpretation of results\u0026nbsp;\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e -\u003c/p\u003e\u003cp\u003eThe authors would like to declare that they have not received any intramural or extramural financial support / grants / funds for this study.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e -\u003c/p\u003e\u003cp\u003eThe materials that were used by the researchers to embalm the cadavers as well as to dissect the cadavers were already in use before the start of this study and had been purchased earlier by the establishment section of the institute prior to the start of this research and they were not procured as a result of funding/ grants and neither did the researchers of this study apply for any grants nor did they receive any monetary support to purchase the materials related to this study. The data pertaining to the profile of the deceased persons who had donated their bodies for dissection were to be kept confidential within the records of the institute as per the mandate issued by the ethics board.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eFarr\u0026eacute; R, Aul\u0026iacute; M, Lecea B, Estrada O, Su\u0026ntilde;ol X, Clav\u0026eacute; P. Mechanisms controlling function in the clasp and sling regions of porcine lower oesophageal sphincter. Br J Surg. 2007 Nov;94(11):1427-36. doi: 10.1002/bjs.5831. PMID: 17542040.\u003c/li\u003e\n \u003cli\u003eLiu JF, Sun J, Drew PA. Characterization of excitatory and inhibitory motor neurons to the human gastric clasp and sling fibers. Can J Physiol Pharmacol. 2011 Sep;89(9):617-22. doi: 10.1139/y11-059. Epub 2011 Aug 17. PMID: 21846301.\u003c/li\u003e\n \u003cli\u003eTian ZQ, Liu JF, Wang GY, Li BQ, Wang FS, Wang QZ, Cao FM, Zhang YF. Responses of human clasp and sling fibers to neuromimetics. J Gastroenterol Hepatol. 2004 Apr;19(4):440-7. doi: 10.1111/j.1440-1746.2003.03307.x. PMID: 15012783.\u003c/li\u003e\n \u003cli\u003eMiller L, Clav\u0026eacute; P, Farr\u0026eacute; R, Lecea B, Ruggieri MR, Ouyang A, Regan J, McMahon BP. Physiology of the upper segment, body, and lower segment of the esophagus. Ann N Y Acad Sci. 2013 Oct;1300:261-277. doi: 10.1111/nyas.12250. Erratum in: Ann N Y Acad Sci. 2014 Sep;1325:269. Erratum in: Ann N Y Acad Sci. 2014 Sep;1325(1):269. PMID: 24117648; PMCID: PMC3889860.\u003c/li\u003e\n \u003cli\u003eLiu JF, Gao LP, Wen SW, Lu HL, Zhang J, Sun J, Zhang SW, Wang QZ. Responses of human sling and clasp fibers to cholecystokinin (CCK) and gastrin through CCK receptors. J Gastroenterol Hepatol. 2008 Oct;23(10):1608-12. doi: 10.1111/j.1440-1746.2008.05327.x. Epub 2008 Apr 28. PMID: 18444993.\u003c/li\u003e\n \u003cli\u003eLiu JF, Lu HL, Wen SW, Wu RF. Effects of acetylcholine on sling and clasp fibers of the human lower esophageal sphincter. J Gastroenterol Hepatol. 2011 Aug;26(8):1309-17. doi: 10.1111/j.1440-1746.2011.06731.x. PMID: 21443668.\u003c/li\u003e\n \u003cli\u003eRomanes G J, Koshi R. Cunningham\u0026rsquo;s Manual Of Practical Anatomy, Vol 2.16\u003csup\u003eth\u003c/sup\u003e-ed.USA:Oxford Univ Press;2017:106-120\u003c/li\u003e\n \u003cli\u003eVegesna AK, Braverman AS, Miller LS, Tallarida RJ, Tiwana MI, Khayyam U, Ruggieri MR Sr. Comparison of human and porcine gastric clasp and sling fiber contraction by M2 and M3 muscarinic receptors. Am J Physiol Gastrointest Liver Physiol. 2010 Apr;298(4):G530-4. doi: 10.1152/ajpgi.00129.2009. Epub 2010 Feb 4. PMID: 20133950; PMCID: PMC2853305.\u003c/li\u003e\n \u003cli\u003eCode CF, Fyke FE, Jr, Schlegel JF. The gastroesophageal sphincter in healthy human beings. \u003cem\u003eGastroenterologia\u003c/em\u003e 86: 135\u0026ndash;150, 1956 [\u003ca href=\"https://pubmed.ncbi.nlm.nih.gov/13384582\"\u003ePubMed\u003c/a\u003e]\u0026nbsp;[\u003ca href=\"https://scholar.google.com/scholar_lookup?journal=Gastroenterologia\u0026title=The+gastroesophageal+sphincter+in+healthy+human+beings\u0026author=CF+Code\u0026author=FE+Fyke\u0026author=JF+Schlegel\u0026volume=86\u0026publication_year=1956\u0026pages=135-150\u0026pmid=13384582\u0026\"\u003eGoogle Scholar\u003c/a\u003e]\u003c/li\u003e\n \u003cli\u003eLerche W. \u003cem\u003eThe Esophagus and Pharynx in Action. A Study of Structure in Relation to Function\u003c/em\u003e Springfield, IL: Charles C. Thomas, 1950 [\u003ca href=\"https://scholar.google.com/scholar_lookup?title=The+Esophagus+and+Pharynx+in+Action.+A+Study+of+Structure+in+Relation+to+Function\u0026author=W+Lerche\u0026publication_year=1950\u0026\"\u003eGoogle Scholar\u003c/a\u003e]\u003c/li\u003e\n \u003cli\u003eLiebermann-Meffert D, Allgower M, Schmid P, Blum AL. Muscular equivalent of the lower esophageal sphincter. \u003cem\u003eGastroenterology\u003c/em\u003e 76: 31\u0026ndash;38, 1979 [\u003ca href=\"https://pubmed.ncbi.nlm.nih.gov/81791\"\u003ePubMed\u003c/a\u003e]\u0026nbsp;[\u003ca href=\"https://scholar.google.com/scholar_lookup?journal=Gastroenterology\u0026title=Muscular+equivalent+of+the+lower+esophageal+sphincter\u0026author=D+Liebermann-Meffert\u0026author=M+Allgower\u0026author=P+Schmid\u0026author=AL+Blum\u0026volume=76\u0026publication_year=1979\u0026pages=31-38\u0026pmid=81791\u0026\"\u003eGoogle Scholar\u003c/a\u003e]\u003c/li\u003e\n \u003cli\u003eBrown DR, Timmermans JP. Lessons from the porcine enteric nervous system. \u003cem\u003eNeurogastroenterol Motil\u003c/em\u003e 16, \u003cem\u003eSuppl\u003c/em\u003e 1: 50\u0026ndash;54, 2004 [\u003ca href=\"https://pubmed.ncbi.nlm.nih.gov/15066005\"\u003ePubMed\u003c/a\u003e]\u0026nbsp;[\u003ca href=\"https://scholar.google.com/scholar_lookup?journal=Neurogastroenterol+Motil\u0026title=Lessons+from+the+porcine+enteric+nervous+system\u0026author=DR+Brown\u0026author=JP+Timmermans\u0026volume=16\u0026issue=Suppl+1\u0026publication_year=2004\u0026pages=50-54\u0026pmid=15066005\u0026\"\u003eGoogle Scholar\u003c/a\u003e]\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"surgical-and-radiologic-anatomy","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"sara","sideBox":"Learn more about [Surgical and Radiologic Anatomy](http://link.springer.com/journal/276)","snPcode":"276","submissionUrl":"https://submission.nature.com/new-submission/276/3","title":"Surgical and Radiologic Anatomy","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Fibres, Cardia, Sphincter, Muscle, Bend","lastPublishedDoi":"10.21203/rs.3.rs-2886782/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-2886782/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cu\u003e\u003cstrong\u003eBackground and Aim:\u003c/strong\u003e\u003c/u\u003e The cardio-esophageal sphincter that is located in close longitudinal proximity to the origin of the lesser curvature of the stomach has a unique pattern of external muscle fibres whose inner oblique layer would normally form an elongated sling and the middle partially circular layer would form a projecting clasp into the already existing muscular sling of the former congruently, which would result in the formation of an anatomical sphincter in that area that would normally be devoid of the external longitudinal muscle layer coat. Certain authors have disagreed with the notion of this standard literature and have proposed that the clasp and sling fibres need not necessarily be congruent and may even remain independent of each other with partial contributions from the longitudinal muscle layers as well that may arise tangentially in different populations, which may in turn contribute to reflux esophagitis in that population. Hence, the clasp and sling fibre muscular patterns were observed in six formalin-embalmed cadavers at the department of anatomy in a tertiary care institute as part of routine dissections in series, and the findings were then reported.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cu\u003e\u003cstrong\u003eFindings\u003c/strong\u003e\u003c/u\u003e: At the junction of the lesser curvature of the stomach with the oesophagus, all 6 cadavers showed a longitudinal sling pattern as opposed to the conventional oblique sling. The circular muscle layer was found to be merged with the outer longitudinal muscle layer to form the sling that pulled away from the clasp, resulting in a loss of congruency for the same. The clasp fibres, however, were found to be contributed by the inner oblique muscle layer. The conventional perpendicular or tangential merging of the clasp with the sling was not observed; instead, an obtuse, blunt angular merging of the clasp with the sling was observed.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cu\u003e\u003cstrong\u003eDiscussion\u003c/strong\u003e\u003c/u\u003e - The deviation of the sling from the clasp could indicate a lack of a proper fit between them at the cardioesophageal sphincter. The lack of robustness in the attachment of the clasp to the sling may possibly contribute to the diminished taut pull of the clasp in this subset of the population. These would be significant determinants for a predisposition to reflux esophagitis and Barrett's oesophagus.\u003c/p\u003e","manuscriptTitle":"A Study On The Congruence and Proximity Of The Sling And Clasp Fibres At The Cardio-Esophageal Junction Of The Stomach","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-05-09 19:55:34","doi":"10.21203/rs.3.rs-2886782/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2023-08-12T18:44:34+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"84077a4e-7d6e-4c8d-a6b3-a11a0a445039","date":"2023-08-10T00:00:49+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2023-08-09T20:01:40+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"84542050-e4cd-4296-8d9f-d6171aa625e5","date":"2023-06-18T17:20:35+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2023-05-09T07:30:11+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2023-05-09T06:37:25+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2023-05-05T10:07:42+00:00","index":"","fulltext":""},{"type":"submitted","content":"Surgical and Radiologic Anatomy","date":"2023-05-02T17:23:14+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"surgical-and-radiologic-anatomy","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"sara","sideBox":"Learn more about [Surgical and Radiologic Anatomy](http://link.springer.com/journal/276)","snPcode":"276","submissionUrl":"https://submission.nature.com/new-submission/276/3","title":"Surgical and Radiologic Anatomy","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"0de9543c-e5e7-4462-bfb8-25d6c244cb4f","owner":[],"postedDate":"May 9th, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2023-10-02T15:04:16+00:00","versionOfRecord":{"articleIdentity":"rs-2886782","link":"https://doi.org/10.1007/s00276-023-03243-3","journal":{"identity":"surgical-and-radiologic-anatomy","isVorOnly":false,"title":"Surgical and Radiologic Anatomy"},"publishedOn":"2023-09-26 15:01:35","publishedOnDateReadable":"September 26th, 2023"},"versionCreatedAt":"2023-05-09 19:55:34","video":"","vorDoi":"10.1007/s00276-023-03243-3","vorDoiUrl":"https://doi.org/10.1007/s00276-023-03243-3","workflowStages":[]},"version":"v1","identity":"rs-2886782","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-2886782","identity":"rs-2886782","version":["v1"]},"buildId":"WrCJVZZCHTDjtuVLN7oU0","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}