Neoadjuvant therapy in the treatment of hilar cholangiocarcinoma:Review of the literature

Cholangiocarcinoma(CCA) is a malignant tumor of the biliary system and includes, according to the anatomical classification, intra hepatic CCA(iCCA),hilar CCA(hCCA) and distal CCA(dCCA). Hilar CCA is the most challenging type in terms of diagnosis, treatment and prognosis. Surgery is the only treatment possibly providing long-term survival, but only few patients are considered resectable at the time of diagnosis. In fact, tumor's extension to segmentary or subsegmentary biliary ducts, along with large lymph node involvement or intrahepatic metastases, precludes the surgical approach. To achieve R0 margins is mandatory for the disease-free survival and overall survival. In case of unresectable locally advanced hCCA, radiochemotherapy(RCT) as neoadjuvant treatment demonstrated to be a therapeutic option before either hepatic resection or liver transplantation. Before liver surgery, RCT is believed to enhance the R0 margins rate. For patients meeting the Mayo Clinic criteria, RCT prior to orthotopic liver transplant(OLT) has proved to produce acceptable 5-years survivals. In this review, we analyze the current role of neoadjuvant RCT before resection as well as before OLT.     

Transplacental IgG Subclass Concentrations in Pregnancies at Risk of Haemolytic Disease of the Newborn

The relationship of haemolytic disease of the newborn (HDN) to the transplacental passage of the four IgG subclasses was assessed at varous gestational ages by comparing the maternal and fetal IgG subclass concentrations in 34 pregnancies at risk of HDN with those in 30 pregnancies not at risk. Higher maternal and fetal IgG1 levels were attained in pregnancies at risk of HDN than in pregnancies not at risk. In contrast, a slight decrease in maternal IgG2 and IgG4 levels occurred in pregnancies at risk of HDN, as compared with a slight rise in maternal IgG2 and IgG4 levels in pregnancies not at risk of HDN. Changes in fetal IgG2 and 4 concentrations in either type of pregnancy were very similar, showing only slight increases between the 19th and 34th week of gestation. A slight decrease in maternal IgG3 occurred in both types of pregnancy. In contrast, higher and fairly steady levels of fetal IgG3 were observed in fetuses not at risk of HDN throughout gestation, when compared with those in 'at risk' pregnancies. However, the statistical reliability of these results is not clear since only small numbers of samples were tested and because wide variations in IgG concentrations were observed. The IgG subclass concentrations in 50 paired maternal and cord blood samples were also measured and revealed that IgG1 levels were substantially higher in cord rather than maternal blood; cord and maternal IgG2, 3 and 4 levels, on the other hand, were fairly similar.     

Rupture of a submitral ventricular aneurysm into the left atrium diagnosed by transesophageal echocardiography.

Submitral ventricular aneurysm is a thoroughly studied pathology but is not well known due to its rarity. Clinically, it is manifested by symptoms and signs of heart failure, mitral regurgitation and/or ventricular arrhythmias, and may be associated with thromboembolic phenomena and myocardial ischemia due to compression of the coronary arteries by the aneurysm. A rare complication of this type of aneurysm is rupture into the left atrium. Transthoracic echocardiography plays an important role in the definitive diagnosis of this pathology, although the role of transesophageal echocardiography in the evaluation of these patients is less known. We report a case of a submitral ventricular aneurysm complicated by rupture into the left atrium, which was diagnosed by transesophageal echocardiography.     

Transjugular percutaneous inoue balloon mitral commissurotomy in a patient with inferior vena cava obstruction after liver transplantation.

Percutaneous transvenous mitral commissurotomy was performed successfully via the transjugular approach in a patient with severe rheumatic mitral stenosis and obstruction of the inferior vena cava due to prior liver transplantation. This case demonstrates the advantage of the jugular approach in patients with difficult anatomy.     

Complete hepatic venous isolation and extracorporeal chemofiltration as treatment for human hepatocellular carcinoma: A phase I study

Background: We performed a phase I study of a novel system of complete hepatic venous isolation and extracorporeal chemofiltration in patients with unresectable hepatocellular carcinoma (HCC) to determine (a) whether systemic exposure to doxorubicin could be limited after high-dose hepatic arterial infusion (HAI), and (b) the hepatic maximum tolerated dose (MTD) of doxorubicin. Methods: Ten patients with biopsy-proven HCC were treated with 20-min HAI of doxorubicin (17 total treatments). Two patients were treated with doxorubicin 60 mg/m², three patients were treated at 90 mg/m², and five patients received 120 mg/m². A newly developed dual-balloon vena cava catheter was advanced from the femoral vein, and the balloons were inflated to isolate and capture total hepatic venous outflow. The hepatic venous blood was pumped through extracorporeal carbon chemofilters before return of the blood to the systemic circulation. Results: Peak systemic doxorubicin levels were an average 85.6% lower than were peak prefilter levels (p<0.01). Because all catheters were placed percutaneously and because the chemofiltration markedly limited systemic chemotherapy exposure, patients were discharged 1 day after 16 of the 17 treatments. The hepatic and systemic MTD of doxorubicin in this treatment protocol was 120 mg/m². Conclusions: This novel system of complete hepatic venous isolation and chemofiltration limits systemic chemotherapy toxicity and will allow use of higher doses of chemotherapeutic agents to treat HCC. The results of this study were presented at the 46th Annual Cancer Symposium of The Society of Surgical Oncology, Los Angeles, California, March 18–21, 1993.     

Midpregnancy plasma zinc in normal and growth retarded fetuses--a preliminary study.

OBJECTIVE: To determine plasma zinc concentrations in normally and abnormally growing fetuses. DESIGN: Prospective observational study. SETTING: Fetal Medicine Unit, Queen Charlotte's Maternity Hospital. SUBJECTS: 53 pregnant women attending for fetal blood sampling at between 18 and 40 weeks gestation. 27 fetuses were normal (central group), 11 fetuses were growth retarded and 15 were malformed. MAIN OUTCOME MEASURES: Plasma zinc concentrations in maternal and fetal blood at time of fetal blood sampling. RESULTS: In normally growing fetuses, between 18 and 40 weeks gestation, there was no fall in maternal plasma zinc concentration; the fetal level fell by 36%. In 10 fetuses with symmetrical growth retardation, plasma zinc concentration tended to be low, but was not significantly different from that in the normal control fetuses. CONCLUSION: The results suggest that (i) placental transfer of zinc is an uphill secretory process and that it is a rate-limiting step in the accumulation of zinc by the fetus and (ii) in fetuses with symmetrical intrauterine growth retardation, a low plasma zinc is probably a parallel phenomenon and not necessarily an aetiological factor.     

Normal amniotic pressure throughout gestation.

OBJECTIVE: To characterize amniotic pressure (AP) in pregnancies with normal amniotic fluid volume. DESIGN: Observational study, mainly cross-sectional. SETTING: Fetal medicine unit within a tertiary referral hospital. SUBJECTS: Patients undergoing transamniotic invasive procedures in whom amniotic fluid volume was subjectively assessed as normal on ultrasound. Those beyond 16 weeks with a deepest vertical pool on ultrasound less than 3.0 or greater than 8.0 cm were excluded. Overall 194 pregnancies were studied on 232 occasions between 7 and 38 weeks gestation. INTERVENTIONS: Manometry readings referenced to the top of the maternal abdomen were obtained via a fluid-filled line from the needle hub and either connected to a pressure transducer (n = 190) or held vertically against a ruler (n = 42). MAIN OUTCOME MEASURES: AP in mm Hg, AP corrected for gestational age (z scores), semi-quantitative ultrasonic indices of amniotic fluid volume, clinical variables. RESULTS: AP in singleton pregnancies increased with advancing gestation (P less than 0.001), and the sigmoid-shaped regression curve plateaued in the mid-trimester. AP z scores were not influenced by volume-related phenomena such as twin gestation, the deepest vertical pool, or amniotic fluid index, nor by maternal age, parity, gravidity, fetal sex, or subsequent spontaneous preterm delivery. CONCLUSIONS: These findings suggest that AP is not principally determined by intrauterine volume. We speculate that AP, which reflects change in uterine tension as a function of radius, may instead be determined by gestation-specific anatomical and hormonal influences on gravid uterine musculature. A reference range for AP has been constructed for use in amnioinfusion and amnioreduction procedures.     

Myocardial protection in adult cardiac surgery: current options and future challenges

Current techniques of myocardial protection are evolving with the use of less conventional modalities of cardioplegia and have reduced the morbidity and mortality of cardiac operations. Blood cardioplegic solutions appear superior to cold cardioplegia in terms of myocardial protection and adjuncts as glutamate/aspartate enhancement, antioxidant supplementation, nitric oxide donors and maintenance of calcium homeostasis seem effective. In the near future, further experimental and clinical investigations about pharmacological preconditioning, sodium–hydrogen exchangers inhibition and gene therapy need to be addressed to well define their potential role in the improvement of current techniques of myocardial protection that are suboptimal in high-risk clinical settings.