Surgical treatment of renal cell carcinoma with inferior vena cava tumor thrombus.

PURPOSE: The present report discusses the indications of cardiopulmonary bypass (CPB) in open nephrectomy and surgical outcomes of conventional and minimally invasive surgical techniques for treating advanced renal cell carcinoma with inferior vena cava tumor thrombus. METHODS: The present study involved a comprehensive retrieval of pertinent literature from the most recent two decades. RESULTS: Comparisons between radical nephrectomy procedures in terms of open, laparoscopic and robotic-assisted surgeries revealed that open surgery had more blood loss, a longer operation time and higher mortality rates than laparoscopic and robotic-assisted surgeries. Furthermore, surgery with CPB was associated with more blood loss than non-CPB surgery. Rates of early and late deaths were much higher in patients with CPB than in those without CPB. CONCLUSIONS: Different surgical techniques had different indications in terms of levels of inferior vena cava tumor thrombus. The laparoscopic, robotic-assisted, open surgical techniques and CPB with deep hypothermic circulatory arrest were indicated for Levels I, II, III and III-IV inferior vena cava tumor thrombus, respectively. Laparoscopic and robotic-assisted surgeries cause less trauma than open surgery but require more complicated equipments to support the procedure. CPB should be avoided in radical nephrectomy whenever possible. The increased application of laparoscopic and robotic techniques in the future is anticipated.

Novel homozygous truncating variants in ZMYND15 causing severe oligozoospermia and their implications for male infertility.

Sequence variants of ZMYND15 cause azoospermia in humans, but they have not yet been reported in infertile men with severe oligozoospermia (SO). We performed whole-exome and Sanger sequencing to identify suspected causative variants in 414 idiopathic participating infertile men with SO or azoospermia. Three novel homozygous truncating variants in ZMYND15 were identified in three of the 219 (1.37%) unrelated patients with SO, including c.1209T>A(p.Tyr403*), c.1650delC (p.Glu551Lysfs*75), and c.1622_1636delinsCCAC (p.Leu541Profs*39). In silico bioinformatic analyses as well as in vivo and in vitro experiments showed that the ZMYND15 variants carried by the affected subjects might be the underlying cause for their infertility. One patient accepted intracytoplasmic sperm injection therapy, using his ejaculated sperm, and his wife successfully became pregnant. Our findings expand the disease phenotype spectrum by indicating that ZMYND15 variants cause SO and male infertility and suggest a possible correlation between the severity of male infertility caused by ZMYND15 variants and male age.

Fetal Intrapericardial Teratomas: An Update.

Fetal intrapericardial teratomas are rare and benign cardiac tumors. By comprehensive literature retrieval of the pertinent articles published since 2000, 49 articles with 61 cases of intrapericadial teratomas were recruited into this study. The intrapericardial teratomas were found during pregnancy in 55 cases (fetal group), while the tumors were detected until neonatal period in 6 cases (neonatal group). In the fetal group, 15 cases were critical with fetal/neonatal respiratory distress or cardiac tamponade. Antenatal treatments including centesis, shunt placement, open fetal surgery and the ex utero intrapartum treatment were required in 24 (43.6%) fetal cases. Postnatal intubation was required in 19 cases with 18 of them having immediate intubation after birth. Postnatal tumor resection was performed in 41 (95.3%) cases. In neonatal group, 4 neonates had respiratory distress and/or cardiac tamponade. Neonatal intubation was required in 1 (16.7%) patient. Surgical tumor resection was performed in all 6 patients. A comparison between the fetal and neonatal groups revealed that the fetal group was associated with higher refractory effusions while the neonatal group had a higher incidence of respiratory distress. Although the all cause death rate was higher in the fetal group than in the neonatal (25.5 vs. 0%), but lack of a statistical significance. Antenatal treatments for fetal intrapericardial teratomas are feasible but carry higher risks in comparison to neonatal cases.

Cardiac and vascular causes of persistent fever: A systematic review.

Fever of unknown origin refers to a prolonged fever with an unknown cause despite adequate medical evaluations. This condition often leads to unnecessary extensive laboratory work-ups and antimicrobial therapies. The atypical presentations often cause a delayed diagnosis and an improper treatment with an increased morbidity rate. In cardiac surgical patients, fever of unknown origin remains an intriguing problem during the diagnostic process of cardiac surgical diseases. Cardiac myxoma or aortic dissection are often misdiagnosed when patients present with fever of unknown origin as an onset symptom. Under such circumstances, medical examinations by echocardiography and chest computed tomography, particularly fluorodeoxyglucose-positron emission tomography/computed tomography, have been proved crucial for early diagnosis. A better understanding of the clinical features of cardiac surgical disorders presenting with fever of unknown origin would facilitate early diagnosis of fever of unknown origin. A further decision-making of prompt treatment of choices of a cardiac operation is important for improving patients' outcomes.

DMC1 mutation that causes human non-obstructive azoospermia and premature ovarian insufficiency identified by whole-exome sequencing.

BACKGROUND: The genetic causes of the majority of male and female infertility caused by human non-obstructive azoospermia (NOA) and premature ovarian insufficiency (POI) with meiotic arrest are unknown. OBJECTIVE: To identify the genetic cause of NOA and POI in two affected members from a consanguineous Chinese family. METHODS: We performed whole-exome sequencing of DNA from both affected patients. The identified candidate causative gene was further verified by Sanger sequencing for pedigree analysis in this family. In silico analysis was performed to functionally characterise the mutation, and histological analysis was performed using the biopsied testicle sample from the male patient with NOA. RESULTS: We identified a novel homozygous missense mutation (NM_007068.3: c.106G>A, p.Asp36Asn) in DMC1, which cosegregated with NOA and POI phenotypes in this family. The identified missense mutation resulted in the substitution of a conserved aspartic residue with asparaginate in the modified H3TH motif of DMC1. This substitution results in protein misfolding. Histological analysis demonstrated a lack of spermatozoa in the male patient's seminiferous tubules. Immunohistochemistry using a testis biopsy sample from the male patient showed that spermatogenesis was blocked at the zygotene stage during meiotic prophase I. CONCLUSIONS: To the best of our knowledge, this is the first report identifying DMC1 as the causative gene for human NOA and POI. Furthermore, our pedigree analysis shows an autosomal recessive mode of inheritance for NOA and POI caused by DMC1 in this family.

Fetal Arrhythmias: Genetic Background and Clinical Implications.

Fetal arrhythmias are a common phenomenon of pregnancies. However, debates remain with regard to the etiologies and early treatment of choices for severe fetal arrhythmias. The gene regulatory networks govern cardiac conduction system development to produce distinct nodal and fast conduction phenotypes. The slow conduction properties of nodes that display automaticity are determined by the cardiac ion channel genes, whereas the fast conduction properties are regulated by the transcription factors. Mutations of genes specific for the developmental processes and/or functional status of cardiac conduction system including ion channel promoter (minK-lacZ), GATA family of zinc finger proteins (GATA4), the homeodomain transcription factor (Nkx2.5), the homeodomain-only protein (Hop) and the T-box transcription factors (Tbx2, Tbx3 and Tbx5), hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4) and connexins, may cause fetal arrhythmias. It is expected that development of investigational antiarrhythmic agents based on genetic researches on cardiac conduction system, and clinical application of percutaneously implantable fetal pacemaker for the treatment of fetal arrhythmias would come to true.

Aortic aneurysm and dissection in systemic lupus erythematosus.

Aortic aneurysm and dissection are rare complications of systemic lupus erythematosus (SLE). The incidence, etiology, risk factors, and outcomes of this entity were largely unknown.The study materials were based on the publications of aortic aneurysm or dissection due to SLE published between 2000 and 2017.A total of 36 articles reporting a single case or case series involving 40 patients were collected. The patients showed an absolute female dominance at a mean aneurysm age of 44.6 years. Steroid use was 13.3 ± 9.4 years prior to admission for management of aortic aneurysm or dissection. Aortic aneurysm occurred more commonly in abdominal than other segments of the aorta, whereas aortic dissection did not show any location predilection. Patients with open aortic operations showed a higher mortality rate than other groups; however, no statistical significance was reached. Interventional therapy was minimally invasive, but postinterventional endoleaks were a concerning problem.SLE patients had significant risks for developing aortic aneurysm and dissection. Hypertension, long-term steroid use, and aortic pathological changes related to SLE seemed to be predominant risk factors for the occurrence of aortic aneurysm and dissection. Upon diagnosis, a surgical, interventional, or hybrid treatment should be performed to prevent severe sequelae and sudden deaths.

Fetal cardiac tumors: clinical features, management and prognosis.

Fetal cardiac tumors are rare and usually benign. While echocardiography is a reliable technique for diagnosing fetal cardiac tumors, their definitive diagnosis relies on pathological examination. The strategies used to manage fetal cardiac tumors are challenging. A good clinical result is their complete regression during pregnancy or shortly after birth, as often occurs with cardiac rhabdomyomas. Moreover, the fetal prognosis depends on the nature of the tumors, namely, their location, size, number and associated complications. The active treatment options for symptomatic fetuses depend on the fetal status and may include fetal open surgery, postnatal tumor resection with or without the bridge of intrauterine pericardiocentesis, and thoracoamniotic shunting. The ex utero intrapartum treatment procedure provides an alternative technique for performing fetal open surgery and has shown promising preliminary results in selected cases, but is invasive for both the mother and fetus.

Congenital Pulmonary Lymphangiectasia: A Disorder not only of Fetoneonates.

Congenital pulmonary lymphangiectasia (CPL) is a rare developmental disorder of the lung, characterized by dilation of pulmonary subpleural, interlobar, perivascular and peribronchial lymphatics. The incidence of CPL among stillborn and neonates was estimated to be <1%. The etiology of CPL is unknown. However, it has been suspected to be of a genetic background. Recent basic studies revealed that it might be caused by the FOXC2, Vegfr-3 and integrin α9ß1gene mutations. A clinical diagnosis of CPL can be made much easier in full-term neonates who present with respiratory distress, pleural (especially chylous) effusions with or without generalized edema. In infancy, the diagnosis seems to be more difficult due to the nonspecific respiratory symptoms like persistent tachypnea, cough and wheeze. Lung biopsy with subsequent histological and immunohistochemical studies is the golden diagnostic method of CPL. Immunohistochemical staining for endothelial cell markers CD31, CD34 and D2-40 confirms lymphatic origin. Therapeutic strategies include supportive, nutritional, investigational, aggressively interventional and surgical regimens, most of which have shown promising outcomes. Although CPL was once regarded as a disorder of very poor prognosis in neonatal onset cases, teenager and adult patients have shown good outcomes upon long-term follow-up.Die angeborene pulmonale Lymphangiektasie (CPL) ist eine seltene Entwicklungsstörung der Lunge, die durch eine Dilatation der pulmonalen subpleuralen, interlobären, perivaskulären und peribronchialen Lymphgefäße charakterisiert ist. Die Inzidenz der CPL bei Totgeburten und Neugeborenen wird <1% geschätzt. Die Ätiologie der CPL ist unbekannt. Allerdings wird ein genetischer Hintergrund vermutet. Neuere Grundlagenstudien zeigten, dass die CPL durch FOXC2, Vegfr-3 und Integrin α9ß1-Genmutationen verursacht sein könnte. Die klinische Diagnose der CPL ist sehr viel einfacher in Reifgeborenen zu stellen, die Atemnot, Pleuraergüsse (vor allem chylöse) mit und ohne generalisiertem Ödem aufweisen. In der frühen Kindheit ist die Diagnose aufgrund der unspezifischen respiratorischen Symptomatik wie persistierende Tachypnoen, Husten oder Röcheln schwerer zu stellen. Die Lungenbiopsie mit anschließenden histologischen und immunhistochemischen Untersuchungen ist der Goldstandard für die Diagnose der CPL. Die immunhistochemische Färbung der Endothelzellmarker CD31, CD34 und D2-40 bestätigt den lymphatischen Ursprung. Die Behandlungsstrategien umfassen unterstützende, alimentäre, in Erprobung befindliche, aggressiv-interventionelle und chirurgische Behandlungspläne, von denen die meisten ermutigende Ergebnisse zeigten. Obwohl die CPL einst bei Fällen mit Ausbruch im Neugeborenenalter als Erkrankung mit sehr schlechter Prognose galt, zeigen Teenager und erwachsene Patienten in der Langzeit-Nachbeobachtung gute Verläufe.

Congenital pulmonary lymphangiectasia.

Congenital pulmonary lymphangiectasia (CPL) is a rare but fatal disease, usually having an onset from the first few hours to days after birth. Inconsistent nomenclatures were used for CPL in the past decades. Patients often present with intractable respiratory failure, hydrops fetalis and even sudden death. The etiologies of CPL remain unclear. Previous hypotheses suggested that CPL might be caused by conditions preventing normal regression of the lymphatics after the 18th-20th week of gestation. Up-to-date biological studies on lymphatic development, lymphatic valve formation and occurrence of hydrops fetalis revealed possible causative relations with mutations of genes of the vascular endothelial growth factor receptor (VEGFR), RAS/MAPK, PI3K/AKT and NF-κB signaling pathways. Lung biopsy with subsequent histological and immunohistochemical studies is a gold standard of CPL diagnosis. Apart from symptomatic and supportive treatments, novel regimens including sirolimus, a mammalian target of rapamycin (mTOR) inhibitor, one of the inhibitors of the pertinent signaling pathways and ethiodized oil lymphatic embolization under ultrasound-guided intranodal lymphangiography have shown encouraging short-term therapeutic effects for lymphatic anomalies. Surgical operations (lobectomy or pneumonectomy) can be the treatment of choice for patients with CPL confined to one lobe or one lung. Patients with CPL usually have a poor prognosis and often die during the neonatal period. Their prognoses are expected to improve with the development of modern therapeutic agents.

Palliative Therapies for Congenital Heart Disease with Ductus Dependent Pulmonary Circulation.

In neonates, the management of ductus dependent pulmonary circulation is challenging. There have been three palliative therapies for this lesion: the modified Blalock-Taussig shunt, ductal stenting and prostaglandin E infusions, for maintaining the ductal patency before definite operations. Debates remain with regard to the indications and disadvantages of three palliative therapies. The aim of this article is to give a brief review of these three palliative therapies.

Fetal Cardiac Myxomas.

Fetal cardiac myxomas are very rare. To date there has been no representative description of fetal cardiac myxomas. The aim of this study is to highlight the clinical features, possible outcomes and the disparities from the adult cardiac myxomas and other fetal cardiac tumors.A comprehensive literature review yielded 27 reports including 32 cases of fetal cardiac myxomas.Apart from the same pedunculated and solitary nature and echogenic appearance, fetal cardiac myxomas differ from those in adults in many aspects, including tumor location, clinical manifestation and malignant potential. Fetal cardiac myxomas are the most common in the left ventricle and the least common in the left atrium. Tumor size and tumor site could be predictive risk factors of adverse cardiac events of fetuses.Their clinical courses are often benign with fewer cases of adverse cardiac events. Prenatal echocardiography is a reliable diagnostic technique, which can detect cardiac myxomas at as early as 18 weeks gestation. Differential diagnosis should be made from other types of fetal cardiac tumors. Postnatal cardiac myxoma resection may provide a good prognosis.

Cardiac Etiologies of Hydrops Fetalis.

Cardiac etiologies of hydrops fetalis have been a topic of concern due to challenging perinatal management. The common cardiac etiologies leading to hydrops fetalis include structural cardiac anomalies, cardiac dysrhythmias, cardiac tumors, cardiomyopathy and myocarditis. The mechanisms of cardiogenic hydrops fetalis may be: 1) elevation of atrial pressure and volume overload, 2) decrease of cardiac output, and 3) development of congestive heart failure. The diagnosis of hydrops fetalis was usually made at 19-36 gestational weeks, when ultrasound is a highly effective diagnostic method. Intrauterine interventions for certain congenital heart defects, maternal transplacental or direct fetal medications and fetal pacing placement for cardiac arrhythmias, and fetal or postnatal tumor resections are important progressions of etiologic treatment for hydrops fetalis. Treatment strategies for hydrops fetalis per se are usually ultrasound-guided pericardiocentesis and feto-amniotic shunting, whereas reaccumulation may require further interventions in utero or postnatally. Hydrops fetalis often carries a poor prognosis, and mortality remains high. Current developments in the management of hydrops fetalis should encourage physicians to attempt further fetal interventions.

Report: Heparin-induced thrombocytopenia associated with cardiopulmonary bypass: Preliminary attempt with recombinant human thrombopoietin therapy.

Recombinant human thrombopoietin (rhTPO) is popularly used for the treatment of chemotherapy-induced thrombocytopenia. However, rhTPO therapy for heparin-induced thrombocytopenia relating to cardiopulmonary bypass has not been previously described. A young patient developed heparin-induced thrombocytopenia during open-heart surgery. Postoperative rhTPO therapy (15000 units injection hypodermatica once daily for consecutive 3 days) made a quick platelet recovery without any side effects. Heparin-induced thrombocytopenia associated with cardiopulmonary bypass is more likely to be benign, and is curable to rhTPO therapy. The preliminary rhTPO administration of heparin-induced thrombocytopenia in association with cardiopulmonary bypass shows satisfactory pharmaceutical effects with lower dose, shorter duration treatment and shorter platelet increase time and recovery time in comparison with those for the treatment of chemotherapy-induced thrombocytopenia. rhTPO therapy does not produce any side effects and it could avoid or minimize necessary blood product infusions.

Warfarin use and dose adjustment in a patient with mitral valve replacement.

Warfarin is an anticoagulant suppressing the synthesis of the specific vitamin K-dependent coagulation factors II, VII, IX and X as well as two vitamin K-dependent plasma proteins C and S. Warfarin therapy may bring about severe consequences including warfarin embryopathy associated with maternal warfarin ingestion, warfarin resistance, excessive anticoagulation and warfarin reversal. A 51-year-old female patient experienced warfarin resistance as well as subsequent excessive coagulation and warfarin reversal. With regulation of warfarin dosage and close monitoring of the international normalized ratio, she eventually obtained a proper target international normalized ratio with stable warfarin dose. The patient was more likely to have an acquired warfarin resistance. To regulate dietary habit might be a good solution for the resistance to this drug. In addition, individualized regimen for warfarin use should be established based on the conditions of individual patient including patient's age, gender, body surface area, dietary habit and target international normalized ratio, etc.

Potential cardioprotective effects of Ginseng preparations.

Ginseng has shown potential cardioprotective effects by way of anti-oxidative, anti-arrhythmic, calcium- channel antagonistic, anti-inflammatory and anti-apoptotic properties. The underlying mechanisms may also lie in certain complex signaling pathways. Clinical evidence seemed to be less convincing as the potential cardioprotective effects of Ginseng have been investigated by using combined preparations rather than by purified bioactive ingredients in most occasions. The exact actions of Ginseng verified by using its individual bioactive ingredients will be our future research work.

Cardiothoracic interventions in Behçet's disease.

OBJECTIVES: Cardiothoracic interventions for cardiovascular complications of Behçet's disease have not been sufficiently elucidated. METHODS: A comprehensive literature search of cardiovascular complications of Behçet's disease was made for year range 2000-2013. The articles on the cardiothoracic procedures for cardiovascular complications of Behçet's disease were screened and analysed. RESULTS: The 221 major cardiothoracic procedures performed in this patient setting included 176 (79.6%) cardiac, 9 (4.1%) thoracic, 31 (14.0%) interventional and 5 (2.3%) hybrid procedures (χ2=478.03, p<0.0001). Of the major cardiac operations, there were 74 (42%) valvular, 58 (33%) aneurysmal, 23 (13.1%) thrombotic, 10 (5.7%) coronary and 11 (6.3%) miscellaneous procedures. The postoperative morbidity, recurrence and mortality rates were 21.4%, 11.7% and 15.0%, and the reintervention rates were 15.4% for recurrence, and 43.2% for morbidity patients. Dehiscence of the prosthetic valve was the major morbidity (52.3%) and the major cause of death (63.6%). The cardiac surgical patients carried the highest mortality rate comparing with thoracic, interventional and hybrid treatment patients. CONCLUSIONS: Cardiovascular operations prevailed thoracic and interventional procedures for the cardiovascular complications of Behçet's disease. Postoperative complications and recurrence rates were high. Aortic valve regurgitation, pulmonary artery aneurysm, and intracardiac and great vessel thrombosis were the most common indications for a cardiothoracic intervention. Dehiscence of the prosthetic valve was the main cause of death of the cardiothoracic interventions. Intense immunosuppressive treatment may reduce the postoperative complications and the need for reinterventions.

Refractory ascites as the only presenting symptom of chronic calcified constrictive pericarditis: a diagnostic challenge.

Extracardiac manifestations of constrictive pericarditis, such as massive ascites and liver cirrhosis, often cover the true situation and lead to a delayed diagnosis. A young female patient was referred to this hospital due to a 4-year history of refractory ascites as the only presenting symptom. A diagnosis of chronic calcified constrictive pericarditis was eventually established based on echocardiography, ultrasonography, and computed tomography. Cardiac catheterization was not performed. Pericardiectomy led to relief of her ascites. Refractory ascites warrants thorough investigation for constrictive pericarditis.

Right Atrial Tumour Thrombus in Advanced Hepatocellular Carcinoma: Surgical Techniques and Prognosis.

Hepatocellular carcinoma (HCC) with right atrium (RA) tumour thrombus is a rare condition but the treatment always poses challenges. Debates remain with regard to the use of cardiopulmonary bypass (CPB) in the surgical procedures. The aim of the present review was to summarise the surgical procedures of RA tumour thrombus removal and to discuss the pertinent indications. Twenty-three articles involving 35 patients were collected and recruited into this study. Surgical operation for HCC was performed in 29 (82.9%) patients and non-surgical operation in 6 (17.1%) patients. RA tumour thrombus removal was performed with the aid of CPB in 25 (71.4%), venovenous bypass in 3 (8.6%), and without CPB in 7 (20%) patients. After tumour thrombus removal, RA or vessel wall reconstruction with a graft was required in 7 (20%) patients. The overall median survival time of this patient cohort was 30.8 months. The median survival time of patients who received a hepatectomy was 30.5 months, in comparison to 6.0 months for those who did not receive a hepatectomy. Aggressive surgical treatment prolongs survival of selective patients with HCC with RA tumour thrombus. CPB is helpful for complete removal of the tumour thrombus from the RA. In patients with tumour thrombus invading the RA or vessel walls, a graft repair is warranted. Key Words: Hepatocellular carcinoma, Inferior vena cava, Right atrium, Tumour thrombus.