W. Van Steenbergen

Patterns of recurrence after curative resection of pancreatic ductal adenocarcinoma

AIMS Despite curative surgery for pancreatic ductal adenocarcinoma (PDAC), most patients develop cancer recurrence and die from metastatic disease. Understanding of the patterns of failure after surgery can lead to new insights for novel therapeutic modalities. The aim of the present study is to describe the patterns of recurrence after curative resection of PDAC. METHODS A retrospective analysis was performed of 145 consecutive resections for PDAC between 1998 and 2005 (M/F 75/70; median (range) age 67 years (32-85 y)). The location of the first and consecutive recurrences, and the time interval to cancer recurrence after surgical resection was studied. The magnitude of tumour-free margin was less than a millimetre in 48 patients, whereas a positive surgical margin was observed in 27 patients. The median duration of follow-up was 18.5 (range 0.3-116.8) months. RESULTS Cancer recurrence was observed in 110 patients. The first location of recurrence was locoregional in 19, extra-pancreatic in 66, and combined locoregional and extra-pancreatic in 25 patients. Extra-pancreatic recurrence developed in the liver in 57, peritoneal in 35, pulmonary in 15, and retroperitoneal in 5 patients. The median (95% CI) overall (OS) and disease-free (DFS) survival was 18.7 (15.7-23.5) and 9.8 (7.5-12.4) months, respectively. The type of cancer recurrence did not significantly influence OS, while the resection margin status had a prognostic effect. CONCLUSION The vast majority of patients who undergo potentially curative surgery for PDAC develop cancer recurrence located in the abdominal cavity. Surgical resection margins with tumour involvement and tumour-free margins of less then 1mm are negative prognostic factors. Further research on better local surgical control, peri-operative locoregional treatment, and more effective adjuvant systemic therapy is necessary to improve long-term survival of patients with curable PDAC.

Budesonide or prednisone in combination with ursodeoxycholic acid in primary sclerosing cholangitis: a randomized double-blind pilot study

Budesonide or prednisone in combination with ursodeoxycholic acid in primary sclerosing cholangitis: a randomized double-blind pilot study

Arsenic and non-cirrhotic portal hypertension: A report of eight cases

It was discovered that eight patients with complications of non-cirrhotic portal hypertension had received an arsenical preparation for psoriasis as Fowlers solution some years age. Seven of them were admitted for bleeding oesophageal varices. Upon admission, splenomegaly and hypersplenism were present. Liver tests were normal and palmar skin keratosis and melanosis were noted. Liver biopsy of six patients showed features of incomplete septal cirrhosis. Malignant skin lesions were present in half of the patients. One patient died from lung carcinoma and another from an ovarium neoplasm. Chronic arsenic intake should be actively looked for in all patients with psoriasis and non-cirrhotic portal hypertension. They should be followed up for many years for development of malignant lesions in skin, lung and liver. Liver abnormalities present in the biopsies are often minor and may escape detection.

Assessment of variceal pressure by continuous non-invasive endoscopic registration: a placebo controlled evaluation of the effect of terlipressin and octreotide.

Octreotide has been proposed for the treatment of variceal bleeding. The effects on portal pressure, however, have been variable in published studies. As bleeding is more directly related to pressure in the varices, this study investigated the effect on variceal pressure of octreotide and terlipressin, a vasoactive drug with a well established effect. Variceal pressure was measured during four to eight minutes by a continuous non-invasive endoscopic registration method. Thirty patients in whom a stable variceal pressure recording had been obtained during at least one minute, were randomised to receive either 2 mg terlipressin, 50 micrograms octreotide or an identical volume of saline, as a single intravenous injection given over 60 seconds. For the final analysis three patients had to be excluded because of lack of a satisfactory recording. There were no significant clinical differences between the three groups of patients. Placebo administration did not induce significant changes, but a mean decrease in variceal pressure of -27% was noted with terlipressin, starting from two minutes onwards. Variceal pressure changes after injection of octreotide were variable and the mean change in pressure did not reach statistical significance. Seven of 10 patients showed a temporary increase in variceal pressure. In conclusion, terlipressin induces a significant and progressive decrease in variceal pressure but inconsistent variations of variceal pressure changes were seen after octreotide administration. This is probably related to its effect on central venous pressure. This study also shows that continuous variceal pressure recording with the non-invasive endoscopic registration technique detects in an accurate way the effect of vasoactive drugs on variceal pressure, because placebo injection did not produce significant changes.

Skip areas in hepatic steatosis: a sonographic-angiographic study

Abstract“Skip areas” in focal steatosis describes a newly proposed “subsegmental type” of focal steatosis, which differs in both extent and topography from the more classic “lobar or segmental type” of focal steatosis.In the subsegmental type of steatosis, fatty infiltration can be considered homogeneous through-out the liver, with the exception of small flattened portions of less affected parenchyma, called “ skip areas.” These regions are mainly located in the subcapsular areas or along the interlobar fissures or the gallbladder bed.Observations using ultrasound in vivo, as well as on postmortem in vitro angiograms, suggest that both the extent and topography of these skip areas can be explained by local differences in vascular anatomy.

Intrahepatic splenosis: imaging features

We report a patient who presented with asymptomatic focal liver lesions and in whom a diagnosis of intrahepatic splenosis was made. This rare condition mostly occurs in patients who previously underwent splenic trauma or surgery. Magnetic resonance imaging (MRI) characteristics suggesting this diagnosis are described. The lesions were mainly hypointense on T1- and hyperintense on T2-weighted images. After administration of small iron oxide particles (SPIO-Endorem), the lesions remained slightly hyperintense relative to the hypointense liver parenchyma but showed a 50% loss in signal intensity. Knowledge of these MRI characteristics may avoid the use of surgical interventions to arrive at the correct diagnosis of these rare liver lesions.

Clinical aspects of incomplete septal cirrhosis in comparison with macronodular cirrhosis.

BACKGROUND/AIMS Incomplete septal cirrhosis (ISC) is a form of macronodular cirrhosis characterized by slender, incomplete septa that demarcate inconspicuous nodules. Its clinical features have not been investigated in a large series. The aims of this study were to review the clinical symptoms and evolution of ISC in 42 patients. METHODS Forty-two patients with at least one liver biopsy strongly suggestive of ISC were selected for the study covering a period between 1968 and 1987. Data for these patients were compared with the evolution of 49 patients with classical macronodular cirrhosis after chronic active hepatitis type B or C. RESULTS Possible etiological factors for ISC were alcohol abuse, arsenic treatment, and hepatitis B infection. In three cases, a genetic factor could not be excluded. Patients with ISC had significantly lower serum concentrations of transaminases and bilirubin at diagnosis. Compared with macronodular cirrhosis, bleeding varices were more frequent (57% vs. 22%) in ISC. Ten-year survivals in the ISC and the macronodular cirrhosis groups were 54% and 57%, respectively. CONCLUSIONS ISC represents a relatively stable burnt-out form of macronodular cirrhosis with an unusually high incidence of variceal bleeding. This could be explained by a superimposed insufficiency of the portal vascular supply.

Diagnosis and treatment of autoimmune hepatitis at age 65 and older

Aim:  To study features in older patients with autoimmune hepatitis, as this was considered mainly a disease of young females.

Alcohol, Levercirrose, En Stoornissen in Het Metabolisme Van De Geslachtshormonen

SummaryAbnormalities in the metabolism of sex hormones are frequently observed in cirrhotic patients, especially in chronic alcoholics. Signs of hypogonadism with’Curbed reproductive and endocrine gonadal functions are found in men as well as in women. Primary hypogonadism as well as hypothalamic-pituitary inhi-Uion seem to play a role. Primary gonadal insufficiency is the result of a direct toxic effect of ethanol and of acetaldehyde on the gonads with inhibition of L.H binding to the Leydig cells, with inhibition of the, Byrnes responsible for the formation of sex hormomones and with inhibition of the intratesticular activation of vitamin A. Hypothalamic-pituitary hypogonadism results from a direct toxic effect of ethanol as well.as from the increasing concentrations of oestrogens in Plasma. Men with alcoholic cirrhosis may also be Chracterized by signs of feminization, which mainly result from an increased peripheral conversion of androgens.In men who abstain from alcohol, a spontaneous recovery of fun...

Thyroid hormones and the hepatic handling of bilirubin: II. Effects of hypothyroidism and hyperthyroidism on the apparent maximal biliary secretion of bilirubin in the Wistar rat

This study was undertaken in the Wistar R/A Pfd rat to investigate the effects of hypothyroidism and of hyperthyroidism on the maximal biliary excretion (Tm) of bilirubin and on the concentration and composition of bilirubin in liver and plasma at the end of a bilirubin load. Hypothyroidism caused a cholestatic condition with a 50% decrease in bile flow and in bilirubin Tm, and with an increased proportion of conjugated bilirubin in liver and plasma. This was associated with an increased ratio of bilirubin diconjugates to monoconjugates in bile, liver, and plasma, which can be ascribed to the increased hepatic conjugation activity towards bilirubin and/or to the prolonged retention of bile pigments in the hepatocytes with increased conversion of monoconjugates to diconjugates. Cholestasis induced by hypothyroidism was further characterized by a decreased biliary output of unconjugated bilirubin. The latter phenomenon might represent an indirect effect related to a decreased output of bilirubin monoconjugates with impaired hydrolysis to unconjugated bilirubin; it might also reflect the cholestatic condition with decreased excretion of the unesterified bile pigment as such. Hyperthyroidism resulted in a 1.3-1.4-fold increase in bile flow. The maximal bilirubin concentration in bile decreased 1.3-1.4-fold, so that the apparent maximal bilirubin excretion rate remained unchanged at 115 nmol.min-1.100 g-1, as observed in untreated rats. Hyperthyroidism lowered the bilirubin UDP-glucuronosyltransferase activity, produced a decreased ratio of bilirubin di- to monoconjugates in bile and plasma, and a decreased ratio of conjugated to total bile pigment concentration in liver and in plasma. Similar findings are present in the heterozygous Gunn rat strain and in patients with hepatic bilirubin UDP-glucuronosyltransferase deficiency. We therefore propose the hyperthyroid rat as an experimental animal model of Gilberts syndrome.