Cryoablation of colorectal liver metastases: minimally invasive tumour control.

BACKGROUND: Freezing is used for in situ destruction (ablation) of liver tumours not eligible for resection. The procedure is typically done during laparotomy. The objective of this report was to study tumour control at the site of freezing and a minimally invasive approach to cryoablation of colorectal liver metastases. METHODS: A prospective study of 19 patients was conducted between 1999 and 2003. Twenty-five tumours were ablated during 24 procedures (i.e. 5 reablations). Sixteen procedures were performed percutaneously, 5 during laparotomy and 3 laparoscopically. Magnetic resonance imaging (MRI) was used for intraprocedural monitoring during most procedures. Nine patients had concomitant liver resections performed (5 during laparoscopy, 4 during laparotomy). RESULTS: Out of 25 ablations, 18 (72%) were assumed adequate. Total ice-ball volume during percutaneous procedures was median 62 cm (range 32-114). Excellent imaging of the extent of freezing was achieved using MRI. Hospital stay for patients treated percutaneously was median 4 days (range 3-30). No perioperative mortality occurred. Tumour recurrence at the site of ablation occurred in 8 of 18 (44%) tumours adequately ablated. Actuarial 2-year tumour-free survival at site of ablation was 48%. At the time of analyses 12 out of 13 (92%) patients assumed to be adequately ablated were alive. Of all patients, 14 out of 19 (74%) survived. CONCLUSIONS: Short-term tumour control can be achieved following cryoablation of colorectal liver metastases. A minimally invasive approach is feasible but the diameter of metastases considered for percutaneous cryoablation should not exceed 3 cm.

Laparoscopic resection of the pancreas: a feasibility study of the short-term outcome.

BACKGROUND: Laparoscopic resection is not an established treatment for tumors of the pancreas. We report our preliminary experience with this innovative approach to pancreatic disease. METHODS: Thirty two patients with pancreatic disease were included in the study on an intention-to-treat basis. The preoperative indications for surgery were as follows: neuroendocrine tumors ( n=13), unspecified tumors ( n=11), cysts ( n=2), idiopathic thrombocytopenic purpura with ectopic spleen ( n=2), annular pancreas ( n=1), trauma ( n=1), aneurysm of the splenic artery ( n=1), and adenocarcinoma ( n=1). RESULTS: Enucleations ( n=7) and distal pancreatectomy with ( n=12) and without splenectomy ( n=5) were performed. Three patients underwent laparoscopic exploration only. Four procedures (13%) were converted to an open technique. One resection was converted to a hand-assisted procedure. The mortality rate for patients undergoing laparoscopic resection was 8.3% (two of 24). Complications occurred after resection in nine of 24 procedures (38%). The median hospital stay was 5.5 days (range, 2-22). Postoperatively, opioid medication was given for a median of 2 days (range, 0-13). CONCLUSION: Resection of the pancreas can be performed safely via the laparoscopic approach with all the potential benefits to the patients of minimally invasive surgery.

A comparative study of the short-term outcome following open and laparoscopic liver resection of colorectal metastases.

BACKGROUND: Laparoscopic resection of liver tumors is feasible, but few studies have compared short-term outcome of the laparoscopic approach to that of a conventional technique. METHODS: Eighteen tumor resections performed during 14 procedures (14 patients) by conventional surgery were compared to 21 similar resections performed laparoscopically during 15 procedures (13 patients). All patients had colorectal liver metastases. RESULTS: No perioperative mortality occurred. Surgical time, peroperative bleeding and blood transfusion requirement were similar in the two groups. The resection margin was involved by tumor tissue in one specimen laparoscopically resected and in two specimens conventionally resected (p = 0.58). Patients operated laparoscopically remained in hospital for median 4 days, while patients operated conventionally stayed median 8.5 days (p <0.001). Patients operated laparoscopically required less opioid medication than patients having conventional surgery (median 1 vs 5 days; p = 0.001). CONCLUSIONS: Short-term outcome of laparoscopic liver resection compares to that of conventional surgery, with the additional benefits derived from minimal invasive therapy.

Laparoscopic cholecystectomy: bile duct and vascular injuries: management and outcome.

BACKGROUND: This is a retrospective study of 32 consecutive patients referred in the period 1992-2000 for management of serious bile duct injuries caused by elective laparoscopic cholecystectomy. METHODS: The patients were referred on median 29 days (0 days to 34 months). Only 7 patients were referred immediately after discovery of the injury. At the local hospital, 25 patients underwent various procedures in attempts at repair. Ten of the patients were treated for bile duct strictures after previous repairs in other hospitals. RESULTS: At referral, 23 patients (72%) had complete transection of the bile duct, while 9 had bile leakage injuries. Additional complications were occlusion of the right hepatic artery in 8 patients (24%) and occlusion of the mesenteric superior artery in 1 patient. Infectious complications were prominent in 21 patients (70%), 6 of whom had septicaemia. Operative management with hepaticojejunostomy Roux-Y was employed in 22 patients. Various non-operative strategies were chosen, including endoscopically or transhepatic stenting of the bile duct and embolization of the right hepatic artery. There was no difference in hospital stay between operative and non-operative procedures which on median was 16 days ( range 7-69 days). Three patients died: one had thrombosis of the superior mesenteric artery, while the other two died of complications to bile peritonitis. Median observation period is 5 years (5 months to 8 years). Two patients have cholangitis; both had injury to the right hepatic artery. The other patients all had normal ultrasonograms of the liver and normal/almost normal liver function tests. CONCLUSIONS: Bile duct injuries continue to occur, are serious and may result in death. Injury to the right hepatic artery is present in many cases. Patients are referred late to a competent center, resulting in serious infection in 70%.

Magnetic-resonance-guided percutaneous cryoablation of hepatic tumours.

OBJECTIVE: To study the feasibility of percutaneous cryoablation of hepatic tumours monitored by magnetic resonance imaging (MRI). DESIGN: Prospective study SETTING: University hospital, Norway PATIENTS: Six patients with hepatic metastases from colorectal cancer. INTERVENTIONS: Percutaneous cryoprobe positioning under general anaesthesia. Positioning and freezing monitored by near-real-time MRI using an open 0.5 Tesla MRI configuration system. MAIN OUTCOME MEASURES: Safety and feasibility of the procedure. Measurement of volumes of cryolesions. RESULTS: One patient developed a biliary leakage that had to be drained. Four patients developed pleural fluid. Two small tumours were adequately cryoablated. In the remaining 4 patients with large (>4 cm) tumours, an adequate cryolesion could not be formed. Cryolesion volumes larger than 105 cm3 were not produced even using 3-4 probes. MRI visualised the growing cryolesion well, but positioning of the cryoprobes was time-consuming. CONCLUSION: MR guided cryoablation is clinically feasible and gives good visualisation of the procedure. Patients with small tumours (<3 cm) seem to be best suited to this percutaneous approach as cryolesion volumes claimed to be adequate for tumour destruction can be produced. Measurement of tumour volume preoperatively may help to select patients who will respond.

Veno-venous bypass in liver transplantation: heparin-coated perfusion circuits reduce the activation of humoral defense systems in an in vitro model.

We studied the effects of bypass circuit surface heparinization on kallikrein-kinin, coagulation, fibrinolytic and complement activation in a closed model system for simulating veno-venous bypass (WBP) in orthotopic liver transplantation (OLT). The circuits were identical to those in routine use during clinical OLT in our institution. Fresh whole human blood diluted 1:2 with Ringer's acetate was circulated at a non-pulsatile flow (2 l/min) and at a constant temperature (37.5 degrees C) for 12 h. In 10 experiments, the entire inner surface of the circuits was coated with end-point attached heparin (HC). In the remaining 10, non-treated PVC tubing was used (NC). Components of the plasma kallikrein-kinin, coagulation, fibrinolytic and complement systems were analyzed using functional techniques (chromogenic peptide substrate assays) and enzyme immunoassays at baseline, 3 and 12 h. Significant activation of the initial (C3bc) and terminal (TCC) components of the complement system were found in both the NC and HC groups after 3 and 12 h: C3bc: NC: baseline = 4 (3.5-7.7), 3 h = 17.3* (12.5-27), 12h = 31* (17.7-63.6), HC: baseline = 4.9 (3.2-6.8), 3h = 9* (6-14.4), 12h = 13.7* (7.4-18.1). TCC: NC: baseline = 0.4 (0.2-0.6), 3h = 5*(0.8-11.9), 12 h: 13.1* (4.2-25.7). HC: baseline = 0.5 (0.1-0.6), 3 h = 0.6* (0.1-0.8), 12 h = 1.2* (0.3-2) AU/ml; median and range (*: p < 0.05). The C3bc and TCC concentrations were significantly higher in the NC group at 3 and 12 h, compared to the HC group: C3bc (NC vs. HC group): 3 h, p < 0.001; 12 h, p < 0.001. TCC (NC vs. HC group): 3h, p < 0.001; 12 h, p < 0.001. Significant increases in the values of thrombin-antithrombin complexes (p = 0.003), prothrombin fragment 1 + 2 (p = 0.006) and plasmin-alpha2-antiplasmin complexes (p = 0.016) were found in the non-coated group, but not in the heparin-coated group during the observation period, showing that the coagulation and fibrinolytic systems were activated in the non-coated circuits. We conclude that heparin-coating of the internal surface of the extracorporeal perfusion circuit used for WBP reduces activation of the plasma cascade systems in a closed venous system in vitro.

Liver tumors and minimally invasive surgery: a feasibility study.

Laparoscopic liver resection has not yet been established, although recent reports document that liver resection can be performed safely by the laparoscopic approach. Other interventional procedures like cryoablation have also been introduced in treatment of liver metastases. In this report 11 liver resections performed laparoscopically in eight patients are presented. Six patients had colorectal metastases, one a metastases from a malignant melanoma, and one patient had focal nodular hyperplasia. Two patients received synchronous cryoablation of remaining liver metastases. During follow up, two patients received percutaneous cryoablation of liver recurrences monitored by an open configuration magnetic resonance scanner. All except one of the tumors we attempted to remove had free resection margins (re-resection of new metastasis). No complications occurred except an atelectasis of the left lower pulmonary lobe in one patient. Median postoperative hospital stay was 3 days, and median postoperative opioid-dependent days was 1. The report demonstrates that minimally invasive techniques may safely be combined in hepatic intervention, and that the advantages of minimally invasive surgery, such as reduced hospital stay and less patient discomfort, also applies to liver resections.

[Liver resection--indications and results]. / Leverreseksjon--indikasjoner og resultater.

BACKGROUND: Liver resection is an established treatment for malignancies like colorectal metastases and hepatocellular carcinoma. MATERIAL AND METHODS: Indications and outcomes of liver resection at the National Hospital, Oslo, Norway was studied retrospectively in 226 patients operated between 1977 and 1999. RESULTS: The main indication for surgery was colorectal metastases (n = 137). The frequency of liver resection for colorectal malignancies was < 1 per 100,000 patients per year in the hospital's catchment area. Other indications included hepatocellular carcinoma (n = 30), benign tumours like hemangioma (n = 14), and various primary and secondary malignant tumours. Reoperation due to postoperative complications was performed in 13 patients (6%). Total perioperative mortality defined as death before hospital discharge or within 30 days after discharge, was 3% (7/226). No perioperative deaths occurred among the 159 patients operated after 1987. Five year survival for patients operated for colorectal metastases and hepatocellular carcinoma were 29% and 24%, respectively. INTERPRETATION: The main indication for liver resection is colorectal metastases. Liver resection is a safe operation with potential curation for selected patients.

[Cryoablation--a treatment option for inoperable liver tumors?]. / Kryoablasjon--aktuell behandling av inoperable leversvulster?

BACKGROUND: Most patients with primary and secondary liver tumours are inoperable by conventional surgery. This has prompted the development of different techniques of local destruction of liver tumours, i.e. cryosurgical ablation radiofrequency, laser, and microwave ablation. MATERIAL AND METHODS: On the basis of relevant literature and our own experience we describe the principles of local destruction by cryoablation of colorectal metastases. RESULTS: Indications for ablation are mainly colorectal metastases and hepatocellular carcinoma. Mechanisms for tumour destruction include intra- and extracellular ice crystal formation, cellular membrane rupture, cellular dehydration and ischaemic damage. Ablation is regularly monitored by ultrasonography, which is suboptimal because of inadequate visualisation of the iceball. Long-term outcome of local destruction of liver tumours is not documented and randomized trials are not ethically acceptable. This complicates analyses of patient outcomes. INTERPRETATION: Local ablation of liver tumours is experimental therapy and should only be performed as a part of prospective trials.

Liver transplantation in patients over 60 years of age.

Liver transplantation was previously only offered to patients under 60 years of age. We have analyzed the outcome after acceptance on the waiting list and after liver transplantation of patients over 60 years old. A total of 150 patients over 60 years old were listed for a first liver transplantation during 1990-1998. The annual number increased throughout the period. Primary biliary cirrhosis, primary sclerosing cholangitis, and acute hepatic failure were the most frequent diagnoses. A total of 119 patients received a first liver allograft. The patient 1-year survival was 75% and 3-year survival 62%, which was not significantly lower (P = 0.21) than that of the younger patients. When correcting for year of transplantation, the survival was, however, moderately but significantly lower than among the younger patients. Survival among those > 65 years (n = 38) did not differ from that of patients 60-65 years of age (n = 81). We conclude that an increasing number of patients over 60 years old can be listed for liver transplantation and receive a liver allograft with highly satisfying results.

p53 accumulation confers prognostic information in resectable adenocarcinomas with ductal but not with intestinal differentiation in the pancreatic head.

The aim of the study was to examine the relation between p53 protein accumulation, clinicopathological variables and prognosis in resectable adenocarcinomas of the pancreatic head. The clinical records and tissue specimens of 82 consecutive patients resected for adenocarcinomas located in the head of the pancreas were reviewed retrospectively. Formalin-fixed and paraffin-embedded specimens from each tumour were stained with the monoclonal antibody DO7, and the nuclear p53 positivity within each tumour was assessed. Histopathological reclassification showed that 60 tumours exhibited ductal differentiation and 22 tumours intestinal differentiation. Twenty-five percent (15/60) of the ductal tumours and 50% (11/22) of the intestinal tumours were positive for p53 accumulation. p53 immunoreactivity was significantly correlated to a worse prognosis in the tumours of ductal differentiation, with median survival 0.76 years for p53 positive and 1.44 years for p53 negative patients. The p53 positivity of tumours with intestinal differentiation showed no such correlation. No correlation was found between p53 accumulation and other known prognostic factors in either the ductal or the intestinal type of tumours. Our results indicate that the tumour biology of ductal adenocarcinomas differs significantly from that of adenocarcinomas of the intestinal type located in the pancreatic head, and that p53 accumulation confers a worse prognosis only of ductal tumours. Subclassification of these tumours based on type of differentiation is therefore suggested since periampullary tumours include ductally as well as intestinally differentiated adenocarcinomas.

Liver transplantation in the Nordic countries, 1982-1998: changes of indications and improving results.

BACKGROUND: Liver transplantation has become an established therapeutic option for patients with life-threatening liver disease. The aim of the present study was to analyse the results of and developments in liver transplantation in the Nordic countries during a 15-year period. METHODS: Data on all patients receiving a liver allograft in the Nordic countries during 1982-98 and waiting list data for all patients listed for a liver transplantation after 1989 were obtained from the Nordic Liver Transplantation Registry. RESULTS: A total of 1485 first liver transplantations were performed during 1982-98. The annual number of first liver transplantations increased steadily up to 1993, thereafter remaining around 150-170 per year. There are major differences between countries both in the number of transplants adjusted to populations performed per year, with more than twice as many performed in Sweden as in Norway, and in the relative distribution of patients in accordance with diagnosis. The number of patients more than 60 years old increased and comprised 13%-14% of the total patient population during 1996-98. Primary biliary cirrhosis, primary sclerosing cholangitis, acute hepatic failure, malignant liver disease, and alcoholic cirrhosis are the five most frequent diagnoses. The over-all 1-year patient survival probability has increased from 66% among patients receiving a transplant in 1982-89 to 83% in 1995-1998. The waiting time remains stable, with a median waiting time of 35 days during 1990-98. The mortality of patients while on the waiting list is 7.4% and is not increasing. CONCLUSION: Results of liver transplantation in the Nordic countries are very similar to those obtained in other countries. Waiting time and mortality remain low. There are, however, major differences between the countries both as to the number of transplantations performed and as to distribution of diagnoses.

Plasma proteolytic activity in liver transplant rejection.

In this study, we evaluated the role of proteolytic enzymes belonging to the coagulation, fibrinolytic, and plasma contact systems in the early postoperative phase after orthotopic liver transplantation (OLT). Twenty-nine patients were studied at the time of OLT and during the first 2 postoperative weeks. Blood samples were collected daily after OLT and analyzed for kallikrein-like activity (KK), functional kallikrein inhibition (KKI), plasmin-like activity (PL), and alpha2-antiplasmin (AP). In addition, prekallikrein (PKK), prothrombin (PTH), antithrombin III (AT III), plasminogen (PLG), prothrombin/antithrombin III complexes (TAT), prothrombin fragment 1 + 2 (F1 + 2), and plasmin/alpha2-antiplasmin complexes (PAP) were measured. Nineteen patients experienced biopsy-verified acute rejections (AR) and ten patients had uneventful courses and served as controls. Plasma analyses showed that the contact, coagulation, and fibrinolytic systems were activated during OLT. Following OLT, continuous thrombin and plasmin generation was observed, and these effects were more pronounced in the group having an uneventful course than in patients with AR. Factors that could possibly affect plasma proteolytic activity, such as blood product usage during and after OLT and cold ischemia time of the liver graft, did not differ between the groups, nor did the routine liver function tests, alanine aminotransferase (ALT) and aspartate aminotransferase (AST).

Loop ileostomy: technical aspects and complications.

OBJECTIVE: To study the incidence of complications of construction and closure of loop ileostomies and the final outcome for the patients. DESIGN: Retrospective study. SETTING: University hospital, Norway. SUBJECTS: 100 patients with 103 loop ileostomies, operated on between 1980 and 1990. MAIN OUTCOME MEASURES: Number of complications after ileostomy construction and closure. RESULTS: 7 required re-operation after construction of the loop ileostomy and 11 after its closure. The most common cause was small intestinal obstruction (4 after construction and 6 after closure). 2 developed stomal necrosis. The mean duration of hospital stay was 13 and 10 days for primary and secondary loop ileostomy, respectively, and the mean time before closure was 31 weeks. After closure another 6 developed leaks from the ileal anastomosis that required further operation. Patients with secondary loop ileostomies had their stomas significantly longer than those with primary loop ileostomies (21 compared with 43 weeks, p = 0.00005). CONCLUSION: Despite the number of complications, we think that faecal diversion is still justified in complex pelvic surgery and we should try to reduce the complication rate further.

An experimental study on effects of monopolar diathermy on the bile ducts.

OBJECTIVE: To study the effects of monopolar diathermy on the bile ducts in pigs. DESIGN: Experimental study. SETTING: University hospital, Norway. MATERIAL: 18 pigs. INTERVENTIONS: Laparotomy, application of diathermy at standard sites along the cystic duct, the bile ducts, and a cystic duct containing a metal clip, 3 to 12 times of 5 seconds' duration at each site. Temperature was subsequently recorded at standard measurement points on the bile ducts. Twelve pigs were killed after three weeks for assessment of the bile ducts at necropsy. MAIN OUTCOME MEASUREMENTS: Increase in temperature in the bile duct walls and late changes in the bile ducts. RESULTS: Temperature increased by 4-6 degrees C during 6 of 330 diathermy applications along the cystic duct, by 4-18 degrees C in 8 of 126 applications along the common bile duct, and by 4-11 degrees C at the clip in 9 of 54 applications. There were no macroscopic or microscopic changes in the bile ducts. CONCLUSION: Monopolar diathermy induced unexpected distant increases in the temperature of the bile duct walls and at a clip on the cystic duct probably because diathermy current energy was distributed along channels of high current conductivity.

Liver transplantation for endstage hepatitis C cirrhosis in a patient with primary hypogammaglobulinaemia.

Liver transplantation was performed in a patient with primary hypogammaglobulinaemia, chronic hepatitis C and hepatic failure. The immediate posttransplant period was uncomplicated. Owing to a stricture of the choledochojejunostomy the patient was reoperated with construction of a hepaticojejunostomy 11 months posttransplant. The patient remained hepatitis C virus (HCV) RNA-positive, with high and increasing levels of HCV. Liver biopsies demonstrated the recurrence of HCV. 14 months after the transplantation the patient developed severe diarrhoea caused by Cryptosporidium parvum. The infection did not respond to available therapeutic measures. He deteriorated with development of liver failure and died 18 months after the transplantation. The present case report illustrates the difficulties associated with organ transplantation in patients with primary hypogammaglobulinaemia.

[Follow up after potential curative surgery of colorectal cancer. Guidelines from the Norwegian Gastrointestinal Cancer Group]. / Kontrollopplegg etter potensiell kurativ operasjon for kolorektalcancer. Anbefaling fra Norsk Gastrointestinal Cancer Gruppe.

In Norway, about 2,800 cases of colorectal cancer are diagnosed every year. Two-thirds of the patients undergo potentially curative surgery and almost half of them develop local or distant metastases. The follow-up of colorectal cancer patients involves four strategies: Educating the patients about the disease, symptoms of relapse, and risk of hereditariness; Early diagnosis of relapse, to make curative re-surgery possible; Diagnosis of metachronous/synchronous cancer(s); Recording the results of current surgical techniques. The Norwegian Gastrointestinal Cancer Group recommend a four-year follow-up programme (every third month for two years and then twice a year) of colorectal cancer patients. It is suggested that patients treated with low anterior resection are followed regularly by means of rectoscopy and local examination (digital or by ultrasound) undertaken by specialist (surgeon or gastroenterologist). The others should be followed up mainly by general practitioners. Carcinoembryonic antigen (CEA)-monitoring is suggested every third month for two years, and then every sixth month. Colonoscopy is recommended at one and four year follow-up. Patients with normal CEA levels prior to surgery should be evaluated by ultrasound of the liver every sixth month for four years.

[Hepatic vein thrombosis. Diagnostic and therapeutic difficulties]. / Levervenetrombose. Diagnostisk og terapeutisk problem.

Budd Chiari syndrome (liver vein thrombosis) may be a diagnostic and therapeutic problem. On the basis of four different cases we review the major diagnostic and therapeutic principles involved. Imaging techniques are necessary in order to establish the diagnosis. Ultrasound examination with Duplex doppler is usually sufficient, but MR angiography is also useful. Treatment options are thrombolysis, surgery or liver transplantation. What treatment is selected will depend on the clinical situation and the prognosis.

Percutaneous technique for venovenous bypass including a heat exchanger is safe and reliable in liver transplantation.

We have introduced and evaluated several modifications of the conventional venovenous bypass (VVBP) in 29 adult patients undergoing liver transplantation (OLT). A percutaneous technique for insertion of a jugular venous return cannula and a femoral vein cannula was applied. The inferior mesenteric vein (IMV) was used for splanchnic decompression, which facilitated dissection of the recipient liver and allowed portal anastomosis to be performed without disconnecting the portal bypass. A heat exchanger was introduced into the bypass circuit to prevent heat loss. The percutaneous technique prevented complications related to dissection in the axilla and groin. Hemodynamic characteristics corresponded to those found using the traditional technique. Complications related to the VVBP were seen in only one patient in whom the femoral catheter was accidentally introduced into the femoral artery. We conclude that percutaneous cannulas, use of the IMV for splanchnic decompression and the introduction of a heat exchanger offer significant benefits and that they are safe and reliable.