bluuebunny/crossref_metadata_2025 huggingface dataset:
Cholestatic liver disease: pathophysiology and therapeutic options
Authors: Hofmann AF. , F. Hofmann Alan
Published: October 2002

Abstract: Cholestasis results from defective canalicular secretion of bile or obstruction to bile flow distal to the canaliculus. In early primary biliary cirrhosis, bile secretion continues, because of the secretory pressure of bile or because some ductules are not obstructed. With complete cholestasis, a bile acid deficiency occurs in the small intestinal lumen leading to lipid maldigestion and fat‐soluble vitamin malabsorption. Bacterial proliferation, bacterial translocation to lymph nodes and endotoxemia may also occur leading to an acute phase reaction. Retention of bile acids in the hepatocyte leads to apoptosis. Accumulation of bile acids in the systemic circulation leads to pruritus, and may contribute to endothelial injury in the lungs and kidney. Early attempts to mimic hepatic excretory function by hemoperfusion over adsorbent columns were unsuccessful for a variety of reasons. Extracorporeal dialysis against albumin offers promise of a realistic albeit partial simulation of hepatic excretory function.
Experiences with MARS liver support therapy in liver failure: analysis of 176 patients of the International MARS Registry
Authors: C Steiner , S. Mitzner , Steiner Christian , Mitzner Steffen
Published: October 2002

Abstract: Extracorporeal liver support using the MARS recently has shown remarkable results in several trials. This study aims to extend the basis for analyses by making available the worldwide data with help of an international registry. One hundred and seventy six patients were analysed, main indications are acute‐on‐chronic liver failure (56%), acute liver failure (22%), primary graft dysfunction (15%), liver failure post liver surgery (4%) and miscellaneous (3%). The predicted survival within the first group based on a mean MELD score of 30.4 pts. and a mean Child score of 12.6 pts. was quite limited. The data suggest an improved survival accompanied by significant improvements of hepatic encephalopathy, mean arterial pressure, serum bilirubin level, creatinine, urea, albumin, INR, ammonia and MELD score. The results are confirming observations of other trials before which have shown MARS therapy to be an effective and safe extracorporeal liver support in liver failure.
Economic evaluation of MARS – preliminary results on survival and quality of life
Authors: Hessel Franz P. , Mitzner Steffen R. , Rief Jana , Greß Stefan , Guellstorff Britta , Wasem Jürgen
Published: October 2002

Abstract: Objectives: The short‐term medical benefit of the liver dialysis system MARS in patients with severe acute liver disease has clearly been demonstrated. An economic analysis of MARS has not been presented previously. Objective of the study is to calculate the costs per life saved and life year gained and to measure health related quality of life in patients who survived acute liver failure. First results on survival and HRQL are presented here. Study design: Cost effectiveness and cost utility analysis of MARS are performed. All patients since 1993 with chronic liver failure (Bilirubin > 300 µmol/l) of the university hospital Rostock are included in the original sample (n = 141). Survival data are calculated. Surviving patients were contacted personally, thus quality of life data (EQ 5D and SF12) determined. Patients were compared in case control study design. In a later stage inpatient hospital costs, direct and indirect outpatients costs are included in the analysis. Preliminary results: MARS‐Patients show a higher survival: Kaplan‐Meier cumulative survival after 100 days: 0.59 after MARS, 0.39 without (P <0.05). There was no significant difference in health related quality of life (SF12 and EQ‐D). Calculations of quality adjusted life years (QALYs) result in 0.116 QALYs gained by treatment of one patient with MARS in one year. Discussion: First preliminary results suggest that 1 year after therapy MARS seems to have a positive effect concerning survival rate, survival time and QALYs gained. Final results of cost‐effectiveness and cost‐utility analysis will soon be presented.
Extracorporeal liver support by recirculating albumin dialysis: analysing the effect of the first clinically used generation of the MARSystem
Authors: Klammt S , Stange J , Mitzner SR , Peszynski P , Peters E , Liebe S. , Klammt S , Stange J , Mitzner S. R. , Peszynski P , Peters E , Liebe S
Published: October 2002

Abstract: Albumin dialysis with the MARSystem is used in many hospitals to support excretory hepatic function in acute or acute on chronic liver failure. Potential pathogenic albumin bound substances accumulated in excretory liver insufficiency can be removed from patients blood by dialysis against albumin solution. A specific membrane enables the selective transport of albumin bound metabolites to the albumin containing dialysate compartment, where the loaded transport albumin is cleared and regenerated at the same time by adsorption columns and a second dialyser. Between 1993 and 1995 different membranes, set‐ups and components in albumin dialysis were tested and led finally to the recirculating MARSystem with a modified polysulphone based membrane (P3/5S Gambro, Hechingen) and two adsorption columns (N350 and BR 350, ASAHI Medical Ltd.), which showed the best performance at this time. This first generation of MARSystems was used clinically between 1995 and 1998 with only minor changes in 15 patients with acute (n = 1) or acute deterioration of chronic liver disease in our department until the improved next generation of MARSystems has been available (MARS set and monitor, Teraklin AG, Rostock, Germany). Changes in blood tests pre/post during 95 single MARS treatments and in clinical status over treatment period were evaluated retrospectively.

Results: A significant decrease of albumin bound substances (average reduction during single MARS treatments: bilirubin −18%, bile acids −43.7%) as well as of water soluble metabolites (creatinine −32%, urea −31%) was observed. During extracorporeal therapy also a significant drop in platelets (− 15.4%) and a prolongation of activated prothrombin time (− 21%) was documented, whereas haemoglobin, WBC, electrolytes as well as transaminases and albumin were not affected significantly. Conclusion: Albumin dialysis with the first generation of MARS enables the removal of albumin bound and water soluble toxins. Unwanted side‐effects and changes in laboratory tests are comparable to conventional haemodialysis (drop of platelets and prolongation of coagulation tests). The elimination of albumin bound and water soluble substances was accompanied by an improvement of clinical status.
Amino acid dysbalance in liver failure is favourably influenced by recirculating albumin dialysis (MARS)
Authors: Loock J , Mitzner SR , Peters E , Schmidt R , Stange J. , Loock J. , Mitzner S. R. , Peters E. , Schmidt R. , Stange J.
Published: October 2002

Abstract: Introduction: Dysbalance between branched chain (BCAA) and aromatic amino acids (AAA), which can be quantified by a low Fischer's Index (ΣBCAA/ΣAAA), as well as elevated levels of free tryptophan in plasma are common in hepatic failure and may contribute to the development of hepatic encephalopathy.

Aim: To evaluate the influence of a new extracorporeal detoxification system for liver failure (Molecular Adsorbents Recirculating System, MARS®, i.e. dialysis against a recirculating albumin solution cleaned online by charcoal and an anion exchange resin) on plasma tryptophan and Fischer's Index.

Methods: Plasma samples were taken before, during and after MARS treatments (n = 11, mean blood flow 135 ml/min, mean dialysate flow 120 ml/min, high flux polysulfone membrane). Simultaneous to blood sampling, aliquots of the albumin dialysate were taken between the elements of the dialysate circuit.

Results: Fischer's Index in systemic blood increased during MARS by 24% (from 1.44 to 1.79, P < 0.001; mean treatment duration, 5.5 h). Systemic tryptophan level was significantly reduced at the same time (−25%, n = 8). Amino acid removal rates from plasma during a single dialyser passage ranged from 10 to 53%. In particular, AAA were preferentially removed (42–44% throughout treatment), while BCAA removal was 28–46% initially and later declined to 24–28%. A maximum concentration gradient between plasma and dialysate was maintained for the AAA throughout treatment through their apparently complete removal by the charcoal adsorber. Conversely, BCAA removal at both adsorbers was only minor. As a result, Fischer's Index showed a significant increase in the processed plasma, which became even more pronounced with increasing treatment duration.

Conclusions: MARS enables an elevation of a pathologically decreased Fischer's Index as well as a reduction of systemic tryptophan levels in patients with liver failure. The effects of MARS on plasma amino acid dysbalance may contribute to an improvement of hepatic encephalopathy.
Albumin dialysis: single pass vs. recirculation (MARS)
Authors: Peszynski P , Klammt S , Peters E , Mitzner S , Stange J , Schmidt R. , Peszynski P. , Klammt S. , Peters E. , Mitzner S. , Stange J. , Schmidt R.
Published: October 2002

Abstract: The single pass albumin dialysis (SPAD) was reported to be an alternative to the Molecular Adsorbent Recirculating System (MARS) for the effective removal of protein bound substances in liver failure. Three SPAD experiments using different albumin concentrations and dialysate flow rates were performed. In each experiment, 1000 ml human donor plasma, spiked with 250 mg unconjugated bilirubin, 200 mg sulfobromophthalein (BSP) and 115 mg glycocholic acid (N‐[3α,7α,12α‐trihydroxy‐24‐oxycholan‐24‐yl]glycine) – a conjugated bile acid (BA), circulated in a closed loop with 150 ml/min and was dialysed against albumin solution. These substances are bound to the different binding sites of albumin and have different association constants. For the comparison, the standard MARS experiment was performed using the same plasma flow rate of 150 ml/min. Moreover, the clearances of bilirubin for MARS and SPAD during clinical treatments were calculated using own data and those reported by Seige, Kreymann, Jeschke, et al. in Transplant Proc 1999; 31: 1371–5. The concentrations of bilirubin, BSP and BA were measured in plasma and dialysate and for these substances clearances (Cl) were calculated. It is known that the elimination rate of bilirubin is not very high during albumin dialysis in comparison to other substances, like bile acids, due to the high association constant. An increase of albumin concentration or the flow rate improved the efficacy but also raised the costs substantially. In this study, we have shown that MARS is the more effective kind of albumin dialysis for the important substances like bile acids. By SPAD an improvement of efficacy can be reached only by dramatic increase of the costs. Also, the earlier experiments showed that MARS is safer because of the removal of the stabilizers, which are normally included in the commercial albumin solutions.
Molecular Adsorbent Recirculating System: clinical experience in patients with liver failure based on hepatitis B in China
Authors: Chen S , Zhang L , Shi Y , Yang X , Wang M. , Chen Shibin , Zhang Lunli , Shi Yufei , Yang Xiaolan , Wang Minmin
Published: October 2002

Abstract: The aim of this study is to evaluate the effect of treatment with the Molecular Adsorbent Recirculating System (MARS) on liver failure based on HBV. In 25 patients (median age, 36.3 years, range, 22–67 years, bilirubin level > 255 µmol/l) admitted with liver failure based on HBV, the 6–8h MARS intermittent treatments were performed without any adverse events, A significant decrease in bilirubin, ammonia and urea levels were observed (P < 0.05). All patients achieved a remarkable neurologic recovery, particularly 2 HE‐III and 3 HE‐IVpatients regained normal consciousness, respectively. The survival rate for the patients whose treatments kept to the MARS art strategy was 76.9% (10/13), while the others only had the survival rate of 16.7% (2/12) due to their giving up sequential MARS treatments after the first time. The rebounding rate of the bilirubin level in the patients after a single MARS treatment was significantly lower than that of patients, who underwent a single plasma‐exchange treatment (P < 0.01). It is concluded that MARS method can contribute to the optimistic treatment of liver failure patients based on HBV which being the major epidemic liver disease in China.
The Molecular Adsorbent Recirculating System in patients with severe liver failure: clinical results at the K.U. Leuven
Authors: Wilmer A , Nevens F , Evenepoel P , Hermans G , Fevery J. , Wilmer Alexander , Nevens Frederik , Evenepoel Pieter , Hermans Greet , Fevery Johan
Published: October 2002

Background: The Molecular Adsorbent Recirculating System (MARS) is a novel extracorporeal technique for liver support. We report the clinical results in the first 13 patients with severe liver failure treated at our institution. Methods: Patients with acute or acute on chronic liver failure of various aetiologies were treated with varying numbers of MARS sessions of six hours duration. Results: Mean APACHE II score was 18. In general, patients with multiple organ failure faired poorly even with MARS treatment. Five patients (38%) survived the hospitalisation. Eight patients (62%) fulfilled criteria for UNOS type I or 2 A status. Two of these patients survived. Five patients had a UNOS 2B status and three survived. In proportion, patients with severe itch, patients with primary non‐function and those where MARS was used as a bridge to transplantation seemed to profit most from the treatment. The median reduction in bilirubin concentrations after the treatment period was −28.2%. In survivors, the median reduction was −37.7% and in patients who died was −15.9%. The median encephalopathy score improved from 1.7 to 0.5. Conclusion: The molecular adsorbent recycling system (MARS) might be lifesaving in patients with severe liver failure of different aetiologies.
Application of Molecular Adsorbent Recirculating System® in patients with severe liver failure after hepatic resection or transplantation: initial single‐centre experiences
Authors: Kellersmann R , Gassel H‐J , Bühler C , Thiede A , Timmermann W. , Kellersmann Richard , Gassel Heinz‐Jochen , Bühler Christoph , Thiede Arnulf , Timmermann Wolfgang
Published: October 2002

Abstract: Acute liver failure after hepatic surgery is still plaqued with high mortality rate. Recently, a liver dialysis system (MARS®) that allows detoxification of albumin‐bound substances and may hereby support liver regeneration and patient's recovery has been developed. In the present study, we report our experiences with MARS® dialysis in patients with liver failure after hepatic resection or transplantation. Between September 1999 and January 2001, five patients were treated with MARS® (2–5 courses). Though beneficial effects such as improvement of encephalopathy and renal function as well as reduced bilirubin levels were recorded during MARS® therapy, only one patient survived. Neither significant technical problems nor adverse effects occurred by using MARS® dialysis. We conclude that in surgical patients, acute liver failure is usually part of a complicated clinical course affecting multipleorgan systems. Thus, it is difficult to determine the specific influence of MARS® on patient's outcome. However, beneficial effects observed in our patients justify its continuous use and may stimulate further evaluation in controlled studies with surgical patients.
First clinical experience with Molecular Adsorbent Recirculating System (MARS) in six patients with severe acute on chronic liver failure
Authors: Mullhaupt B , Kullak‐Ublick GA , Ambühl P , Maggiorini M , Stocker R , Kadry Z , Clavien PA , Renner EL. , Mullhaupt B. , Kullak‐Ublick G. A. , Ambühl P. , Maggiorini M. , Stocker R. , Kadry Z. , Clavien P. A. , Renner E. L.
Published: October 2002

Abstract:Despite recent advances in general supportive care, the mortality rate of patients with severe liver insufficiency remains high. Recently a new artificial liver support system MARS has been used for selective removal of albumin‐bound toxins.Aim:To assess the safety and efficacy of MARS treatment in patients with acute on chronic liver disease (n = 5) or liver failure after extended hepatic resection (n = 1).Design/Patients:Six patients, aged 34–58 years, with severe liver insufficiency (mean MELD‐score 31 (range 24–35)) were treated one to 16 times with the MARS system. At baseline three patients were intubated, three were encephalopathic (HE) and three had multifactorial kidney failure requiring kidney replacement therapy.Results and Conclusion:In all the patients MARS treatment significantly reduced the serum bilirubin levels. In three patients encephalopathy improved. In two patients the extracorporeal treatment precipitated a disseminated intravascular coagulation with clinically significant bleeding. Bridging to liver transplantation was possible in one patient, the other five patients died 30 days (2–74 days) after starting MARS therapy. Our case series shows that MARS treatment in general can be safely performed in patients with severe liver disease. However, in patients with an activated clotting system severe bleeding complication can be triggered and MARS treatment should be used very cautiously in these situations. MARS seems to be a promising new treatment option for patients with acute on chronic liver failure. However, carefully conducted randomized controlled trials are necessary to define its potential place in the treatment of patients with severe liver disease.
Emerging indications for MARS® dialysis
Authors: Schachschal G , Morgera S , Küpferling S , Neumayer HH , Lochs H , Schmidt HH‐J , Schachschal G. , Morgera S. , Küpferling S. , Neumayer H. H , Lochs H. , Schmidt H. H.‐J
Published: October 2002

Abstract:MARS® stands for Molecular Adsorbent Recirculating System and represents an interesting option in treating patients with liver disease. There is still little known about the best time point of initiating this treatment and the exact selection criteria for patients who may benefit from this therapy. The list of potential applications using this procedure is expanding. We report on the experience in seven patients being treated with MARS® dialysis for chronic cholestatic liver disease and acute on chronic liver failure. From August 2000 to October 2001 seven patients received 27 MARS® treatments in our clinic, ranging from 2 to 12 treatments per subject. Presented cases were diagnosed as steatohepatitis because of alcoholism (n = 3), vanishing bile duct disease (n = 1), metabolic liver disease (n = 1), primary biliary cirrhosis (n = 1) and drug‐induced hepatitis (n = 1). Based on this experience, we discuss the ongoing questions of various indications and the decision to initiate MARS® dialysis.
Modular extracorporeal life support for multiorgan failure patients
Authors: Peek GJ , Killer HM , Sosnowski MA , Firmin RK , Peek Giles J. , Killer Hilliary M. , Sosnowski Marcin A. , Firmin Richard K.
Published: October 2002

Abstract: Adults receiving respiratory Extracorporeal Membrane Oxygenation (ECMO) have 66% survival. Nonsurvivors develop multisystem organ failure (MSOF). Once hepatic failure develops, death usually follows shortly. Serum bilirubin > 300 μmol/l predicted death with 87.8% sensitivity and 90.3% specificity in 41 adults who received ECMO in our institution during 1998 and 1999. No patients survive with a peak bilirubin > 400 μmol/l. The Molecular Adsorbent Recirculating System (MARS) is a cell‐free extracorporeal liver support device; we hypothesized that using MARS in adult respiratory ECMO patients with a bilirubin >300 μmol/l could improve survival in MSOF. The MARS was used in five such patients aged 19–56 who developed liver failure secondary to a respiratory illness. Mean peak bilirubin was 529 μmol/l and the lowest peak bilirubin was 436 μmol/l. Patients received between 1 and 8 MARS treatments, mean reduction in serum bilirubin for each patient ranging between 30 and 162 μmol/l. Two of five patients survived (40%), survivors showing the greatest reduction in serum bilirubin in response to MARS. All patients would have been expected to die according to our previous experience. We believe that MARS may prove a useful therapy for patients with MSOF.
Extracorporal albumin dialysis (MARS) improves cholestasis and normalizes low apo A‐I levels in a patient with benign recurrent intrahepatic cholestasis (BRIC)
Authors: Sturm E , Franssen CFM , Gouw A , Staels B , Boverhof R , De Knegt RJ , Stellaard F , Bijleveld CMA , Kuipers F. , Sturm E. , Franssen C. F. M , Gouw A , Staels B , Boverhof R , De Knegt R. J , Stellaard F , Bijleveld C. M. A , Kuipers F
Published: October 2002

Abstract: The familial cholestatic diseases Benign Recurrent Intrahepatic Cholestasis (BRIC) and Progessive Familial Intrahepatic Cholestasis type 1 (PFIC1) are characterized by intermittent or permanently elevated plasma bile salt levels, therapy‐resistant extreme pruritus and peculiar biochemical abnormalities including low apolipoprotein apo A‐I. Previously, symptomatic improvement has been demonstrated in BRIC patients after extracorporal albumin dialysis (MARS). We hypothesized that MARS improves cholestasis, induces changes in the bile salt profile and normalizes apo A‐I serum levels in BRIC. A 17‐year‐old‐female patient with BRIC experienced an episode of cholestasis lasting for more than 6 months with extreme pruritus and diarrhoea not responding to standard therapy. During a period of five days the patient was treated 3 × 8 h with MARS. The procedures were well tolerated and resulted in reduction of plasma bile salts by 58%. The plasma bile salt profile changed into a more hydrophilic composition after MARS. Diarrhoea discontinued and the pruritus improved significantly from 9 to 4 on a subjective scale. These effects lasted 4 months until a relapse occurred. Low plasma apo A‐I levels (0.52 g/l) normalized after MARS (0.98 g/l). The procedures were well tolerated. Fatigue was noted as the only transient side‐effect. In conclusion, MARS may induce a long‐term symptomatic improvement and decrease of cholestatic markers in BRIC. Further studies evaluating efficacy and mechanism of MARS in patients with BRIC are needed.
MARS procedure as a bridge to combined liver–kidney transplantation in severe chromium–copper acute intoxication: a paediatric case report
Authors: Prokurat S , Grenda R , Lipowski D , Kaliciński P , Migdal M. , Prokurat S , Grenda R , Lipowski D , Kaliciński P , Migdal M
Published: October 2002

Abstract: We describe a case of multi‐organ failure (liver–kidney insufficiency and brain oedema) caused by accidental, acute intoxication with a chromium and copper‐containing substance, as an example of the introduction of the new extracorporeal procedure MARS (molecular adsorbents recirculating system) in a girl 3.5 years old.
Clinicopathological analysis of early gastric cancer with solitary lymph node metastasis
Authors: Arai K , Iwasaki Y , Takahashi T
Published: October 2002

Background

The sentinel node concept has not yet been established in gastric cancer.

Methods

Fifty-four patients with early gastric cancer who had only one lymph node metastasis were regarded retrospectively as patients with a possible sentinel node metastasis, and the morphological features of these nodes were assessed. The level I nodes in seven patients with a possible skip metastasis at routine haematoxylin and eosin staining were re-examined using cytokeratin (CK) immunostaining.

Results

The shape of the gastric cancer lesion could be examined in 53 of the patients; more than one-third (20 of 53) were microfocal type. Concerning the intranodal cancer foci, the marginal sinus type was found in 32 affected nodes, medullary sinus type in 14 and mixed type in seven. Forty-three per cent of suspected sentinel nodes were the largest in size among all nodes from the station. CK immunostaining of seven non-metastatic nodes with haematoxylin and eosin revealed that three were CK positive.

Conclusion

These findings suggest that possible sentinel nodes detected by conventional means may not always be primary portions of any metastasis. Adoption of sentinel node biopsy in gastric cancer must await the development of improved procedures for diagnosis during surgery.
Early postoperative compensatory anti-inflammatory response syndrome is associated with septic complications after major surgical trauma in patients with cancer
Authors: Mokart D , Capo C , Blache J L , Delpero J R , Houvenaeghel G , Martin C , Mege J L
Published: October 2002

Background

Patients who undergo major surgery for cancer are at high risk of postoperative infection. Postoperative immunosuppression may be due to dysregulation of cytokine production. The aim of this study was to investigate the association between changes in serum proinflammatory and anti-inflammatory cytokine concentrations and postoperative septic complications after major surgery.

Methods

Serial blood samples were collected from 30 consecutive patients for determination of serum cytokine levels. Healthy volunteers were used as the control group.

Results

Eleven patients developed no complications (group 1), 14 developed sepsis or severe sepsis (group 2), and five developed septic shock (group 3). On day 1 the patients in groups 2 and 3 had significantly higher levels of interleukin (IL) 6 than those in group 1. IL-6 levels remained high until day 5. Tumour necrosis factor (TNF), IL-1, interferon (IFN) γ and IL-12 levels were not affected by surgical trauma or by the occurrence of septic complications. After operation the circulating IL-1 receptor antagonist (IL-1ra) concentration was increased in all groups, but patients in group 3 had significantly higher levels of IL-1ra than those in group 1. IL-1ra levels correlated with IL-6 levels. The pattern of IL-10 levels was similar to that of IL-1ra levels.

Conclusion

Serum concentrations of proinflammatory cytokines (TNF, IL-1, IFN-γ and IL-12) were not affected by operation or the occurrence of septic complications. The postoperative increase in IL-6 concentration was associated with septic morbidity, while raised IL-1ra concentration was associated with postoperative septic shock.
Value of palliative resection in gastric cancer
Authors: Hartgrink H H , Putter H , Klein Kranenbarg E , Bonenkamp J J , van de Velde C J H
Published: October 2002

Background

Western patients with gastric cancer often present with incurable disease. The role of palliative surgical resection is still debatable. Non-curatively treated patients from the Dutch Gastric Cancer Trial were studied to define more accurately which patients might benefit from palliative resection.

Methods

In the Dutch Gastric Cancer Trial 285 (26 per cent) of the randomized patients were found to have incurable tumours at laparotomy. Four signs of incurability were noted: irresectable tumour (T+), hepatic metastasis (H+), peritoneal metastasis (P+) and distant lymph node metastasis (N4+). Patients had either an explorative laparotomy, a gastroenterostomy, or a resection (partial or total). In the analysis, particular attention was paid to the prognostic factors of age, number of metastatic features, and a combination of these.

Results

Overall survival time was greater if a resection was performed (8·1 versus 5·4 months; P < 0·001). For patients aged over 70 years there was still a survival advantage of about 3 months if resection was carried out. Morbidity and perioperative mortality rates in this older age group were, however, high (50 and 20 per cent respectively). For patients with one metastatic site a resection was of significant benefit (survival 10·5 versus 6·7 months; P = 0·034). For patients with two or more metastatic sites resection had no significant survival advantage (5·7 versus 4·6 months; P = 0·084). Combination of these factors indicates that patients aged less than 70 years with one metastatic site will benefit significantly from a palliative resection, in contrast to other combinations of factors.

Conclusion

Age as well as the number of metastatic sites should be taken into account when a palliative resection is considered. Palliative resection may be beneficial for patients under 70 years of age if the tumour load is restricted to one metastatic site.
Management of popliteal aneurysm
Authors: Galland R B , Magee T R
Published: October 2002

Background

The best management of patients with a popliteal aneurysm has yet to be established. This paper describes an experience of managing both patent and acutely thrombosed popliteal aneurysms.

Methods

A prospective study was carried out of all patients who presented with a popliteal aneurysm from January 1988 to December 2001. Since 1993 asymptomatic popliteal aneurysms less than 3 cm in diameter without distortion have been managed conservatively. Ultrasonography was repeated at 6-month intervals. These results were compared with conservative management of popliteal aneurysms greater than 3 cm in diameter in patients who declined or were unfit for operation, and with the outcome of patients who underwent elective bypass of a popliteal aneurysm.

Results

Fifty-eight patients (two women) presented with 92 popliteal aneurysms. Some 39 had a thrombosed aneurysm and these patients were significantly more likely to have bilateral aneurysms (P < 0·001). Of patent popliteal aneurysms managed conservatively, none below 3 cm in diameter thrombosed. The risk of postoperative complications was greater after repair of a thrombosed than a patent aneurysm (P < 0·005). Preoperative lysis for a thrombosed popliteal aneurysm was associated with more complications than operation and on-table lysis (P < 0·05).

Conclusion

Careful monitoring of asymptomatic popliteal aneurysms less than 3 cm in diameter is safe. Preoperative lysis is associated with increased risks compared with operation alone in patients with a thrombosed popliteal aneurysm.
p53, DCC and thymidylate synthase as predictors of survival after resection of hepatic metastases from colorectal cancer
Authors: Saw R P M , Koorey D , Painter D , Gallagher P J , Solomon M J
Published: October 2002

Background

Hepatic metastasis from colorectal cancer is a common problem. Hepatic resection offers the only chance of cure. Prognosis of patients following hepatic resection is currently based on clinicopathological factors (of both the primary cancer and the hepatic metastasis), which do not accurately predict the subsequent behaviour of the tumour. The aim of this study was to evaluate three molecular genetic markers – p53, DCC (deleted in colonic cancer) and thymidylate synthase – in both the primary colorectal tumour and the resected hepatic metastases, and to determine their correlation, if any, with survival in patients with resected hepatic metastases from colorectal cancer.

Methods

Sixty-three patients with hepatic metastases and 40 corresponding colorectal primary tumours were studied using immunohistochemical staining for p53, DCC and thymidylate synthase, as well as p53 gene mutations using polymerase chain reaction–single-stranded conformational polymorphism (PCR-SSCP) analysis. The results were correlated with survival.

Results

There was no correlation between p53, DCC or thymidylate synthase immunohistochemical staining, or between p53 PCR-SSCP analysis, and survival for either hepatic metastases or the colorectal primary tumour.

Conclusion

Prediction of prognosis in patients having resection of hepatic metastases from colorectal cancer continues to be problematic. Other genetic markers or combination of markers need to be evaluated.
Ranitidine as adjuvant treatment in colorectal cancer
Authors: Nielsen H J , Christensen I J , Moesgaard F , Kehlet H
Published: October 2002

Background

Results from short-term studies of histamine type 2 (H2) receptor antagonists on survival of patients with solid tumours are debatable. In this study the efficacy of the H2–receptor antagonist ranitidine on long-term survival of patients with colorectal cancer was evaluated.

Methods

Patients scheduled for elective resection of primary tumours were consecutively included in a randomized double-blind placebo-controlled clinical study designed to evaluate the effect of ranitidine on survival. Before skin incision ranitidine 100 mg or placebo was given intravenously twice daily followed by oral ranitidine 150 mg or placebo twice daily for 5 years. Adjuvant cytotoxic or radiation therapy was not given. An observer-blinded interim analysis performed after 40 months showed that there was no effect of ranitidine on overall survival, and the study was discontinued in accordance with the protocol. The patient cohort has been followed continuously without loss of any patient, and a final statistical analysis was performed on an intention-to-treat basis after more than 5 years; this included a subgroup analysis of perioperative blood transfusion and postoperative infectious complications.

Results

The median observation period of the 740 patients included was 6·8 (range 5·4–7·9) years. A univariate analysis of all 740 patients and of the subgroup of 560 who underwent curative resection showed no significant effect of ranitidine on survival. Furthermore, ranitidine had no survival benefit in curatively resected patients who received a perioperative blood transfusion (n = 358), but it improved the survival of non-transfused patients (n = 202; hazard ratio (HR) 0·6 (95 per cent confidence interval (c.i.) 0·4 to 0·9), P = 0·02) and of non-transfused patients who did not develop postoperative infectious complications (n = 170; HR 0·6 (95 per cent c.i. 0·4 to 0·9), P = 0·01). In multivariate analysis of patients who had a curative resection, including Dukes' stage, age, gender, tumour location, blood transfusion, postoperative infectious complications and treatment, ranitidine still had an independent, beneficial effect on survival (HR 0·6 (95 per cent c.i. 0·4 to 1·0), P = 0·04) within the subgroup of patients who did not receive perioperative blood transfusion and did not develop postoperative infectious complications.

Conclusion

Ranitidine may prolong the survival of patients who undergo curative resection of colorectal cancer and who do not receive perioperative blood transfusion and do not develop postoperative infectious complications.
Granulocyte colony-stimulating factor but not peritoneal lavage increases survival rate after experimental abdominal contamination and infection
Authors: Bauhofer A , Stinner B , Kohlert F , Reckzeh B , Lorenz W , Celik I
Published: October 2002

Background

The value of peritoneal lavage for intra-abdominal contamination and infection has never been proven scientifically. In contrast, the stimulation of host defence mechanisms with cytokines such as granulocyte colony-stimulating factor (G-CSF) has appeared promising in recent clinical trials.

Methods

Clinic modelling randomized trials (CMRTs), which model the complexity of the clinical reality, were used in rats in which peritoneal contamination and infection (PCI) was produced with human stool bacteria. The following groups were compared: trial 1, intraoperative peritoneal lavage with saline versus taurolin (18 rats per group); trial 2, no lavage versus saline lavage versus saline lavage plus subcutaneous administration of G-CSF (18 rats per group); trial 3, lavage with saline versus no lavage (30 rats per group). The primary endpoint was mortality at 120 h. Secondary endpoints were the phagocytic activity of granulocytes, and systemic and peritoneal cytokine levels.

Results

In trial 1 lavage with taurolin was not superior to that with saline (five of 18 versus eight of 18 animals survived; P = 0·32). In trial 2, six of 18 animals having no lavage and three of 18 receiving saline lavage survived. The combination of lavage and G-CSF increased the number of animals surviving to 11 of 18 (P < 0·05). Lavage combined with G-CSF stimulated granulocyte phagocytic activity (P < 0·01) and reduced the levels of interleukin (IL) 6 (P < 0·01) and tumour necrosis factor α (P < 0·05) in peritoneal fluid, as well as plasma levels of IL-6 (P < 0·05) and IL-10 (P < 0·01). In trial 3, survival was not significantly different in animals having lavage (14 of 30) and no lavage (19 of 30) (P = 0·14).

Conclusion

In these CMRTs of intra-abdominal contamination and infection, peritoneal lavage was not beneficial, but when lavage was combined with subcutaneous administration of G-CSF mortality was reduced and the local and systemic cytokine response was downgraded. Results from these CMRTs were used directly to define the trial conditions of a randomized clinical trial with G-CSF. Peritoneal lavage is not recommended.
Peritoneal response to pneumoperitoneum and laparoscopic surgery
Authors: Bergström M , Ivarsson M-L , Holmdahl L
Published: October 2002

Background

It is generally believed that laparoscopic surgery inflicts less trauma to the peritoneum than open surgery. Local peritoneal fibrinolysis is a critical factor in adhesion development. The objective was to investigate fibrinolytic changes in the peritoneum during laparoscopic and open surgery.

Methods

At laparotomy (n = 10) peritoneal biopsies were taken at opening of the abdomen and just before closure. At laparoscopy (n = 12) opening peritoneal biopsies were taken after carbon dioxide insufflation, and closure biopsies just before exsufflation. Tissue concentrations of tissue-type plasminogen activator (tPA), plasminogen activator inhibitor type 1 (PAI-1) and the resulting tPA activity were assayed.

Results

Concentrations of tPA in peritoneal tissue declined during operation in both groups, but significantly so only in the laparotomy group (−53 per cent; P = 0·01). PAI-1 levels were higher in opening biopsies from the laparoscopy group (P = 0·004). There was an increase in PAI-1 concentration during laparotomy, but not during laparoscopy. At the end of the operation, there was no difference between the groups. The resulting tPA activity did not differ between groups at opening or closure. In both groups there was a significant decline during operation (laparotomy: −59 per cent, P = 0·02; laparoscopy: −63 per cent, P = 0·01).

Conclusion

These findings indicate that the peritoneal response to open and laparoscopic surgery is similar. The initial rise in peritoneal PAI-1 concentration during laparoscopy suggests an adverse effect of carbon dioxide insufflation, which might affect peritoneal repair.
Apoptosis in Barrett's oesophagus following antireflux surgery
Authors: Chen L Q , Hu C Y , Der Sarkissian S , Ferraro P , Pera M , deBlois D , Gaboury L , Duranceau A C
Published: October 2002

Background

Intestinal metaplasia persists in Barrett's mucosa despite control of reflux. Tissue homeostasis is maintained by the balance between apoptosis and proliferation. There is an unexplained temporary increase in proliferation in patients with Barrett's mucosa after antireflux surgery, and the long-term effect of any therapy in altering this balance remains unclear. The aim of this study was to assess apoptosis in Barrett's oesophagus following antireflux surgery.

Methods

Apoptosis was evaluated in endoscopic biopsy specimens from 19 patients with Barrett's oesophagus 4 years after Collis–Nissen gastroplasty using an in situ terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate–biotin nick end labelling (TUNEL) method.

Results

Intestinal metaplasia had a lower apoptosis index than gastric metaplasia (0·27 versus 2·14 per cent; P < 0·001). After operation there was a steady increase of apoptosis in intestinal metaplasia over time (from 0·23 per cent before operation to 0·42 per cent within 2 years and to 0·59 per cent 4 years after operation; P = 0·015). Patients with persistent acid exposure did not show any increase in apoptosis in comparison with patients without acid exposure (0·41 versus 0·59 per cent; P = 0·91).

Conclusion

Apoptosis is less in intestinal metaplasia than in gastric metaplasia, although there is an increase after antireflux surgery. Persistent acid reflux may predispose to malignancy.
Salvage abdominoperineal resection in anal epidermoid cancer
Authors: Nilsson P J , Svensson C , Goldman S , Glimelius B
Published: October 2002

Background

In the management of isolated locoregional failure after (chemo)radiation therapy for anal epidermoid cancer, salvage abdominoperineal resection (APR) is the treatment of choice. The results of a 15-year consecutive population-based series are reviewed.

Methods

Details of all patients with anal epidermoid cancer treated from 1985 to 2000 in the Stockholm Health Care Region were recorded prospectively. Among 308 patients with biopsy-proven anal epidermoid cancer, there have been 39 isolated locoregional failures after sphincter-preserving therapy. Thirty-five patients have undergone salvage APR. The medical records of these 35 patients were reviewed retrospectively with regard to surgical and oncological results.

Results

There were no postoperative deaths. There was considerable morbidity related to the perineal wound, with postoperative perineal infections in 13 patients and delayed healing beyond 3 months in 23 patients. Complications unrelated to the perineal wound were found in 13 patients. The crude 5-year survival rate for the 35 patients was 52 per cent (median follow-up 33 months). Patients with persistent disease fared significantly worse than those with locoregional recurrence (crude 5-year survival rate 33 versus 82 per cent; P < 0·05, log rank test).

Conclusion

Salvage APR in anal epidermoid cancer is associated with a high complication rate but may result in long-term survival.
Evaluation of axillary lymph nodes using touch imprint cytology and immunohistochemistry
Authors: Salem A A , Douglas-Jones A G , Sweetland H M , Newcombe R G , Mansel R E
Published: October 2002

Background

The success of sentinel node biopsy in determining axillary lymph node status necessitates an accurate and rapid method for intraoperative examination of the nodes. The aim was to determine the feasibility and accuracy of immunohistochemistry (IHC) of touch imprints in detecting axillary nodal metastases intraoperatively.

Methods

Some 344 axillary nodes from 30 patients with early breast cancer were bisected, imprinted and subjected to IHC. Results were compared with those of routine haematoxylin and eosin examination of the same nodes.

Results

Using IHC, 29 nodes from nine patients were positive for metastases. Using haematoxylin and eosin, 28 nodes from eight patients were positive. On a patient basis, the sensitivities of IHC and haematoxylin and eosin were 100 and 88·9 per cent, and negative predictive values (NPVs) were 100 and 95·5 per cent, respectively. On a node basis, the sensitivities were 96·7 and 93·3 per cent, and NPVs were 99·7 and 99·3 per cent, respectively. There were no false positives. The results were obtained within 30–45 min, depending on the number of nodes examined.

Conclusion

IHC of touch imprints can provide a fast and sensitive method for detecting metastases in axillary nodes during breast cancer surgery.
Clinical impact of false-negative sentinel node biopsy in primary breast cancer
Authors: Nano M T , Kollias J , Farshid G , Gill P G , Bochner M
Published: October 2002

Background

The aim was to assess the false-negative sentinel node biopsy rate in women with early breast cancer and its implications in patient treatment.

Methods

Between January 1995 and March 2001, 328 consecutive patients with clinically lymph node-negative primary operable breast cancer underwent lymphatic mapping and sentinel node biopsy using a combination of preoperative lymphoscintigraphy and/or blue dye. All underwent immediate axillary dissection. The intraoperative success rate in sentinel node identification, false-negative rate, predictive value of negative sentinel node status and overall accuracy were assessed. The clinical features and primary tumour characteristics for each false-negative case were reviewed.

Results

The sentinel node was identified in 285 (86·9 per cent) of 328 women. The false-negative rate was 7·9 per cent (eight of 101). Most members of the breast multidisciplinary team would have instituted adjuvant systemic therapy for six false-negative cases based on clinical features and primary tumour histology. In all, only two (0·7 per cent) of 285 women who had sentinel node biopsy may have had their management and survival prospects potentially jeopardized owing to a false-negative sentinel node.

Conclusion

The results of this study suggest that the clinical impact of a false-negative sentinel node is low.
Model for experimental revascularized laryngeal allotransplantation
Authors: Birchall M A , Bailey M , Barker E V , Rothkötter H-J , Otto K , Macchiarini P
Published: October 2002

Background

Although a human laryngeal transplant has been undertaken successfully, important questions remain that require a suitable animal model.

Methods

A pig model for allotransplantation has been developed. Organ perfusion was studied in nine animals before four transplants were performed in congenic (unrecovered) animals and eight in unmatched (recovered) animals. Larynges were regularly examined endoscopically until death at 14 days. Immunosuppression included the use of tacrolimus. Revascularization was achieved by anastomosing the donor right cervical vascular tree to the recipient common carotid. In recovered animals, four allografts were placed orthotopically and four heterotopically.

Results

The pig larynx was perfused adequately via the right cervical vascular tree and congenic grafts were well tolerated. Of eight allografts, seven were well tolerated and remained healthy for the duration of the study (14 days). One allograft became infected between days 4 and 7 after operation. Median operating time was 6 h, with a median cold ischaemia time of 3 h.

Conclusion

Revascularized allotransplants of the larynx can be undertaken reliably in pigs and this provides a preclinical model for studies of laryngeal transplantation.
Randomized study of the effectiveness of closing laparoscopic trocar wounds with octylcyanoacrylate, adhesive papertape or poliglecaprone
Authors: Maartense S , Bemelman W A , Dunker M S , de Lint C , Pierik E G J M , Busch O R C , Gouma D J
Published: October 2002

Background

Several methods for skin closure are used, i.e. sutures, adhesive papertape and tissue adhesives. Little is known about the efficacy of these techniques in laparoscopic surgery. This study was performed to analyse the efficacy of octylcyanoacrylate, a new tissue adhesive, adhesive papertape and poliglecaprone for wound closure in laparoscopy.

Methods

From May 2000 to September 2001, 140 patients were included in a prospective randomized trial. Wounds were closed with octylcyanoacrylate (n = 48), adhesive papertape (n = 42) or poliglecaprone (n = 50). Closing time, wound infection, cosmetic results and costs were evaluated. A time–motion analysis was also performed.

Results

The patients in the three groups were well matched for age, gender and body mass index. Closing times per wound were 26, 33 and 65 s respectively for adhesive papertape, octylcyanoacrylate and poliglecaprone (P < 0·001). Cosmetic results, as scored by the patients, were no different. The number of actions required to close each wound was 5·7, 8·3 and 21·0 for octylcyanoacrylate, adhesive papertape (P = 0·05 versus octylcyanoacrylate) and poliglecaprone (P < 0·01 versus octylcyanoacrylate and adhesive papertape) respectively. Octylcyanoacrylate was significantly more expensive than poliglecaprone and adhesive papertape.

Conclusion

Closure with adhesive papertape was the fastest method. The smallest number of actions required to close a wound was with octylcyanoacrylate. Adhesive papertape was the most cost-effective.