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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_1649_Библиотеки_им_академика_М_И_Перельмана.pdf
Management of Acute Biliary Pancreatitis
121
alternatively one could use no nutrition in some patients in case of diagnostic
doubt, ACS ecc… [94]
The use of antibiotics in ABP is still under discussion. There are two
relevant points in this topic: first point quite defined is the treatment of an
infection already present that requires only the choice of the antibiotics. On the
other hand the prophilactic use of antibiotics is not well defined.
In the evolution of severe acute pancreatitis the main aim of the
propylactic use of antibiotics is to avoid the contaminations of the fluid-
necrotic pancreatic or peripancreatic collections. Therefore the antibiotics
employed should have well defined antimicrobial activity such as penetration
rate, persistence and therapeutic concentrations rate in the necrotic area.
Study of several years ago had suggested the use of pefloxacin and
metronidazol or, to varying degrees, imipenem and mezocillin [95].
In conclusion the prophilactic uses of antibiotics in AP should b initiated
at the admission, because half of infective complications occur in the first few
days after the onset and should be continued for 14 days [96, 97].
In the medical specific therapeutic approach of AP there are three drugs
largely employed: antiproteases, somatostatin and octreotide.
The use of antiproteases shows results highly debatable [98].
Somatostatin and octreotide develop positive action of inhibition of
pancreatic secrection but they are also splanchnic vasoconstrictors with
hypoperfusion of the pancreas that can promote pancreatic necrosis. Therefore
its employment is controversial [99].
In summary the therapeutic approach of ABP usually develops in two
phases following the evolution of the disease. In mild-moderate forms at the
onset of the disease (first phase) the treatment includes simple fluid
rehydratation and control of abdominal pain. In the severe forms, at first
phase, the therapeutic approach consists of intensive care, initial fluid,
aggressive resuscitation, low dose steroides, anticoagulatory agents for anti-
inflammatory properties, correction of hypoxaemia, enteral nutrition to
preserve the intestinal integrity and antibiotic prophylaxis. In conclusion in
this first phase of severe forms the central purpose is to control and treat, by
intensive care support, the damage of the general conditions and possible
organ failure [100].
In the ABP the control of papillary patency and, if necessary, its treatment
with endoscopic retrograde cholangiopancreatography/endoscopic
sphyncterotomy (ERCP/ES), can be considered the cornerstone of therapeutic
program based on the confirmation by instrumental exams (US, MRCP) of
papillary obstacle (stones, sludge, papillary sclerosis, ecc…) or, if it is present,
Vincenzo Neri
122
cholestasis or cholangitis. ERCP/ES can assure papillary flow and CBD
cleaning if lithiasis obstacle, sludge, microlithiasis are present. Following this
general considerations on the pathophysiology of acute biliary pancreatitis, the
therapeutic use of ERCP/ES is based on several data to be evaluated:
a. Confirmation of papillary obstacle, persistent or transient, generally
due to biliary lithiasis.
b. Indication of procedure: wich patients (with ABP) should be
submitted to ES
c. Timing of the procedure
d. Complications.
Biliary etiology of pancreatitis can be established at the onset with first
level etiological assessment by the research, on abdominal US, of gallbladder
lithiasis, and/or gallstones, sludge, microlithiasis in the CBD or also a
dilatation of CBD (>8 mm) besides with liver function tests/cholestasis
indexes, fasting serum calcium and lipid profile.
The second level diagnostic study, that is MRCP and/or endoscopic US
usually should confirm the biliary origin of pancreatitis in majority of patients.
In very few patients the etiology of pancreatitis remain unexplained [101].
More complex is the answer to the following question: which patients
should be submitted to ERCP/ES?
The choice of the patients for ERCP/ES and its timing in ABP are
nowadays still controversial despite many years since its introduction in the
therapeutic program. There are many studies in the literature about this topic.
Some of these are now “historic”: Neoptolemos [102], Fan [103], Nowak
[104], Folsch [105].
Recent systematic review have been published [106, 107, 108]. The
conclusion of these studies agree on some points:
Early ERCP/ES has not advantage for patients with mild pancreatitis
and is not indicated;
Early ERCP/ES may be indicated in patients with severe disease,
biliary obstruction or cholangitis.
Also in one review [108] early ERCP/ES may reduce complications in
patients with predicted severe pancreatitis.
Management of Acute Biliary Pancreatitis
123
Tse F et al. published a cochrane database Systematic Review. Their
conclusions are that early ERCP/ES does not significatly nodify mortality,
local and systematic complications [109]. However early ERCP/ES should be
recomended for patients with severe or moderate pancreatitis with co-existing
papillary obstruction (laboratory – instrumental dimonstration) or cholangitis.
In conclusion this therapeutic procedure can be proposed in all patients
with severe, early severe acute biliary pancreatitis and recurrent pancreatitis
and also in several patients with moderate or moderate – severe disease.
Obviously all these patients should achieve laboratoristic, strumental (US or
MRCP), confirmation of a papillary or CBD lithiasis obstacle, sometime
complicated by angiocholithis. The timing of ERCP/ES after identification of
patients should be choiced within the first 48 – 72 hous from the onset of
pancreatic attack. Finally ERCP/ES in patients with severe acute pancreatitis,
severe impairment of general conditions and requirement of intensive care and
assisted ventilation can be high risk procedure. This therapeutic choice is very
difficult and without worldwide consent.
Complicatons of ERCP/ES are not unusual. They include post-procedural
pancreatitis, perforations, bleeding, infections.
Some data from the literature show that the incidence rate of these
complications ranges about 10%. The complications with major morbidity
reach 1, 5% and mortality less than 0, 5% [110, 111].
More recent data show that the majority of events are of mild-to-moderate
severity; but on the other hand the overall complication rate not diminiuished
[112].
In all patients with pancreatitis with biliary pathogenesis, submitted to
ERCP/ES or not, it is necessary to perform lapaoscopic cholecystectomy in the
same hospital stay to complete the gallstone treatment. The timing of
laparoscopic cholecystectomy is connetted with acute pancreatitis evolution
because it is preferable to wait for the stabilization and improvement of the
general conditions and of phlogistic impairment of pancreatic and
peripancreatic tissue. An algorithm of ERCP/ES employment in ABP is shown
in Figure 1.
The pathological basis of therapeutic perspectives in severe acute biliary
pancreatitis are linked on grade of impairment of pancreatic parenchyma and
peripancreatic tissues. The advanced phase of severe acute pancreatitis is
characterized by a counteractive anti-inflammatory response syndrome
(CARS), with the risk of infected necrosis and worsening of organ failure.
Vincenzo Neri
124
Figure 1. ERCP/ES in Acute Biliary pancreatitis.
Severe acute pancreatitis in its late phase can have some evolutions:
amelioration of early organ failure after intensive care but infection of peri-
pancreatic necrotic tissues causes worsening of general conditions in the
second, late phase of disease; or uninterrupted serious conditions without
improvement between the first phase of early organ failure and the infected
necrosis in the following third – fourth weeks. Also persistent organ failure
requires control of collections infection -fine nidle aspiration bacteriology
(FNAB), gas bubbles on CECT-; in these latter cases interventional procedures
should be employed [113].
The prevalence of necrotizing forms is 15-20%, that are characterized by
hypoperfusion of the parenchyma on a CECT (Balthazar score) [89]. The
necroting process involves the gland parenchyma and peripancreatic tissues
with very variable extension. The extensive interstitial oedema is associated
with pancreatic and peripancreatic necrosis in a short period of 48 – 72 hours
after the onset of acute attack. These inflammatory, necrotic tissues give rise to
acute fluid collections with an amount of devitalized tissue.
The further evolution of these fluid gatherings is characterized by
demarcation between viable and necrotic tissue and the limit is set with a wall
of granulation tissue. The management of these pancreatic and peripancreatic
fluid – necrotic collections and their complications is the longest and most
debated therapeutic problem. This therapeutic program includes some specific
surgical decision based on the following questions:
Management of Acute Biliary Pancreatitis
125
a. How long the control and observation of not complicated fluid-
necrotic gatherings may be prolonged?
b. How to differentiate infected pancreatic necrosis from those sterile?
c. In some patients with infected necrosis may be delayed the surgical
treatment?
d. Which is the best treatment of the fluid – necrotic complicated
gatherings?
The therapeutic program should follow the evolution of ABP. In the early
toxic phase (first two weeks), besides the control and treatment of papillary
and CBD lithiasic obstacle by ERCP/ES, to obtain the normal biliary and
pancreatic papillary flow and CBD cleaning, the central therapeutic purpose is
to improve the severe involvement of general conditions, to avoid the start of
the dreaded SIRS and minimizing the mortality from MODS. Therefore in this
phase all surgical procedures should be avoided.
The following phase from the third/fourth weeks is characterized by the
fluid necrotic collections with or without septic complications, such as
infected pancreatic necrosis.
a. How long the control and observation of not complicated fluid-
necrotic gatherings may be prolonged?
If not complicated the gatherings may be submitted to conservative
procedure also for several weeks (four/eight weeks). The pathological
conclusion of persisiting peripancreatic fluid collection generally
greater than 5 cm can be acute postnecrotic pseudocyst. In the
asyntomatic gatherings surgical manoeuvres and percutaneous
drainage should be avoided because the risk of secondary infections
[114]. In selected patients with persistent severe impairment of
general conditions and organ failure interventional procedures can be
indicated also for sterile fluid – necrotic collections [115].
b. How to differentiate infected pancreatic necrosis from those sterile?
The first step is the control of clinical and laboratory signs of sepsis.
The suspicious of infection may be based on the demonstration by
CECT of gas bubbles into the gatherings. Only if there is doubt of
infections in necrotic collections, the FNAB should be performed,
because of a potential risk of secondary infections [116].
c. In some patients with infected necrosis may be delayed the surgical
treatment?
Vincenzo Neri
126
In the general assessment, surgical procedures are indicated in
patients with fluid – necrotic septic gatherings because to avoid the
impairment of general conditions by sepsis. Septic complication of
pancreatic and peripancreatic necrotizing tissues can occur in the first
phase of the disease and causes the true pancreatic abscess with
further worsening of the general conditions. In this case the drainage
of the infected collection should be mandatory by percutaneous or
endoscopic or open approach [117]. Therefore with worldwide
antimicrobic therapy, in patients without compromission of general
conditions may be to delay the surgical procedure for some weeks
when the collection has become walled off [118, 119]. Surgery in the
first phase of the disease (first two weeks from the onset) has a very
high mortality rate (75%), generally because of necrosectomy for
infected collections, but if delayed later than four weeks from the
onset the mortality decrease to 5% [120]. The better results in the
surgical treatment of fluid – necroting pancreatic – peripancreatic
gatherings are connected to a suitable time interval –between the
onset of disease and intervention- for encapsulation of collection and
the recovery of general conditions of patients.
d. Which is the best treatment of the fluid – necrotic complicated
gatherings?
The treatment of pancreatic – peripancreatic necrotic gatherings in the
last decade is oriented, with a progressive evolution, toward
minimally invasive surgical procedures. There are no, in these
therapeutic programs, indications and surgical procedures
unanimously standardized and employed. In the past has been
proposed and used for infected necrotic collections, the open
necrosectomy with complete debridment, necrosectomy,
retroperitoneal lavage system and drains in the lesser sac. The
mortality was 25% [121]. Other open procedures have been also
proposed: closed packing intervention with mortality 11% and open
abdomen strategy with planned relaparotomy with high mortality 70%
[122, 115]. Lately necrosectomy by a mininvasive procedures are
getting popular: percutaneous minimally invasive retroperitoneal
necrosectomy, video- assisted retroperitoneal debridement (VARS)
(with removing some pieces of less adherent necrosis and reducing
the risk of bleeding and the remnant necrotic tissue can be resorbed),
necrosectomy with minimally invasive step-up approach, endoscopic
transluminal necrosectomy (ETN), percutanoeus drainage [123, 124,
Management of Acute Biliary Pancreatitis
127
125, 136]. The comparison between open necrosectomy and step-up
approach with percutaneous or transgastric drainage and drain-guided
necrosectomy, showed for the latter minor complications [127].
In summary under the procedures minimally invasive could be revalued
the simple percutaneous drainage of septic necrotic collections. We should
keep in mind that it can be a first step of therapeutic program, with a real
possibility that the necrotic tissue can be resorbed; it also if the drainage of the
collection is incomplete, it should be possible to perform a complete
necrosectomy.
Recent data from the literature showed the high number of patients treated
with percutaneous drainage (22 – 55%) and the technical success rate of 99%
[123]. In conclusion it is not clear the best procedure for the treatment of
septic necrotic pancreatic collections. No single approach can be right and
suitable for all patients. The procedures for drainage of collections and/or
debridement of septic – necrotic tissue among the several therapeutic choices
proposed should be tailored based on patient presentation and anatomy [128].
Open necrosectomy ramains the last option after the failure of less invasive
procedures.
Algorithm of management of pancreatic – peripancreatic fluid – necrotic
collections is shown in Figure 2.
Figure 2. Management of pancreatic – peripancreatic gatherings.
Vincenzo Neri
128
Fluid – necrotic pancreatic – peripancreatic collections not infected may
have a dual evolutions: resorption of collections and resolution of disease or
the collection forms the acute postnecrotic pseudocyst. Two factors influence
these trends, the size of gatherings and time.
Necrotizing pancreatic gatherings not complicated can develop a complete
separation of the tissues with liquid content and a fibrous wall (acute
postnecrotic pseudocyst). The evolution of a lesion with a fibrous wall can be
complete in many weeks (12-16 weeks). Small cysts lesser than 5-6cm can
show a spontaneous resorption in many months without clinical appearance.
The incidence of acute postnecrotic pseudocysts is low, at 5-16% [129].
Pseudocysts larger than 6 – 7cm, or symptomatic, or persistent over many
months require surgical treatment.
The choice of the procedures should be guided by a fundamental
pathological characteristic: the connection with pancreatic ducts. If the
connection is present should be avoided simple percutaneous US/CT guided
drainage because the risk of persistent leakage of pancreatic juice from the
drain, infection and the possible repeated changes of drain. The procedures to
be proposed are surgical with open or minimally invasive approach
(laparoscopic, endoscopic): always pseudocystodigestive prolonged
connection such as anastomosis or fistulas [130]. The choice of the digestive
tract for the surgical drainage is based on the site of the development of the
pseudocyst: lesser sac, epiploic foramen, infracolic compartment, ecc…
Intestinal organs usually employed for the anastomosis are stomach,
duodenum, small intestine: pseudocystojejunostomy, pseudocystogastrostomy,
pseudocystoduodenostomy [131].
CONCLUSION
In the past twenty years many important advances have been made in the
management of ABP.
In severe, moderate – severe, recurrent acute pancreatitis with cholestasis
– cholangitis or with instrumental confirmation (US – MRCP) of papillary –
CBD obstacle is indicated the therapeutic ERCP/ES within 72 hours.
The interventional procedures in the treatment of severe acute pancreatitis
require a radical revision. In septic necrotic collections the role of the surgery
should be limited to percutaneous drainage, that in most cases could reduce the
need for surgery. If major surgical interventions are required, these should be
more conservative as possible and preferred minimally invasive approaches.
Management of Acute Biliary Pancreatitis
129
ACKNOWLEDGMENT
I’m very grateful to the doctors Libero Luca Giambavicchio and
Francesco Lapolla for their valuable assistance in the typographical
transcription of the manuscript.
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