The Warren Shunt in Treating Bleeding Esophageal Varices

In patients who have impaired hepatic reserve, the Warren shunt has been proposed as an effective operation because it decompresses the esophageal varices without disturbing portal perfusion of the liver. However, early reports of high operative mortality and technical difficulties have impeded acceptance of the procedure.The operation was done in a series of 17 patients. All patients in whom elective variceal decompression with a patent splenic vein was required and without clinical ascites were candidates for this operation. Follow-up ranged from 2 to 48 months. Six patients had alcoholic cirrhosis, two had primary biliary cirrhosis and seven had postnecrotic cirrhosis; in two the cause of the liver disease was unknown. Five patients were categorized as Child''s class A, nine as class B and three as class C. No intraoperative or early postoperative deaths owing to hemorrhage occurred. However, there was one death two weeks postoperatively from pulmonary sepsis and one death five weeks postoperatively due to antigen-positive hepatitis. Two patients died from hepatic failure six weeks and five months after operation, respectively; in the first of these, chronic active hepatitis was diagnosed at the time of operation. In one patient hemorrhage recurred and transfusion was required. Although ascites, which eventually resolved, developed in eight patients after operation, the results in 76 percent of patients have been good without new episodes of hemorrhage or encephalopathy. We conclude that the Warren shunt is a safe and effective elective operation for the treatment of patients in whom hemorrhage from esophageal varices has occurred.     

Simplified oesophageal transection for bleeding varices.

Thirty patients with bleeding oesophageal varices were treated by oesophageal transection using the SPTU gun. Any form of shunt was contraindicated in all the patients. Twelve operations were done as urgent procedures within 36 hours of haemorrhage. The overall operative mortality rate was 10%, and there were two late deaths during follow-up, which has so far extended from two months to two years. Three of the patients had recurrent bleeding, and residual varices were probably the source in two. There were no cases of portal systemic encephalopathy. Although the follow-up is too short to allow any definite conclusions, these early results suggest that oesophageal transection with the SPTU gun may be useful in the large proportion of patients in whom injection sclerotherapy, shunt surgery, or conservative treatment is inappropriate.     

Selection of operation in patients with bleeding esophageal varices.

The results of surgical treatment of bleeding esophageal varices over an 8-year period in 155 patients are reviewed. Primary treatment of bleeding was conservative, with intravenous administration of vasopressin and balloon tamponade. Emergency operations were carried out after 48 hours in persons with persistent bleeding who were surgical candidates. Operative mortality was higher in this group (40%) than in those undergoing elective or urgent operations (each 10%). Postoperative encephalopathy occurred in 35% of patients and was correlated closely to late death after establishment of a shunt. The mesocaval shunt is no better than the portacaval but appears to be a good alternative in an emergency. In a controlled trial the distal splenorenal shunt was found to be associated with a lower rate of postoperative encephalopathy than the portacaval shunt, but thus far the long-term survival rates have not differed.     

Patients with Congenital Systemic-to-Pulmonary Shunts and Increased Pulmonary Vascular Resistance: What Predicts Postoperative Survival?

Background

We carried out a retrospective data review of patients with systemic to pulmonary shunts that underwent surgical repair between February 1990 and February 2012 in order to assess preoperative pulmonary vascular dynamic risk factors for predicting early and late deaths due presumably to pulmonary vascular disease.

Methods and Results

A total of 1024 cases of congenital systemic-to-pulmonary shunt and advanced pulmonary vascular disease beyond infancy and early childhood were closed surgically. The mean follow up duration was 8.5±5.5 (range 0.7 to 20) years. Sixty-one in-hospital deaths (5.96%, 61/1024) occurred after the shunt closure procedure and there were 46 late deaths, yielding 107 total deaths. We analyzed preoperative pulmonary vascular resistance index (PVRI), pulmonary vascular resistance index on pure oxygen challenge (PVRIO), difference between PVRI and PVRIO (PVRID), Qp∶Qs, and Rp∶Rs as individual risk predictors. The results showed that these individual factors all predicted in-hospital death and total death with PVRIO showing better performance than other risk factors. A multivariable Cox regression model was built,and suggested that PVRID and Qp∶Qs were informative factors for predicting survival time from late death and closure of congenital septal defects was safe with a PVRIO<10.3 WU.m² and PVRID>7.3 WU.m² on 100% oxygen.

Conclusions

All 4 variables, PVRI, PVRIO, PVRID and Qp∶Qs, should be considered in deciding surgical closure of congenital septal defects and a PVRIO<10.3 WU.m² and PVRID>7.3 WU.m² on 100% oxygen are associated with a favorable risk benefit profile for the procedure.     

食管胃底静脉曲张患者行内镜下静脉曲张套扎术及内镜下组织胶注射术后早期再出血的危险因素研究

目的：研究行内镜下静脉曲张套扎术及内镜下组织胶注射术治疗的食管胃底静脉曲张患者的术后早期出血的危险因素。方法：回顾性分析在我院治疗的103例食管胃底静脉曲张患者的临床资料,对患者的性别、年龄、发病原因、有无脾切除史、是否有肝脏病史、有无分流及断流等临床情况进行统计分析,同时结合治疗前后患者的临床表现、相关实验室检查指标、影像学指标及胃镜指标等对患者早期再出血发生的原因进行分析,寻找独立的危险因素。结果：103例患者在术后早期再出血发生率10．7％;对其危险因素进行分析可知,肝功能分级、凝血酶原时间、门静脉血栓、血红蛋白含量为术后早期再出血的独立危险因素。结论：在进行手术前,应充分的最好术前准备,尽最大能力使患者的各项危险因素（肝功能分级、凝血酶原时间、门静脉血栓、血红蛋白含量）维持在正常水平,以减少术后出血的发生。     

Left Ventricular Dilation and Pulmonary Vasodilatation after Surgical Shunt for Treatment of Pre-Sinusoidal Portal Hypertension

ObjectiveThe aim of this study was to prospectively investigate the long-term cardiovascular and pulmonary hemodynamic effects of surgical shunt for treatment of portal hypertension (PH) due to Schistosomiasis mansoni.LocationThe University of São Paulo Medical School, Brazil; Public Practice.MethodsHemodynamic evaluation was performed with transesophageal Doppler and contrast-enhanced echocardiography (ECHO) on twenty-eight participants with schistosomal portal hypertension. Participants were divided into two groups according to the surgical procedure used to treat their schistosomal portal hypertension within the last two years: group 1—distal splenorenal shunt (DSRS, n = 13) and group 2—esophagogastric devascularization and splenectomy (EGDS, n = 15).ResultsThe cardiac output (5.08 ± 0.91 L/min) and systolic volume (60.1 ± 5.6 ml) were increased (p = 0.001) in the DSRS group. DSRS participants had a significant increase (p < 0.0001) in their left ventricular end-systolic and end-diastolic diameters as well as in their left ventricular end-diastolic and end-systolic volumes (p < 0.001) compared with the preoperative period. No statistically significant difference was found in the patients who underwent EGDS. ECHO revealed intrapulmonary vasodilatation (IPV) in 18 participants (64%), 9 DSRS and 9 EGDS (p > 0.05).ConclusionsThe late increase in the cardiac output, stroke volume and left ventricular diameters demonstrated left ventricular dilatation after a distal splenorenal shunt. ECHO revealed a greater prevalence for IPV in patients with schistosomiasis than has previously been described in patients with PH from liver cirrhosis.     

Alterations of GABA-A and dopamine D-2 brain receptors in dogs with portal-systemic encephalopathy.

The binding characteristics of gamma-aminobutyric acid-A (GABA-A) receptors and the kinetic characteristics of the target enzyme of GABA synthesis in nerve terminals, glutamic acid decarboxylase (GAD), were studied in a dog model of portal-systemic encephalopathy obtained by porta-caval shunt performed in dimethylnitrosamine pretreated animals. Furthermore the properties of dopamine receptors and the levels of catecholamines of encephalopathic dogs were investigated. The mild stage of encephalopathy was characterized by an up-regulation of the inhibitory GABA-A receptors probably related to a decrese of GABA in nerve terminals since GAD was decreased and by a slight decrease of catecholamines and by an increased synthesis of octopamine associated with a decreased affinity of dopamine receptors. In the severe stage there was a selection of high affinity GABA-A receptors with an increased number of benzodiazepine recognition sites which were supersensitive to GABA stimulation, a decreased number of Dopamine D-2 receptors and a marked reduction of catecholamines. These data seem to suggest that the neurological disturbances of experimental portal-systemic encephalopathy might be the result of an imbalance between inhibitory and excitatory systems leading to a prevalence of the first one.     

Dopamine and Serotonin Metabolism in Hepatic Encephalopathy

Patients with stupor or coma from fulminant hepatic failure were found to have high cerebrospinal fluid concentrations of homovanillic acid (HVA) and 5-hydroxyindole acetic acid (5-HIAA), metabolites of dopamine and serotonin respectively. Excessive amounts of their precursors—phenylalanine and tyrosine and free tryptophan—were found in the patients'' plasma. Methionine, which participates in dopamine degradation, was also much increased. Similar disturbances were found in patients suffering an acute exacerbation of chronic encephalopathy. These abnormalities would be consistent with other evidence of an increased turnover of serotonin and possibly dopamine in the brain during hepatic encephalopathy.     

The Activated Coagulation Time of Whole Blood as a Routine Pre-Operative Screening Test

Patients with disorders of hemostasis who undergo surgical procedures are in danger of hemorrhage. While the careful medical history remains the most sensitive test of a bleeding tendency, some such patients can give no suggestive history. In three patients with coagulopathy—one with mild classical hemophilia, one with Christmas disease, and one with warfarin toxicity—the abnormality was missed by routine preoperative history but promptly detected by the routine preoperative use of the activated coagulation time (act). Either this test or the activated partial thromboplastin time should be included in the routine preoperative work-up, along with appropriate additional tests of the hemostatic mechanism.     

Splanchnic and systemic hemodynamic alterations in chronic, progressive portal hypertensive rats

Systemic and splanchnic hemodynamics were studied by using the radioactive microsphere technique, in rats in which a chronic and progressive portal or intrahepatic hypertension was produced by the placement of a nonconstricting, well fitted ligature around the portal or suprahepatic vein when the rat weighted about 100 g. The hemodynamic measurements were performed 80-90 days after ligature placement. Suprahepatic ligated rats presented portal and intrahepatic hypertension, but nonportal-systemic shunts (PSS). The only hemodynamic disturbance observed was a decrease in renal blood flow. Portal ligated rats showed a wide range of PSS and were divided in two subgroups. The subgroups with high PSS rate (greater than 10%) showed increased cardiac output and plasma renin content, as well as decreased splanchnic blood flow, portal venous inflow, hepatic blood flow and renal blood flow. Low portal-systemic shunts subgroups showed decreased cardiac output while its distribution was similar to the control rats. There was no correlation between portal pressure and shunt rate. Low shunt groups, furthermore, showed increased levels of plasma renin concentration.     

Surgical management of portal hypertension.

Portal hypertension is frequently complicated by upper gastrointestinal tract bleeding and ascites. Hemorrhage from esophageal varices is the most common cause of death from portal hypertension. Medical treatment, including resuscitation, vasoactive drugs, and endoscopic sclerosis, is the preferred initial therapy. Patients with refractory hemorrhage frequently are referred for immediate surgical intervention (usually emergency portacaval shunt). An additional cohort of patients with a history of at least 1 episode of variceal hemorrhage is likely to benefit from elective shunt operations. Shunt operations are classified as total, partial, or selective shunts based on their hemodynamic characteristics. Angiographically created shunts have been introduced recently as an alternative to operative shunts in certain circumstances. Devascularization of the esophagus or splenectomy is done for specific indications. Medically intractable ascites is a separate indication for surgical intervention. Liver transplantation has been advocated for patients whose portal hypertension is a consequence of end-stage liver disease. In the context of an increasingly complex set of treatment options, we present an overview of surgical therapy for complications of portal hypertension.     

Portacaval anastomosis causes selective alterations of peripheral-type benzodiazepine receptor expression in rat brain and peripheral tissues.

There is a growing body of evidence to suggest that peripheral-type benzodiazepine receptors (PTBRs) and their endogenous ligands are implicated in the pathogenesis of end-organ failure in chronic liver disease. Portal-systemic encephalopathy, a major neuropsychiatric complication associated with chronic liver disease, results in activation of brain PTBR and probably in peripheral organs. In order to address these issues, PTBR mRNA was measured using semi-quantitative RT-PCR in extracts of cerebral cortex, kidney and testis of rats four weeks after end-to-side portacaval anastomosis and sham-operation (controls). Densities of PTBR sites were measured concomitantly by in vitro receptor binding using the selective PTBR ligand [3H]PK11195. Portacaval shunting resulted in a 2 to 3-fold increase in expression of PTBR in brain and kidney and a 37% reduction in expression in testis. Densities of [3H]PK11195 sites changed in parallel with the alterations of gene expression. These findings suggest that selective alterations of PTBR expression are implicated in the pathogenesis of peripheral tissue hypertrophy (kidney) and/or atrophy (testis) which accompanies portal-systemic shunting in chronic liver failure. In brain, activation of PTBR could result in an increase in the production of neurosteroids with potent inhibitory action in the CNS, which could contribute to the pathogenesis of portal-systemic encephalopathy.     

Diabetes Diminishes the Portal-Systemic Collateral Vascular Response to Vasopressin via Vasopressin Receptor and Gα Proteins Regulations in Cirrhotic Rats

Liver cirrhosis may lead to portal-systemic collateral formation and bleeding. The hemostatic effect is influenced by the response of collateral vessels to vasoconstrictors. Diabetes and glucose also influence vasoresponsiveness, but their net effect on collaterals remains unexplored. This study investigated the impact of diabetes or glucose application on portal-systemic collateral vasoresponsiveness to arginine vasopressin (AVP) in cirrhosis. Spraque-Dawley rats with bile duct ligation (BDL)-induced cirrhosis received vehicle (citrate buffer) or streptozotocin (diabetic, BDL/STZ). The in situ collateral perfusion was done after hemodynamic measurements: Both were perfused with Krebs solution, D-glucose, or D-glucose and NaF, with additional OPC-31260 for the BDL/STZ group. Splenorenal shunt vasopressin receptors and G_α proteins mRNA expressions were evaluated. The survival rate of cirrhotic rats was decreased by STZ injection. The collateral perfusion pressure changes to AVP were lower in STZ-injected groups, which were reversed by OPC-31260 (a V₂R antagonist) and overcome by NaF (a G protein activator). The splenorenal shunt V₂R mRNA expression was increased while G_α proteins mRNA expressions were decreased in BDL/STZ rats compared to BDL rats. The G_αq and G_α11 mRNA expressions also correlated with the maximal perfusion pressure changes to AVP. Diabetes diminished the portal-systemic collateral vascular response to AVP in rats with BDL-induced cirrhosis, probably via V₂ receptor up-regulation and G_α proteins down-regulation.     

Hepatic encephalopathy: An update of pathophysiologic mechanisms

Hepatic encephalopathy (HE) is a neuropsychiatric disorder that occurs in both acute and chronic liver failure. Although the precise pathophysiologic mechanisms responsible for HE are not completely understood, a deficit in neurotransmission rather than a primary deficit in cerebral energy metabolism appears to be involved. The neural cell most vulnerable to liver failure is the astrocyte. In acute liver failure, the astrocyte undergoes swelling resulting in increased intracranial pressure; in chronic liver failure, the astrocyte undergoes characteristic changes known as Alzheimer type II astrocytosis. In portal-systemic encephalopathy resulting from chronic liver failure, astrocytes manifest altered expression of several key proteins and enzymes including monoamine oxidase B, glutamine synthetase, and the so-called peripheral-type benzodiazepine receptors. In addition, expression of some neuronal proteins such as monoamine oxidase A and neuronal nitric oxide synthase are modified. In acute liver failure, expression of the astrocytic glutamate transporter GLT-1 is reduced, leading to increased extracellular concentrations of glutamate. Many of these changes have been attributed to a toxic effect of ammonia and/or manganese, two substances that are normally removed by the hepatobiliary route and that in liver failure accumulate in the brain. Manganese deposition in the globus pallidus in chronic liver failure results in signal hyperintensity on T1-weighted Magnetic Resonance Imaging and may be responsible for the extrapyramidal symptoms characteristic of portal-systemic encephalopathy. Other neurotransmitter systems implicated in the pathogenesis of hepatic encephalopathy include the serotonin system, where a synaptic deficit has been suggested, as well as the catecholaminergic and opioid systems. Further elucidation of the precise nature of these alterations could result in the design of novel pharmacotherapies for the prevention and treatment of hepatic encephalopathy.     

Mesentericocaval “Jump” Graft in Management of Portal Hypertension: Experience with 24 Cases

A series of 24 patients with cirrhosis have undergone mesentericocaval shunt operations for the relief of portal hypertension. Overall the results have been satisfactory. Four of the five patients treated as an emergency and 17 of the 19 who had the operation two to six weeks after haemorrhage had been controlled left hospital alive and well. Separation of the patients into three categories according to the findings of clinical and biochemical tests, however, showed that subsequent survival was satisfactory for patients in categories A and B but that all four patients in category C had died within one year after surgery. Assessment at three months showed that in three patients moderate hepatic encephalopathy had developed.Evidence that the shunt remains patent was shown by a low incidence of repeated gastrointestinal haemorrhage and a marked diminution in variceal size in 18 of the 19 cases examined serially. Radiographic techniques for confirming shunt patency were compared and cannulation of the graft via the femoral vein was found to provide a reliable and rapid means of assessment.     

The Association between Preoperative Serum C-Reactive Protein and Hepatocellular Carcinoma Recurrence in Patients with Chronic Hepatitis B Virus (HBV) Infection—A Retrospective Study

The prognosis of the patients with hepatocellular carcinoma (HCC) recurrence following curative hepatectomy is usually dismal. Whether preoperative serum C-reactive protein (CRP) can predict the recurrence of HCC in patients with chronic HBV infection is not clear. Total 232 patients with chronic HBV infection were included in this retrospective study. We investigated the association between detailed preoperative serum CRP levels and early (≤ 2 year) and late (> 2 year) HCC recurrence following curative hepatectomy. After adjusting for potential confounders, we found a saturation effect for preoperative serum CRP of 2.1 mg/dl existed for early HCC recurrence (ER). The incidence of ER increased with preoperative serum CRP less than 2.1 mg/dl (OR = 3.5, 95% CI 1.6–7.6, P = 0.001), and higher preoperative serum CRP (>2.1 mg/dl) did not increase the incidence of ER (OR = 0.8, 95% CI 0.2–2.7, P = 0.703). Whereas there is a linear relationship between preoperative serum CRP and late HCC recurrence (LR) (OR = 0.2, 95% CI, 0.1- 0.4) (OR = 1.8, 95% CI, 1.2–2.5, P = 0.002). In addition, the optimal cutoff point for serum CRP level was 1.5 mg/dl, instead of 1.0 mg/dl, in predicting both ER and LR. Patients with higher preoperative serum CRP level (>1.5 mg/dl) had lower recurrence free survival rates and overall survival rates (P<0.01). These results suggest that preoperative serum CRP played different roles on ER and LR following curative hepatectomy, thus further predictingthe prognosis in patients with chronic HBV infection.     

Clinical experience with Ex-press Mini Glaucoma Shunt implantation

In this prospective study we wanted to report our experience and to evaluate the efficacy and safety of Ex-press Mini-Glaucoma Shunt implantation under a superficial scleral flap, as a newly and improved surgical technology in a treatment of POAG (Primary open-angle glaucoma) and refractory glaucoma. 44 eyes (35 patients) underwent an implantation of Ex-Press Mini Glaucoma Shunt. We had 21 patients with POAG (60%) and 14 patients with PEXG-pseudoexfoliation glaucoma (40%). The follow-up period was 8.62 + 7.48 months (range 2-22 months). Main outcome measures included postoperative IOP control, postoperative medications and early postoperative complications. The IOP was measured in the following postoperative time-points of 1 day, 1 week, 1, 3, 6, 9 and 12 months. The mean IOP values 1 year postoperatively were reduced for 52.8% compared to preoperative values and the use of medications were reduced for 77%. We had complications like postoperative hypotony (3.5%), choroidal ablation (7%), intraocular hemorrhage (3.5%) and postoperative shunt closure (3.5%). The Ex PRESS Mini Glaucoma Shunt implanted under a superficial scleral flap is relatively safe and effective surgical procedure and provides satisfactory IOP control and medication reduction. However, device related complications remain still a problem.     

Evolution of Plastic Transmission Strategies in Avian Malaria

Malaria parasites have been shown to adjust their life history traits to changing environmental conditions. Parasite relapses and recrudescences—marked increases in blood parasite numbers following a period when the parasite was either absent or present at very low levels in the blood, respectively—are expected to be part of such adaptive plastic strategies. Here, we first present a theoretical model that analyses the evolution of transmission strategies in fluctuating seasonal environments and we show that relapses may be adaptive if they are concomitant with the presence of mosquitoes in the vicinity of the host. We then experimentally test the hypothesis that Plasmodium parasites can respond to the presence of vectors. For this purpose, we repeatedly exposed birds infected by the avian malaria parasite Plasmodium relictum to the bites of uninfected females of its natural vector, the mosquito Culex pipiens, at three different stages of the infection: acute (∼34 days post infection), early chronic (∼122 dpi) and late chronic (∼291 dpi). We show that: (i) mosquito-exposed birds have significantly higher blood parasitaemia than control unexposed birds during the chronic stages of the infection and that (ii) this translates into significantly higher infection prevalence in the mosquito. Our results demonstrate the ability of Plasmodium relictum to maximize their transmission by adopting plastic life history strategies in response to the availability of insect vectors.     

Correlation of Lung Collapse and Gas Exchange - A Computer Tomographic Study in Sheep and Pigs with Atelectasis in Otherwise Normal Lungs

Background

Atelectasis can provoke pulmonary and non-pulmonary complications after general anaesthesia. Unfortunately, there is no instrument to estimate atelectasis and prompt changes of mechanical ventilation during general anaesthesia. Although arterial partial pressure of oxygen (PaO₂) and intrapulmonary shunt have both been suggested to correlate with atelectasis, studies yielded inconsistent results. Therefore, we investigated these correlations.

Methods

Shunt, PaO₂ and atelectasis were measured in 11 sheep and 23 pigs with otherwise normal lungs. In pigs, contrasting measurements were available 12 hours after induction of acute respiratory distress syndrome (ARDS). Atelectasis was calculated by computed tomography relative to total lung mass (M_total). We logarithmically transformed PaO₂ (lnPaO₂) to linearize its relationships with shunt and atelectasis. Data are given as median (interquartile range).

Results

M_total was 768 (715–884) g in sheep and 543 (503–583) g in pigs. Atelectasis was 26 (16–47) % in sheep and 18 (13–23) % in pigs. PaO₂ (FiO₂ = 1.0) was 242 (106–414) mmHg in sheep and 480 (437–514) mmHg in pigs. Shunt was 39 (29–51) % in sheep and 15 (11–20) % in pigs. Atelectasis correlated closely with lnPaO₂ (R² = 0.78) and shunt (R² = 0.79) in sheep (P-values<0.0001). The correlation of atelectasis with lnPaO₂ (R² = 0.63) and shunt (R² = 0.34) was weaker in pigs, but R² increased to 0.71 for lnPaO₂ and 0.72 for shunt 12 hours after induction of ARDS. In both, sheep and pigs, changes in atelectasis correlated strongly with corresponding changes in lnPaO₂ and shunt.

Discussion and Conclusion

In lung-healthy sheep, atelectasis correlates closely with lnPaO₂ and shunt, when blood gases are measured during ventilation with pure oxygen. In lung-healthy pigs, these correlations were significantly weaker, likely because pigs have stronger hypoxic pulmonary vasoconstriction (HPV) than sheep and humans. Nevertheless, correlations improved also in pigs after blunting of HPV during ARDS. In humans, the observed relationships may aid in assessing anaesthesia-related atelectasis.     

Portal hypertension complicating myelofibrosis: reversal following splenectomy.

Portal hypertension occurs in approximately 10% of patients with myelofibrosis. Increased portal blood flow secondary to splenomegaly has been proposed to explain its development. In a 60-year-old woman with proven myelofibrosis of 10 years'' duration and gross splenomegaly, portal hypertension developed with esophageal varices and ascites. There was no demonstrable obstruction to portal blood flow. Following splenectomy the ascites and esophageal varices disappeared. Despite the presence of splenic myeloid metaplasia, splenectomy did not impair the patient''s hematologic status. Portal hypertension complicating myelofibrosis has a poor prognosis, so careful attention should be given to its detection. Splenectomy may be preferable to portal-systemic shunting in the management of this complication.