The absence of warfarin treatment and situs inversus are associated with the occurrence of hepatocellular carcinoma after Fontan surgery.

BACKGROUND: Hepatocellular carcinoma (HCC) is a long-term complication of Fontan-associated liver disease (FALD). However, risk factors for HCC in patients with FALD remain unclear. This study aimed to identify factors associated with HCC development post-Fontan procedure. METHODS: We retrospectively examined 103 post-Fontan patients who underwent hepatic imaging at our institution. HCC incidence and patient characteristics were analyzed. A Cox proportional hazards model was used to identify risk factors for HCC. RESULTS: The median interval between Fontan surgery and final hepatic imaging was 19.6 (1.0-37.7) years. Among 103 patients, nine developed HCC. The cumulative incidence rates of HCC at 10, 20, and 30 years postoperatively were 0%, 7%, and 13%, respectively. In the univariate analysis, age at Fontan surgery, situs inversus, and warfarin absence were associated with HCC occurrence. The multivariate analysis identified the warfarin absence (adjusted hazard ratio [aHR], 22.71; 95% confidence interval: 3.29-507.1; p = 0.0005) and situs inversus (aHR, 14.36; 95% confidence interval: 2.75-105.5; p = 0.002) as risk factors. The prevalence of situs inversus and the warfarin absence was 12% and 50%, respectively. The 20- and 30-year incidence rates of HCC among patients who received warfarin were 0% and 7%, respectively, while those among patients who did not receive warfarin were 14% and 21%, respectively. HCC incidence was significantly higher in the non-warfarin group than in the warfarin group (p = 0.006) and among patients with situs inversus than among those with situs solitus (p = 0.004). CONCLUSIONS: Warfarin absence and situs inversus were associated with HCC development post-Fontan procedure.

Human Laterality Disorders: Pathogenesis, Clinical Manifestations, Diagnosis, and Management.

Human laterality disorders comprise a group of diseases characterized by abnormal location (situs) and orientation of thoraco-abdominal organs and vessels across the left-right axis. Situs inversus totalis is mirror image reversal of thoraco-abdominal organs/great vessels. Situs ambiguus, better known as heterotaxy, is abnormal arrangement of thoraco-abdominal organs across the left-right axis excluding situs inversus totalis. Heterotaxy, also referred to as atrial or atrial appendage isomerism, is characterized by abnormal location of left-sided or right-sided organs with loss of asymmetry of normally paired asymmetric organs. It is associated with a variety of anomalies involving the heart, great vessels, lungs and intra-abdominal organs. Right and left atrial isomerism are associated with multiple complex congenital cardiac and vascular anomalies, many of which are lethal when untreated. Isomerism may also affect the lungs, spleen, liver, gall bladder, and intestines. Innovative surgical therapy of heterotaxy/isomerism has reduced early mortality and markedly improved long-term prognosis.

Comorbidities in situs inversus totalis: A hospital-based study.

BACKGROUND AND OBJECTIVE: Few studies have assessed the comorbid diseases in situs inversus totalis (SIT) comprehensively. The aim of this study was to provide insight into the spectrum and prevalence of comorbidities in SIT. METHODS: Children ≤18 years of age with SIT were enrolled in this retrospective observational study. Situs status and comorbidities were independently confirmed by two physicians, based on review of radiologic, ultrasonic examination, operative records, and case notes. RESULTS: A total of 155 children (median age: 1.24 years; range: 1 day-17.8 years) confirmed to have SIT were recruited between January 2008 and December 2018. Associated conditions were diagnosed in 114 children (73.5%). Among them, 25 children (16.1%) had multiple anomalies affecting two or more organ systems. The most commonly associated conditions were congenital heart defects (n = 72, 46.5%) followed by primary ciliary dyskinesia (n = 19, 12.3%), renal disorders (n = 12, 7.7%), biliary atresia (n = 7, 4.5%), skeletal dysplasia (n = 8, 5.2%), and mental retardation (n = 4, 2.6%). CONCLUSION: A substantial proportion of children with SIT have comorbidities affecting multiple systems, especially cardiovascular and respiratory abnormalities. Children with SIT warrant careful examination for the presence of congenital and acquired abnormalities.

Síndrome de Kartagener / Kartagener Syndrome

Introducción: El síndrome de Kartagener es una variación clínica de la discinesia ciliar primaria, se caracteriza por la triada clásica de sinusitis crónica, bronquiectasia y situs inversus (total o parcial), catalogada como enfermedad rara de herencia autosómica recesiva. Objetivo: Analizar las manifestaciones clínicas, análisis complementarios y tratamiento de los pacientes diagnosticados con síndrome de Kartagener en la República del Ecuador. Presentación de caso: Paciente femenina, de nacionalidad ecuatoriana, con manifestaciones clínicas de la tríada del síndrome de Kartagener y rasgo de infertilidad, con antecedente de sinusitis crónica desde 14 años de edad. Los estudios imagenológicos de rayos X de tórax y tomografía axial computarizada de tórax y senos paranasales confirmaron las manifestaciones de síndrome de Kartagener, que representa el séptimo caso reportado en el país. Se analizaronn las características clínicas de la serie de siete casos reportados en el Ecuador hasta el presente, correspondiente al período 2015-2018 y exámenes complementarios realizados para el diagnóstico de certeza y diferencial. Conclusiones: Se presentó el séptimo caso de síndrome de Kartagener diagnosticado en el Ecuador y se analizó la serie de una totalidad de 7 pacientes reportados en el país entre 2015-2018(AU)

Introduction: Kartagener syndrome is a clinical variation of primary ciliary dyskinesia, characterized by the classic triad of chronic sinusitis, bronchiectasis and situs inversus (total or partial), classified as a rare autosomal recessive inheritance disease. Objective: To analyze the clinical manifestations, complementary tests and treatment of patients diagnosed with Kartagener syndrome in the Republic of Ecuador. Case presentation: Female patient, of Ecuadorian nationality, with clinical manifestations of the Kartagener syndrome triad and infertility trait, with a history of chronic sinusitis since 14 years of age. Imaging studies of thorax, x-rays and computed tomography of chest and paranasal sinuses confirmed the manifestations of Kartagener syndrome, which represents the seventh case reported in the country. Respiratory evolution and therapeutic management are exposed. In this context, we analyze the clinical characteristics of the series of seven cases reported in Ecuador up to the present, corresponding to the period 2015-2018 and complementary tests performed for the certainty and differential diagnosis. Conclusions: The seventh case of Kartagener syndrome diagnosed in Ecuador is presented, and the series of a totality of 7 patients reported in the country between 2015-2018 is analyzed(AU)

Risk factors for situs defects and congenital heart disease in primary ciliary dyskinesia.

Primary ciliary dyskinesia (PCD) is associated with abnormal organ positioning (situs) and congenital heart disease (CHD). This study investigated genotype-phenotype associations in PCD to facilitate risk predictions for cardiac and laterality defects. This retrospective cohort study of 389 UK patients with PCD found 51% had abnormal situs and 25% had CHD and/or laterality defects other than situs inversus totalis. Patients with biallelic mutations in a subset of nine PCD genes had normal situs. Patients with consanguineous parents had higher odds of situs abnormalities than patients with non-consanguineous parents. Patients with abnormal situs had higher odds of CHD and/or laterality defects.

Thoraco-Abdominal Abnormalities in Bardet-Biedl Syndrome: Situs Inversus and Heterotaxy.

OBJECTIVES: To characterize the diversity and prevalence of thoraco-abdominal abnormalities in Bardet-Biedl syndrome (BBS), a model ciliopathy for understanding the role of cilia in human health. STUDY DESIGN: The Clinical Registry Investigating BBS, a worldwide registry exploring the phenotype and natural history of BBS, was used to conduct the study. Protected health information was obtained by subject or family interview and Health Insurance Portability and Accountability Act-approved release of data including imaging studies and genetic testing. Echocardiography and imaging findings were independently confirmed by 2 cardiologists. RESULTS: Thoraco-abdominal abnormalities were identified in 6 of 368 (1.6%) subjects with a minimum prevalence of 1 in 60 Clinical Registry Investigating BBS participants. Diverse laterality defects were observed suggesting that the underlying ciliopathy randomly alters embryonic left-right axis orientation. Congenital heart disease, common in heterotaxy, was present in 2 subjects. Additional defects, uncommonly reported in BBS, were observed in the central nervous, genitourinary, gastrointestinal, and musculoskeletal systems in the subjects. No BBS genotype was favored in the cohort. One subject had genetic and clinical phenotype diagnostic of both primary ciliary dyskinesia and BBS. CONCLUSIONS: The variety of thoraco-abdominal abnormalities in BBS suggests the pleiotropic nature of these anomalies is not confined to a single pattern or genotype. Clinicians providing care to individuals with BBS should consider the increased prevalence of thoraco-abdominal anomalies in BBS. Individuals with features suggestive of other ciliopathies, such as primary ciliary dyskinesia, should undergo further evaluation for additional genetic disorders. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02329210.

A case of concomitant intralobar bronchopulmonary sequestration and situs inversus totalis.

BACKGROUND AND AIMS: Situs inversus is a rare congenital abnormality involving partial or complete transposition of the thoracic or abdominal viscera. In situs inversus totalis, both the thoracic and abdominal viscera are transposed. The incidence of this condition is 0.01% to 0.02%. Bronchopulmonary sequestration (BPS) is a rare congenital abnormality of the respiratory tract with an incidence of 0.15% to 1.80%. Intralobar sequestration is uncommonly associated with congenital anomalies. METHODS: A routine chest X-ray of a 41-year-old asymptomatic man showed dextrocardia, a left-sided liver, right-sided stomach, and left paracardiac opacity. RESULTS: Computed tomography (CT) and CT pulmonary angiography revealed dextrocardia with situs inversus totalis and left paracardiac intralobar BPS in the lingular segment of the left upper lobe. CONCLUSION: We present a rare case of combined situs inversus totalis and intralobar BPS with an atypical location and feeder artery.

Heterotaxy in southern Nevada: prenatal detection and epidemiology.

We retrospectively analyzed a combination of prenatally detected and postnatally diagnosed patients with heterotaxic situs that included those with situs inversus, bilateral left-sidedness, and bilateral right-sidedness for the period between April 2002 and July 2014. We found a statistically higher prevalence in the Hispanic population of Southern Nevada of 2.7/10,000 live births (95 % confidence intervals of 1.7-3.9) versus the non-Hispanic population of 1.6/10,000 live births (95 % confidence intervals of 1.1-2.1), p = 0.04. Additionally, we noted a high prenatal detection rate of 68 % over the 12-year period of time, rising to 100 % over the last 2 years.

Laterality defects in the national birth defects prevention study (1998-2007): birth prevalence and descriptive epidemiology.

Little is known epidemiologically about laterality defects. Using data from the National Birth Defects Prevention Study (NBDPS), a large multi-site case-control study of birth defects, we analyzed prevalence and selected characteristics in children born with laterality defects born from 1998 to 2007. We identified 517 nonsyndromic cases (378 heterotaxy, 73.1%; 139 situs inversus totalis [SIT], 26.9%) resulting in an estimated birth prevalence of 1.1 per 10,000 live births (95% confidence interval 1.0­1.2). Prevalence did not differ significantly across sites, over time, or by inclusion of pregnancy termination. Laterality defects were more common among preterm cases compared to term cases, and in children born to mothers who were non-white or younger than 20 years compared to white mothers or those age 25­29 years. The distribution of associated cardiac and extra-cardiac defects, excluding the expected heterotaxy anomalies, varied by type of laterality defect. Cases with heterotaxy were significantly more likely than those with SIT to have double outlet right ventricle, atrioventricular canal defects, pulmonary stenosis, non-tetralogy of Fallot pulmonary atresia with ventricular septal defect, totally and partially anomalous pulmonary venous return; also more likely to have orofacial clefts, esophageal atresia, bowel atresias, and omphalocele, though not reaching statistical significance. Relatively more common among cases with SIT were Dandy- Walker malformation, anotia/microtia, and limb deficiency. The similarity in the demographic characteristics of heterotaxy and SIT supports the hypothesis that they are part of a continuum of abnormal left-right axis patterning. These findings on laterality defects may help guide clinical care, future research, and prevention strategies.

Laparoscopic nephroureterectomy in renal pelvic urothelial carcinoma with situs inversus totalis: preoperative training using a patient-specific simulator.

OBJECTIVE: To report the first case of preoperative training using a patient-specific laparoscopic simulator for a patient with situs inversus totalis (SIT). MATERIALS AND METHODS: A 61-year-old man presented with gross hematuria and was diagnosed with right renal pelvic cancer T1N0M0. A whole-body computed tomography (CT) scan also revealed his organs showed a mirror image, with left-to-right reversal, and SIT was diagnosed. A laparoscopic right nephroureterectomy through a retroperitoneal approach was scheduled. Before the operation, we practiced the operation using a patient-specific laparoscopic surgical simulator that we have developed. The patient's CT data were used to reproduce the retroperitoneal space in the simulator, and the surgeon trained and became familiar with his SIT anatomy. RESULTS: The insufflation time was 182 minutes, and the estimated blood loss was 50 mL. The surgeon was able to complete the right retroperitoneoscopic nephroureterectomy safely, without any problems. CONCLUSION: To our knowledge, we report the first case of preoperative training using a patient-specific simulator for a patient with SIT. Preoperative training was useful, and retroperitoneoscopic nephroureterectomy was successfully performed in a patient with renal pelvic urothelial carcinoma and SIT.

Single-incision laparoscopic cholecystectomy in situs inversus totalis.

BACKGROUND AND OBJECTIVES: Situs inversus totalis (SIT) is a rare congenital anomaly that can cause difficulties during standard laparoscopic cholecystectomy due to its mirror-image anatomy. These cases require more technically demanding procedures, and handedness of the surgeon may influence performance of these operations. Single-incision laparoscopic surgery (SILS) has been proposed as a less-invasive alternative to conventional laparoscopic surgery. We report the first case of successful SILS cholecystectomy in a patient with SIT and discuss technical aspects of the operation related to the handedness of the surgeon. CASE: A 49-year-old man who was known to have situs inversus totalis presented with symptomatic cholelithiasis. This patient was operated on by a right-handed surgeon. The surgeon and camera assistant were positioned on the right and left side respectively with the video monitor above the patient's left shoulder. The SILS port (Covidien), which has 3 operating channels, was placed in the abdomen via a 2-cm intraumbilical incision. SILS cholecystectomy was performed successfully. Dissection of Calot's triangle and the gallbladder bed was performed using a dissector and hook in the right hand without any technical problems. CONCLUSION: SIT may confer an advantage over the orthotopic position for right-handed surgeons. SILS cholecystectomy can be performed safely in SIT.

Factors influencing age at diagnosis of primary ciliary dyskinesia in European children.

Primary ciliary dyskinesia (PCD) is a hereditary disorder of mucociliary clearance causing chronic upper and lower airways disease. We determined the number of patients with diagnosed PCD across Europe, described age at diagnosis and determined risk factors for late diagnosis. Centres treating children with PCD in Europe answered questionnaires and provided anonymous patient lists. In total, 223 centres from 26 countries reported 1,009 patients aged < 20 yrs. Reported cases per million children (for 5-14 yr olds) were highest in Cyprus (111), Switzerland (47) and Denmark (46). Overall, 57% were males and 48% had situs inversus. Median age at diagnosis was 5.3 yrs, lower in children with situs inversus (3.5 versus 5.8 yrs; p < 0.001) and in children treated in large centres (4.1 versus 4.8 yrs; p = 0.002). Adjusted age at diagnosis was 5.0 yrs in Western Europe, 4.8 yrs in the British Isles, 5.5 yrs in Northern Europe, 6.8 yrs in Eastern Europe and 6.5 yrs in Southern Europe (p < 0.001). This strongly correlated with general government expenditures on health (p < 0.001). This European survey suggests that PCD in children is under-diagnosed and diagnosed late, particularly in countries with low health expenditures. Prospective studies should assess the impact this delay might have on patient prognosis and on health economic costs across Europe.

Laparoscopic adjustable gastric banding in a morbidly obese patient with situs inversus totalis.

Laparoscopic adjustable gastric banding is a commonly performed bariatric operation worldwide. The presence of an anatomical variation like situs inversus demands preoperative assessment and preparedness on the part of the surgeon. We report a laparoscopic gastric banding performed on a morbidly obese patient with situs inversus totalis in the Kingdom of Saudi Arabia.

Laparoscopic Roux-en-Y gastric bypass in a patient with situs inversus.

We report the case of a morbidly obese patient with situs inversus totalis presenting for laparoscopic Roux-en-Y gastric bypass (RYGBP). The operative technique is detailed and we recommend the use of a mirror image approach to all parts of the operation. Consequently, the operative time is only moderately longer than usual. Laparoscopic RYGBP can be safely performed in patients with situs inversus.

Situs anomalies and gastrointestinal abnormalities.

BACKGROUND/PURPOSE: The aim of the study was to review the gastrointestinal abnormalities occurring in association with situs anomalies. METHODS: Patients with situs anomalies were identified from the medical records of pediatric patients of Seoul National University Children's Hospital from January 1980 to July 2004. Retrospective study was undertaken. Diagnosis was made on the basis of the information obtained from a combination of echocardiography, angiography, abdominal ultrasonography, liver scan, upper gastrointestinal study, or abdominal computed tomography. RESULTS: A total 67 patients diagnosed as having situs anomalies were identified. There were 40 males and 26 females (1.54:1). Of these 67 patients, 45 patients (67%) were diagnosed as having situs inversus, 16 patients (24%) as having right isomerism, and 6 patients (9%) as having left isomerism. Of 45 patients with situs inversus, there were 26 patients (58%) who had intraabdominal abnormalities. These were duodenal atresia, biliary atresia, gastroschisis with malrotation, congenital hepatic fibrosis, tracheoesophageal fistula (type C), Currarino's triad, and pheochromocytoma. Of 16 patients with right isomerism, there were 14 patients (88%) who had intraabdominal abnormalities. These were hiatal hernia and diaphragmatic hernia. Of 6 patients with left isomerism, there were 4 patients (67%) who had intraabdominal abnormalities. These were malrotation and biliary atresia. CONCLUSION: When a patient is noted to have congenital heart disease as part of situs anomalies, or if an atypical position of organs is noted at imaging evaluation, we recommend that the patient undergo chest radiography, abdominal ultrasonography, upper gastrointestinal study, and abdominal computed tomography.

Pancreaticoduodenectomy for common bile duct cancer in a patient with situs inversus totalis: a case report.

We describe the first case of successfully performed pancreaticoduodenectomy to treat common bile duct cancer in a patient with situs inversus totalis. A 65-year-old man was admitted to our hospital with the working diagnosis of obstructive jaundice. He had a history of cholecystectomy, and situs inversus totalis had been diagnosed at that time in another hospital. Preoperative work-ups with ultrasonography, computed tomography, and percutaneous cholangiography were followed by drainage lead to the diagnosis of common hepatic artery arising from the superior mesenteric artery. He underwent curative pancreaticoduodenectomy without complications. The postoperative course was uneventful, and he was discharged on postoperative day 29. He is doing well, with no evidence of recurrence 40 months after surgery. Deliberately performed preoperative imaging studies, especially selective angiography, were essential for the surgical resection of bile duct cancer in this patient with situs inversus totalis.

The implications for fetal outcome of an abnormal arrangement of the abdominal vessels.

In a prospective audit of consecutive referrals for fetal echocardiography between 1997 and 2003, we documented all instances of an abnormal arrangement of the abdominal vessels. We then established the structure of the heart in these fetuses, noting any extra-cardiac associations, and the eventual outcomes. We found a cardiac abnormality in 572 of the 2,136 fetuses examined during this period (27 percent), with 16 (0.8 percent) having an abnormal arrangement of the abdominal great vessels. Mirror-imaged arrangement was found in 3, while the arrangement suggested right isomerism in 6, and left isomerism in 7. Of these 16 fetuses, 14 had cardiac malformations. Isomerism of the right atrial appendages was found in 7 fetuses, all with either a right-sided stomach or cardiac apex, and 6 with a common atrioventricular junction guarded by a common valve. Only 1 of these fetuses survived. Of the 3 fetuses with mirror-imaged abdominal great vessels, 2 also had mirror-imaged atrial arrangement, while the 3rd had isomeric right appendages. Only one of 7 fetuses with an abdominal great vein posterior to the aorta had bilateral left atrial appendages. The remaining 6 had usual atrial arrangement, with normal pulmonary venous connections in all but one, who had infra-diaphragmatic totally anomalous pulmonary venous connection. Of these fetuses, 2 had coarctation of the aorta, and 2 others had complex cardiac malformations resulting in neonatal death. One died in childhood from biliary atresia, and three are alive. Abnormal arrangements of the abdominal great vessels, therefore, were found in 0.8 percent of our total fetuses, and in 2.4 percent of those with cardiac malformations. Those with an abnormal arrangement of the abdominal vessels combined with an abnormal arrangement of the atrial appendages, however, made up only 0.5 percent and 1.6 percent, respectively. While screening for an abnormal arrangement of the abdominal vessels overestimated the incidence of left, but not right, isomerism of the atrial appendages, it did predict the presence of important extra-cardiac malformations that required urgent recognition and management after birth.

Hepatectomy for proximal bile duct carcinoma in a patient with situs inversus; a case report.

Situs inversus is a rare condition which mandates a full understanding of all anatomic relationships prior to invasive procedures. A 76-year-old woman with situs inversus presented with fever and rigors. She had previously undergone endoscopic sphincterotomy and lithotomy for choledocholithiasis, and laparoscopic cholecystectomy for cholecystolithiasis. Laboratory examination revealed hyperbilirubinemia and transaminasimia. Percutaneous transhepatic biliary drainage, percutaneous transhepatic cholangioscopy, percutaneous transhepatic portography, percutaneous transhepatic portal embolization, and visceral angiography were performed without complications. She underwent right hepatic lobectomy, caudate lobectomy and extrahepatic bile duct resection for papillary adenocarcinoma of the proximal bile duct. Full investigation of the anatomical relationships between the biliary tree and the vascular system in the hepatic hilus enabled safe hepatectomy in a patient with situs inversus.