Tumour response 3 months after neoadjuvant single-fraction radiotherapy for low-risk breast cancer.

Introduction: Standard treatment for early-stage invasive breast cancer (bca) consists of breast-conserving surgery and several weeks of adjuvant radiotherapy (rt). Neoadjuvant single-fraction rt is a novel approach for early-stage bca. We sought to investigate the effect of delaying surgery after neoadjuvant rt with respect to the rate of pathologic response (pr). Methods: Women 65 years of age or older with a new diagnosis of stage i luminal A bca were eligible for inclusion. A single 20 Gy dose to the primary breast tumour was given, followed by breast-conserving surgery 3 months later. The primary endpoint was the pr rate assessed by microscopic evaluation using the Miller-Payne system. Results: To date, 10 patients have been successfully treated. Median age of the patients was 72 years (range: 65-84 years). In 8 patients, neoadjuvant rt resulted in a tumour pr with median residual cellularity of 3%. No immediate rt complications other than mild dermatitis were noted. Conclusions: This study demonstrates a method for delivering single-fraction rt that can lead to a high level of pr in most patients. Continued accrual to this study and subsequent trials are needed to determine the feasibility, safety, and role of this novel technique in the management of early-stage bca.

Relationship between pre-TIPS liver perfusion by the portal vein and the incidence of post-TIPS chronic hepatic encephalopathy.

OBJECTIVE: In the present study we evaluated the predictive value of pretransjugular intrahepatic portosystemic shunt (TIPS) portal perfusion as assessed by Doppler ultrasonography for the onset of chronic encephalopathy after TIPS. METHODS: A total of 231 cirrhotic patients were followed-up prospectively after TIPS placement. The pattern of intrahepatic portal flow was assessed before TIPS. Patients were divided into two groups according to Doppler findings. Group 1 comprised patients with prograde portal flow (n = 200), whereas group 2 comprised those with loss of portal perfusion (hepatofugal or back-and-forth flow or portal vein thrombosis; n = 31). The presence of chronic encephalopathy during a median follow-up of 32 months was prospectively recorded. The prognostic value of the following parameters for the onset of chronic recurrent encephalopathy after TIPS was evaluated: age, presence of encephalopathy before TIPS, alcoholism, Pugh score, and loss of portal perfusion before TIPS. The independent prognostic value of each variable was tested with a multiple logistic regression analysis. RESULTS: The two groups were comparable in terms of age, incidence of prior episodes of hepatic encephalopathy, and portacaval gradient before and after the procedure; however, liver failure was more severe in patients in group 2 (Pugh score: 9.2 +/- 1.9 vs 10.3 +/- 1.7). The 3-yr survival was identical for both groups; 25% of the 200 patients in group 1 developed chronic encephalopathy as compared to 6% of the 31 patients in group 2 (p = 0.03). Multiple logistic regression analysis demonstrated that loss of portal perfusion and age >65 yr were the only independent predictors of the onset of post-TIPS chronic encephalopathy (odds ratios 0.24 and 1.98, respectively). CONCLUSIONS: Cirrhotic patients with loss of portal perfusion before TIPS were protected against post-TIPS chronic hepatic encephalopathy despite a more severe liver dysfunction at baseline. The only other independent predictive factor for the onset of this complication was age.

Arterial embolotherapy for upper gastrointestinal hemorrhage: outcome assessment.

PURPOSE: To identify predictors of clinical outcome after arterial embolotherapy for upper gastrointestinal (UGI) hemorrhage. MATERIALS AND METHODS: Seventy-five consecutive patients (mean age, 62.5 y) underwent arterial embolization for acute UGI hemorrhage. Bleeding was detected at endoscopy and angiography in 22 patients, at endoscopy alone in 29 patients, and at angiography alone in 24 patients. As such, embolization was directed by angiography in 46 patients (61.3%) and by endoscopy (referred to as "blind" embolization) in 29 patients (38.7%). The embolic agents used were metallic coils, polyvinyl alcohol particles (size range, 355-710 microm), gelatin sponge, and tissue adhesive. Predictors of bleeding recurrence and mortality were analyzed with logistic regression and Cox models, respectively. RESULTS: The technical success rate of embolization was 98.7%. Primary clinical success was achieved in 57 patients (76%). Secondary clinical success occurred in five additional patients (82.5%) after repeat embolization. There were four (5.3%) complications: two cases of self-resolving duodenal ischemia, one hepatic infarct, and one inguinal hematoma. The periprocedural mortality rate was 34.6% (26 of 75), mostly related to underlying illness. Early recurrence of bleeding (within 30 days of embolization) was associated with coagulation disorders (international normalized ratio >1.5, partial thromboplastin time >45 seconds, or platelet count <80,000/microL; odds ratio, 19.46; P = .001) and with the use of coils as the only embolic agent (odds ratio, 7.73; P = .01). Cirrhosis and cancer shortened the overall survival of patients after embolic therapy. The mean patient follow-up time was 34.5 months. CONCLUSION: Arterial embolotherapy for UGI hemorrhage is safe, effective, and durable. Coagulopathy and the use of coils as the only embolic agent were associated with a higher risk of early bleeding recurrence.

Transjugular intrahepatic portosystemic shunt (TIPS) versus endoscopic variceal ligation in the prevention of variceal rebleeding in patients with cirrhosis: a randomised trial.

BACKGROUND AND AIMS: The transjugular intrahepatic portosystemic shunt (TIPS) is a new therapeutic modality for variceal bleeding. In this study we compared the two year survival and rebleeding rates in cirrhotic patients treated by either variceal band ligation or TIPS for variceal bleeding. METHODS: Eighty cirrhotic patients (Pugh score 7-12) with variceal bleeding were randomly allocated to TIPS (n=41) or ligation (n=39), 24 hours after control of bleeding. RESULTS: Mean follow up was 581 days in the ligation group and 678 days in the TIPS group. The two year survival rate was 57% in the TIPS group and 56% in the ligation group (NS); the incidence of variceal rebleeding after two years was 18% in the TIPS group and 66% in the ligation group (p<0.001). Uncontrolled rebleeding occurred in 11 patients in the ligation group (eight were rescued by emergency TIPS) but in none of the TIPS group. The incidence of encephalopathy at two years was 47% in the TIPS group and 44% in the ligation group (NS). CONCLUSIONS: TIPS did not increase the two year survival rate compared with variceal band ligation after variceal bleeding in cirrhotic patients with moderate or severe liver failure. It significantly reduced the incidence of variceal rebleeding without increasing the rate of encephalopathy.

Predictors of clinical response to transjugular intrahepatic portosystemic shunt (TIPS) in cirrhotic patients with refractory ascites.

OBJECTIVE: Transjugular intrahepatic portosystemic shunt (TIPS) is used increasingly as a treatment for refractory ascites. The aim of the present study was to determine the prognostic value of different parameters in predicting a favorable evolution following TIPS in a cohort of 53 cirrhotic patients without organic renal disease and with refractory ascites. METHODS: Patients were classified as good responders if they survived more than 6 months, without severe chronic hepatic encephalopathy and with good control of ascites. The prognostic value for a good outcome was evaluated using age, creatinine clearance, plasma renin activity, plasma aldosterone, and Pugh score. RESULTS: Good control of ascites was obtained in 90%. The cumulative survival rate was 54% at 6 months, 48% at 1 yr, and 39% at 2 yr. The vast majority of patients died of complications of hepatic insufficiency. Severe chronic hepatic encephalopathy developed in 26%. Overall, a good clinical response was observed in 47%. Creatinine clearance was identified as the only pre-TIPS factor to be significantly and independently associated with a good clinical response to TIPS for refractory ascites. A good clinical response was observed in 57% of patients with a creatinine clearance >36 ml/min compared to 9% of those with a clearance <36 ml/min (p < 0.01). This cutoff point in creatinine clearance had a sensitivity of 96% and a specificity of 36%; positive predictive and negative predictive values were 57% and 90%, respectively. CONCLUSIONS: TIPS might be useful for the treatment of refractory ascites in cirrhotic patients without severe renal function impairment. However, the TIPS usefulness still has to be demonstrated compared to large volume paracentesis or Leveen shunt. In patients with poor renal function or with liver failure after TIPS, liver transplantation should be considered.

Gastric antral vascular ectasia in cirrhotic patients: absence of relation with portal hypertension.

BACKGROUND: Portal hypertensive gastropathy and gastric antral vascular ectasia (GAVE) are increasingly recognised as separate entities. The pathogenic role of portal hypertension for the development of GAVE is still controversial. AIMS: To evaluate the effects of portal decompression on chronic bleeding related to GAVE in cirrhotic patients. METHODS: Eight patients with cirrhosis and chronic blood loss related to GAVE were included. GAVE was defined endoscopically and histologically. RESULTS: All patients had severe portal hypertension (mean portocaval gradient (PCG) 26 mm Hg) and chronic low grade bleeding. Seven patients underwent transjugular intrahepatic portosystemic shunt (TIPS) and one had an end to side portacaval shunt. Rebleeding occurred in seven patients. In these, TIPS was found to be occluded after 15 days in one patient; in the other six, the shunt was patent and the PCG was below 12 mm Hg in five. In the responder, PCG was 16 mm Hg. Antrectomy was performed in four non-responders; surgery was uneventful, and they did not rebleed after surgery, but two died 11 and 30 days postoperatively from multiorgan failure. In one patient, TIPS did not control GAVE related bleeding despite a notable decrease in PCG. This patient underwent liver transplantation 14 months after TIPS; two months after transplantation, bleeding had stopped and the endoscopic appearance of the antrum had normalised. CONCLUSIONS: Results suggest that GAVE is not directly related to portal hypertension, but is influenced by the presence of liver dysfunction. Antrectomy is a therapeutic option when chronic bleeding becomes a significant problem but carries a risk of postoperative mortality.

Treatment of refractory ascites using transjugular intrahepatic portosystemic shunt (TIPS): a caution.

Ascites becomes refractory to medical treatment in nearly 10% of cirrhotic patients, who then require repeated large-volume paracentesis. In this prospective study we evaluated the use of transjugular intrahepatic portosystemic shunt (TIPS) in 30 patients with refractory ascites. TIPS was successful in all and resulted in a 54% reduction in portacaval gradient (from 22.8 +/- 0.8 to 10.4 +/- 0.6 mm Hg). Ascites became easily controlled with diuretics in 26 patients following TIPS. Ascites recurrence associated with shunt stenosis was observed during follow-up in eight patients; revision could be undertaken in five of them and resulted in good control of ascites. In responders, a marked decrease in plasma aldosterone and renin activity, a reduction in serum creatinine, and a rise in urinary sodium excretion were observed. Creatinine and inulin clearances improved significantly; PAH clearance remained unchanged. However, new-onset or worsening hepatic encephalopathy was seen in 14 patients. Severe disabling chronic encephalopathy occurred in five patients; it could be reversed successfully by balloon occlusion of the shunt in three. The cumulative survival rate was 41 and 34% at 1 and 2 years, respectively. In summary, TIPS can control refractory ascites in a majority of patients but is associated with a high rate of chronic disabling HE. In addition, the survival rate is poor. Randomized trials are needed to evaluate the exact role of TIPS in the management of refractory ascites. It is unlikely to improve survival but can ameliorate quality of life in nontransplant candidates and be useful as a bridge to transplantation, in particular, to improve denutrition associated with longstanding tense ascites.

Changes in plasma endothelin-1 and Big endothelin-1 induced by transjugular intrahepatic portosystemic shunts in patients with cirrhosis and refractory ascites.

BACKGROUND/AIMS: Endothelin-1 (ET-1) is a potent vasoconstrictor that may be involved in the pathogenesis of splanchnic and renal hemodynamic changes associated with portal hypertension. The aim of this study was to measure the concentration of ET-1 and of its precursor Big endothelin-1 (Big ET-1) in the systemic circulation as well as in the splanchnic and renal venous beds and to evaluate changes after the relief of portal hypertension following transjugular intrahepatic portosystemic shunt placement. METHODS: Plasma concentrations of ET-1 and of Big ET-1 were measured in the vena cava, renal vein, hepatic vein and portal vein in ten patients with cirrhosis and refractory ascites before and 1-2 months after transjugular intrahepatic portosystemic shunt. The porto-caval gradient, creatinine clearance, plasma aldosterone and renin activity, as well as daily urinary sodium excretion were measured at the same time. RESULTS: The plasma concentration of ET-1 and Big ET-1, respectively, in peripheral blood of normal volunteers were 0.28 +/- 03 and 3.95 +/- 0.34 pg/ml; the concentrations of both peptides were higher in patients with cirrhosis, both in vena cava (0.61 +/- 0.14 and 10.01 +/- 1.47 pg/ml), hepatic vein (0.62 +/- 0.13 and 13.93 +/- 1.77 pg/ml), portal vein (1.21 +/- 0.12 and 17.84 +/- 1.98 pg/ml) and renal vein (0.76 +/- 0.12 and 14.21 +/- 1.55 pg/ml). Moreover ET-1 and Big ET-1 concentrations were more elevated in the portal vein than in the vena cava (+98% and +70%) and slightly higher in the renal vein as compared to the vena cava (+25% and +42%). After transjugular intrahepatic portosystemic shunt, a rise in creatinine clearance and urinary sodium excretion (+49%; and +53%) was observed together with a marked reduction in plasma aldosterone and renin activity (-59% and -49%). ET-1 and Big ET-1 concentrations remained unchanged in the vena cava whereas a significant reduction of ET-1 and Big ET-1 occurred both in the portal vein (-43% and -44%) and in the renal vein (-53% and -29%). Portal vein and renal vein concentrations of both peptides became similar to vena cava levels. CONCLUSIONS: Splanchnic and renal hemodynamic changes occurring in patients with cirrhosis and refractory ascites could be related to the production of ET-1 by splanchnic and renal vascular beds. This was abolished by transjugular intrahepatic portosystemic shunt, which could explain the exacerbation of systemic vasodilation and the improvement in renal perfusion observed after the procedure.

Haemodynamic adaptation two months after transjugular intrahepatic portosystemic shunt (TIPS) in cirrhotic patients.

BACKGROUND AND AIMS: In portal hypertensive patients, transjugular intrahepatic portosystemic shunt (TIPS) acutely increases cardiac output and exaggerates peripheral vasodilatation. It has been suggested that the worsened hyperdynamic state may progress to high output heart failure. The aim was to evaluate the acute and short-term haemodynamic adaptation to this procedure. METHODS: Systemic, splanchnic, and pulmonary haemodynamics were studied in 15 cirrhotic patients under stable haemodynamic conditions before placement of TIPS, then 15-30 minutes after and two months later. For inclusion in the final analysis, an uneventful post-TIPS at two months follow up and a stable portacaval gradient were required. The following variables were measured or calculated: portacaval gradient; cardiac index (thermodilution); systolic and diastolic mean arterial, atrial, pulmonary arterial, and wedged pulmonary capillary pressures; heart rate; and total peripheral and pulmonary vascular resistances. Blood flow in the shunt was measured using duplex Doppler ultrasound. RESULTS: The portacaval gradient decreased by 56% and remained stable thereafter. Shunt blood flow was unchanged when measured immediately after TIPS and two months later. Immediately after TIPS there was a pronounced increase in cardiac index (+32%; p < 0.05) in association with a decrease in peripheral and pulmonary vascular resistance (-21%; p < 0.05 and -14%; NS). Two months later, whereas the initial rise in cardiac index was attenuated, peripheral vascular resistances remained similar and pulmonary vascular resistances decreased further (-33%; p < 0.05) compared with immediate post-TIPS values. CONCLUSIONS: Hyperdynamic circulation worsened immediately after TIPS, with a progressive adaptation during follow up. The mechanisms of post-TIPS induced haemodynamic changes include an abrupt volume load resulting from splanchnic decompression and an increased delivery of gut derived vasodilators to the systemic circulation. The persistence of decreased peripheral and pulmonary vascular resistances despite the reduction in high cardiac output two months after TIPS suggests that vasodilatation is not solely a compensatory response to a TIPS induced increased preload. Vasodilatory substances shunted away from the liver probably play an important part in this phenomenon.

Improvement of hepatorenal syndrome by transjugular intrahepatic portosystemic shunt.

Hepatorenal syndrome (HRS) is a functional renal failure occurring in advanced liver cirrhosis with ascites. It is due to renal cortical vasoconstriction resulting from complex hemodynamic disturbances related to cirrhosis and portal hypertension. There is no consistently effective therapy except for liver transplantation. We report a case of severe HRS in a patient with advanced liver cirrhosis and portal hypertension. Three sessions of hemodialysis were performed because of severe renal failure (serum urea 83 mg/dl, serum creatinine 6 mg/dl). Creation of an intrahepatic portosystemic shunt reduced the portocaval gradient from 18 to 7 mm Hg. Spectacular improvement of the renal function was observed soon after the procedure, with spontaneous recovery of diuresis and a return of serum urea and creatinine to baseline values. The patient unfortunately died 2 months later from adult respiratory distress syndrome post emergency surgery for a massive bleed related to a duodenal ulcer. Throughout this episode, the renal function remained stable. The postmortem examination showed histologically normal kidneys. We conclude that the intrahepatic portosystemic shunt can improve renal function in cirrhotic patients with HRS; it could be used in patients awaiting liver transplantation to reverse preoperative renal failure.

Short- and long-term hemodynamic effects of transjugular intrahepatic portosystemic shunts: a Doppler/manometric correlative study.

OBJECTIVE: The purposes of this study were to evaluate the effect of a well-functioning transjugular intrahepatic portosystemic shunt (TIPS) on the splanchnic and intrahepatic circulation, to determine if sonographic measurements can predict shunt dysfunction before clinical manifestations of portal hypertension occur, and to compare Doppler sonographic findings with portocaval gradient measurements before and after shunt revision. SUBJECTS AND METHODS: Forty-four patients with cirrhosis (n = 43) and myelofibrosis (n = 1) who underwent successful TIPS insertion were included in this prospective study. Indications for TIPS placement were: refractory ascites (24 patients), bleeding esophageal varices (17 patients), portal hypertensive gastropathy (two patients), and bleeding colonic varices (one patient). The portal vein and the inferior vena cava were catheterized; and the portocaval gradient was recorded before TIPS placement, at 2 and 12 months after TIPS placement, and when clinical or Doppler findings suggested shunt dysfunction. Doppler studies were done within 1 week before TIPS placement, within 2 days after TIPS placement, every 2-3 months thereafter, and before and after a TIPS revision. The Doppler studies included flow volume measurements in the portal vein and in the stent, as well as determination of the direction of flow in the segmental branches of the portal vein, in the splanchnic veins, and in portosystemic collaterals. Changes in Doppler findings and in catheter pressure measurements were compared using Spearman's rank correlation test. Significance was set at the .05 level. RESULTS: A marked decrease (-51%) in portocaval gradient was observed after TIPS placement. At Doppler sonography, portal vein velocity and diameter were both higher after TIPS placement, resulting in a marked increase in portal venous flow (170%). Mean flow velocity in the shunt was 55.8 +/- 3.6 cm/sec, and flow volumes in the shunt and in the main portal vein were 1596 ml/min and 1731 ml/min, respectively (p = nonsignificant). Dysfunction of the stent occurred in 27% of the patients. Changes in stent blood flow volume were closely related to changes in the portocaval gradient (r = -0.67, p < .001). Reduction of blood flow volume in the stent or change of direction of flow in intrahepatic portal veins or in collateral veins signaled shunt dysfunction (84% sensitivity, 89% specificity). CONCLUSION: Marked hemodynamic changes in the portal venous system occur soon after a TIPS procedure. Monitoring of shunt function with periodic Doppler sonography, including calculation of shunt blood flow, is useful in detecting shunt dysfunction before clinical signs occur.

Iatrogenic injury to the bile duct: a working classification for radiologists.

PURPOSE: To assess the usefulness of the Bismuth classification method in the preoperative localization of iatrogenic bile duct lesions with cholangiography and to correlate these cholangiographic findings with surgical findings. MATERIALS AND METHODS: The records of 33 patients who underwent open or laparoscopic cholecystectomy and who sustained injuries to the biliary tract during the course of these procedures were reviewed retrospectively. The accuracy of the cholangiographic localization of bile duct injury was assessed with the Bismuth classification method, which is based on the localization of the traumatic lesion according to the distance from the biliary confluence. RESULTS: An exact correspondence between cholangiographic and surgical findings was found in 85% of the subjects. A minimal discrepancy was found in the remainder. There was no interobserver variation. CONCLUSION: The use of the Bismuth classification method appears to be an accurate and practical method for the grading of postoperative bile duct lesions with cholangiography.

Transhepatic portal vein stenting for treatment of ruptured duodenopancreatic varices in a patient with chronic pancreatitis.

BACKGROUND: Portal vein obstruction with secondary variceal bleeding in the setting of chronic pancreatitis has not been recognized as frequently as splenic vein occlusion. This condition can be difficult to diagnose and treat. METHODS: A 54-year old man was referred for massive recurrent endoscopy-negative upper-gastrointestinal bleeding. The diagnosis of duodenopancreatic varices was finally made. Direct portography showed a high-grade stenosis of the proximal portal vein that was dilated and stented with a balloon expandable prosthesis. RESULTS: The gradient across the stenosis fell from 9 to 2 mm Hg. Bleeding stopped. After 7 months of follow-up, the patient has experienced no rebleeding, and a Doppler examination is normal. CONCLUSIONS: In patients with chronic pancreatitis and upper gastrointestinal tract bleeding of unknown origin, obstruction of one of the major splanchnic veins must be excluded. Portal vein dilatation and stenting appears to be a safe procedure with good short-term results.

[Experience with the transjugular intrahepatic portocaval shunt]. / Expérience avec la dérivation portocave intrahépatique transjugulaire.

Liver transplantation and the intrahepatic shunt have changed the management of variceal hemorrhage and refractory ascites. The purpose of this work is to review the results obtained with intrahepatic shunting. From January 1991 to May 1993, 45 patients underwent a transjugular intrahepatic portosystemic shunt. In 23 patients, liver insufficiency was considered moderate and in 21 severe. Indications for the procedure were: variceal bleeding (23), refractory ascites (19) and portal hypertensive gastritis (3). The portocaval gradient was lowered from 24.2 +/- 5.1 mm Hg to 12.9 +/- 3.9 (-47%). The procedure was effective in 78% of variceal bleeders and in 89% of patients with ascites. Thirty-day mortality was 22%. One-year survival was 39%. Liver failure or severe encephalopathy occurred in 27% of patients. Four patients (9%) presented intra-abdominal bleeding. Four patients developed renal failure. Transjugular intrahepatic portosystemic shunts are effective in lowering portal pressure and controlling complications of portal hypertension. However, important side effects are present and controlled studies are required to evaluate this new treatment.

Vascular complication of a transjugular intrahepatic portacaval stent.

The percutaneous transjugular intrahepatic portacaval stent shunt is a nonsurgical approach to portosystemic shunting. The case of a large defect seen on a radiocolloid liver--spleen scan is attributed to a hepatic infarct related to the shunting procedure.

Renal arterial stenosis: slowed systole in the downstream circulation--experimental study in dogs.

To test the effect of stenosis of the renal artery on the downstream intrarenal blood flow, a snare was placed around the renal artery in 10 dogs and compressed to create stenosis while Doppler curves were obtained from interlobar arteries. Pulsed Doppler examination of the segmental and interlobar arteries was performed by means of placement of a 7.5-MHz mechanical sector transducer directly on the surface of the kidney. The following calculations were made: degree of stenosis (evaluated with aortography), acceleration index (AI) (the acceleration of systole), and resistive index. The Doppler measurements were compared with findings on angiograms. The AI for normal arteries ranged from 2.2 to 4.3, and for arteries with 75% or greater stenosis, from 1.0 to 1.3. Systolic peaks disappeared as near occlusion was achieved. These changes were reversible within seconds of release of the arterial snare. Such change is identical to change in the pulsus tardus and parvus waveforms seen in both acute and chronic severe stenosis of the renal artery in humans.

Detection of an asymptomatic gastroduodenal artery aneurysm by real-time and pulsed Doppler sonography.

We describe an asymptomatic gastroduodenal artery aneurysm detected by real-time sonography. This lesion had the ultrasonographic characteristics of an aneurysm except for its unusual location and the absence of turbulent echogenic flow and pulsation. Pulsed-Doppler sonography confirmed the diagnosis by demonstrating bidirectional flow with systolic acceleration in the anechoic portion of the lesion.