Interventional treatment of postthrombotic syndrome.

BACKGROUND: Postthrombotic syndrome (PTS) is the development of symptoms and signs of chronic venous insufficiency following deep vein thrombosis (DVT) and has a significant negative effect on the quality of life. The current understanding is that the clinical manifestation of PTS is related more to venous obstruction than it is to venous reflux. The use of interventional techniques for the treatment of venous obstruction and/or venous occlusion has rapidly increased in recent years. OBJECTIVE: This article summarizes the current concept of endovenous and hybrid interventions and presents the optimized treatment of choice in patients with chronic symptomatic venous obstruction. METHODS: We performed a systematic literature search in the Medline database to identify relevant studies on the treatment of patients with PTS. RESULTS: A meta-analysis of the relevant studies showed that this minimally invasive procedure is an effective treatment option with low morbidity and no mortality. Use of the newly developed dedicated venous stents showed promising results with good mid-term patency rates and a significant decrease in related symptoms. CONCLUSION: Interventional therapy for the treatment of symptomatic chronic venous obstruction has become the method of choice in recent years. More studies are needed to evaluate the long-term success rate of dedicated venous stents.

Late rupture after EVAR: a new trend?

AIM: Endovascular aortic repair (EVAR) is an adequate therapy for abdominal aortic aneurysms (AAA). Late aortic ruptures caused by endoleaks after EVAR still remain a critical issue. The aim of this study was to assess the causes of ruptured aortic aneurysms after EVAR in a single center study. METHODS: All patients, who were treated in our University hospital with a ruptured juxtra- or infrarenal AAA between January 2011 and October 2013, were included in this retrospective analysis. RESULTS: Thirty patients with ruptured infra- or juxtrarenal aneurysms were treated in this time frame. Six out of these 30 patients had previous EVAR repair. The median maximal aneurysm diameter of these post-EVAR patients was 82 (75-95) mm. The median time between primary EVAR and rupture was 42.5 (14-99) months. Three patients with type Ia endoleaks were treated by stent removal and conventional aortic reconstruction. In two patients with type II endoleak the bleeding was controlled by occluding the back bleeding lumbar arteries. One type III endoleak was sealed by an additional stent-graft implantation into the right iliac artery. CONCLUSION: We observed a considerable number of patients with a ruptured AAA after EVAR. Surprisingly, we observed two ruptured aneurysms due to type II endoleaks.

Competition between native liver and graft in auxiliary liver transplantation in a rat model.

The competition between the native and the grafted liver in heterotopic auxiliary liver transplantation (HALT) with portal vein arterialization (PVA) was investigated in a rat model. The experimental groups were: HALT with flow-regulated PVA and 70% resection of a native liver and graft (n = 32; group I) versus 70% liver resection (n = 32; group II). After HALT, the weight of the native liver increased until the sixth postoperative week (431% +/- 55% of the intraoperative weight), whereas, the graft weight was only 76% +/- 31% of the intraoperative weight at this time. In group II, liver weight increased continuously to 529% +/- 30% of the intraoperative weight after 6 weeks. On postoperative day 2, there was significantly increased proliferative hepatocellular activity in all groups. This was highest in the resected livers of group II, followed by the native livers of group I, and the grafts of group I (301 +/- 126 vs 262 +/- 97 vs 216 +/- 31 Ki-67-positive hepatocytes/10 visual fields). However, the differences between the groups were not significant. With regard to hepatocellular apoptosis, the livers were similar among all groups and at all time points, M30-positive hepatocyte counts were

Successful renal transplantation in a child with thrombosis of the inferior vena cava and both iliac veins.

An 8-year-old girl who was born premature in the 24th gestational week suffered a septic venous thrombosis due to an indwelling central line during the early perinatal period. As a result the inferior vena cava including the intrahepatic segment and both iliac veins was obliterated. The right kidney was primarily dysplastic, and the left kidney developed a partial infarction. Renal function was compensated until the age of 6 years. Magnetic resonance angiography at that time showed a collateral system via the azygos vein. The venous pressure and its variation with breathing as measured invasively showed normal values. During pretransplant initiation of immunosuppressive therapy, the child developed cerebral convulsions after the third dose of cyclosporine. Therefore we utilized a regimen of rapamycin, mycophenolate mofetil, and steroids. The transplantation was performed using a living donor graft from the child's mother. The relatively long vein from the left kidney was used for anastomosis with a large presacral collateral vein. Twelve months after transplantation the kidney function is stable with a serum creatinine of 0.5 mg/dL. The recipient thrombosis of the caval and iliac veins is not a principal contraindication for successful renal transplantation. MR angiography and invasive pressure measurements facilitated evaluation of the collateral venous system. The living donation setting allowed the initiation of an immunosuppressive regimen that was tailored to the concomitant diseases of the child.

Portal hyperperfusion causes disturbance of microcirculation and increased rate of hepatocellular apoptosis: investigations in heterotopic rat liver transplantation with portal vein arterialization.

Clinical results of portal vein arterialization (PVA) in liver transplantation are controversial. One reason for this is the lack of a standardized flow regulation. Our experiments in rats compared PVA with blood-flow regulation to PVA with hyperperfusion in heterotopic auxiliary liver transplantation (HALT). In group I (n = 19), the graft's portal vein was completely arterialized via the right renal artery in-stent technique, using a 0.3-mm stent, leading to a physiological average portal blood flow. In group II (n = 19), a 0.5-mm stent was used. In group II, the average portal blood flow after reperfusion was significantly elevated (group II: 6.4 +/- 1.5; group I: 1.7 +/- 0.4 mL/min/g of liver weight; P < .001). The sinusoidal diameter after reperfusion was significantly greater in group II (9.8 +/- 0.5 microm) than in group I (5.5 +/- 0.2 microm; P < .001). Red blood cell velocity in the dilated sinusoids was significantly lower in group II (171 +/- 18 microm/s) than in group I (252 +/- 13 microm/s). Stasis of erythrocytes occurred; consequently, the functional sinusoidal density was significantly reduced in group II (38 +/- 7%) compared with group I (50 +/- 3%; P < .01). Two hours after reperfusion of the portal vein, the number of apoptotic hepatocytes was significantly higher in group II than in group I (I: 0 +/- 0 vs II: 7 +/- 9 M30-positive hepatocytes/10 high-power fields). The 6-week survival rate was 9 of 11 in both groups. In group II, 6 of 9 grafts showed massive hepatocellular necroses after 6 weeks, whereas in group I, only 1 of 9 presented a slight hepatocellular necrosis. Finally, our results demonstrate negative effects of portal hyperperfusion in transplanted livers, which are correctable by adequate flow regulation.

Successful use of sirolimus in a patient with bulky ovarian metastasis of hepatocellular carcinoma after liver transplantation.

This 44-year-old woman developed multifocal hepatocellular carcinoma (HCC) within hepatitis B-induced liver cirrhosis. At the time of listing for transplantation the HCC had progressed beyond the Milan criteria. Due to her young age, high grade of histological differentiation according to biopsy, and lack of therapeutic alternatives, she was listed for transplantation. She received an organ from the Eurotransplant marginal liver list. Immunosuppression was reduced to tacrolimus monotherapy within 4 months. Five months after transplantation bilateral bulky ovarian metastases were seen on computed tomography (CT) scan. A bilateral salphingo-oophorectomy was performed and immunosuppression switched to sirolimus monotherapy. Fourteen months after this procedure and 19 months after transplantation, the patient is asymptomatic with stable liver function. She is free of recurrence as judged by CT scan, bone scan, and alpha-fetoprotein. In conclusion, radical surgical treatment and immunosuppression using sirolimus may achieve tumor-free survival in selected patients with advanced or recurrent HCC.

First case of isolated small bowel transplantation at the university of cologne: rejection-free course under quadruple immunosuppression and endoluminal monitoring with video-capsule.

Intestinal transplantation is the only curative form of treatment for fulminant short bowel syndrome. Results have been hampered by frequent rejection episodes as well as technical and infectious complications. We report the first case of complete small bowel transplantation performed at our institution. A 37-year-old male patient suffered from massive gut infarction due to a superior mesenteric artery embolus from a thrombus in the descending aorta resulting from hereditary protein S and C deficiency. The primary surgery resulted in a duodenocolostomy requiring total parenteral nutrition. The course was further complicated by multiple central line infections and pre-renal kidney failure induced by dehydration. After 17 months, we performed a cadaveric small bowel transplant using systemic venous drainage. The ileum was anastomosed end-to-end to the recipient ascending colon. The proximal jejunum was used to create a jejunostomy, with an end-to-side duodenojejunostomy. Immunosuppression consisted of a single-administration of antithymocyte globulin (ATG), tacrolimus, mycophenolate mofetil (MMF), and methylprednisolone given enterally from day 1. Biopsies of the upper jejunum showed no signs of rejection. The graft was monitored via capsule video endoscopy after 9 weeks and appeared normal. The patient was discharged on day 35, completely on an enteral diet and gaining weight with a good quality of life. Oral valganciclovir was given for the cytomegalovirus prophylaxis infection (donor-positive, recipient-negative constellation), with no clinical or serologic signs of infection. The early course after small bowel transplantation using a quadruple regimen was clinically successful. The use of video-capsules allows for noninvasive visual monitoring of bowel segments that cannot be reached endoscopically.

[Right portal vein ligation prior to extended right hemihepatectomy for synchronous colorectal liver metastases]. / Präliminare Pfortaderligatur rechts vor erweiterter Hemihepatektomie bei synchronen kolorektalen Lebermetastasen.

INTRODUCTION: A two-step procedure is suggested to reduce the overall operative risk in patients with colorectal cancer and large synchronous liver metastases, which demand an extended right hemihepatectomy for R0 resection. METHODS: The clinical course and volumetric evaluation of the liver is described in three patients in whom preliminary ligation of the right branch of the portal vein was performed at the time of colon resection. RESULTS: The size of the left lateral lobes increased by 9.9%, 13.7%, and 4.9% of total liver volume, respectively. At the same time, the noninfiltrated part of the right lobes shrunk by 36.7%, 36%, and 6% ukereas metastatic growth was 26.8%, 22.3%, and 12%. After 7 weeks, extended right hemihepatectomy could be performed in all three patients without signs of hepatic insufficiency, yielding R0 resection. CONCLUSION: Can reduce the risk for extended right hemihepatectomy in selected patients with synchronous colorectal liver metastases.

Underestimation of nodules while staging hepatocellular carcinoma prior to neoadjuvant treatment on waiting list for transplantation.

Neoadjuvant therapy of hepatocellular carcinoma (HCC) has increasing importance for patients awaiting liver transplantation, as waiting time increases. The therapeutic options (ethanol injection, radiofrequency ablation, chemoembolization) are only effective locally. Therefore, occult carcinomas can overcome the efficacy of these therapies. To evaluate the impact of occult nodules, we analyzed the staging results and histology from 21 HCC patients. The average pretransplant waiting time was 5.2 +/- 3.2 months. The staging before transplantation was reliable concerning the maximum diameter of the HCC. The number of HCC nodules increased from 30 at the time of clinical staging to 59 in histology, hence from 1.4 +/- 1.5 to 2.8 +/- 1.9 per patient. Patients with pT1/2 HCCs experienced an even larger increase (from 1.3 to 3.2 nodules) than patients suffering of pT3/4 HCCs (2.6 to 3.4 nodules). All occult HCCs were less than 2 cm in diameter and showed no prognostically negative histological features such as vascular invasion. The 3-year survival of the patients with small HCCs was 86% compared to 34% for those with advanced cancer. The survival of patients with small HCCs was similar to the survival of patients receiving a transplant for a nonmalignant indication. Only after neoadjuvant therapy with radiofrequency ablation or ethanol injection but not with chemoembolization, was significant necrosis of HCC observed. Considering the current average waiting time, repetitive staging and treatment of new nodules seems justified to achieve a low dropout rate during the waiting time.

Auxiliary rat liver transplantation with portal vein arterialization in acute hepatic failure.

BACKGROUND: The aim of our work was to study the effect of the portal vein arterialization of an auxiliary liver graft on survival, liver function, and regeneration of the native liver suffering from surgically induced acute liver failure (ALF). METHODS: In Lewis rats (control group: n=10), ALF was induced by resection of about 85% of liver tissue. The auxiliary liver graft (reduced size of 30%) was transplanted into the right upper quadrant of the abdomen (trial group: n=12). The portal vein was arterialized via the renal artery. The infrahepatic vena cava was anastomosed end-to-side, and the bile duct was implanted into the duodenum. RESULTS: Survival rate over a 3-month period was 10/12 in the trial group vs. 2/10 in the controls. In the trial group, the prothrombin time rose up to 38+/-2 sec on day 1 after surgery (control group: 66+/-6 sec); on day 5 after surgery, it returned to values of 30+/-1 sec. On day 1 after surgery, serum albumin fell to 25+/-1 g/L (preoperative value: 32+/-1 g/L). Within 3 weeks, it returned to normal. The hepatobiliary scan on day 7 after surgery showed normal uptake in the liver graft, whereas the uptake of the native liver was distinctly reduced. After 3 months, the transplanted liver had atrophied (0.6% of body weight), the native liver hypertrophied (2.5% of body weight), with a normal total weight for both livers of 3.1% of body weight. CONCLUSIONS: Thus, auxiliary liver transplantation with arterialized portal vein allows maintenance of liver function at the time of ALF and regeneration of the native liver.

Effect of angiotensin-converting enzyme inhibition on growth factor mRNA in chronic renal allograft rejection in the rat.

BACKGROUND: Despite considerable progress in immunosuppression, the incidence of chronic renal allograft rejection has not decreased. Recent studies have revealed that angiotensin-converting enzyme (ACE) inhibition ameliorates graft arteriosclerosis, glomerulosclerosis, and tubular atrophy. Moreover, it decreases systemic and glomerular capillary hydrostatic pressure in a rat kidney allograft model. We evaluated the effects of the ACE inhibitor enalapril on cytokine and growth factor expression in chronically rejecting rat kidney allografts. METHODS: Kidneys of Fisher (F344) rats were orthotopically transplanted into Lewis (Lew) rats. To prevent acute rejection, cyclosporine A (1.5 mg/kg/day) was given to all recipients during the first 10 days after transplantation. Enalapril (60 mg/L) or vehicle was added to the drinking water 10 days after transplantation. Animals were harvested 20 weeks after transplantation for histologic and immunohistologic studies, as well as for evaluation of cytokine and growth factor mRNA by semiquantitative polymerase chain reaction. RESULTS: Controls developed severe signs of chronic rejection, such as glomerular and vascular lesions, associated with a large number of infiltrating leukocytes. Enalapril-treated animals developed less proteinuria and other signs of chronic rejection. The mRNA levels of transforming growth factor-beta 1 (TGF-beta 1), platelet-derived growth factor A and B chain (PDGF A and B), insulin-like growth factor-I (IGF-I), interleukin-1 (IL-1), and monocyte chemoattractant protein-1 (MCP-1) were significantly reduced in the enalapril group and were most pronounced for IL-1 and PDGF A. In addition, we found an increased level of renal angiotensinogen mRNA after treatment with enalapril. CONCLUSIONS: Treatment with enalapril attenuated the development of proteinuria, ameliorated morphological damage, decreased leukocyte infiltration, and prevented a rise in renal mRNA levels of growth factors and cytokines in kidney grafts in a rat model of chronic renal allograft rejection.

Organ preservation with EC, HTK, and UW, solution in orthotopic rat liver transplantation. Part II. Morphological study.

The quality of organ preservation is of major importance in minimizing the incidence of primary graft nonfunction and organ rejection. For this study a new semiquantitative score was developed that grades morphologic tissue alterations in the liver according to their frequency and severity. It was applied to assess commonly used perfusion solutions for their efficacy in preventing early and late tissue damage after rat liver transplantation. For transplantation the livers were stored in Euro-Collins (EC, group I; n = 11), histidine-tryptophan-alpha-ketoglutarate (HTK, group II; n = 11), or University of Wisconsin solution (UW, group III; n = 11). Rat liver transplantation was performed with graft arterialization by the method of Engemann. Biopsies were taken for morphological examination and semiquantitative scoring during the donor operation, after 4 h of cold storage, 1 h after reperfusion, and 4 weeks postoperatively. An immunohistological bromodeoxyuridine (BrdU) assay was also performed on the day of dissection to assess the rate of hepatic proliferation. Semiquantitative morphological analysis gave widely differing results in all experimental groups after 4 h of ischemia. There was less intracellular and interstitial edema, fatty degeneration, intralobular necrosis, and hepatocellular proliferation in the HTK group than in the other groups. Neither after cold ischemia nor 1 h after reperfusion did Kupffer-cell activation occur; this is known to play a major role in the development ofischemia and reperfusion injury. Furthermore, late changes such as bile-duct proliferation and vascular and sinusoidal alterations appeared less frequently in this group. The hepato-protective powers of HTK solution might therefore be due to decreased Kupffer-cell activation.

Auxiliary liver transplantation in acute liver failure in the rat -- an illustrated description of a new surgical approach.

INTRODUCTION: To investigate auxiliary liver transplantation successfully in rats suffering from acute liver failure, we developed a new surgical approach. METHODS: A 70% hepatectomized liver graft was implanted into the right upper quadrant of the abdomen. The donor portal vein was anastomosed with the recipient's right renal artery using the splint technique. The donor infrahepatic vena cava was attached onto the recipient vena cava end to side. The bile duct was implanted into the duodenum.

Organ preservation with EC, HTK, and UW solutions in orthotopic liver transplantation in syngeneic rats. Part I: Functional parameters.

Ischemic injury to the liver is known to influence the outcome of liver transplantation. In this study the efficacy of Euro-Collins (EC), histidine-tryptophan-ketoglutarate (HTK), and University of Wisconsin (UW) preservation solution was analyzed in the model of orthotopic liver transplantation in syngeneic rats. The study design was as follows: Group I, Euro-Collins solution (n = 11); Group II, Histidine-Tryptophan-Ketoglutarate solution (n = 11); Group III, University of Wisconsin solution (n = 11). The rat liver transplantation was performed with arterialization of the graft as described by Engemann. The postoperative follow-up was 28 days. The perfusion flow rate of the preservation solution measured during organ perfusion revealed lowest levels in the UW group and comparable levels in Groups I and II. Postoperative graft function was monitored by measuring liver enzymes (aspartate amino-transferase, ASAT, alanine aminotransferase, ALAT), bilirubin and bile production. The survival rate was 10/11 in each group. Liver enzymes and bilirubin increased postoperatively and went back to normal within 2 or 3 weeks. In contrast to bilirubin, the liver enzymes showed a biphasic increase with maxima on the 1st and 5th days (range: ALAT, 220-264 U/L; ASAT, 145-177 U/L). Bile production was observed in all groups, but was significantly higher after UW-preservation (P < .005). Analysis of inflammatory cells revealed high concentrations of intrasinusoidal leukocytes and lymphocytes in the graft with a maximum on the 5th day.

Orthotopic rat liver transplantation and bile duct reconstruction by a splint technique.

The aim of the present study is to investigate the impact of bile duct reconstruction by a splint technique, a method which has not been sufficiently researched in animals after liver transplantation. Three experimental groups were set up: I = control, sham operation; II = bile duct reconstruction; III = orthotopic rat liver transplantation (ORLT). After bile duct reconstruction, serum levels of ASAT and ALAT in group II revealed a peak on the first postoperative day. The transplanted animals (group III) showed a second peak in liver enzyme levels on the fifth postoperative day; it was significantly higher than in group II. Serum bilirubin was more elevated in the transplant group, with a peak on day 7. Morphological investigations at the end of surgery revealed only intralobular necrosis and reactive changes in the liver capsule (group II); after transplantation (group III), there was also interstitial and intracellular edema, fatty degeneration and disintegration of the sinusoidal lining. One month later, necrosis, bile duct proliferation, cholestasis, cholangitis and vascular alterations were found in groups II and III. Furthermore, an increased rate of hepatocellular and bile duct proliferation was observed. These findings are partly due to the bile duct reconstruction. We recommend that a bile duct reconstruction control group should be included in ORLT experiments.

Dieting in teenage schoolgirls. A longitudinal prospective study.

The aim of the present study was to demonstrate what far-reaching consequences dieting may produce in teenage girls and to determine whether there is a direct relation between dieting and the development of anorexia nervosa. The study took the form of a longitudinal prospective investigation of dieting teenage schoolgirls over a 10-year observation period, particularly as regards physical and mental state of health and general psychosocial development. The questionnaire study underlying the present work--entitled "The feeling of being fat and dieting in a school population"--was published in 1971 by Ingvar Nylander. With the aim of determining how often teenagers feel overweight, how often they diet and how often they develop disorders from dieting, Nylander interviewed 2370 students (1129 boys and 1241 girls). His study was published in Acta Socio-Medica Scand 1971, 1. In the present work a primary material of 130 girls was selected from the dieting schoolgirls and 111 of these were examined by the author. The methods included a personal interview, examination of physical and mental health, an EEG examination and an intelligence test. Moreover, information was obtained concerning the subjects from their parents and from school health records and hospital case records. A follow-up study was done 10 years later, in which 97 of the subjects were again examined by the author while 12 subjects merely answered a questionnaire. The methods used were very similar to the foregoing ones. The subjects' dieting behaviour was evaluated on the basis of an anorectic behaviour scale. Further information was obtained from hospital case records. The overall situation of the subjects was evaluated on the basis of case histories and of data from case records concerning heredity, environment, psychosocial adjustment, state of health and findings on examination. Some of the subjects had had a dieting problem for a long time; they had generally dieted for short but repeated periods, but, in most cases, with little effect on their weight. Some patients had developed anorectic behaviour, or even AN, others did not. The former group had shown such behaviour at an early stage--or other signs of mental insufficiency--while the latter group was healthy and during dieting periods developed neither anorectic behaviour nor anorexia nervosa. Thus no direct causal relation between dieting and anorexia nervosa could be demonstrated. If dieting is caused by mental insufficiency, this may lead to the development of anorectic behaviour and/or anorexia nervosa.(ABSTRACT TRUNCATED AT 400 WORDS)