Clinical care and technical recommendations for 90yttrium microsphere treatment of liver cancer.

Selective internal radiation therapy (SIRT) with (90)yttrium microspheres is a relatively new clinical modality for treating non-resectable malignant liver tumours. This interventional radiology technique employs percutaneous microcatheterisation of the hepatic arterial vasculature to selectively deliver radioembolic microspheres into neoplastic tissue. SIRT results in measurable tumour responses or delayed disease progression in the majority of eligible patients with hepatocellular carcinoma or hepatic metastases arising from colorectal cancer. It has also been successfully used as palliative therapy for non-colorectal malignancies metastatic to the liver. Although most adverse events are mild and transient, SIRT also carries some risks for serious and--rarely--fatal outcomes. In particular, entry of microspheres into non-target vessels may result in radiation-induced tissue damage, such as severe gastric ulceration or radiation cholecystitis. Radiation-induced liver disease poses another significant risk. By careful case selection, considered dose calculation and meticulous angiographic technique, it is possible to minimise the incidence of such complications to less than 10% of all treatments. As the number of physicians employing SIRT expands, there is an increasing need to consolidate clinical experience and expertise to optimise patient outcomes. Authored by a panel of clinicians experienced in treating liver tumours via SIRT, this paper collates experience in vessel mapping, embolisation, dosimetry, microsphere delivery and minimisation of non-target delivery. In addition to these clinical recommendations, the authors propose institutional criteria for introducing SIRT at new centres and for incorporating the technique into multidisciplinary care plans for patients with hepatic neoplasms.

Increasing cycles of intermittent ischemia can effectively maintain liver function during the acute phase of ischemia reperfusion injury by promotion of bile flow and reduction in bile salt toxicity.

BACKGROUND/AIMS: Intermittent ischemia (INT) can improve liver function following inflow occlusion. The aim was to test whether the number of cycles of INT can be increased without impairing liver function. METHODS: Liver function in the acute phase of ischemia reperfusion injury was assessed by measuring bile flow in rat livers. Phospholipid and bile salts in bile, liver marker enzymes in blood, and liver histology were measured. Aged livers were compared with young livers. RESULTS: Clamping for 45 min reduced postperfusion bile flow to 13% of the initial value compared with 88 +/- 5% for control livers (means +/- SEM, n = 5-8), and substantially reduced the phospholipid:bile salt ratio in bile. Application of 3, 4, 5 and 6 cycles of INT (15 min) restored bile flow to 70 +/- 11, 61 +/- 4, 48 +/- 2 and 35 +/- 3% (p < 0.01) of the initial value, respectively, and restored the phospholipid:bile salt ratio. Multiple cycles of INT were less effective in aged rats. CONCLUSION: Several cycles of INT, through promotion of bile flow recovery and reduction in the cytotoxic actions of bile salts, may provide an effective clinical strategy for increasing clamping time in liver resections.

Perioperative morbidity affects long-term survival in patients following liver resection for colorectal metastases.

BACKGROUND: Hepatic resection is the treatment of choice in patients with colorectal liver metastases. Perioperative morbidity is associated with decreased long-term survival in several cancers. The aim of this study was to assess the impact of perioperative morbidity and other prognostic factors on the outcome of patients undergoing liver resection for colorectal metastases. METHODS: One hundred ninety seven patients undergoing liver resection with curative intent were investigated. The influence of prognostic factors, such as complications, tumor stage, margins, age, sex, number of lesions, transfusion, portal inflow obstruction, and era and type of resection, was assessed using univariate and multivariate analysis. Complications were graded using an objective surgical complication classification. RESULTS: The 5-year survival rate was 38%, with a median follow up of 4.5 years. The disease-free survival rate at 5 years was 23%. The perioperative morbidity and mortality rates were 30 and 2.5%, respectively. The median survival of patients with perioperative complications was 3.2 years, compared to 4.4 years in those patients without complications (p < 0.01). For patients with positive resection margins, the median survival was 2.1 years, compared 4.4 years in patients with a margin (p = 0.019). CONCLUSION: Perioperative morbidity and a positive resection margin had a negative impact on long-term survival in patients following liver resection for colorectal metastases.

Liver transplantation for HCV-associated liver cirrhosis: predictors of outcomes in a population with significant genotype 3 and 4 distribution.

End-stage liver disease associated with hepatitis C virus (HCV) infection is now the leading indication for liver transplantation in adults. However, reinfection of the graft is universal. We aimed to determine predictors of outcome of HCV-liver transplant recipients in the Australian and New Zealand communities. The following variables were analysed: demographic factors, coexistent pathology at the time of transplantation, HCV genotype, and donor age. Outcomes measures were: 1. mortality; 2. development of HCV-related complications, which were stage 3 or 4 fibrosis, or mortality from HCV-related graft failure, or both. Between January 1989 and December 30, 1999, 182 patients were transplanted for HCV-associated cirrhosis. The median follow-up period was 4 years (range, 0 to 13 years). Genotype data were available on 157 patients. The distribution of genotypes among the 157 patients was as follows: 36 (23%) genotype 1a, 30 (19%) genotype 1b, 4 (9%) genotype 1, 17 (11%) genotype 2, 41 (26%) genotype 3a, and 16 (10%) genotype 4. Eight (5%) patients were HCV-polymerase chain reaction (PCR)-negative (but HCV-antibody-positive). Donor age and genotype 4 were associated with an increased risk of retransplantation or death (P <.001 and.05, respectively). Meanwhile, donor age, genotype 4, and pretransplant excess alcohol were risk factors for the development of HCV-related complications (P =.004,.008, and.02, respectively). In contrast, patients with genotype 3a were less likely to develop HCV-related complications (P =.05). In a population of HCV liver transplant recipients with a heterogeneous genotype distribution, donor age, and genotype 4, were predictors of a worse outcome, whereas genotype 3 was associated with a more favorable outcome.

Sphincter of Oddi dysfunction associated with choledochal cyst.

The pathophysiology of choledochal cysts remains unclear, although an association with anomalous pancreato-biliary junction and the reflux of pancreatic enzymes into the biliary tree is known. Sphincter of Oddi (SO) manometry was performed in three patients with choledochal cysts. All patients exhibited an elevated basal pressure diagnostic of sphincter of Oddi dysfunction. Two patients exhibited anomalous pancreato-biliary junction. This report suggests an association between the choledochal cyst and sphincter of Oddi dysfunction, and may suggest that SO dysfunction plays a role in choledochal cyst formation.

A prospective randomized trial of day-stay only versus overnight-stay laparoscopic cholecystectomy.

BACKGROUND: Although the feasibility of laparoscopic cholecystectomy performed as day surgery has been established, cost and recovery time have not previously been evaluated in a prospective comparative fashion. METHODS: Patients were randomized to day stay only or overnight stay, and a nurse assessed the former postoperatively at home. All patients were reviewed weekly or as required if problems occurred. Costing comparisons were made between the two groups using Trendstar software. RESULTS: A total of 131 patients were evaluated after randomization (60 day-stay only patients and 71 overnight-stay patients). A total of 18.3% of the day-stay patients required in-hospital admission for nausea, vomiting, or pain, or after conversion to open operation; 18.3% of the overnight group required an extended length of stay for similar reasons. After discharge, two day-stay and three overnight-stay patients required readmission, only one had a significant complication. The mean times to return to normal activity averaged 1.8 weeks (SE: 0.1 weeks) and 1.9 weeks (SE: 0.1 weeks) for day-stay and overnight-stay groups, respectively (P = 0.63), and costs of $2732 (SE: $76) compared to $2835 (SE $110), respectively (P = 0.94). CONCLUSIONS: In the present randomized controlled study, day-stay management did not compromise postoperative patient outcome. In the setting of a major teaching hospital there was no cost advantage when compared to overnight-stay management.

A modification of isolated Roux loop reconstruction after pancreaticoduodenectomy.

BACKGROUND: Different techniques of reconstruction following pancreaticoduodenectomy have been described. A new modification using an isolated Roux-en-Y loop is reported. METHODS: The isolated loop is taken up to bile duct rather than pancreas as previously described. RESULTS: Seventeen patients have undergone this procedure. Two pancreatic fistulae developed, both following postoperative abscess formation. There was no operative mortality. CONCLUSION: This reconstruction provides separation of biliary and pancreatic fluid but adds two further benefits: the wide jejunal lumen allows for an easier pancreaticojejunal anastomosis, particularly when operating on a soft pancreas, and separation of gastric and biliary anastomoses prevents the efflux of bile into stomach.

Somatostatin stimulates the brush-tailed possum sphincter of Oddi in vitro and in vivo.

BACKGROUND & AIMS: Somatostatin, a neuropeptide and hormone, is found in the biliary tract of several species. The aim of this study was to map the distribution of somatostatin-like immunoreactive nerve fibers in the extrahepatic biliary tract of the Australian possum and to determine the pharmacological effects of somatostatin 1-14 on sphincter of Oddi activity in vitro and in vivo. METHODS: Tissue was harvested for immunohistochemistry and sphincter of Oddi for circular or longitudinal muscle contractility. In anesthetized possums, sphincter of Oddi motility was measured by manometry, and transsphincteric flow was measured gravimetrically. RESULTS: Somatostatin immunoreactivity was evident in gallbladder ganglia nerve cell bodies and in nerve fibers of the common bile duct and sphincter of Oddi. Somatostatin 1-14 increased circular and longitudinal muscle contraction amplitude 3-4-fold (P < 0.05), but only the longitudinal muscle contraction amplitude was tetrodotoxin sensitive. Somatostatin 1-14 stimulated spontaneous sphincter of Oddi motility in a tetrodotoxin-insensitive manner, increasing basal pressure, contraction frequency, and amplitude 2-4-fold (P < 0.05) and reducing transsphincteric flow to 25% of control (P < 0.0001). CONCLUSIONS: Somatostatin-like immunoreactivity is present in the extrahepatic biliary tree, and somatostatin 1-14 stimulates sphincter of Oddi smooth muscle and nerves. The major action is direct stimulation of sphincter of Oddi circular muscle, which reduces transsphincteric flow.

Gastrin-releasing peptide stimulates gallbladder motility but not sphincter of Oddi motility in Australian brush-tailed possum.

The neural distribution and action of gastrin-releasing peptide in the extrahepatic biliary tree of the Australian brush-tailed possum was investigated. Immunohistochemical staining of fixed specimens demonstrated gastrin-releasing peptide-containing nerves throughout the neural plexuses of the gallbladder, sphincter of Oddi, and mucosa of the common bile duct. Gastrin-releasing peptide (5-2000 ng/kg) increased gallbladder tone to a level equivalent to that produced by cholecystokinin octapeptide (160 ng/kg). This action was tetrodotoxin-insensitive. Sphincter of Oddi motility and transsphincteric flow were not altered. Possible mediation of the gallbladder response by gastrin was examined. Gastrin (50-2500 ng/kg) stimulated gastric acid secretion, elevated gallbladder motility to 64% of that produced by gastrin-releasing peptide, and did not alter sphincter of Oddi motility. In conclusion, gastrin-releasing peptide-containing nerves are found in the neural plexus of the possum extrahepatic biliary tree. Gastrin-releasing peptide induces gallbladder contraction in part by a direct action on gallbladder smooth muscle and also via release of gastrin.

Substance P stimulates sphincter of Oddi motility and inhibits trans-sphincteric flow in the Australian brush-tailed possum.

Substance P containing nerves are widely distributed throughout the gastrointestinal tract. The aims of this study were to determine the distribution of substance P containing nerves in the extrahepatic biliary tree of the Australian brush-tailed possum and to characterize the effect of exogenous substance P on the sphincter of Oddi (SO) motility and transphincteric flow in vivo. Immunohistochemical staining of fixed specimens (n = 8) found moderate numbers of substance P containing nerve cell bodies and fibres throughout the neural plexuses of the SO, in particular in the serosal and intraluminal nerve trunks of the SO and gallbladder. Synthetic porcine substance P (1-2000 ng kg-1), administered by close intra-arterial injection (i.a.; n = 7), produced a dose-dependent elevation in basal pressure [P < 0.01] and an associated dose-dependent reduction in trans-sphincteric flow [P < 0.0001]. Substance P had no significant dose-dependent effect on SO phasic contraction amplitude or frequency. Tetrodotoxin (9 micrograms kg-1, i.a.) did not inhibit the effect of substance P on SO motility and trans-sphincteric flow (n = 5). In conclusion, substance P containing nerves are found throughout the possum extrahepatic biliary tree. Exogenous substance P stimulates SO motility and reduces trans-sphincteric flow in vivo by acting directly on the sphincter smooth muscle.

Treatment of a giant haemangioma of the liver with Kasabach-Merritt syndrome by orthotopic liver transplant a case report.

We describe a case of giant cavernous haemangioma of the liver with disseminated intravascular coagulopathy (Kasabach-Merritt syndrome) which was cured by orthotopic liver transplant. A 47 year old man presented with bleeding and tender massive hepatomegaly after tooth extraction. Investigations showed disseminated intravascular coagulopathy and a giant hepatic haemangioma involving both lobes of the liver. Initial treatment failed to resolve the coagulopathy and liver resection was attempted. At laparotomy the tumour was unresectable and the only option for cure was to offer a liver transplantation. The orthotopic liver transplant was performed 20 days after initial laparotomy. Subsequently, all coagulation parameters returned to normal and the patient remains well after 12 months. Orthotopic liver transplant can be considered for giant hepatic haemangioma with Kasabach-Merritt syndrome when resection is necessary and a partial hepatectomy is not technically feasible.

Prospective randomized comparison of open versus laparoscopic appendectomy in men.

A prospective, randomized trial was performed to compare open appendectomy with laparoscopic appendectomy in men with a clinical diagnosis of acute appendicitis. Sixty-four patients with a median age of 25 years (range 18-84 years) were randomized to open appendectomy (n = 31) or laparoscopic (n = 33) appendectomy. Of the 64 men, 56 (87.5%) had appendicitis (27 open, 29 laparoscopic procedures). The mean operating times were 50.6 +/- 3.7 minutes (+/- SEM) for open and 58.9 +/- 4.0 minutes for laparoscopic appendectomy (p = 0.13). Five (15%) patients randomized to laparoscopic appendectomy had an open operation. The mean postoperative hospital stay was significantly longer for open appendectomy (3.8 +/- 0.4 days) than for laparoscopic appendectomy (2.9 +/- 0.3 days) (t = 2. 05,df = 62,p = 0.045). The complication rate after open appendectomy (25.8%) was not significantly different from that after laparoscopic appendectomy (12.1%). There was a single postoperative death due to a pulmonary embolus in the laparoscopic group and a single death due to cardiac and renal failure in the open group. The mean time to return to normal activities was significantly longer following open appendectomy (19.7 +/- 2.4 days) than after laparoscopic appendectomy (10.4 +/- 0.9 days), (t = 3.75,df = 49,p = 0.001). In conclusion, laparoscopic appendectomy in men has significant advantages in terms of a more rapid recovery compared to open appendectomy. There were no significant disadvantages to laparoscopic appendectomy compared to open appendectomy.

Percutaneous cystogastrostomy with a new catheter for drainage of pancreatic pseudocysts and fluid collections.

We describe a new catheter for the initial percutaneous drainage of large symptomatic pancreatic fluid collections and abscesses using a transgastric approach to allow fluid drainage into the gastric lumen. A double-mushroom stent is placed secondarily for long-term internal drainage to the stomach, avoiding the need for an extended period of external catheter drainage. This technique, termed percutaneous cystogastrostomy (PCG), has been used in 19 consecutive patients with one recurrent symptomatic pseudocyst in the follow-up period fo 9-43 months. There was one death within 30 days of PCG and 1 patient proceeded to surgical necrosectomy. After evidence of resolution of the pseudocysts, the internal stent was retrieved in 17 patients by endoscopic snare.

Galanin modulates sphincter of Oddi function in the Australian brush-tailed possum.

The neuropeptide galantin (GAL) is found in neurons in the biliary tract of several species. We mapped the distribution of GAL-like immunoreactive nerve (GAL-LI) fibers in the sphincter of Oddi of the Australian brush-tailed possum by immunohistochemistry. The pharmacological effects of GAL in vitro and in vivo were studied by measuring sphincter of Oddi muscle strip contractility and transsphincteric flow, respectively. Muscle layers, and ganglionated and perivascular plexuses, contained GAL-LI nerve fibers. Exogenous GAL caused a concentration-dependent (10(9)-10(-6)M) increase in the spontaneous longitudinal but not circular muscle contractions. At 10(-6) M GAL, contractile activity was elevated two- to fourfold. This response was tetrodotoxin insensitive but competitively inhibited by galantide (10(-8)-10(-7) M). In vivo, intra-arterial bolus injections of GAL (1001000 ng/kg), decreased transsphincteric flow, with a maximum reduction to 80.2 +/- 6.8% of control. In conclusion, GAL appears to selectively stimulate longitudinally oriented sphincter of Oddi smooth muscle via a direct mechanism, which results in a modest reduction in transsphincteric flow.

Gastric devascularization and splenectomy for bleeding gastric varices.

Gastric varices may be associated with oesophageal varices in patients with portal hypertension. Control of haemorrhage from gastric varices is often difficult. Between June 1988 and February 1990, six patients underwent gastric devascularization in an effort to control life-threatening haemorrhage from bleeding gastric varices after non-operative measures failed. In all six patients the bleeding was controlled. There was one peri-operative death due to hepatic failure. Four patients experienced postoperative respiratory or urinary tract infections that responded to appropriate antibiotic and respiratory support measures. After a mean follow-up period of 44 months, eradication of gastric varices was achieved in all five survivors. Gastric devascularization is an effective surgical measure for good palliation and control of life-threatening haemorrhage from bleeding gastric varices.

Laparoscopic surgery in women with a clinical diagnosis of acute appendicitis.

OBJECTIVES: To assess the routine use of diagnostic laparoscopy and laparoscopic appendicectomy in women with a clinical diagnosis of acute appendicitis. METHODS: Women who presented with a clinical diagnosis of acute appendicitis between 1 January 1992 and 31 August 1993 were prospectively assessed and 107 underwent diagnostic laparoscopy. RESULTS: Appendicitis was confirmed in 63 women (59%) and no diagnosis could be made in seven (6%). An alternative diagnosis, most commonly a gynaecological disorder, was made in 37 women (35%). Twenty-eight women with an alternative diagnosis (76%) did not require a laparotomy. Seventy-three patients had a laparoscopic appendicectomy, with an 8% conversion rate to an open operation. The morbidity rate for laparoscopic procedures was 3%, the median inpatient stay was two days and the median time to return to normal activities was eight days. CONCLUSIONS: Diagnostic laparoscopy should be performed in women who present with a clinical diagnosis of acute appendicitis to confirm the diagnosis, reduce the rate of unnecessary appendicectomy and avoid an unnecessary laparotomy. When acute appendicitis is confirmed, appendicectomy may be performed laparoscopically.

Endoscopic retrograde cholangiopancreatography following laparoscopic cholecystectomy.

Laparoscopic cholecystectomy is the preferred method of treatment for symptomatic choledocholithiasis. Since its introduction there has been an increase in postoperative diagnostic and therapeutic endoscopic retrograde cholangiopancreatography (ERCP). The aim of this study was to assess the indications and results of ERCP following laparoscopic cholecystectomy. Sixty-one patients had an ERCP following laparoscopic cholecystectomy. Two broad groups were identified: Group 1 (35 patients) had filling defects (consistent with stones) noted on operative cholangiography, which were not successfully flushed or extracted at the time of laparoscopic cholecystectomy; Group 2 consisted of patients who developed problems following laparoscopic cholecystectomy. Nine patients had post-laparoscopic cholecystectomy pain with abnormal liver function tests (LFT), four of whom had common bile duct (CBD) injuries and three had CBD stones. Eleven patients had post-laparoscopic cholecystectomy pain with a normal diameter common bile duct on ultrasound and normal LFT; only one had a CBD stone. Five patients with a persisting bile leak following laparoscopic cholecystectomy had an ERCP and endoscopic sphincterotomy. In three the leak ceased, while two required subsequent open surgery to drain bile collections and ligate the cystic duct. One patient presented with an episode of transient jaundice but had a normal ERCP. There were six post-ERCP complications; three patients had mild pancreatitis, two had a minor haemorrhage and one an asymptomatic duodenal perforation. Endoscopic retrograde cholangiopancreatography post-laparoscopic cholecystectomy was most valuable for the management of retained stones and the diagnosis and management of post-laparoscopic cholecystectomy pain in association with abnormal LFT. The diagnostic yield was low (9%) when the LFT were normal.

Minimizing the risk of bile duct injury at laparoscopic cholecystectomy.

The introduction of laparoscopic cholecystectomy (LC) has been associated with an increase in the incidence of operative bile duct injuries. An operative technique that involves commencing the laparoscopic dissection on the body of the gallbladder and dissecting toward the cystic duct has been developed that minimizes the risk of major duct injury. The aim of this study was to assess prospectively the safety of this dissection technique. A group of 410 patients underwent LC for symptomatic cholelithiasis from January 1991 to December 1992. There was a single common hepatic duct injury: a small (1 mm) side hole in a patient with acute cholecystitis and choledocholithiasis. It was managed at open operation with exploration of the common bile duct and insertion of a T-tube. There were no partial or complete common bile duct transections in this series. We concluded that the technique of commencing the dissection on the gallbladder is safe and minimizes the risk of serious common bile duct injury at LC.

Extended preservation of the liver with UW solution--is it justifiable?

The outcome of 228 liver grafts in 208 elective adult recipients was assessed to identify any adverse effects of extending the length of cold preservation with UW solution beyond 12 hr. A total of 114 grafts had been preserved < 12 hr--median 9.5 (group I) and 114 > 12 hr--median 14.5 (group II). Intraoperative blood and blood product usage, graft function, hospital stay, and graft and patient survival were identical in the two groups. Biliary strictures occurred in 5.7% of grafts (8 anastomotic (3 group I, 5 group II; 5 hilar/nonanastomotic: 3 group I, 2 group II). There was no graft or patient loss due to the hilar strictures but 1 patient died following reconstruction of an anastomotic stricture (0.4%). It is concluded that extending the cold preservation to approximately 15 hr does not adversely affect outcome after liver transplantation.