Compared with parenteral nutrition, enteral feeding attenuated the acute
phase response and improves disease severity in acute pancreatitis.
Windsor A C J, Kanwar S, Li A G K et al. Gut 1998; 42: 431-435.
Early enteral nutrition attenuates the inflammatory
response following major surgery and trauma. Total enteral nutrition (TEN)
has been shown to reduce the acute phase response and septic complications
in burns patients. The aim of this study was to assess whether TEN
attenuated the acute phase response and reduced disease severity in acute
pancreatitis. Thirty-four patients with acute pancreatitis (amylase >1,000
IU/ml, symptoms <48 hours and no evidence of chronic pancreatitis) were
evaluated by the Glasgow score, APACHE II score, CT scan, CRP,
anti-endotoxin core antibody and total oxidant capacity. Patients were
stratified by disease severity and randomised to receive either TEN or TPN
for seven days. No patients were intolerant of the enteral feed. Enteral
nutrition reduced the incidence of SIRS, sepsis, multiple organ failure
and lessened the ITU stay. It reduced both CRP and APACHE II scores.
Anti-endotoxin core antibody levels remained unchanged. In the TPN group
there was no reduction in the inflammatory response. Anti-endotoxin core
antibody levels were increased. It was concluded that early enteral
nutrition is practical and is well tolerated in patients with acute
pancreatitis. TEN reduces the acute phase response and improves disease
severity and clinical outcome. Enteral nutrition modifies the inflammatory
response, limits septic complications and is clinically beneficial in
patients with acute pancreatitis.
Is prophylactic
gastrojejunostomy indicated for unresectable periampullary cancer?
Lillemoe K D, Cameron J L, Hardacre J M et al. Ann Surg
1999; 230: 322-330. 
Between 25% and 75% of patients with periampullary
carcinoma (cancer of the head of pancreas, distal common bile duct,
ampulla of Vater and duodenum) who undergo laparotomy with with a view to
curative surgery (pancreaticoduodenectomy) are found to have unresectable
disease. Most undergo a biliary-enteric bypass to relieve obstructive
jaundice. The role of prophylactic gastrojejunostomy to prevent late
gastric outflow obstruction is however controversial. Retrospective
reviews of both surgical series and patients having their jaundice
palliated by endoscopic stenting have shown that late gastric outflow
obstruction develops in 10 - 20% of patients with unresectable
periampullary tumours. This study was a prospective, randomised,
single-institution trial aiming to evaluate the role of prophylactic
gastrojejunostomy in patients found to have irresectable periampullary
carcinoma. Over a four year period 194 patients with periampullary cancer
were found at surgery to have irresectable disease. Of these, 107 were
felt to have evidence of impending duodenal obstruction and a
gastrojejunostomy was performed in all patients. The remaining 87
patients, thought not to be at risk of obstruction, were randomised to
receive or not receive a prophylactic retrocolic gastrojejunostomy. Of
these 87 patients, 44 patients received a gastrojejunostomy and 43 did not
undergo a bypass procedure. The groups were demographically well matched.
There were no post-operative deaths in either group and the post-operative
morbidity and hospital stay were comparable. Mean survival was 8.3 months
in both groups. 8 of the 43 (19%) patients in the group that did not
receive a jejunostomy developed late gastric outflow obstruction requiring
therapeutic intervention. No patient in the other group required further
surgery. It was concluded that the addition of a prophylactic retrocolic
gastrojejunostomy at the time of the initial surgical procedure prevents
late gastric outflow obstruction and does not add to the post-operative
morbidity or hospital stay.
Emergency cholecystotomy and subsequent
cholecystectomy for acute gallstone cholecystitis in the elderly.
Borzellino G, de Manzoni G, Ricci F et al. Br J Surg
1999; 86: 1521-1525.
Acute cholecystitis is one of the commonest reasons for
surgical admission in western countries. The incidence of cholelithiasis
increases with age and with an increasingly elderly population more
patients are at risk of developing gallstone-related complications. The
morbidity and mortality rates associated with acute cholecystitis are
increased. As a result this retrospective cohort review investigated the
role of emergency ultrasound-guided percutaneous cholecystotomy followed
by elective cholecystectomy after endoscopic treatment of any common bile
duct stones in elderly patients with acute cholecystitis. In the 10 years
between 1989 and 1998, 84 patients over the age of 70 years with
ultrasonographic signs of severe cholecystitis and ASA grades II to IV
underwent ultrasound-guided percutaneous cholecystotomy. Transcatheter
cholangiography was performed in all patients and ERCP and sphincterotomy
was performed in all patients (n=18) with common bile duct stones. After
resolution of infection and pre-operative optimisation of the patients
condition 70 patients proceeded to cholecystectomy with no deaths and a
morbidity rate of 24%. It was concluded that the combination of emergency
ultrasound-guided percutaneous cholecystotomy, preoperative endoscopic
treatment of of common bile duct stones and subsequent elective
cholecystectomy constituted an optimal treatment regimen for acute
gallstone cholecystitis in elderly patients.
Comparison of magnetic resonance and
endoscopic retrograde cholangiopancreatography in malignant
pancreaticobiliary obstruction. Georopoulos S K, Shwartz L H, Jarnagin W R
et al. Arch Surg 1999; 134: 1002-1007.
Endoscopic retrograde cholangiopancreatography (ERCP) has
revolutionised the diagnosis and management of pancreaticobiliary disease
and remains the gold standard for imaging the pancreatic and common bile
duct. It is, however, an often difficult and operator dependent technique,
occasionally associated with significant complications. It also fails to
provide information regarding the extent of pancreatic cancers;
information needed to assess operability of tumours. As a result ERCP has
to be combined with other imaging modalities, usually CT scanning.
Magnetic resonance cholangiopancreatography (MRCP) is a relatively new
noninvasive imaging technique for the evaluation of pancreaticobiliary
disease. It can provide high resolution images of the biliary and
pancreatic ducts as well as providing information on size, character,
vascular invasion and metastatic spread of the tumour. Whether MRCP will
supplement standard imaging studies in patients with malignant biliary
obstruction is unclear. The aim of this study was to assess the
comparability of ERCP and MRCP as a diagnostic tool in patients with
malignant biliary obstruction. In 1996, 18 patients with suspected
pancreaticobiliary malignancy underwent both ERCP and MRCP. Images from
both modalities were retrospectively analysed in a blinded fashion and
compared with the intraoperative findings. Diagnostic-quality MR images
were obtained in all patients. Diagnostic ERCP images were obtained from
16 (89%) of biliary cannulations. MR accurately delineated the level of
biliary obstruction in 89% of patients and provided valuable staging
information in most patients. Findings from MR correlated well with
intraoperative findings (size, location, mesenteric vascular involvement).
It was concluded that MRCP is sensitive for detecting the presence and
level of biliary obstruction. It is comparable to ERCP but in addition
provided additional useful staging information.
Evaluation of magnetic resonance
cholangiography in the management of bile duct stones. Demartines N,
Eisner L, Schnabel K, Fried R, Zuber M, Harder F.
Arch Surg 2000; 135: 148-152.
Common bile duct stones (CBD) can be diagnosed by
endoscopic retrograde cholangiopancreatography (ERCP) or intraoperative
cholangiography (IOC). The former is popular because it can be both
diagnostic and therapeutic. However, the number of negative
investigations is significant and complications can occur. Magnetic
resonance cholangiography (MRC) offers the potential for accurate,
non-invasive detection of common bile duct stones prior to cholecystectomy
with a reduction in the incidence of negative investigations associated
with ERCP. This study was a prospective cohort study of 70 patients
with suspected CBD stones scheduled for cholecystectomy. Forty
patients at high risk of CBD stones (increased bilirubin, increased
alkaline phosphatase and a dilated CBD) underwent preoperative ERCP.
Thirty patients at moderate risk of CBD stones (moderately increased
bilirubin, normal CBD) underwent IOC. All patients
underwent MRC the results of which were assessed without knowledge of the
ERCP or IOC results. Results of MRC were positive for CBD stones in
21 (52%) of high risk patients a finding confirmed by ERCP in 19 (90%) of
patients. Results of MRC were positive for CBD stones in 6 (20%) of
moderate risk patients all of which were confirmed by IOC. The
overall sensitivity and specificity of MRC for CBD stones were 100% and
96% respectively. The positive and negative predictive values were
93% and 100% respectively. It was concluded that MRC is a reliable,
non-invasive method for the detection of CBD stones. It has the potential
to reduce the number of invasive diagnostic procedures and their
associated risks.
A comparison of paracentesis and
transjugular intrahepatic portosystemic shunting in patients with ascites.
Rossle M, Ochs A, Gulberg V et al. N Eng J Med 2000; 342:
1701-1707. 
Refractory or recurrent ascites is frequently encountered
in patients with ascites. Effective therapy is difficult but the
options available include repeated large-volume paracentesis,
peritoneovenous shunting, portosystemic shunting and liver
transplantation. Increased portal venous pressure is believed to be
an important aetiological factor and it can be effectively reduced with
either the surgical creation of a portosystemic shunt or by the
percutaneous insertion of a transjugular intrahepatic portosystemic
shunt (TIPSS). In patients with cirrhosis and ascites creation of a
TIPSS has been shown to reduce ascites and improve renal function.
In this study the role of TIPSS was directly compared with repeated
large-volume paracentesis. In total 60 patients with cirrhosis and
refractory ascites (Child-Pugh B n=42, Child-Pugh C n=18) were randomly
allocated to either TIPSS (n=29) or repeated paracentesis (n=31).
The median follow up was 44 months. The primary outcome measure was
survival without liver transplantation. Amongst the patients
receiving a shunt 15 died and one patient underwent liver transplantation.
In the paracentesis group 23 patients died and 2 underwent liver
transplantation. The overall probability of survival at both one and
two years was similar in the two groups. In a multivariate analysis,
treatment with TIPSS was independently associated with survival without
the need for transplantation (p=0.02). At three months, 61% of
patients in the shunt group and 18% in the paracentesis group had no
ascites (p=0.006). The frequency of hepatic encephalopathy was
similar in the two groups. It was concluded that in comparison with
large-volume paracentesis, the creation of a TIPSS can improve the chance
of survival without liver transplantation in patients with refractory or
recurrent ascites.
Acute necrotising pancreatitis:
treatment strategy according to the status of infection. Buchler M
W, Gloor B, Muller C A, Friess H, Seiler C A,
Uhl W. Ann Surg 2000; 232: 619-626.
Necrotising pancreatitis represents the most severe form
of acute pancreatitis. Superadded infection occurs in between 40%
and 70% of patients and is the most important risk factor predicting for
death. It is generally accepted that infected pancreatic necrosis
should be managed surgically. In contrast, the management of of sterile
pancreatic necrosis, accompanied by organ failure, remains controversial.
Recent evidence has suggested that conservative management of sterile
pancreatic necrosis with early antibiotic administration is safe. The aim
of this study was to assess prospectively in a single-centre trial the
role of the non-surgical management of patients with sterile necrosis and
the surgical treatment of patients with infected necrosis. Between
1994 and 1999, 204 consecutive patients with acute pancreatitis were
recruited. In total 86 (42%) had necrotising disease of whom 57
(66%) had sterile and 29 (34%) had infected necrosis. The presence of
pancreatic necrosis was determined by culture of percutaneous fine needle
aspiration specimens. Fine needle aspiration had a sensitivity of
96% for detecting pancreatic infection. Patients with infected
necrosis had more organ failures and a greater extent of necrosis compared
with those with sterile necrosis. When early antibiotic treatment
was used in all patients with necrotising pancreatitis the characteristics
of pancreatic infection changed to predominantly gram-positive and fungal
infection. An intention-to-treat analysis showed a death rate of 5%
with conservative treatment compared with 21% with surgery. It was
concluded that non-surgical management, including early antibiotic
treatment, in patients with sterile pancreatic necrosis was safe.
Infected pancreatic necrosis remains a significant complication and in
these patients surgical treatment is preferable.
Procalcitonin strip test in the early
detection of severe acute pancreatitis. Kylanpaa-Back M-L, Takala A,
Kemppainen E, Puolakkainen P, Haapiainen R, Repo H. Br J Surg
2001; 88: 222-227.
Acute pancreatitis involves an inflammatory process that
can range in severity from localised pancreatic inflammation to a severe
systemic disease affecting several remote organ systems. There is a
continuum from the development of the systemic inflammatory response
syndrome (SIRS) through to multiple organ dysfunction (MODS) and failure
(MOF). The latter occurs in approximately one quarter of patients and
carries a high mortality. Most patients with acute pancreatitis recover
quickly with simple supportive therapy. There is however a need to detect
those patients with severe pancreatitis early in the course of the disease
so as to allow supportive therapy in an intensive care unit. Several
biochemical parameters, contrast-enhanced CT and clinicobiochemical scores
have been developed to assess the severity of acute pancreatitis. An ideal
prognostic method should be simple, inexpensive, routinely available and
should be accurate with a high negative predictive value. Such a method is
not yet available. Procalcitonin is a 116-amino acid propeptide,
detectable in both plasma and serum, early in severe infection and
inflammation. A rapid semi-quantitative strip test (PCT-Q, Brahms
diagnostica, Berlin) for procalcitonin is now available. The aim of this
prospective study was to assess the ability of this test to predict
outcome in patients with acute pancreatitis and to compare it with
C-reactive protein (CRP) and multiple factor scoring systems. On admission
and 24 hours thereafter, serum procalcitonin level was measure in 162
consecutive patients with acute pancreatitis. There were 38 severe and 124
mild cases. The accuracy of procalcitonin and CRP in predicting severe
acute pancreatitis was compared with the Ransom and APACHE II scores. The
PCT-Q test was more accurate in predicting severe acute pancreatitis
(sensitivity 92%, specificity 84%) than CRP, Ransom or APACHE II scores.
Its negative predictive value was 97% and it detected all patients who
developed subsequent organ failure. It was concluded that PCT-Q was a
useful screening method for detecting severe acute pancreatitis. It was
simple, quick to perform and unlike current multiple factor scoring
systems could easily be adopted into routine clinical practice.
The effect of preoperative biliary
drainage on postoperative complications after pancreaticoduodenectomy.
Sewnath M E, Birjmohun R S, Rauws E A J, Huibregtse K,
Obertop H, Gouma D J. J Am Coll Surg 2001; 192:
726-734.
Surgery on patients with obstructive jaundice increases
the risk of postoperative complications. Consequently, preoperative
biliary drainage has been advocated with the potential of reducing
postoperative morbidity and mortality. Drainage can be achieved
externally by inserting a percutaneous drain or internally by placing a
stent at ERCP. Early non-randomised studies reported encouraging
results on reduction of mortality in jaundiced patients undergoing
pancreaticoduodenectomy for suspected pancreatic carcinoma, but subsequent
randomised clinical trials have failed to show a reduction in
postoperative complications. The aim of this study was to evaluate whether
preoperative biliary drainage improved postoperative outcome in such a
group of patients. A cohort of 311 patients undergoing
pancreaticoduodenectomy between 1992 and 1999 was studied. Overall,
21 patients who underwent external surgical biliary drainage were
excluded. The 232 patients who had preoperative internal drainage
were divided into three groups according to the extent of their jaundice.
(<40 µm (n=177), 40 to 100 µM (n=32) and > 100µM (n=32)). These
groups were compared with patients who underwent immediate surgery (n=58)
without preoperative drainage. The median number of stent placements was
2(range 1-6) with a median drainage duration of 41 days. The stent
dysfunction rate (blockage or cholangitis) was 33%. There was no
difference in overall morbidity between the drained and non-drained
groups. There was no difference on overall mortality between
patients with and without preoperative drainage. It was concluded
that preoperative biliary drainage did not influence the incidence of
postoperative complications and although it can be safely performed in
jaundiced patients its routine use is not necessary.
Late mortality in patients with severe
acute pancreatitis. Gloor B, Muller C A, Worni M, Martignoni M E, Uhl W,
Buchler M W. Br J Surg 2001; 88: 975-979.
Over the past decade it has become apparent that acute
severe pancreatitis progresses in two phases. The first 14 days are
characterized by a systemic inflammatory response syndrome (SIRS) due to
the release of various mediators. Two peaks in mortality can be
identified. Patients who die early usually do so a result of a massive
SIRS without apparent infection. Late death often results from multiorgan
dysfunction syndrome (MODS) caused by secondary infection of pancreatic or
peripancreatic necrosis. The aim of this study was to analyse the course
of the disease in patients suffering from severe acute pancreatitis and to
compare survivors with non-survivors. Between 1994 and 2000 details of 263
consecutive patients with acute pancreatitis were entered prospectively
into a database. All patients were treated in high dependency or intensive
care unit. Overall, 10 (4%) patients died. The mortality was 9% (10/106)
in patients with necrotising disease. No deaths occurred in the with
oedematous disease. No patient died within the first two weeks of disease
onset. The median day of death was 91 (range 15-209). Six patients died
from septic MODS. Ransom score, APACHE II score during the first week of
disease, pre-existing co-morbidity, body mass index, infection and extent
of necrosis were significantly associated with death (p<0.01 for all
parameters). However, only infected pancreatic necrosis was an independent
risk factor in multivariate analysis. It was concluded that early deaths
in patients with severe acute pancreatitis are rare, mainly as a result of
modern intensive care treatment. Over 90% of deaths occurred more than 3
weeks after disease onset. Infection of pancreatic necrosis was the main
risk factor for death.
Adjuvant chemoradiotherapy and
chemotherapy in resectable pancreatic cancer: a randomised
controlled trial. J Neoptolemos J P, Dunn J A, Stocken D
D et al. Lancet 2001; 358: 1576-1585.
Pancreatic ductal adenocarcinoma remains one of the most
difficult cancers to treat with an overall 5-year survival of only 0.4%.
Although 10-15% of patients undergo potentially curative surgery with a
low postoperative mortality rate, the median survival is only 10-18 months
with a 5-year survival of 15-25%. The best predictors of survival
after surgery are stage of disease, tumour grade and resection margin
status. The role of adjuvant therapy in the management of pancreatic
cancer remains uncertain. The aim of this study performed under the
auspices of the European Study Group for Pancreatic Cancer (ESPAC) was to
assess the role of chemoradiotherapy and chemotherapy in a randomised
study. After resection patients were randomised to adjuvant
chemoradiotherapy of chemotherapy. Clinicians could randomise
patients in 2 x 2 factorial design or into one of the main treatment
comparisons. The primary endpoint was death and all analyses were by
intention to treat. Overall, 541 eligible patients with pancreatic
ductal adenocarcinoma were randomised. 285 in the 2 x 2 factorial
design, a further 68 were randomly assigned chemoradiotherapy or no
chemoradiotherapy and 188 chemotherapy or no chemotherapy. Median
follow-up of the 227 (42%) patients still alive was 10 months.
Overall results shoed no benefit for adjuvant chemoradiotherapy (median
survival 15.5 vs. 16.1 months) with a HR 1.18 (95% CI; 0.90-1.55).
There was evidence of a survival benefit for adjuvant chemotherapy (median
survival 19.7 vs 14.0 months) with a HR 0.66 (95% CI; 0.52-0.83). It
was concluded that there was no survival benefit from adjuvant
chemoradiotherapy but the results suggested a potential benefit from
adjuvant chemotherapy alone. It was felt that further randomised
controlled trials of adjuvant chemotherapy in the management of pancreatic
cancer were justified.
Laparoscopic cholecystectomy versus
mini-laparotomy cholecystectomy: a prospective, randomised, single-blind
study. Ros A, Gustafsson L, Krook H et al. Ann Surg
2001; 234: 741-749.
During the late 1980s and early 1990s, randomised
controlled trials showed that recovery from open cholecystectomy (OC)
performed through a small subcostal incision was quicker than that
performed via a conventional Kocher's approach. Following the introduction
of laparoscopic cholecystectomy (LC), it too was shown to be superior to
OC. Despite taking longer to perform, it caused less postoperative pain
and was associated with a shortened hospital stay and convalescence. Many
of these studies comparing LC and OC were performed by surgeons in
specialist units. The aim of this study was to compare laparoscopic
cholecystectomy (LC) and 'mini' open cholecystectomy (MC) in a routine
healthcare system with surgery performed by both consultants and trainees.
Between March 1997 and April 1999, a randomised, single-blind, multicentre
trial was performed comparing LC and MC. Both elective and acute patients
were eligible for inclusion. All surgeons performing cholecystectomies
operated on randomised patients. LC was a routine procedure in all
hospitals whereas MC was introduced after a short training period. All
non-randomised cholecystectomies at participating units during the study
period were also recorded to analyse the external validity of the trial
results. Of 1705 cholecystectomies performed, 724 entered the trial and
362 patients were randomised to each of the procedures. The groups were
well matched for age and sex. There were fewer acute operations in the LC
group. In the LC group 264 and in the MC group 150 operations were
performed by surgeons who had done less than 25 operations of that type.
Median operating time was 100 and 85 minutes for the LC and MC groups
respectively (p<0.001). Median hospital stay was 2 days in each group, but
was significantly shorter after LC (p=0.04). Return to normal activities
was shorter after LC (p<0.001). Intraoperative complications were less
frequent in the MC group but there was no difference in postoperative
complications between the two groups. There was one serious bile duct
injury in each group but no deaths. It was concluded that operating time
was longer but postoperative convalescence quicker after LC compared with
MC.
Arterial embolisation or
chemoembolisation versus symptomatic treatment in patients with
unresectable hepatocellular carcinoma: a randomised controlled trial.
Llovet J M, Real M I, Montana X et al. Lancet 2002;
359: 1734-1739.
The incidence of hepatocellular carcinoma is increasing
worldwide. Curative therapies, such as resection, liver
transplantation or percutaneous treatments benefit only 25% of patients
and are the only chance of improving life expectancy. Despite the
implementation of surveillance programmes for early hepatocellular
carcinoma, most tumours are diagnosed at an advanced stage for which no
standard treatment has been established. The aim of this study was
to assess the survival benefit of arterial embolisation or
chemoembolisation in patients with unresectable hepatocellular carcinoma
in comparison with conservative management. Patients with Child-Pugh
class A or B and Okuda stage I and II disease were randomised to repeated
arterial embolisation (gelatin sponge), chemoembolisation (gelatin sponge
and doxorubicin) or conservative management. Overall 903 patients
were assessed and 112 (12%) were finally included in the study. The
primary endpoint was survival. Analysis was on an intention to treat
basis. The trial was stopped when the ninth sequential inspection
showed that chemoembolisation had a survival benefit compared with
conservative treatment (HR of death 0.47. 95% CI 0.25-0.91. p=0.025).
Overall 25 of 37 patients assigned embolisation, 21 of 40 patients
assigned chemoembolisation and 25 of 35 assigned conservative treatment
died. Probability of survival at one and two years were 75% and 50% for
embolisation, 82% and 63% for chemoembolisation and 62% and 27% for
conservative therapy. Chemoembolisation induced objective responses
sustained for at least 6 months in 35% of cases and was associated with a
significantly lower rate of portal invasion than conservative therapy.
Treatment allocation was the only variable independently related to
survival (OR 0.45. 95% CI 0.25-0.81. p=0.02). It was
concluded that chemoembolisation improved survival in stringently selected
patients with unresectable hepatocellular carcinoma.
Hepatitis B e antigen and the risk of
hepatocellular carcinoma. Yang H-I, Lu S-N, Liaw Y-F et al.
N Eng J Med 2002; 347: 168-174.
Chronic
hepatitis B virus infection is a serious clinical problem because of its
world wide distribution and potential for adverse sequelae, including
hepatitis, cirrhosis and hepatocellular carcinoma. It is particularly
prevalent in the Asian-Pacific region, where patients usually acquire the
infection at the time of birth or in early childhood. The presence of the
hepatitis B e antigen (HBeAg) in serum indicates active viral replication
in hepatocytes. HBeAg is thus a surrogate marker for the presence of
hepatitis B virus DNA. The aim of this study was to determine the
relationship between positivity for hepatitis B surface antigen (HBsAg)
and HBeAg and the development of hepatocellular carcinoma. In 1991 and
1992, 11,893 men in Taiwan, aged 30-65 years and without evdience of
hepatocellular carcinoma, were enrolled in the study. Serum samples were
obtained and tested for HBsAg and HBeAg by radioimmunoassay. The diagnosis
of hepatocellular carcinoma was ascertained through data linkage with the
computerised National Cancer Registry in Taiwan and with death
certificates. A multiple regression analysis was performed to determine
the relative risks of hepatocellular carcinoma among men who were positive
for HBsAg alone or HBsAg and HBeAg, as compared with those who were
negative for both. Overall, there were 111 cases of newly diagnosed
hepatocellular carcinoma during 92,359 person-years of follow-up. The
incidence rate of hepatocellular carcinoma was 1169 cases per 100,000
person-years amongst men who were positive for both HBsAg and HBeAg, 324
per 100,000 person-years for those who were positive for HBsAg only and 39
per 100,000 person-years for those who were negative for both. After
adjustment for age, sex, the presence or absence of antibodies to
hepatitis C virus, cigarette smoking, and use or nonuse of alcohol, the
relative risk of hepatocellular carcinoma was 9.6 (95% CI 6.0-15.2) among
men who were positive for HBsAg alone and 60.2 (CI 95% 35.5-102.1) amongst
those who were positive for both HbsAg and HBeAg, as compared with men who
were negative for both. It was concluded that positivity for HBeAg is
associated with an increased risk of hepatocellular carcinoma.
Wait-and-see policy or laparoscopic
cholecystectomy after endoscopic sphincterotomy for bile-duct stones: a
randomised trial. Boerma D, Rauws E A J, Keulemans C A et al.
Lancet 2002; 360: 761-765.
Endoscopic
sphincterotomy is widely accepted as the treatment of choice for patients
with common bile duct stones. Stones extraction is successful in 97%
of patients with a procedure-related morbidity of 6% and a mortality rate
of 0.2%. Whether subsequent laparoscopic cholecystectomy is
indicated in patients with concomitant gallbladder stones remains a matter
of debate. In several retrospective and non-randomised prospective
studies, it has been shown that only 4-12% of patients not operated on
develop biliary complications during the period of follow-up. The
aim of this study was to assess whether a wait-and-see policy after
endoscopic sphincterotomy is justified. A prospective, randomised,
multicentre trial was undertaken in 120 patients (18-80 years) who
underwent endoscopic sphincterotomy and successful stone extraction and
who also had proven gallbladder stones. Patients were randomly allocated
to a wait-and-see group (n=64) or laparoscopic cholecystectomy group
(n=56). Primary outcome was recurrence of at least one biliary event
during a 2-year follow-up period and secondary outcome measures were
complications after cholecystectomy and quality of life. Analysis
was on an intention to treat basis. Twelve patients were lost to
follow-up. Of the 59 patients allocated to a wait-and-see policy, 27
(47%) had recurrent biliary symptoms compared with one (2%) of the 49
patients allocated to laparoscopic cholecystectomy (RR=22.4, 95% CI
3.16-159.1. p<0.0001). 22 (81%) of these 27 patients underwent
cholecystectomy for biliary pain (n=13) or acute cholecystitis (n=7).
Conversion rate to open surgery was 55% in the patients allocated to the
wait-and see group compared with 23% in those who were allocated to the
laparoscopic cholecystectomy group (p=0.105). Morbidity and median
hospital stay was higher in the wait-and-see group. It was concluded
that a wait-and-see policy after endoscopic sphincterotomy in those with
gallbladder stones can not be justified. No major biliary
complications arose but conversion rates were high.
Early prediction of acute pancreatitis:
Prospective study comparing computed tomography scans, Ranson, Glasgow,
Acute Physiology and Chronic Health Evaluation II scores and various serum
markers. Roberts J H, Frossard J L, Mermillod B et al.
World J Surg 2002; 26: 612-619.
Acute
pancreatitis is a disease of variable severity. Although
approximately 80% of patients experience mild attacks that resolve with
little morbidity, the remaining 20% suffer from severe disease, with
mortality rates as high as 30%. Early prediction of the severity of
an attack remains the main goal of clinicians treating such patients.
Multifactorial scales including the Ranson, Imrie and Acute Physiology and
Chronic Health Evaluation (APACHE II) systems have been used since the
1980s. However, the complexity of these multifactorial scales
accounts for the increasing interest in serum markers of severity.
The aim of this study was to assess the early predictability of a variety
of parameters in acute pancreatitis. Overall, 137 consecutive
patients with acute pancreatitis confirmed by CT scan were prospectively
included. The predictive value of each parameter was studied by
univariate and multivariate analysis comparing mild and severe
pancreatitis. A total of 111 attacks were graded as mild (81%) and
26 as severe (19%). Ranson and APACHE II scores appeared
insufficiently predictive in univariate analysis. Pancreatic imaging
was insufficiently predictive whereas the presence of extra-pancreatic
fluid collections was more indicative of outcome. In the univariate
analysis, the four most reliable serum markers were pancreatic amylase (p<0.001),
neutrophil elastase (p<0.05), albumin (p<0.002) and
C-reactive protein (p<0.001). Serum albumin plus the presence
of extra-pancreatic fluid collections (negative predictive value 92-96%
and positive predictive value 67-100%) comprised the best indicator of
severity. None of the parameters testes achieved sufficient
predictability when used alone. It was concluded that serum albumin
plus extra-pancreatic fluid collections comprise the best indicator of
severity in acute pancreatitis at the time of admission.
Improvement in perioperative outcome
after hepatic resection. Jarnagin W R, Gonen M, Fong Y
et al. Ann Surg 2002; 236: 397- 407.
Over the past
decade, many large series have reported improved outcome following hepatic
resection performed for a variety of indications, with operative mortality
rates typically of less than 5% being reported from high-volume centres.
As a result, hepatic resection has evolved into the treatment of choice
for selected patients with benign and malignant hepatobiliary disease.
No single factor has been responsible for the marked improvement in
perioperative outcome, but improved anaesthetic and operative techniques
and better patient selection have all probably played a role. This
study analyses a consecutive series of unselected patients undergoing
hepatic resection over a ten-year period to further define factors
associated with morbidity and mortality. Demographics, extent of
resection, concomitant major procedures, operative and transfusion data,
complications and hospital stay were analysed for 1,803 consecutive
patients undergoing hepatic resection at the Memorial Sloan-Kettering
Cancer Centre. Malignant disease was the commonest diagnosis
(n=1,642 patients, 91%) and of these cases, metastatic colorectal cancer
accounted for 62% (n=1,021). 387 resections (21%) were performed for
primary hepatic or biliary cancer and 161 (9%) for benign disease.
Anatomical resections were performed in 1,568 patients (87%) and included
544 extended hepatectomies, 483 hepatectomies and 526 segmental
resections. The median blood loss was 600 ml and 49% patients were
transfused. Median hospital stay was 8 days, morbidity was 45% and
operative mortality was 3%. Over the study period there was a
significant increase in the use of parenchymal-sparing segmental
resections and a decrease in the number of hepatic segments resected. In
parallel with this was a significant decline in blood loss, the use of
blood products and hospital stay. Despite an increase in the number
of concomitant major procedures, operative mortality decreased and with no
perioperative deaths occurred in the last 184 cases. On multivariate
analysis, the number of hepatic segments resected and operative blood loss
were the only independent predictors of both operative morbidity and
mortality. It was concluded that, over the past decade, the use of
parenchymal-sparing segmental resections has increased significantly.
The number of hepatic segments resected and operative blood loss were the
only predictors of both perioperative morbidity and mortality.
Selective cholangiography in 600
patients undergoing cholecystectomy with 5-year follow-up for residual
bile duct stones. Charfare H, Cheslyn-Curtis S. Ann R
Coll Surg Engl 2003; 85: 167-173.
Laparoscopic
cholecystectomy id the treatment of choice for patients with symptomatic
gallstones, but the management of bile duct stones in these patients is
controversial. The use of selective cholangiography has been
criticised because of the risk of missing bile duct stones that will cause
significant complications later in life. The incidence of
symptomatic bile duct stones in patients undergoing cholecystectomy in
3-12%, but it is probable that only stones causing symptoms require
treatment and that other stone pass spontaneously or remain silent.
ERCP and sphincterotomy can successfully remove common bile duct stones in
over 90% of patients. In this paper the experience of a single
surgeon unit performing selective ERCP in the diagnosis and treatment of
common bile duct stones is presented. The incidence and management
of post-operative symptomatic bile ducts stones with a median 5-year
follow-up is reported. Between 1993 and 1999, 600 patients underwent
laparoscopic cholecystectomy. Patients were selected for
preoperative or postoperative ERCP based on symptoms, liver function tests
and abnormalities on ultrasound examinations. Of the 600 patients,
107 (18%) with a median age of 57 years were selected to undergo
preoperative ERCP. Of these patients 41 (38%) had bile duct stones.
Postoperative ERCP was performed in 30 patients (5%) and stones were
identified in 7 (23%) patients. Three patients had stones removed
within 15 days of their operation. The overall incidence of bile
duct stones was 48 (8%) cases. Stones were successfully extracted at
ERCP in 43 (90%) patients. It was concluded that a policy of
selective pre-operative ERCP is the most effective technique for
identifying and removing bile duct stones and that the incidence of
symptomatic gallstones following laparoscopic cholecystectomy is very low.
Role of somatostatin in the prevention
of pancreatic stump-related morbidity following elective
pancreaticoduodenectomy in high-risk patients and elimination of
surgeon-related factors. Shan Y-S, Sy E D, Lin P-W.
World J Surg 2003; 27: 709-714.
Pancreaticoduodenectomy remains the 'gold standard' operation in the
treatment of periampullary tumours. As a result of improved surgical
technique and perioperative care, mortality in the past 20 years following
this operation has declined, but the morbidity rate often remains high.
Most of the local complications are related to the exocrine secretion from
the pancreatic remnant. Somatostatin and its analogues have an
inhibitory effect on both exocrine and endocrine pancreatic secretions and
may reduce postoperative morbidity after pancreatic resection. The
aim of this study was to evaluate, in a prospective randomised controlled
fashion, the efficacy of somatostatin in the prevention of pancreatic
stump-related complications in high-risk patients undergoing
pancreaticoduodenectomy. Over a three year period, 54 patients (28
men and 26 women) undergoing pancreaticoduodenectomy were randomly
assigned to a somatostatin group (n=27) or placebo group (n=27). All
operations were performed by one high-volume surgeon. 94% patients
had pancreatic or periampullary lesions. All patients underwent
either a standard pancreaticoduodenectomy or a pylorus preserving
pancreaticoduodenectomy. A trans-anastomotic tube was inserted into
the pancreatic duct and remained in position for three weeks. The
somatostatin group received intravenous somatostatin at a dose of 250
micrograms per hour for seven days postoperatively. The placebo
group received a saline infusion. There was one perioperative death
in each group giving a postoperative mortality rate of 3.7%. In the
somatostatin group the overall morbidity and rate of pancreatic
stump-related complications were significantly lower. This was
associated with a 50% decrease in pancreatic juice output and shortened
duration of hospital stay. It was concluded that, after excluding
surgeon related factors, prophylactic use of somatostatin reduces the
incidence and severity of pancreatic stump-related complications in
high-risk patients undergoing pancreaticoduodenectomy.
Implementation of a specialist-led
service for the management of acute gallstone disease. Mercer S J,
Knight J S, Toh S K C et al. Br J Surg 2004; 91:
504-508.
Acute
cholecystitis and biliary colic commonly require emergency admission to
hospital. Traditionally, treatment was conservative followed by
delayed cholecystectomy, usually 6-8 weeks after discharge.
Laparoscopic techniques introduced in the late 1980s were initially
thought to be contraindicated for urgent cholecystectomy, but urgent
laparoscopic cholecystectomy for acute cholecystitis has been shown to be
safe. Two randomised trials, reported that early laparoscopic
cholecystectomy resulted in reduced hospital stay with no increased
morbidity. Few hospitals in the UK routinely perform urgent
cholecystectomy for acute gallstone admissions. The aim of this
audit was to assess the implementation of a protocol for urgent
cholecystectomy by a specialist upper gastrointestinal surgical team.
A 6 month retrospective audit of emergency admissions with acute
cholecystitis or biliary colic led to the development of a specialist-led
protocol for the management of acute gallstone disease. A second
audit was carried out over a 6 month period after the implementation.
Overall, 158 patients were admitted with acute cholecystitis or biliary
colic in the first audit period and 110 in the second interval. The
rate of cholecystectomy in the index admission increased from 37% to 67%,
at median of 3 days following admission. The conversion rate to open
surgery fell from 32% to 12%. Median hospital stay fell from 9 to
5.5 days and the unplanned readmission rate decreased from 19% to 4%.
It was concluded that urgent cholecystectomy for the management of acute
gallstone disease is feasible and achievable in an acute services hospital
with a specialist upper gastrointestinal team. It can lead to a
reduced conversion rate, short hospital stay, fewer unplanned
readmissions, an acceptable operating time and low complication rates.
Octreotide in the prevention of
intra-abdominal complications following elective pancreatic resection.
Suc B, Msika S, Piccinini M et al. Arch Surg
2004; 139: 288-294.
Mortality and
morbidity rates after pancreatic resection range from zero to 10% and 20%
to 40% respectively. The most common major complication is
pancreatic fistula, usually related to persistent pancreatic secretion
which hinders the healing of the pancreatic stump. Octreotide, a
synthetic somatostatin analogue, inhibits exocrine secretion of the
pancreas and therefore might lower the rate of postoperative pancreatic
fistula formation. This large prospective multicentre randomised
trial was undertaken to determine whether octreotide might decrease the
incidence and severity of postoperative intra-abdominal complications in
patients undergoing elective pancreatic resection. Overall, 230
patients undergoing pancreaticoduodenectomy and pancreatic enteric
anastomosis for either benign or malignant tumours or chronic pancreatitis
were randomised intraoperatively to receive either octreotide (n=122) or
control (n=108). All patients were available for analysis. All
patients were comparable except that significantly more patients in the
octreotide groups had biological glue injected into the main pancreatic
duct (p<0.001) or reinforcing of the pancreatic enteric anastomosis
(p=0.002). Fewer patients in the octreotide group sustained
one or more intra-abdominal complications. In subgroup analysis,
octreotide significantly reduced the intra-abdominal complications when
the pancreatic duct was less than 3mm in diameter (p<0.02), when a
pancreaticojejunostomy was performed (p<0.02) or both (p<0.02).
Overall, 23 (10%) patients died postoperatively and 16 (70%) had one or
more intra-abdominal complications. The only independent risk factor
for these complications was pancreaticoduodenectomy compared distal
pancreatectomy. It was concluded that octreotide is not necessary
for all patients undergoing pancreatic resection but that it may be useful
when the main pancreatic duct is less than 3mm in diameter and when
pancreaticoduodenectomy is completed by a pancreaticojejunostomy.
A randomised trial of chemoradiotherapy
and chemotherapy after resection for pancreatic cancer. Neoptolemos
J P, Stocken D D, Friess H et al. N Engl J Med
2004; 350: 1200-1210.
Pancreatic
cancer with an overall five-year survival rate ranging from 0.4 to 4% has
a poor prognosis and is one of the top 10 causes of death from cancer in
the Western world. Surgical resection improves the outlook, although
only about 10% of patients with pancreatic cancer are eligible for
surgery. Most treatment failures are due to local recurrence,
hepatic metastases or both and occur within one or two years of surgery.
Adjuvant therapy may improve long-term survival but is routine use is not
universal because the results of randomised trials have been inconclusive.
The European Study Group for Pancreatic Cancer (ESPAC) undertook a
multicentre trial to investigate the possible benefit of adjuvant
chemoradiotherapy and maintenance chemotherapy in patients with pancreatic
cancer. The study involved a 2x2 factorial design. Patients
were randomly assigned after resection for pancreatic ductal
adenocarcinoma to chemoradiotherapy (20Gy over 2 weeks plus flurouracil;
n=73), chemotherapy alone (flurouracil; n=75), both chemoradiotherapy and
maintenance chemotherapy (n=72) or observation (n=69). The analysis
was based on 237 deaths among 289 patients (82%) and a median follow-up of
47 months (IQR 33-62). The estimated five-year rate was 10% amongst
patients assigned to receive chemoradiotherapy and 20% among patients who
did not receive chemoradiotherapy (p=0.05). The five-year
survival rate was 21% among patients who received chemotherapy and 8%
among patients who did not receive chemotherapy (p=0.009).
The benefit of chemotherapy persisted after adjustment for major
prognostic factors. It was concluded that adjuvant chemotherapy has
a significant survival benefit in patients with resected pancreatic
cancer, whereas adjuvant chemoradiotherapy has a deleterious effect on
survival.
Randomized clinical trial of
pylorus-preserving duodenopancreatectomy vs. classical Whipple resection -
long term results. Seiler C A, Wagner M, Redaelli C A
et al. Br J Surg 2005; 92: 547-556
Advances in surgical technique have
reduced the operative mortality of patients undergoing pancreatic head
resection to below 5% in specialist centres. Because of the relative
resistance of these tumours to chemotherapy and radiotherapy, any attempt
to achieve a cure must include radical resection. For many years,
the surgical procedure of choice was duodenopancreatectomy (Whipple's
procedure). This was associated with side effects related to the
partial gastric resection, notably postoperative weigh loss and dumping
syndrome. A more conservative procedure, the pylorus-preserving
pancreaticoduodenectomy (PPPD) has been reported. It is unknown as
to whether PPPD is as effective as the classical Whipple's procedure in
the resection of pancreatic and periampullary tumours. A prospective
randomised trial was undertaken to compare the results of the two
procedures. Clinical data, histological findings, short-term
results, survival and quality of life of all patients undergoing surgery
for suspected pancreatic or periampullary tumours between June 1996 and
September 2001 were analysed. Overall, 214 patients were randomised
to undergo either a standard Whipple's procedure or PPPD. After
exclusion of 84 patients on the basis of intraoperative findings, 130
patients (66 standard Whipple's procedure and 64 PPPD) were entered into
the trial. Of these 110 patients with proven adenocarcinoma (57
standard Whipple's procedure and 53 PPPD) were analysed for long-term
survival and quality of life. There were no differences in
perioperative morbidity. Long-term survival, quality of life and
weigh gain were identical after median follow-up of 63 (range 4-93)
months. At 6 months, capacity to work was better after PPPD (77% vs.
56%. p=0.019). It was concluded that both procedures were
equally effective for the treatment of pancreatic and periampullary
cancer. PPPD offers some minor advantages in the early postoperative
period, but not in the long term.
Surgical intervention in patients with
necrotizing pancreatitis. Besselink M G, de Bruijn M T,
Rutten J P et al. Br J Surg 2006; 93: 593-599.
There is international consensus that surgical
intervention is acute pancreatitis is indicated only in the case of
suspected or proven infected pancreatic necrosis. However, there is
no agreement as to the optimal surgical strategy. Several specialist
centres have reported the outcome of various surgical approached with
mortality rates ranging from 6% to 47%. The different surgical
strategies have never been compared in randomised controlled trials.
The aim of this study was to evaluate the various surgical strategies for
the treatment of infected pancreatic necrosis and to determine the
referral patterns in the Netherlands for this condition. This
retrospective study included all 106 patients who had surgery for infected
pancreatic necrosis in the period 2000-2003. Surgical approaches
included an open abdomen strategy, laparotomy with continuous
postoperative lavage, minimally invasive procedures or laparotomy with
primary abdominal closure. The National Hospital Registration System
was searched to identify patients with acute pancreatitis who were
admitted to the 90 Dutch hospitals that did not participate in the present
study. The overall mortality was 34%, 70% (16 of 23) for the open
abdomen strategy, 25% (13 of 53) for continuous peritoneal lavage, 11% (2
of 18) for minimally invasive procedures and 42% (5 of 12) for primary
abdominal closure (p<0.001). During the study interval, 44
(12%) of 362 patients with acute pancreatitis who were likely to require
surgical intervention had been referred to university medical centres.
It was concluded that laparotomy with continuous postoperative lavage is
the surgical strategy most often used in the Netherlands. The
results of the open abdomen strategy are poor whereas the minimally
invasive approach seems encouraging.
Association between early systemic
inflammatory response, severity of multiorgan dysfunction and death in
acute pancreatitis. Mofidi R, Duff M D, Wigmore S J
et al. Br J Surg 2006; 93: 738-744.
Acute pancreatitis has a spectrum of clinical presentation
ranging from mild self-limiting disease to severe pancreatitis which
results in the development of local and systemic complications with a
significant risk of death. Mortality in patients with acute
pancreatitis is associated with the number of ailing organs and the
severity and reversibility of organ dysfunction. The aim of this
study was to assess the significance of early systemic inflammatory
response syndrome (SIRS) in the development of multiorgan dysfunction
syndrome (MODS) and death from acute pancreatitis. Data for all
patients with a diagnosis of acute pancreatitis between 200 and 2004 was
reviewed. Serum C-reactive protein (CRP), Acute and Chronic Health
Evaluation (APACHE) II scores and the presence of SIRS were recorded on
admission and at 48 hours. Marshall organ dysfunction scores were
calculated during the first week of presentation. Presence of SIRS
and raised serum CRP levels on admission and at 48 hours were correlated
with the cumulative organ dysfunction scores in the first week.
Overall, 759 patients with acute pancreatitis were identified of whom 45
(6%) died during the index admission. SIRS was identified in 162
patients and was persistent in 138 at 48 hours. The median (range)
cumulative Marshall score in patients with persistent SIRS was
significantly higher than that in patients in whom SIRS resolved and in
those with no SIRS. Thirty-five patients (25%) with persistent SIRS
died from acute pancreatitis, compared to 6 patients (8%) with transient
SIRS and 4 patients (1%) without SIRS (p>0.001). No
correlation was observed between CRP level on admission and Marshall score
(p=0.81). There was however a close correlation between CRP
level at 48 hours and Marshall score (p<0.001). It was
concluded that persistent SIRS is associated with MODS and death in
patients with acute pancreatitis and is an early indicator of the likely
severity of acute pancreatitis.
Randomised clinical trial of liver
resection with and without hepatic pedicle clamping. Capussotti L,
Muratore A, Ferrero A et al. Br J Surg 2006; 93:
685-689.
Operative blood loss and perioperative transfusions are
predictors of morbidity and mortality after hepatic surgery.
Prospective randomised trials comparing liver transection with and without
hepatic pedicle clamping (HPC) have shown a significantly lower blood loss
in the former group. Intermittent pedicle clamping has been shown to
have benefits in terms of liver tolerance to ischaemic injury when
compared with continuous clamping. Intermittent clamping has become
the most commonly used procedure to control bleeding during hepatectomy.
The aim of this study was to compare perioperative outcome of liver
resections with and without intermittent hepatic pedicle clamping.
Between 2002 and 2004, 126 consecutive patients with resectable liver
tumours were randomised to undergo resection with (n=63) or without (n=63)
intermittent hepatic pedicle clamping. The transection time was
significantly higher in the group without hepatic pedicle clamping.
The blood loss per cm2 was similar in the two groups (2.7 ml/cm2
in the groups with versus 3.2 ml/cm2 in the groups
without hepatic pedicle clamping (p=0.425). In the subset with an
abnormal liver, there was no difference in blood loss per transection
surface. The rate of blood transfusion was not higher in the
non-clamping group. No differences were observed in the
postoperative liver enzyme serum levels, the in-hospital mortality or the
number of complications. It was concluded that liver resection
without hepatic pedicle clamping is safe, even in patients with a diseased
liver.
Early warning scores predict outcome in
acute pancreatitis. Garcea G, Jackson B, Pattenden C J
et al. J Gastrointest Surg 2006; 10: 1008-1015.
For most patients with acute pancreatitis it is a mild
self-limiting condition. However, in 20-30% of cases, severe
lift-threatening complications may ensue with the development of
associated organ dysfunction. The reliable identification of these
patients would be useful in selecting individuals requiring critical care
support. An ideal prognostic index should be able to identify severe
cases of acute pancreatitis within 2-3 days of the onset of symptoms.
To this end, several clinical scoring systems have been adopted including
the Ransom, Imrie and APACHE II systems. The Early Warning
Score (EWS) is a widely used general scoring system to monitor progress in
critically unwell patients. The aim of this study was to evaluate
the EWS compared with other established scoring systems in patients with
acute pancreatitis. EWS was compared with APACHE scores, Imrie
scores, CT grading scores and Ranson criteria for 110 admissions with
acute pancreatitis. A favourable outcome was considered to be
survival without ITU admission or surgery. Non-survivors,
necrosectomy and critical care admission were considered adverse outcomes.
EWS was the best predictor of adverse outcome in the first 24 hours after
admission (receiver operating curve, 0.768). The most accurate
predictor of mortality was EWS on day 3 of admission (receiver operating
curve, 0.920). EWS correlated with duration of intensive therapy
unit stay and the number of ventilated days (p<0.05) and selected
those patients who went on to develop pancreas-specific complications such
as pseudocysts or ascites. EWS of 3 or above was an indicator of
adverse outcome in patients with acute pancreatitis. It was
concluded that EWS can accurately predict and reliable select both
patients with severe acute pancreatitis and those at risk of local
complications.
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