Situs inversus totalis with single extrahepatic portosystemic shunt and azygos continuation of the caudal vena cava in a dog: a case report | 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 Case Report Situs inversus totalis with single extrahepatic portosystemic shunt and azygos continuation of the caudal vena cava in a dog: a case report Ryo Takeuchi, Kumiko Ishigaki, Hiromichi Kuramoto, Teppei Fujimoto, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4550692/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 22 Feb, 2025 Read the published version in BMC Veterinary Research → Version 1 posted 16 You are reading this latest preprint version Abstract Background The normal visceral arrangement is called situs solitus, whereas the state of the visceral arrangement in a mirror-like positional relationship is called situs inversus. Among the SI, the state in which the positions of only some thoracoabdominal organs are reversed is called situs inversus partialis, and the state in which the positions of all thoracoabdominal organs are reversed is called situs inversus totalis (SIT). Clinical information on dogs with SIT is limited. Case presentation A 4-month-old Shiba dog was referred with depression and neurological symptoms as the chief complaints. Computed tomography (CT) revealed the patient had SIT with an extrahepatic portosystemic shunt (EHPSS) and azygos continuation of the caudal vena cava. In addition, complete reversal of the lung lobes and cardiovascular system in the thoracic cavity was confirmed. The patient underwent surgery for partial attenuation of EHPSS on day 8 after the initial examination. On day 124, after the initial examination, a second surgery was performed for complete attenuation. Under celiotomy, the positions of all abdominal organs, except for the rectum, were inverted; thus, SIT was confirmed via gross observation. In addition, the braided nylon sutures partially attenuated the concurrent splenocaval shunt. At the conclusion of this study, approximately 6 years had passed since the second surgery, and the patient had a good general condition without any medications. Conclusion In SIT, the complex anatomy of the abdominal organs and vessels is difficult to identify via gross observation; in contrast, CT is effective for detecting vascular abnormalities, confirming the anatomical position of each organ, and it allows for the definitive diagnosis of SIT. computed tomography dog portosystemic shunt situs inversus totalis surgery Figures Figure 1 Figure 2 Figure 3 1 Background The normal visceral arrangement is called situs solitus, whereas the state of the visceral arrangement in a mirror-like positional relationship is called situs inversus (SI) [ 1 , 2 ]. Among the SI, the state in which the positions of only some thoracoabdominal organs are reversed is called situs inversus partialis (SIP), and the state in which the positions of all thoracoabdominal organs are reversed is called situs inversus totalis (SIT). In addition, when the entire anatomical left–right axis is neither normal nor mirror image-inverted and shows an abnormal arrangement across the left–right axis, it is called heterotaxy (or situs ambiguus) [ 1 , 2 ]. SIT is often associated with congenital malformations, such as vascular abnormalities [ 3 , 4 ] and is extremely rare [ 4 ]. In veterinary medicine, there have been case reports of only 12 dogs [ 5 – 15 ]; however, the accurate incidence rate remains unknown in clinical settings. In particular, two reports have described dogs showing SI concurrently with an extrahepatic portosystemic shunt (EHPSS) and azygos continuation of the caudal vena cava (CVC) [ 8 , 16 ]. However, there is no veterinary literature on the long-term course of surgical treatment after a definitive diagnosis using pre-operative computed tomography (CT) in dogs with SIT. This report aimed to describe the CT and surgical findings and post-operative prognosis of a dog with SIT, EHPSS, and azygos continuation of a CVC. 2 Case presentation The patient was a spayed 4-month-old female Shiba, weighing 3.7 kg. The patient was examined at the referring hospital with the chief complaints of depression and neurological symptoms. The patient had high levels of total bile acid (TBA) and underwent dietary management and lactulose administration. Ten days later, the patient was referred to our hospital. During the first evaluation, general physical examination revealed no obvious neurological abnormalities. Hematology, serum chemistry, and coagulation test results are shown in Table 1 . Serum chemistry showed abnormal levels of total serum protein (4.1 g/dL), albumin (2.0 g/dL), glucose (88 mg/dL), blood urea nitrogen (3 mg/dL), and total cholesterol (92 mg/dl). Blood coagulation tests also showed prolonged activated partial thromboplastin time (APTT; 23.3 s) and low antithrombin III activity (AT III; 51%). Radiography revealed microhepatitis and dextrocardia. Ultrasonography was not performed as the patient was restless. Electrocardiography revealed normal sinus rhythm and right-axis deviation. Contrast-enhanced CT under general anesthesia confirmed complete reversal of the lung lobes and cardiovascular system in the thoracic cavity (Fig. 1 ). In addition, complete inversion of the internal organs and vascular system in the abdomen, splenocaval shunt (EHPSS), and azygos continuation of the CVC were confirmed (Supplementary File S1). The owner was informed of the surgical treatment for attenuation of the EHPSS. Informed consent was obtained, and the patient underwent surgery eight days after the initial examination. Table 1 Hematology, serum chemistry, and coagulation test results of the patient Parameter Unit Initial examination POD 97* POD 129† Normal range RBC 10 6 /µL 6.0 8.1 6.9 5.5–8.5 PCV % 35 46 41 37–55 WBC /µL 8,900 11,000 9,500 6,000–17,000 Stab /µL 0 NA NA 0–300 Seg /µL 5,207 NA NA 3,000–11,500 Lym /µL 2,581 NA NA 1,000–4,800 Mono /µL 845 NA NA 150–1,350 Eos /µL 267 NA NA 100–750 Plt 10 3 /µL 126 188 184 200–500 TP g/dL 4.1 5.6 5.8 4.8–7.2 Alb g/dL 2.0 2.7 2.8 2.1–3.6 Glu mg/dL 88 90 89 90–140 AST U/L 86 26 30 0–50 ALT U/L 190 19 24 8–75 ALP U/L 226 129 112 46–337 GGT U/L 6 10 4 0–2 BUN mg/dL 3 10 14 7–29 Cr mg/dL 0.3 0.6 0.7 0.3–1.2 T-CHO mg/dL 92 231 210 100–400 NH3 µmol/L 30 24 0 0–99 Na mmol/L 145 144 144 134–153 K mmol/L 4.1 4.4 3.9 3.4–4.6 Cl mmol/L 113 110 110 105–118 CRP mg/dL 0.61 0.27 0.09 0–1.0 APTT s 23.3 NA NA 10–16 PT s 7.6 NA NA 6–8 Fib mg/dl 155.7 NA NA 86–375 ATⅢ % 51 NA NA 102–156 RBC, red blood cell count; PCV, packed cell volume; WBC, white blood cell count; Stab, stab neutrophil; Seg, segmented neutrophil; Lym, lymphocyte; Mono, monophil; Eos, eosinophil; Plt, platelet count; TP, total protein; Alb, albumin; AST, aspartate aminotransferase; ALT, alanine aminotransferase; ALP, alkaline phosphatase; GGT, gamma-glutamyltransferase; BUN, blood urea nitrogen; Cr, creatinine; T-CHO, total cholesterol; NH3, ammonia; CRP, c-reactive protein; APTT, activated partial thromboplastin time; PT, prothrombin time; Fib, fibrinogen; ATⅢ, antithrombinⅢ *POD 97, postoperative day 97; 97 days after the first operation, prior to the second operation. †POD 129, postoperative day 129; 129 days after the first operation, which was 13 days after the second operation. The pre-anesthesia medications were subcutaneously injected:0.04 mg/kg atropine (Mitsubishi Tanabe Pharma Co., Osaka, Japan), 1.0 mg/kg prednisolone (Kyoritsu Seiyaku Co., Tokyo, Japan), 1.0 mg/kg maropitant (Cerenia®; Zoetis, Parsippany, NJ, USA), and 2.0 mg/kg ranitidine (Zantac®; GlaxoSmithKline K.K., London, UK). Anesthesia was induced by the intravenous administration of 2.4 mg/kg propofol (Mylan; Mylan Seiyaku Ltd., Tokyo, Japan). Tracheal intubation was performed for mechanical ventilation using isoflurane (IsoFlo; Zoetis) and pure oxygen (2 L/min). For intra-operative and post-operative medical management, dopamine (2.5–6.0 µg/kg/min) (Teva Takeda Pharma Ltd., Nagoya, Japan), dobutamine (2.5–5.0 µg/kg/min; Kyowa Pharmaceutical Industry Co. Ltd., Osaka, Japan) and nafamostat (0.1–0.2 mg/kg/h; serine protease inhibitor; Nichi-Iko Pharmaceutical Co. Ltd., Toyama, Japan) were continuously infused. For analgesic management, continuous infusion of remifentanil (2.0–35 µg/kg/h) during and after surgery, and intramuscular administration of morphine (0.3 mg/kg each dose) before and after surgery were used. Furthermore, 20 mg/kg cefazolin (Nichi-Iko Pharmaceutical Co., Ltd.) was administered intravenously at the time of anesthesia induction and every 2-h during general anesthesia. As abnormalities in APTT and AT III were revealed in the pre-operative blood coagulation test, whole blood transfusion (total volume, 100 ml) was administered intra-operatively and post-operatively to enhance hemostatic function. Under general anesthesia, the patient was placed in dorsal recumbency and prepared for abdominal surgery. A celiotomy was performed from the xiphoid to the middle between the umbilicus and pubis. The positions of the internal organs in the abdominal cavity were confirmed, and the positions of all abdominal organs, except for the rectum, were inverted (Fig. 2 A). The hepatic lobe corresponding to the right lateral lobe was atrophied, the hepatorenal ligament was absent, and polysplenia was observed (Fig. 2 B). The gastric and intestinal tracts were pulled caudally to identify splenocaval shunts. One greater omentum was manually separated, and the stomach was lifted to expose and detach the shunt vessels. A cannula was placed in the mesenteric vein using a 24–G indwelling needle (Surflow® indwelling needle, Terumo Co., Ltd., Tokyo, Japan) to measure portal pressure (10 mmHg). Iohexol (350 mg I/ml) was administered through the mesenteric vein, and intra-operative mesenteric portography (IOMP) was performed to visualize abnormal blood flow (see Supplementary file S2). Additionally, IOMP was performed again by temporarily closing the shunt vessel using atraumatic bulldog forceps. Portal vein blood flow toward the cranial side of the closed site was poor, and no abnormal blood flow other than that in the shunt blood vessel was observed, while the portal pressure increased to 44 mmHg (Fig. 2 C). Partial ligation was performed using a coated braided nylon suture, size 0 (Surgilon; Medtronic Inc., Minneapolis, MN, USA), to a portal pressure of 12 mmHg. A portion of the margin of the left hepatic lateral lobe was obtained for histopathological examination. Subsequently, ovariohysterectomy was performed, and the abdominal wall, subcutaneous tissues, and skin were closed. The mean operative time was 75 min. The patient recovered well after anesthesia. No abnormalities were observed in the general condition during hospitalization, and medical management was performed with cefalexin (35 mg/kg bid; Larixin®; FUJIFILM Toyama Chemical Co., Ltd., Tokyo, Japan) and oral administration of lactulose (2 mL/head bid; Kowa Co. Ltd., Osaka, Japan). The patient was discharged six days after surgery. Histopathological examination of liver biopsy samples revealed poor vascular development of the portal system, irregular lobular structures, and mild atrophy of hepatocytes. At 97 days after the first surgery, blood examination revealed that the abnormal values observed at the first visit had improved (Table 1 ). Contrast-enhanced CT under general anesthesia revealed narrowing of the shunt vessel and development of an intrahepatic portal vein branch (Fig. 3 A, Supplementary file S3). Therefore, 116 days after the first surgery, a second surgery was performed to completely attenuate the shunt vessel. The same anesthetic management was used as in the first surgery; however, no blood transfusions were performed. When the portal pressure was measured during celiotomy, as in the first surgery, the portal pressure was 11 mmHg. Although the portal pressure increased to 15 mmHg after temporary occlusion of the shunt vessel, cyanosis of the pancreas and intestinal tract and increased peristaltic motility of the gastrointestinal tract were not observed. In addition, IOMP revealed the development of intrahepatic portal branches (Fig. 3 B, Supplementary File S4). The shunt vessel was completely ligated using a size 0 coated braided nylon suture (Surgilon). The abdominal wall, subcutaneous tissue, and skin were closed. The second surgery lasted for 44 min. The patient's general condition was good during the second hospital stay, and she was discharged 6 days after surgery, following continued medical management with cefovecin sodium (8 mg/kg sc; Convenia®; Zoetis) and dietary management with a liver therapy diet. On the 13th day after the second surgery, the patient was in a good general condition without dietary control. No abnormal values were detected in the blood test (Table 1 ), and TBA level was within the normal range (fasting:1.8 µmol/L; postprandial:2.1 µmol/L). At the conclusion of this study, approximately 6 years had passed since the second surgery, and the patient had a good general condition without any medications. 3 Discussion and Conclusions SIT is extremely rare in humans. A study using human data from the National Birth Defects Prevention Study reported an estimated prevalence of 0.3 per 10,000 live births [ 4 ]. Although no epidemiological studies have been conducted in veterinary medicine, it is highly likely that the incidence is as low in animals as it is in humans. Laterality defects, also known as defects in left–right axis patterning or malpositioned complexes of embryos, have been recognized as pathological conditions, including SIT and heterotaxy [ 2 , 4 ]. The mechanism for determining the left–right axis of the embryo is as follows [ 17 ]. First, a one-way rotation of the cilia occurs in the node of the early embryo (symmetry breaking), producing fluid pointing to the left. Next, the asymmetric downstream signals generated at the node are transmitted laterally and the cilia sense the flow of the node. Then, asymmetric gene expression occurs. Nodal expression is induced throughout the lateral plate mesoderm, and Nodal activates the expression of the transcriptional regulator Pitx2. Finally, the organs are asymmetrically formed through the action of Pitx2. In addition, intracardiac cilia that play a potential role in cardiac development, unlike those that play a role in left–right asymmetry, have been identified [ 18 ]. Thus, cilia play an important role in the establishment of left–right asymmetry and cardiac development during embryogenesis, and ciliary dysfunction may cause laterality defects. Previous reports have revealed that laterality defects are caused by defects in signal transduction at the nodes, including in the structure and function of cilia and asymmetrically expressed genes [ 2 , 17 ]. Dextrocardia and congenital heart disorders associated with laterality defects may also result from abnormalities and ciliary dysfunction at various stages of left–right axis formation [ 17 ]. Lateral defects are associated with autosomal dominant, autosomal recessive, and X-linked modes of inheritance caused by mutations in ZIC3 [ 1 , 3 , 17 ]. Primary ciliary dysfunction (PCD), which can be associated with SI in 41–48% of cases [ 19 , 20 ], is a rare hereditary disease caused by mutations in genes related to cilia, such as DNAH5 and DNAI1 , and exhibits autosomal recessive or X-linked modes of inheritance [ 17 , 19 ]. Patients with PCD also have been shown to have an increased risk of congenital heart disease [ 19 ]. Although reports suggest autosomal recessive inheritance in dogs with PCD [ 21 , 22 ], no extensive genetic studies have been conducted in dogs. Nodal flow has been found to be a universal mechanism across vertebrate species as a trigger for left–right axis formation [ 17 ]. Because our canine case showed the same pathological condition as that found in humans, the genetic or embryological mechanisms reported in humans may have occurred. The portal vein develops embryologically from the right ventricle. Development of the venous system in the abdominal cavity has been reported to differ among animal species; however, it is generally recognized that the CVC and azygos veins are formed as a result of the appearance, anastomosis, and disappearance of the caudal cardinal, subcardinal, and supra-cardinal veins [ 23 ]. During interruption of the CVC and azygos continuation, the right subcardinal vein, which forms the suprarenal segment of the CVC during development, fails to connect with the right vitelline vein, which forms the intrahepatic segment. In this malformation, blood in the caudal region flows through the azygos vein and cranial vena cava to the heart because of the switching of the blood passage to the right supracardinal vein [ 8 , 24 – 26 ]. EHPSS is an abnormal congenital anastomosis thought to be caused by the influx of right vitelline veins from the caudal site into the right cardinal vein [ 27 ]. The association between the SI and vascular malformations is unclear because the placement of internal organs is determined prior to developmental changes in the cardiovascular system [ 8 ]. However, an abnormal visceral placement can predispose individuals to errors during the development of complex cardiovascular systems. SIT is usually asymptomatic and is often accidentally diagnosed [ 1 , 2 ]. However, SI may be associated with airway abnormalities, such as chronic rhinosinusitis and bronchiectasis, that is, Kartagener syndrome (KS), which is recognized as a subtype of PCD [ 3 , 9 , 22 ]. In human medicine, 20–25% of patients with SIT are estimated to have KS [ 3 ]. Although respiratory symptoms were expected, no clinical symptoms indicative of KS were observed in this patiant. In humans, laterality defects are associated with various congenital malformations, including those of the cardiovascular system [ 3 , 4 ], which result in clinical symptoms. Previous reports of SIT patients in veterinary medicine have shown that hydrocephalus [ 9 , 21 ], congenital heart disease [ 9 , 14 ], vascular malformation [ 8 ], diaphragmatic hernia [ 13 ], and respiratory diseases, including KS [ 5 , 7 , 9 , 11 , 12 , 21 ], may occur. There have also been a few cases [ 10 , 15 ] with no comorbidities. In these reports, clinical symptoms caused by congenital malformations emerged and led to therapeutic interventions. In human medicine, interruption of the CVC and azygos continuation is generally considered asymptomatic [ 28 , 29 ]. In veterinary medicine, there are case reports of vascular malformations, such as EHPSS [ 8 , 25 , 28 ], deep vein thrombosis [ 24 ], and pulmonary thromboembolism [ 29 ], associated with azygos continuation in CVC. In this case, SIT may have caused EHPSS, which is a vascular malformation and azygos continuation of the CVC. Therapeutic intervention was sought due to the clinical symptoms caused by EHPSS. In humans, SIT can be accidentally detected when CT is performed before surgery. Additionally, if the altered anatomical positional relationship is understood to be the result of CT, surgical treatment can be performed in the same manner as in patients with normal anatomical structures [ 30 ]. CT is also been shown to be effective in detecting congenital malformations of the superior and inferior vena cava [ 31 ]. CT is effective in detecting cardiovascular malformations associated with heterotaxy patients [ 32 ]. Furthermore, CT examinations of patients have been reportedly effective in determining the presence or absence of bronchiectasis and its severity [ 33 ]. In addition to EHPSS, which was the main cause of the clinical symptoms, SIT and azygos continuation of the CVC were incidentally detected. Therefore, this case illustrates that pre-operative CT is very effective in detecting SIT and EHPSS, which require therapeutic intervention. CT is essential for assessing the presence of anatomical abnormalities that may interfere with surgical procedures. Due to the unusual anatomical position of the abdominal organs in this case, surgery after laparotomy was expected to be difficult. However, the CT findings made it possible to safely perform the operation. Surgical treatment of congenital malformations associated with SIT has been reported in veterinary medicine. A Doberman–Pinscher patient with SIT underwent surgical treatment for a congenital diaphragmatic hernia and was clinically normal at the time of examination 13 months after surgery [ 13 ]. There have been two previous reports of EHPSS and azygos continuation in CVC associated with SI. Of these, a report on ligation for EHPSS in patients with SIT reported that patients were clinically normal at the examination 22 months after surgery if dietary protein restriction was implemented [ 8 ]. Additionally, a study on ameroid constrictor placement for EHPSS in a patient with SIP reported normal post-operative clinical signs and test results, although no detailed description was provided [ 16 ]. These reports suggest that the prognosis may be good if congenital malformations are treated despite SI. In conclusion, the complex anatomy of the abdominal organs and vessels is difficult to identify grossly in cases of SIT, whereas CT is effective for detecting vascular abnormalities, confirming the anatomical position of each organ, and for the definitive diagnosis of SIT. Abbreviations APTT Activated partial thromboplastin time AT III antithrombin III CT Computed tomography CVC Caudal vena cava EHPSS Extrahepatic portosystemic shunt IOMP Intraoperative mesenteric portography KS Kartagener syndrome PCD Primary ciliary dysfunction SI Situs inversus SIP Situs inversus partialis SIT Situs inversus totalis TBA Total bile acid Declarations Funding No third-party funding or support was received in connection with this study or the writing or publication of this manuscript. Availability of data and materials All data supporting the conclusions of this article are included within the article. Ethics approval and consent to participate Informed consent was obtained from the owner before all procedures were performed. All methods in this study were performed in accordance with the relevant guidelines and regulations in compliance with the ARRIVE guidelines. This study was approved by our Institutional Ethical Committee (ANMEC-03-017). Competing interests The authors declare no competing interests. Consent for publication Not applicable. References Casey B. Genetics of Human Site Abnormalities. Am J Med Genet. 2001;101(4):356–8. Bisgrove BW, Morelli SH, Yost HJ. Genetics of human laterality disorders: insights from vertebrate model systems. Annu Rev Genomics Hum Genet. 2003;4:1–32. Aylsworth AS. Clinical aspects of defects in the determination of laterality. Am J Med Genet. 2001;101(4):345–55. Lin AE, Krikov S, Riehle-Colarusso T, et al. Laterality defects in the national birth defects prevention study (1998–2007): birth prevalence and descriptive epidemiology. 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J Cardiovasc Comput Tomogr. 2013;7(6):408–16. Kennedy MP, Noone PG, Leigh MW, et al. High-resolution CT of patients with primary ciliary dyskinesia. AJR Am J Roentgenol. 2007;188(5):1232–8. Additional Declarations No competing interests reported. Supplementary Files Additionalfile1.mp4 Additional file 1. Movie of three-dimensional (3D) reconstruction of computed tomography angiography (CTA) before the first surgery. CTA 3D reconstruction showed complete inversion of the vascular system in the abdomen, a splenocaval shunt (EHPSS), and azygos continuation of the caudal vena cava. Additionalfile2.mp4 Additional file 2. Movie of intraoperative mesenteric portography (IOMP) with digital subtraction angiography in the first surgery. During temporary occlusion of the shunt vessel using atraumatic bulldog forceps, portal venous flow was indicated to enter the inverted liver via IOMP. Additionalfile3.mp4 Additional file 3. Movie of three-dimensional (3D) reconstruction of computed tomography angiography (CTA) before the second surgery. CTA 3D reconstruction revealed a reduction in shunt flow due to partial surgical ligation and the development of intrahepatic portal vascularity. Additionalfile4.mp4 Additional file 4. Movie of intraoperative mesenteric portography (IOMP) with digital subtraction angiography in the second surgery. During the temporary occlusion of the narrowed shunt vessel using atraumatic bulldog forceps, IOMP revealed no shunt vessels or the development of intrahepatic portal vascularity; therefore, complete surgical ligation was achieved. Cite Share Download PDF Status: Published Journal Publication published 22 Feb, 2025 Read the published version in BMC Veterinary Research → Version 1 posted Editorial decision: Revision requested 25 Nov, 2024 Reviews received at journal 25 Nov, 2024 Reviewers agreed at journal 23 Nov, 2024 Reviewers agreed at journal 23 Nov, 2024 Reviewers agreed at journal 22 Nov, 2024 Reviews received at journal 21 Nov, 2024 Reviewers agreed at journal 21 Nov, 2024 Reviewers agreed at journal 21 Nov, 2024 Reviewers agreed at journal 21 Nov, 2024 Reviewers agreed at journal 21 Nov, 2024 Reviewers agreed at journal 30 Jul, 2024 Reviewers invited by journal 24 Jul, 2024 Editor invited by journal 12 Jun, 2024 Editor assigned by journal 11 Jun, 2024 Submission checks completed at journal 11 Jun, 2024 First submitted to journal 08 Jun, 2024 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. 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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-4550692","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":314762651,"identity":"1da0c6c6-e33f-4358-8793-896728d45235","order_by":0,"name":"Ryo Takeuchi","email":"","orcid":"","institution":"Nihon University","correspondingAuthor":false,"prefix":"","firstName":"Ryo","middleName":"","lastName":"Takeuchi","suffix":""},{"id":314762652,"identity":"6f812712-83a4-48f8-a4a3-b54c4cadd944","order_by":1,"name":"Kumiko Ishigaki","email":"","orcid":"","institution":"Nihon University","correspondingAuthor":false,"prefix":"","firstName":"Kumiko","middleName":"","lastName":"Ishigaki","suffix":""},{"id":314762654,"identity":"b52c43bd-d01e-4e02-ae21-e161f5fa68d6","order_by":2,"name":"Hiromichi Kuramoto","email":"","orcid":"","institution":"Kuramoto Animal Hospital","correspondingAuthor":false,"prefix":"","firstName":"Hiromichi","middleName":"","lastName":"Kuramoto","suffix":""},{"id":314762655,"identity":"004d7669-5e7f-425b-8790-7e4790e209d3","order_by":3,"name":"Teppei Fujimoto","email":"","orcid":"","institution":"Nihon University","correspondingAuthor":false,"prefix":"","firstName":"Teppei","middleName":"","lastName":"Fujimoto","suffix":""},{"id":314762658,"identity":"49a70c13-5e11-4882-8773-1127ce35e4e3","order_by":4,"name":"Yumi Sakamoto","email":"","orcid":"","institution":"Nihon University","correspondingAuthor":false,"prefix":"","firstName":"Yumi","middleName":"","lastName":"Sakamoto","suffix":""},{"id":314762659,"identity":"055949eb-3564-4407-8a2f-260a155d9d2c","order_by":5,"name":"Manabu Sakai","email":"","orcid":"","institution":"Nihon University","correspondingAuthor":false,"prefix":"","firstName":"Manabu","middleName":"","lastName":"Sakai","suffix":""},{"id":314762660,"identity":"0c25f932-7e3f-4944-89af-44733b2087dc","order_by":6,"name":"Kazushi Asano","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABDklEQVRIie2QsUrEQBCGJxzEZiHtHIr7CrNNgoXeq+wSSJqtJaDgiRCbiG2KQ98idSBgmvWuTWFxNqmuuEoEGxMRbRLxOpH9iimG+fhnBsBi+bvIvrggE2D03S1/o5idFScFoJ/merzbql1vIeI8j9v1893TQbB3U04YnHBwHgdjsIkCkYMWl7kOSBUtO8qWslNCMYelHIxpwN9nkDhXqF1URcWo0cEbg0k3bgaX5Kv6pVdmKcYtqsWHQl3KxahCpe5TtMpQ+qjmX0o1qohGn05zisKcbXyUD51iDDkLqkU6csvhqi5wm4TH99dxO309r2ZUZwSb5Ix7OPyxz/WGOi6acWMEL9tZsVgsln/JO3YCWUfWR4cwAAAAAElFTkSuQmCC","orcid":"","institution":"Nihon University","correspondingAuthor":true,"prefix":"","firstName":"Kazushi","middleName":"","lastName":"Asano","suffix":""}],"badges":[],"createdAt":"2024-06-08 12:59:48","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4550692/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4550692/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12917-025-04565-7","type":"published","date":"2025-02-22T15:57:07+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":59964754,"identity":"81cf1bfc-e945-4cf3-b845-0fbd761ee589","added_by":"auto","created_at":"2024-07-10 01:52:54","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":469989,"visible":true,"origin":"","legend":"\u003cp\u003ePre-operative 3D computed tomography. The heart (white arrow) is inverted, and a right aorta (red) has been formed. Furthermore, the caudal vena cava (blue) runs on the left side of the aorta; after the caudal vena cava merges with the renal vein; it connects to the azygos vein (white arrowhead). There is no caudal vena cava from the kidney to the liver. The left and right kidneys are reversed, and a shunt blood vessel (green) is present between the portal vein and the caudal vena cava, confirming the extrahepatic portosystemic shunt complication.\u003c/p\u003e","description":"","filename":"Figure12.png","url":"https://assets-eu.researchsquare.com/files/rs-4550692/v1/c0d913511e3d4fe8d83a415d.png"},{"id":59964752,"identity":"f8137ae9-f05a-4345-83a1-bb1f8cfc9fbb","added_by":"auto","created_at":"2024-07-10 01:52:54","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":3439109,"visible":true,"origin":"","legend":"\u003cp\u003eIntra-operative findings of the first surgery. \u003cstrong\u003eA: \u003c/strong\u003eLaparotomy findings. Most of the intra-abdominal organs, exception for the rectum, were inverted. In the stomach, the pylorus was located on the left side of the patient, and the duodenum (black arrow) also descended on the left side of the patient. The pancreas (black arrowhead) was also inverted. \u003cstrong\u003eB:\u003c/strong\u003e Laparotomy findings: The liver was also inverted, and the left liver area was located in what would be the position of the right liver area in a healthy dog. The position of the left kidney was located at the position of the right kidney in a healthy dog and was in contact with the liver. However, no hepatorenal mesentery formation was observed. \u003cstrong\u003eC: \u003c/strong\u003eMesenteric portography after the temporary closure of the shunt vessel using intact bulldog forceps during the first surgery. The portal vein blood flow toward the cranial side of the closed site is poor, and the intrahepatic portal vein is clearly underdeveloped. No abnormal blood vessels (other than shunt blood vessels) can be observed.\u003c/p\u003e","description":"","filename":"Figure2A.png","url":"https://assets-eu.researchsquare.com/files/rs-4550692/v1/cd4368c3c321d629fa0e7c5e.png"},{"id":59964751,"identity":"d007d7bf-1f1f-4bc4-9973-5a32466eb6cd","added_by":"auto","created_at":"2024-07-10 01:52:54","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1204727,"visible":true,"origin":"","legend":"\u003cp\u003ePre-operative 3D computed tomography and intra-operative mesenteric portography of the second surgery. \u003cstrong\u003eA: \u003c/strong\u003epre-operative 3D computed tomography. Compared with those in the pre-operative 3D computed tomography, narrowing of the shunt blood vessel and development of the intrahepatic portal vein branch due to partial ligation can be observed. \u003cstrong\u003eB:\u003c/strong\u003eintra-operative mesenteric portography after temporary closure of the shunt vessel using intact bulldog forceps during the second surgery. The intrahepatic portal vein branch can be visualized up to the tertiary branch. The development of the intrahepatic portal vein is confirmed, as compared to observations during the first operation.\u003c/p\u003e","description":"","filename":"Figure3A.png","url":"https://assets-eu.researchsquare.com/files/rs-4550692/v1/f2c1fda8a21ab485e988def6.png"},{"id":77052696,"identity":"a2250133-a297-4439-9b45-eee7f9679ef4","added_by":"auto","created_at":"2025-02-24 16:23:22","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":7163178,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4550692/v1/91a2d71b-3fa1-459b-a355-f20cead1b784.pdf"},{"id":59964750,"identity":"c3b4f200-add5-49ab-9e25-44778254d7ea","added_by":"auto","created_at":"2024-07-10 01:52:53","extension":"mp4","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":510568,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eAdditional file 1.\u003c/strong\u003e Movie of three-dimensional (3D) reconstruction of computed tomography angiography (CTA) before the first surgery. CTA 3D reconstruction showed complete inversion of the vascular system in the abdomen, a splenocaval shunt (EHPSS), and azygos continuation of the caudal vena cava.\u003c/p\u003e","description":"","filename":"Additionalfile1.mp4","url":"https://assets-eu.researchsquare.com/files/rs-4550692/v1/b82bd89b96046d8f1e276295.mp4"},{"id":59964753,"identity":"edd27bb8-b26b-4b42-b49b-efa9de3adbe0","added_by":"auto","created_at":"2024-07-10 01:52:54","extension":"mp4","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":3309195,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eAdditional file 2. \u003c/strong\u003eMovie of intraoperative mesenteric portography (IOMP) with digital subtraction angiography in the first surgery. During temporary occlusion of the shunt vessel using atraumatic bulldog forceps, portal venous flow was indicated to enter the inverted liver via IOMP.\u003c/p\u003e","description":"","filename":"Additionalfile2.mp4","url":"https://assets-eu.researchsquare.com/files/rs-4550692/v1/ecc8b47a8fd34ef8ea9c04eb.mp4"},{"id":59964755,"identity":"3615ddd7-a614-4264-9a46-9a627dac0807","added_by":"auto","created_at":"2024-07-10 01:52:54","extension":"mp4","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":535587,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eAdditional file 3.\u003c/strong\u003e Movie of three-dimensional (3D) reconstruction of computed tomography angiography (CTA) before the second surgery. CTA 3D reconstruction revealed a reduction in shunt flow due to partial surgical ligation and the development of intrahepatic portal vascularity.\u003c/p\u003e","description":"","filename":"Additionalfile3.mp4","url":"https://assets-eu.researchsquare.com/files/rs-4550692/v1/ae51f3c14c924da0be699b94.mp4"},{"id":59965759,"identity":"76e50947-a4b3-45b6-aa49-446d18b6690e","added_by":"auto","created_at":"2024-07-10 02:00:54","extension":"mp4","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":3229343,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eAdditional file 4.\u003c/strong\u003e Movie of intraoperative mesenteric portography (IOMP) with digital subtraction angiography in the second surgery. During the temporary occlusion of the narrowed shunt vessel using atraumatic bulldog forceps, IOMP revealed no shunt vessels or the development of intrahepatic portal vascularity; therefore, complete surgical ligation was achieved.\u003c/p\u003e","description":"","filename":"Additionalfile4.mp4","url":"https://assets-eu.researchsquare.com/files/rs-4550692/v1/02e3397b0010de1308b33c05.mp4"}],"financialInterests":"No competing interests reported.","formattedTitle":"Situs inversus totalis with single extrahepatic portosystemic shunt and azygos continuation of the caudal vena cava in a dog: a case report","fulltext":[{"header":"1 Background","content":"\u003cp\u003eThe normal visceral arrangement is called situs solitus, whereas the state of the visceral arrangement in a mirror-like positional relationship is called situs inversus (SI) [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Among the SI, the state in which the positions of only some thoracoabdominal organs are reversed is called situs inversus partialis (SIP), and the state in which the positions of all thoracoabdominal organs are reversed is called situs inversus totalis (SIT). In addition, when the entire anatomical left\u0026ndash;right axis is neither normal nor mirror image-inverted and shows an abnormal arrangement across the left\u0026ndash;right axis, it is called heterotaxy (or situs ambiguus) [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. SIT is often associated with congenital malformations, such as vascular abnormalities [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] and is extremely rare [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn veterinary medicine, there have been case reports of only 12 dogs [\u003cspan additionalcitationids=\"CR6 CR7 CR8 CR9 CR10 CR11 CR12 CR13 CR14\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]; however, the accurate incidence rate remains unknown in clinical settings. In particular, two reports have described dogs showing SI concurrently with an extrahepatic portosystemic shunt (EHPSS) and azygos continuation of the caudal vena cava (CVC) [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. However, there is no veterinary literature on the long-term course of surgical treatment after a definitive diagnosis using pre-operative computed tomography (CT) in dogs with SIT. This report aimed to describe the CT and surgical findings and post-operative prognosis of a dog with SIT, EHPSS, and azygos continuation of a CVC.\u003c/p\u003e"},{"header":"2 Case presentation","content":"\u003cp\u003eThe patient was a spayed 4-month-old female Shiba, weighing 3.7 kg. The patient was examined at the referring hospital with the chief complaints of depression and neurological symptoms. The patient had high levels of total bile acid (TBA) and underwent dietary management and lactulose administration. Ten days later, the patient was referred to our hospital.\u003c/p\u003e \u003cp\u003eDuring the first evaluation, general physical examination revealed no obvious neurological abnormalities. Hematology, serum chemistry, and coagulation test results are shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Serum chemistry showed abnormal levels of total serum protein (4.1 g/dL), albumin (2.0 g/dL), glucose (88 mg/dL), blood urea nitrogen (3 mg/dL), and total cholesterol (92 mg/dl). Blood coagulation tests also showed prolonged activated partial thromboplastin time (APTT; 23.3 s) and low antithrombin III activity (AT III; 51%). Radiography revealed microhepatitis and dextrocardia. Ultrasonography was not performed as the patient was restless. Electrocardiography revealed normal sinus rhythm and right-axis deviation. Contrast-enhanced CT under general anesthesia confirmed complete reversal of the lung lobes and cardiovascular system in the thoracic cavity (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). In addition, complete inversion of the internal organs and vascular system in the abdomen, splenocaval shunt (EHPSS), and azygos continuation of the CVC were confirmed (Supplementary File S1). The owner was informed of the surgical treatment for attenuation of the EHPSS. Informed consent was obtained, and the patient underwent surgery eight days after the initial examination.\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\u003eHematology, serum chemistry, and coagulation test results of the patient\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\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 \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" 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colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eg/dL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.1\u0026ndash;3.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGlu\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003emg/dL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e90\u003c/p\u003e \u003c/td\u003e 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align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eU/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e190\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e8\u0026ndash;75\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eALP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eU/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e226\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e129\u003c/p\u003e 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\u003cp\u003eCl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003emmol/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e113\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e110\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e110\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e105\u0026ndash;118\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCRP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003emg/dL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u0026ndash;1.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAPTT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003es\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e23.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e10\u0026ndash;16\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003es\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6\u0026ndash;8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFib\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003emg/dl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e155.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e86\u0026ndash;375\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eATⅢ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e102\u0026ndash;156\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003eRBC, red blood cell count; PCV, packed cell volume; WBC, white blood cell count; Stab, stab neutrophil; Seg, segmented neutrophil; Lym, lymphocyte; Mono, monophil; Eos, eosinophil; Plt, platelet count; TP, total protein; Alb, albumin; AST, aspartate aminotransferase; ALT, alanine aminotransferase; ALP, alkaline phosphatase; GGT, gamma-glutamyltransferase; BUN, blood urea nitrogen; Cr, creatinine; T-CHO, total cholesterol; NH3, ammonia; CRP, c-reactive protein; APTT, activated partial thromboplastin time; PT, prothrombin time; Fib, fibrinogen; ATⅢ, antithrombinⅢ\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003e*POD 97, postoperative day 97; 97 days after the first operation, prior to the second operation.\u003c/p\u003e \u003cp\u003e\u0026dagger;POD 129, postoperative day 129; 129 days after the first operation, which was 13 days after the second operation.\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\u003e \u003c/p\u003e \u003cp\u003eThe pre-anesthesia medications were subcutaneously injected:0.04 mg/kg atropine (Mitsubishi Tanabe Pharma Co., Osaka, Japan), 1.0 mg/kg prednisolone (Kyoritsu Seiyaku Co., Tokyo, Japan), 1.0 mg/kg maropitant (Cerenia\u0026reg;; Zoetis, Parsippany, NJ, USA), and 2.0 mg/kg ranitidine (Zantac\u0026reg;; GlaxoSmithKline K.K., London, UK). Anesthesia was induced by the intravenous administration of 2.4 mg/kg propofol (Mylan; Mylan Seiyaku Ltd., Tokyo, Japan). Tracheal intubation was performed for mechanical ventilation using isoflurane (IsoFlo; Zoetis) and pure oxygen (2 L/min). For intra-operative and post-operative medical management, dopamine (2.5\u0026ndash;6.0 \u0026micro;g/kg/min) (Teva Takeda Pharma Ltd., Nagoya, Japan), dobutamine (2.5\u0026ndash;5.0 \u0026micro;g/kg/min; Kyowa Pharmaceutical Industry Co. Ltd., Osaka, Japan) and nafamostat (0.1\u0026ndash;0.2 mg/kg/h; serine protease inhibitor; Nichi-Iko Pharmaceutical Co. Ltd., Toyama, Japan) were continuously infused. For analgesic management, continuous infusion of remifentanil (2.0\u0026ndash;35 \u0026micro;g/kg/h) during and after surgery, and intramuscular administration of morphine (0.3 mg/kg each dose) before and after surgery were used. Furthermore, 20 mg/kg cefazolin (Nichi-Iko Pharmaceutical Co., Ltd.) was administered intravenously at the time of anesthesia induction and every 2-h during general anesthesia. As abnormalities in APTT and AT III were revealed in the pre-operative blood coagulation test, whole blood transfusion (total volume, 100 ml) was administered intra-operatively and post-operatively to enhance hemostatic function.\u003c/p\u003e \u003cp\u003eUnder general anesthesia, the patient was placed in dorsal recumbency and prepared for abdominal surgery. A celiotomy was performed from the xiphoid to the middle between the umbilicus and pubis. The positions of the internal organs in the abdominal cavity were confirmed, and the positions of all abdominal organs, except for the rectum, were inverted (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA). The hepatic lobe corresponding to the right lateral lobe was atrophied, the hepatorenal ligament was absent, and polysplenia was observed (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB). The gastric and intestinal tracts were pulled caudally to identify splenocaval shunts. One greater omentum was manually separated, and the stomach was lifted to expose and detach the shunt vessels. A cannula was placed in the mesenteric vein using a 24\u0026ndash;G indwelling needle (Surflow\u0026reg; indwelling needle, Terumo Co., Ltd., Tokyo, Japan) to measure portal pressure (10 mmHg). Iohexol (350 mg I/ml) was administered through the mesenteric vein, and intra-operative mesenteric portography (IOMP) was performed to visualize abnormal blood flow (see Supplementary file S2). Additionally, IOMP was performed again by temporarily closing the shunt vessel using atraumatic bulldog forceps. Portal vein blood flow toward the cranial side of the closed site was poor, and no abnormal blood flow other than that in the shunt blood vessel was observed, while the portal pressure increased to 44 mmHg (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eC). Partial ligation was performed using a coated braided nylon suture, size 0 (Surgilon; Medtronic Inc., Minneapolis, MN, USA), to a portal pressure of 12 mmHg. A portion of the margin of the left hepatic lateral lobe was obtained for histopathological examination. Subsequently, ovariohysterectomy was performed, and the abdominal wall, subcutaneous tissues, and skin were closed.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe mean operative time was 75 min. The patient recovered well after anesthesia. No abnormalities were observed in the general condition during hospitalization, and medical management was performed with cefalexin (35 mg/kg bid; Larixin\u0026reg;; FUJIFILM Toyama Chemical Co., Ltd., Tokyo, Japan) and oral administration of lactulose (2 mL/head bid; Kowa Co. Ltd., Osaka, Japan). The patient was discharged six days after surgery. Histopathological examination of liver biopsy samples revealed poor vascular development of the portal system, irregular lobular structures, and mild atrophy of hepatocytes.\u003c/p\u003e \u003cp\u003eAt 97 days after the first surgery, blood examination revealed that the abnormal values observed at the first visit had improved (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Contrast-enhanced CT under general anesthesia revealed narrowing of the shunt vessel and development of an intrahepatic portal vein branch (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA, Supplementary file S3). Therefore, 116 days after the first surgery, a second surgery was performed to completely attenuate the shunt vessel. The same anesthetic management was used as in the first surgery; however, no blood transfusions were performed. When the portal pressure was measured during celiotomy, as in the first surgery, the portal pressure was 11 mmHg. Although the portal pressure increased to 15 mmHg after temporary occlusion of the shunt vessel, cyanosis of the pancreas and intestinal tract and increased peristaltic motility of the gastrointestinal tract were not observed. In addition, IOMP revealed the development of intrahepatic portal branches (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eB, Supplementary File S4). The shunt vessel was completely ligated using a size 0 coated braided nylon suture (Surgilon). The abdominal wall, subcutaneous tissue, and skin were closed.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe second surgery lasted for 44 min. The patient's general condition was good during the second hospital stay, and she was discharged 6 days after surgery, following continued medical management with cefovecin sodium (8 mg/kg sc; Convenia\u0026reg;; Zoetis) and dietary management with a liver therapy diet. On the 13th day after the second surgery, the patient was in a good general condition without dietary control. No abnormal values were detected in the blood test (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e), and TBA level was within the normal range (fasting:1.8 \u0026micro;mol/L; postprandial:2.1 \u0026micro;mol/L).\u003c/p\u003e \u003cp\u003eAt the conclusion of this study, approximately 6 years had passed since the second surgery, and the patient had a good general condition without any medications.\u003c/p\u003e"},{"header":"3 Discussion and Conclusions","content":"\u003cp\u003eSIT is extremely rare in humans. A study using human data from the National Birth Defects Prevention Study reported an estimated prevalence of 0.3 per 10,000 live births [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Although no epidemiological studies have been conducted in veterinary medicine, it is highly likely that the incidence is as low in animals as it is in humans. Laterality defects, also known as defects in left\u0026ndash;right axis patterning or malpositioned complexes of embryos, have been recognized as pathological conditions, including SIT and heterotaxy [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. The mechanism for determining the left\u0026ndash;right axis of the embryo is as follows [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. First, a one-way rotation of the cilia occurs in the node of the early embryo (symmetry breaking), producing fluid pointing to the left. Next, the asymmetric downstream signals generated at the node are transmitted laterally and the cilia sense the flow of the node. Then, asymmetric gene expression occurs. Nodal expression is induced throughout the lateral plate mesoderm, and Nodal activates the expression of the transcriptional regulator Pitx2. Finally, the organs are asymmetrically formed through the action of Pitx2. In addition, intracardiac cilia that play a potential role in cardiac development, unlike those that play a role in left\u0026ndash;right asymmetry, have been identified [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Thus, cilia play an important role in the establishment of left\u0026ndash;right asymmetry and cardiac development during embryogenesis, and ciliary dysfunction may cause laterality defects. Previous reports have revealed that laterality defects are caused by defects in signal transduction at the nodes, including in the structure and function of cilia and asymmetrically expressed genes [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Dextrocardia and congenital heart disorders associated with laterality defects may also result from abnormalities and ciliary dysfunction at various stages of left\u0026ndash;right axis formation [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Lateral defects are associated with autosomal dominant, autosomal recessive, and X-linked modes of inheritance caused by mutations in \u003cem\u003eZIC3\u003c/em\u003e [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Primary ciliary dysfunction (PCD), which can be associated with SI in 41\u0026ndash;48% of cases [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e], is a rare hereditary disease caused by mutations in genes related to cilia, such as \u003cem\u003eDNAH5\u003c/em\u003e and \u003cem\u003eDNAI1\u003c/em\u003e, and exhibits autosomal recessive or X-linked modes of inheritance [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Patients with PCD also have been shown to have an increased risk of congenital heart disease [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Although reports suggest autosomal recessive inheritance in dogs with PCD [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e], no extensive genetic studies have been conducted in dogs. Nodal flow has been found to be a universal mechanism across vertebrate species as a trigger for left\u0026ndash;right axis formation [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Because our canine case showed the same pathological condition as that found in humans, the genetic or embryological mechanisms reported in humans may have occurred.\u003c/p\u003e \u003cp\u003eThe portal vein develops embryologically from the right ventricle. Development of the venous system in the abdominal cavity has been reported to differ among animal species; however, it is generally recognized that the CVC and azygos veins are formed as a result of the appearance, anastomosis, and disappearance of the caudal cardinal, subcardinal, and supra-cardinal veins [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. During interruption of the CVC and azygos continuation, the right subcardinal vein, which forms the suprarenal segment of the CVC during development, fails to connect with the right vitelline vein, which forms the intrahepatic segment. In this malformation, blood in the caudal region flows through the azygos vein and cranial vena cava to the heart because of the switching of the blood passage to the right supracardinal vein [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan additionalcitationids=\"CR25\" citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. EHPSS is an abnormal congenital anastomosis thought to be caused by the influx of right vitelline veins from the caudal site into the right cardinal vein [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. The association between the SI and vascular malformations is unclear because the placement of internal organs is determined prior to developmental changes in the cardiovascular system [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. However, an abnormal visceral placement can predispose individuals to errors during the development of complex cardiovascular systems.\u003c/p\u003e \u003cp\u003eSIT is usually asymptomatic and is often accidentally diagnosed [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. However, SI may be associated with airway abnormalities, such as chronic rhinosinusitis and bronchiectasis, that is, Kartagener syndrome (KS), which is recognized as a subtype of PCD [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. In human medicine, 20\u0026ndash;25% of patients with SIT are estimated to have KS [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Although respiratory symptoms were expected, no clinical symptoms indicative of KS were observed in this patiant.\u003c/p\u003e \u003cp\u003eIn humans, laterality defects are associated with various congenital malformations, including those of the cardiovascular system [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], which result in clinical symptoms. Previous reports of SIT patients in veterinary medicine have shown that hydrocephalus [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e], congenital heart disease [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e], vascular malformation [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], diaphragmatic hernia [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e], and respiratory diseases, including KS [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e], may occur. There have also been a few cases [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] with no comorbidities. In these reports, clinical symptoms caused by congenital malformations emerged and led to therapeutic interventions. In human medicine, interruption of the CVC and azygos continuation is generally considered asymptomatic [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. In veterinary medicine, there are case reports of vascular malformations, such as EHPSS [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e], deep vein thrombosis [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e], and pulmonary thromboembolism [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e], associated with azygos continuation in CVC. In this case, SIT may have caused EHPSS, which is a vascular malformation and azygos continuation of the CVC. Therapeutic intervention was sought due to the clinical symptoms caused by EHPSS.\u003c/p\u003e \u003cp\u003eIn humans, SIT can be accidentally detected when CT is performed before surgery. Additionally, if the altered anatomical positional relationship is understood to be the result of CT, surgical treatment can be performed in the same manner as in patients with normal anatomical structures [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. CT is also been shown to be effective in detecting congenital malformations of the superior and inferior vena cava [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. CT is effective in detecting cardiovascular malformations associated with heterotaxy patients [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Furthermore, CT examinations of patients have been reportedly effective in determining the presence or absence of bronchiectasis and its severity [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. In addition to EHPSS, which was the main cause of the clinical symptoms, SIT and azygos continuation of the CVC were incidentally detected. Therefore, this case illustrates that pre-operative CT is very effective in detecting SIT and EHPSS, which require therapeutic intervention. CT is essential for assessing the presence of anatomical abnormalities that may interfere with surgical procedures. Due to the unusual anatomical position of the abdominal organs in this case, surgery after laparotomy was expected to be difficult. However, the CT findings made it possible to safely perform the operation.\u003c/p\u003e \u003cp\u003eSurgical treatment of congenital malformations associated with SIT has been reported in veterinary medicine. A Doberman\u0026ndash;Pinscher patient with SIT underwent surgical treatment for a congenital diaphragmatic hernia and was clinically normal at the time of examination 13 months after surgery [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. There have been two previous reports of EHPSS and azygos continuation in CVC associated with SI. Of these, a report on ligation for EHPSS in patients with SIT reported that patients were clinically normal at the examination 22 months after surgery if dietary protein restriction was implemented [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Additionally, a study on ameroid constrictor placement for EHPSS in a patient with SIP reported normal post-operative clinical signs and test results, although no detailed description was provided [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. These reports suggest that the prognosis may be good if congenital malformations are treated despite SI.\u003c/p\u003e \u003cp\u003eIn conclusion, the complex anatomy of the abdominal organs and vessels is difficult to identify grossly in cases of SIT, whereas CT is effective for detecting vascular abnormalities, confirming the anatomical position of each organ, and for the definitive diagnosis of SIT.\u003c/p\u003e"},{"header":"Abbreviations","content":" \u003cp\u003eAPTT Activated partial thromboplastin time\u003c/p\u003e \u003cp\u003eAT III antithrombin III\u003c/p\u003e \u003cp\u003eCT Computed tomography\u003c/p\u003e \u003cp\u003eCVC Caudal vena cava\u003c/p\u003e \u003cp\u003eEHPSS Extrahepatic portosystemic shunt\u003c/p\u003e \u003cp\u003eIOMP Intraoperative mesenteric portography\u003c/p\u003e \u003cp\u003eKS Kartagener syndrome\u003c/p\u003e \u003cp\u003ePCD Primary ciliary dysfunction\u003c/p\u003e \u003cp\u003eSI Situs inversus\u003c/p\u003e \u003cp\u003eSIP Situs inversus partialis\u003c/p\u003e \u003cp\u003eSIT Situs inversus totalis\u003c/p\u003e \u003cp\u003eTBA Total bile acid\u003c/p\u003e \u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo third-party funding or support was received in connection with this study or the writing or publication of this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data supporting the conclusions of this article are included within the article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInformed consent was obtained from the owner before all procedures were performed. All methods in this study were performed in accordance with the relevant guidelines and regulations in compliance with the ARRIVE guidelines. This study was approved by our Institutional Ethical Committee (ANMEC-03-017).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eCasey B. Genetics of Human Site Abnormalities. Am J Med Genet. 2001;101(4):356\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBisgrove BW, Morelli SH, Yost HJ. Genetics of human laterality disorders: insights from vertebrate model systems. Annu Rev Genomics Hum Genet. 2003;4:1\u0026ndash;32.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAylsworth AS. Clinical aspects of defects in the determination of laterality. Am J Med Genet. 2001;101(4):345\u0026ndash;55.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLin AE, Krikov S, Riehle-Colarusso T, et al. Laterality defects in the national birth defects prevention study (1998\u0026ndash;2007): birth prevalence and descriptive epidemiology. Am J Med Genet A. 2014;164A(10):2581\u0026ndash;91.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAfzelius BA, Carlsten J, Karlsson S. Clinical, pathological, and ultrastructural features of situs inversus and immotile-cilia syndrome in a dog. J Am Vet Med Assoc. 1984;184(5):560\u0026ndash;3.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEdwards DF, Kennedy JR, Toal RL, Maddux JM, Barnhill MA, Daniel GB. Kartagener's syndrome in a chow chow dog with normal ciliary ultrastructure. Vet Pathol. 1989;26(4):338\u0026ndash;40.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFoodman MS, Giger U, Stebbins K, Knight D. Kartagener syndrome in an old miniature poodle. J Small Anim Pract. 2019;30(2):96\u0026ndash;100.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHunt GB, Bellenger CR, Borg R, Youmans KR, Tisdall PL, Malik R. Congenital interruption of the portal vein and caudal vena cava in dogs: six case reports and a review of the literature. Vet surg. 1998;27(3):203\u0026ndash;15.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eReichler IM, Hoerauf A, Guscetti F, et al. Primary ciliary dyskinesia with situs inversus totalis, hydrocephalus internus and cardiac malformations in a dog. J Small Anim Pract. 2001;42(7):345\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJerram RM, Warman CG, Wu CT. Echocardiographic and radiographic diagnosis: complete situs inversus in a cat. Vet Radiol Ultrasound. 2006;47(3):313\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCavrenne R, De Busscher V, Bolen G, Billen F, Clercx C, Snaps F. Primary ciliary dyskinesia and situs inversus in a young dog. Vet Rec. 2008;163(2):54\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDurant AM. What is your diagnosis? Thoracic and abdominal situs inversus totalis. J Am Vet Med Assoc. 2008;232(2):197\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWitsberger TH, Dismukes DI, Kelmer EY. Situs inversus totalis in a dog with a chronic diaphragmatic hernia. J Am Anim Hosp Assoc. 2009;45(5):245\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePiantedosi D, Cortese L, Meomartino L, Di Loria A, Ciaramella P. Situs inversus totalis associated with subaortic stenosis, restrictive ventricular septal defect, and tricuspid dysplasia in an adult dog. Can Vet J. 2011;52(11):1237\u0026ndash;42.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCahua J, Dias D, Gonzales-Viera O. Complete situs inversus in 2 asymptomatic dogs. Top Companion Anim Med. 2015;30(2):68\u0026ndash;71.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOui H, Kim J, Bae Y, et al. Computed tomography angiography of situs inversus, portosystemic shunt and multiple vena cava anomalies in a dog. J Vet Med Sci. 2013;75(11):1525\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSutherland MJ, Ware SM. Disorders of left-right asymmetry: heterotaxy and situs inversus. Am J Med Genet C Semin Med Genet. 2009;151C(4):307\u0026ndash;17.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSlough J, Cooney L, Brueckner M. Monocilia in the embryonic mouse heart suggest a direct role for cilia in cardiac morphogenesis. Dev Dyn. 2008;237(9):2304\u0026ndash;14.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKennedy MP, Omran H, Leigh MW, et al. Congenital heart disease and other heterotopic defects in a large cohort of patients with primary ciliary dyskinesia. Circulation. 2007;115(22):2814\u0026ndash;21.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShapiro AJ, Davis SD, Ferkol T, et al. Laterality defects other than situs inversus totalis in primary ciliary dyskinesia: insights into situs ambiguus and heterotaxy. Chest. 2014;146(5):1176\u0026ndash;86.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEdwards DF, Kennedy JR, Patton CS, Toal RL, Daniel GB, Lothrop CD. Familial immotile-cilia syndrome in english springer spaniel dogs. Am J Med Genet. 1989;33(3):290\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWatson PJ, Herrtage ME, Peacock MA, Sargan DR. Primary ciliary dyskinesia in Newfoundland dogs. Vet Rec. 1999;144(26):718\u0026ndash;25.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHyttel P. Development of the blood cells, heart, and vascular system. In: Hyttel P, Sinowatz F, Vejlsted M, editors. Essentials of domestic animal embryology. St. Louis, Missouri: Elsevier; 2009. pp. 182\u0026ndash;207.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHarder MA, Fowler D, Pharr JW, Tryon KA, Shmon C. Segmental aplasia of the caudal vena cava in a dog. Can Vet J. 2002;43(5):365\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZwingenberger AL, Spriet M, Hunt GB. Imaging diagnosis-portal vein aplasia and interruption of the caudal vena cava in three dogs. Vet Radiol Ultrasound. 2011;52(4):444\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi SJ, Lee J, Hall J, Sutherland TR. The inferior vena cava: anatomical variants and acquired pathologies. Insights Imaging. 2021;12(1):123.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePayne JT, Martin RA, Constantinescu GM. The anatomy and embryology of portosystemic shunts in dogs and cats. Semin Vet Med Surg Small Anim. 1990;5(2):76\u0026ndash;82.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFischetti AJ, Kovak J. Imaging diagnosis: azygous continuation of the caudal vena cava with and without portocaval shunting. Vet Radiol Ultrasound. 2008;49(6):573\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLockwood AJ, Sinnott-Stutzman VB, Mouser PJ, Tsai SL. Azygos continuation of the caudal vena cava with segmental aneurysm, lung lobe torsion and pulmonary thromboembolism in a dog. Clin Case Rep. 2018;6(2):363\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStiru O, Geana RC, Ilie RR, et al. Transseptal approach for mitral valve replacement in dextrocardia with situs inversus totalis: a case report and review of the literature. Heart Surg Forum. 2020;23(1):E030\u0026ndash;3.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIezzi R, Posa A, Carchesio F, Manfredi R. Multidetector-row CT imaging evaluation of superior and inferior vena cava normal anatomy and caval variants: report of our cases and literature review with embryological correlation. Phlebology. 2019;34(2):77\u0026ndash;87.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWolla CD, Hlavacek AM, Schoepf UJ, Bucher AM, Chowdhury S. Cardiovascular manifestations of heterotaxy and related situs abnormalities assessed with CT angiography. J Cardiovasc Comput Tomogr. 2013;7(6):408\u0026ndash;16.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKennedy MP, Noone PG, Leigh MW, et al. High-resolution CT of patients with primary ciliary dyskinesia. AJR Am J Roentgenol. 2007;188(5):1232\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e\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":"bmc-veterinary-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [BMC Veterinary Research](http://bmcvetres.biomedcentral.com/)","snPcode":"12917","submissionUrl":"https://submission.nature.com/new-submission/12917/3?","title":"BMC Veterinary Research","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"computed tomography, dog, portosystemic shunt, situs inversus totalis, surgery","lastPublishedDoi":"10.21203/rs.3.rs-4550692/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4550692/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eThe normal visceral arrangement is called situs solitus, whereas the state of the visceral arrangement in a mirror-like positional relationship is called situs inversus. Among the SI, the state in which the positions of only some thoracoabdominal organs are reversed is called situs inversus partialis, and the state in which the positions of all thoracoabdominal organs are reversed is called situs inversus totalis (SIT). Clinical information on dogs with SIT is limited.\u003c/p\u003e\u003ch2\u003eCase presentation\u003c/h2\u003e \u003cp\u003eA 4-month-old Shiba dog was referred with depression and neurological symptoms as the chief complaints. Computed tomography (CT) revealed the patient had SIT with an extrahepatic portosystemic shunt (EHPSS) and azygos continuation of the caudal vena cava. In addition, complete reversal of the lung lobes and cardiovascular system in the thoracic cavity was confirmed. The patient underwent surgery for partial attenuation of EHPSS on day 8 after the initial examination. On day 124, after the initial examination, a second surgery was performed for complete attenuation. Under celiotomy, the positions of all abdominal organs, except for the rectum, were inverted; thus, SIT was confirmed via gross observation. In addition, the braided nylon sutures partially attenuated the concurrent splenocaval shunt. At the conclusion of this study, approximately 6 years had passed since the second surgery, and the patient had a good general condition without any medications.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eIn SIT, the complex anatomy of the abdominal organs and vessels is difficult to identify via gross observation; in contrast, CT is effective for detecting vascular abnormalities, confirming the anatomical position of each organ, and it allows for the definitive diagnosis of SIT.\u003c/p\u003e","manuscriptTitle":"Situs inversus totalis with single extrahepatic portosystemic shunt and azygos continuation of the caudal vena cava in a dog: a case report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-10 01:52:43","doi":"10.21203/rs.3.rs-4550692/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-11-25T09:53:04+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-11-25T09:40:57+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"248324880578372272088727861307074625136","date":"2024-11-23T12:14:20+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"246679506115350477038061407541959118967","date":"2024-11-23T07:53:34+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"172880780218141404950817973076486138765","date":"2024-11-22T09:23:41+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-11-22T01:06:28+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"222962202627336968152766473478100015431","date":"2024-11-21T14:46:25+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"189933260176767315084938736478812162496","date":"2024-11-21T12:36:37+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"127007133902285283445679526855028738542","date":"2024-11-21T12:35:42+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"180837783200639124172579009291890514725","date":"2024-11-21T12:05:09+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"113997908402129472496227006317498801330","date":"2024-07-30T15:06:41+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-07-24T08:31:44+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-06-13T02:26:31+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-06-12T03:35:43+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-06-12T03:35:07+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Veterinary Research","date":"2024-06-08T12:58:32+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"
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