)
Table of contents :
| Anatomical classification : | Symptoms, signs, and syndromes :
|
Diseases of the esophagus
or Down
syndrome
within 24-48 hours
within 24-48 hours
in type I and type III (60%)
stops after 10 cm,
air in stomach is found in type III, IV, and V (distended,
tympanic abdomen)
but not in type I (depressed, dull abdomen)
shows pulmonary atelectasis or bronchopneumonia
for excessive gastric distension (in type III and high-risk
newborns)
since month 8-12 of age : cervical esophagostomy + gastrostomy.
is extremely rareref.;
aspiration
pneumonia
ref
(expecially tubercolar lymphadenitis)
who undergo EGD examinations. The prevalence of Cameron lesions
seems to
be dependent on the size of the hernia sac, with an increased
prevalence
the larger the hernia sac. In about 66% of the cases, multiple
Cameron
lesions are noted rather than a solitary erosion or ulcer
=> empyema of mediastinum and usually pleural
empyema
(chagasic achalasia)
concentrations
and ESCC
(RR =
33 for chagasic achalasia)
infiltrations
)
followed by sub aortic esophagogastrostomy
followed by cervical transmediastinal anterior
esophagogastroplasty.
Overlying mucosa is thinned.
with up to 2 liters of cold physiological solution
with addedd antacids]
=>,
vasopressin
or Sengstaken-Blakemore
tube
=>
=>
(timolol) are ineffective in preventing varices in unselected
patients
with cirrhosis and portal hypertension and are associated with an
increased
number of adverse eventsref
,
resulting in abdominal distention or belching,
often interpreted by the patient as signs of a physical disorder),
defective esophageal clearance)
during meals
occurring in children as a symptom of reflux esophagitis or
hiatal
hernia
has sensitivity = 90% and specificity = 10% ; only in cases
with atypical
symptoms,
hiatal hernia, gastric
emptying,
thickening of esophageal walls
: lansoprazole 20 mg/day resolves symptoms in 1-2 months; 25%
of patients
using metachlopramide (10 mg 3 times a day) experience CNS
side effects/hematemesis/melena
=> sideropenic
anemia,
hypoproteinemia
(Candida esophagitis)
or peritonitis
(TOC) / palmoplantar ectodermal dysplasia type III,
c-MYC) and inactivation of several tumor suppressor genes.
LOH on chromosome
17q25-qter, telomeric to the keratin II gene cluster, has
been linked with
tylosis, a rare autosomal dominant syndrome associated with
high predisposition
to ESCC. Whether this locus is also involved in sporadic
ESCC remains to
be elucidated. Chronic esophagitis is a frequent occurrence
in populations
at high risk of ESCC. These lesions often show focal
accumulation of p53
protein and in some instances, patches of positive cells in
esophagitis
area at the margins of tumors were found to contain a
mutation in the p53
gene
(differential diagnosis with sarcomas with IHC for
epithelial cytokeratins).
Its prevalence is increasing at the most rapid rate of any
cancer in the
USA
-like
carcinoma
(LELC) of the esophagusref
(from melanocytes in basal layers of oesophagus)
is
exceptionally rare. A dozen or so esophageal carcinoids have
been reported.
On the whole, prognosis is poor, and most tumors
metastasize.
in von
Trendelenburg's
position
shows ulcers or vegetations
=> biopsy
or MRI
for staging (longitudinal and transverse spreading in lymph
nodes, metastases
to liver and lungs)|
|
|
|
|
| cervical esophagus cancer |
|
|
|
| upper thoracic esophagus cancer |
|
|
|
| midthoracic esophagus cancer |
|
||
| lower thoracic esophagus cancer |
|
60-70 Gy (SCC is a radiosensitive tumor) in unresectable
tumors
> 5-FU
> mitomycin C
> vincristine
> bleomycin
(partial and short-lasting response in 50%)
or mucosal resection has become attractive for many of these
patients with
co-morbidity
:
with electrodes in small gastric curve and LES (distances from
incisors
are taken by endoscopy). It detects :
in von
Trendelenburg's
position.
It is expecially useful to detect spastic oesophagitis,
undiagnosticable
by oesophagoscopy.
for submucosal tumors/
gastropathy / gastrosis
;
because they may bleed intermittently, and only be
endoscopically evident
during hemorrhage, their diagnosis can be challenging because of
its small
size and hidden location; multislice helical CTref
injection plus heater probe coagulation is significantly
superior to epinephrine
injection alone in achieving hemostasis. Embolotherapyref,
endoscopic sclerotherapyref,
histoacryl injection, endoscopic hemoclipping, and endoscopic
band ligation
(EBL)ref
are safe and effective alternate therapiesref.
Long-term recurrence was not evident following endoscopic
ablation. Follow-up
after ablative therapy appears unnecessaryref.
.
and gastrojejunostomy,
or nasogastric
tube
feeding
,
often a sensation of warmth, and sometimes diarrhea
due to hypertonic gastrorrhea
=> hyperinsulinemia after 3 hours => late hypoglycemia
which creates a large passage, but has the inconvenience of a
marginal
ulcer or the late recurrence of the stenosis (narrowing of the
gastrojejunostomy
due to the decrease of the gastric dilatation)
and
a funnel shaped reconstruction. The upper part of this funnel
is located
at the level of the major gastric curvature favoring
gravitational drainage
to the duodenum through the gastroduodenal anastomosis.
during CPR
either direct (e.g. for pertussis post-exposure prophylaxisref1,
ref2,
ref3,
ref4,
ref5,
ref6,
ref7,
ref8,
ref9,
ref10,
ref11)
or through breast milk after maternal postnatal use of
macrolidesref
(erythromycin (EM) is a MTLR1
agonist with prokinetic effect at low doses (1-3 mg/kg) used for
for feeding
intolerance in preterm infants : motilin, a gastrointestinal
peptide, stimulates
propagative contractile activity during phase III of the
migratory motor
complex in the interdigestive stateref1,
ref2)
(as this is a dynamic condition, it should not be excluded
after a single
negative examination; also used for prenatal diagnosis)
shows thickening
> 4.1 +/- 1.1 mm and enlengthnment > 13.6 +/- 2.5 mm
in an avascular region (also in laparoscopy)
)
following fibrous stenosis.).
Silk suture should be avoided when constructing surgical
gastrostomies.
When the tube is in place for > 9 months before removal the
incidence of
GCF can be as high as 45%
is injected subcutaneously to stimulate gastric secretion
of the stomach associated with well-differentiated
adenocarcinoma of
the transverse colonref
: in body and fundus of stomach, with pyloric and
intestinal metaplasia.
The great angular incision of the small curve has
increased susceptibility
due to-producing
epithelium
infection. Hypertone of pyloric sphincter => delay in
gastric emptying
causes H+ hypersecretion.,
particularly to cows' milk
,
iron
deficiency anemia,
elevated levels of serum IgE, and protein-losing
enteropathy.
)
(inhibits acid secretion, stimulates mucosal restitution
after injury (cell
migration and proliferation), and augments gastric mucin
levels) => fundic
gland hyperplasia, hypochlorhydria, increased gastric
mucus => diffuse
enlargement and thickening gastric folds => marked protein
losing gastropathy;
inflammatory changes may be associated =>
premalignant disorder
and generalized edema, epigastric pain, and weight loss.
During childhood,
the main features of this condition include an abrupt
onset and a spontaneous
recovery in a 2-3 weeks time.
series cannot distinguish between carcinoma of the
stomach with certainty,
high fecal a1-antitrypsin
excretion
(a marker of the protein-losing enteropathy)
infection
/ adenomatous polyp of the stomach : a type of
adenomatous polyp usually
found in the antrum of the stomach, with branching
tubules or fingerlike
projections and glandular tissue; it may be
premalignant (with intraepithelial
neoplasia) or a sign of malignancy nearby. Usually
single and sexile.,
usually of the stomach, in which the cells are
polygonal rather than spindle-shaped,
ATM5, BRCA2, blood group A-857
T allele was found in 15.1% of patients
with low-grade lymphoma and
9.1% of H. pylori-infected patients.
Carrier of the rare allele
T had a 1.8-fold increased risk to develop
low-grade lymphoma. Patients
with high-grade lymphoma were significantly more
frequent carriers of the
TNF-857 T allele than healthy blood donors
(30.9%vs 18.9%). Carriage of
the T allele conferred a 1.9-fold increased
risk. There were no associations
found between any of the SNPs and disease
progressionref,
Cu]field,
[NO3-]H2O)),
ethanol,
tobacco
chewing
and smoking)
infection lasting > 10 years => atrophic
gastritis => production of NO.
and increased cell proliferation,
increased pH => colonization by reductase+
anaerobic bacteria
which reduce dietary nitrates into nitrites.
The incidence of gastric cancer after a
follow-up of 7.5 years (July 194-January
2002) is similar among people who received H.pylori
eradication
treatment (a 2-week course of omeprazole, 20
mg, a combination product
of amoxicillin and clavulanate potassium, 750
mg, and metronidazole, 400
mg, all twice daily) and those who received
placebo (7 and 11 cases out
of 1,630 chronic carrier - 988 of whom did not
have any precancerous lesions,
as determined by endoscopic evaluation - in
the high-risk Fujian Province
of southern China). In those carriers who do
not have precancerous lesions,
however, eradication of H.pylori
seemed to prevent the development
of gastric cancer - none of the treated
patients developed gastric cancer,
whereas 6 in the placebo group did itref.,
induces death of most normal stomach cells and
repopulation of the stomach
with BMDCs. Subsequently, these cells progress through
metaplasia and dysplasia
to intraepithelial cancer. The researchers wiped out
the animals' own bone
marrow with radiation and then infused them with fresh
BMDCs. These were
labelled with GFP so that they could be tracked
through the body. 20 weeks
after the mice were infected with H. pylori,
some of the BMDCs had
homed in on the stomach and divided, and tumours had
formed. Cancers are
spawned by cells from the bone marrow rather than ones
already resident
in the stomach, and the researchers believe this may
apply to humans too.These
findings suggest that epithelial cancers can originate
from marrow-derived
sources, rather than from gastric stem cells contained
in the lining of
the stomach, and thus have broad implications for the
multistep model of
cancer progressionref.
Besides stomach cancers, the results suggest that
bone-marrow cells may
be the starting point for many other cancers linked to
infection and inflammation.
These include cancers of the oesophagus, lung, colon,
cervix and liver,
in which BMDCs may also infiltrate the inflamed
tissue. The study also
raises a cautionary note for doctors who are using
injections of BMDCs
as experimental therapy for treating heart disease and
other conditions
: such an infusion might increase the risks of these
cells lodging in the
stomach or another inflamed area and triggering
cancer.
,
laryngeal
nerve
paralysis
=> dysphonia, cough, hemoptysis,
hematemesis,
laterocervical
lymphadenitis,
affects patients aged < 50 years, no
prodromic symptoms, worse prognosis
: branched glands, columnar, cuboid or
flat cells
: cuboid or columnar cells, preserved
polarity, inflammatory infiltrate
: > 50% mucus in tumor massof
the stomach : > 50% isolated or
poorly grouped cells with intracytoplasmatic
mucins. Cell types
:
: > 95%; 90% after 10 years
: 65%,
dysphagia,
weight loss, and persistent epigastralgia =>
weight loss and anemia,
vomiting
(including hematemesis),
ascites,
abdominal mass, hepatomegaly
and CA19-9
(from mucoid cells in bulge zone) and CEA
> TK
and TPA
-like
carcinoma (LELC) of the stomach / Epstein-Barr
virus (EBV)-associated gastric
carcinoma (GC) (EBVaGC)
(EBV is detected in 5.2% of gastric carcinomas and in
24.7% of infiltrating
lymphocytes by the ISH method)
expression. The infiltration of lymphocytes in the
EBV-positive GC does
not necessarily means better prognosis and the EBV
status is not a significant
prognostic factor in the patients with gastric cancer.
Diffuse or intestinal
type, in the proximal region of the stomach
(0.5% of gastric tumors) : multiple gastric carcinoid
tumors are associated
with ECL cell hyperplasia, chronic
atrophic gastritis, and pernicious
anemia,
and they have a low risk of malignancy
and Zollinger-Ellison
syndrome,
and they are prone to lymph node metastases.
(5%) : diffuse mucosal and submucosal thickening, low
malignancy (locoregional
lymph nodes), rare transformation to large
cell
lymphoma)
and CT
or CT
and PET
during staging
or total
gastrectomy
of all group 1+2(+3) lymph nodes,
gastroenteroanastomosis,
endoprosthesis, gastrostomy
or jejunostomy+chemotherapy
after radical surgery,
doxorubicin,
cisplatin,
mitomycin
C,
taxans,
irinotecan
(25%) => hypoperfusion and direct damage
=> hypoperfusion)
: homogenous necrosis
with reconstruction via Billroth
I
or Billroth
II
operation has advantages in control of hemostaisis,
cure of disease and
histological examination, but has a high mortality
in urgence
+ pyloroplasty has advantages in control of
hemostasis, cure of disease,
histological examinatrion and reduced mortality in
urgence, but is an inadequate
operation when neoplasia is suspectedto
detect wall thickenings
to detect wall thickenings)
is raised in duodenal, gastric and pyloric ulcer even though
gastrin is
normal.
antibodies
produced by principal cells
> GR
agonists
(they prevent PGE2, PGI2 and PGF2a
production : these autacoids stimulate secretion of mucus
and HCO3-
and local blood flow),
secretin
and SST
: the latter inhibits gastrin
secretion)
for H.pylori eradication : clarithromycin
(side effects : diarrhea, nausea and vomiting, abdominal pain,
hepatitis),
amoxicillin
(side effects : diarrhea and pseudomembranous colitis), metronidazole
(side effects : nausea and vomiting, disulfiram-like), and
tetracycline
(side effects : rash, anaphylaxis, hepatitis)
:
antagonists
inhibitors (PPI)is
used
for gastroprotection in chronic NSAIDs
therapies
500-250 mg
1 g bid/tid
500 mg
500-250 mg
1 g bid/tid
500 mg
500 mg
can be used
=> hepatism (ill health due to liver disease)
,
right pleural
effusion
or empyema, subphrenic
abscess,
or spinal deformity.
due to simultaneous inflammation of the liver and kidneys
from the same
cause, e.g., leptospiral infection.
of hepatocytes => spotty necrosis =>
hepatocyte regeneration =>
macronodular fibrosis diffused to whole liver =>
endophlebitis of terminal
hepatic venulae => mild intracellular and canalicular cholestasis.
(jaundice)
(jaundice)
(jaundice)
(typhoid nodule : a mass of macrophages and other
necrotic cells
observed in the liver in typhoid
fever)
overdose is the most common cause of acute liver failure
in the USA. In
the United Kingdom, changes in legislation in 1998
limited the number of
tablets in a packet of acetaminophen sold by pharmacies
to 32 (16 g) and
by other outlets to 16 (8 g). This limitation has
resulted in a significant
change in the incidence of acetaminophen overdoses.1 The
rates of admission
to liver units have dropped by 30% since this
legislation came into force,
with a commensurate drop in the number of patients
listed for liver transplantation.
Approximately 39 deaths appear to have been avoided per
yearref
(halothane hepatitis : the extremely rare cases
of transient jaundice
or massive hepatic necrosis associated with halothane
anesthesia),
propylthiouracil and methimazole, are known rarely to
cause liver dysfunction,
which is among the small number of their idiosyncratic
toxic effects. The
antithyroid drugs have distinct patterns of injury:
propylthiouracil has
hepatocellular toxic effects and methimazole induces
cholestasis (Braverman
LE, Utiger RD, eds. Werner and Ingbar's the thyroid: a
fundamental and
clinical text. 9th ed. Philadelphia: Lippincott Williams
& Wilkins,
2005:670-1). The severity of these toxic effects ranges
from elevated levels
of enzymes without permanent injury to fulminant hepatic
failure leading
to liver transplantationref.
Although the mechanism of the cholestatic picture seen
with methimazole
is
unclear, propylthiouracil may induce vasculitides
related to antineutrophil
cytoplasmic antibodies, suggesting an immunologic
mechanism underlying
hepatocellular injury due to propylthiouracil. As the
authors suggest with
regard to other drugs, we do not routinely monitor liver
enzymes in patients
receiving antithyroid medications, since mild elevations
of aminotransferase
levels are common when 300 mg or more of
propylthiouracil is prescribed
daily, independent of baseline levels of liver enzymes
in patients with
thyrotoxicosis (Liaw Y-F, Huang M-J, Fan K-D, Li KL, Wu
SS, Chen TJ. Hepatic
injury during propylthiouracil therapy in patients with
hyperthyroidism:
a cohort study. Ann Intern Med 1993;116:424-428)
used to treat pulmonary hypertension. These oral
medications are now the
cornerstone of therapy for this conditionref.
In the Bosentan Randomized Trial of Endothelin
Antagonist Therapy (BREATHE-1)
study, hepatitis developed in 3% of the patients
receiving bosentan after
16 weeks, as compared with no cases of hepatitis in the
placebo groupref.
In this study cohort, 14.9% of patients had hepatic
aminotransaminase levels
elevated more than three times the upper limit of
normal, including 4.2%
of patients with levels more than eight times the upper
limit of normalref.
The effects were seen as late as 26 weeks into therapy,
thus necessitating
serial monitoring of liver enzymesref.
This hepatotoxicity appears to be a class effectref.
Physicians who are not familiar with these medications
need to be aware
of potential complications. Awareness is important
because these agents
have proved to be effective therapy in patients with
pulmonary hypertension
is used both as a prescription medication for the
treatment of hyperlipidemia
and as an over-the-counter vitamin supplement. Although
cholestasis may
occur in association with niacin useref,
the liver injury is most commonly hepatocellular in
natureref.
It is unclear whether niacin or one of its metabolites
is the cause of
the toxic effectsref.
Both the crystalline and sustained-release formulations
of niacin can induce
hepatotoxic effects, but the sustained-release form
causes more cases and
with greater severityref.
Toxic effects can occur with the sustained-release form
even at low doses
taken for a short timerefrefref
or D4-3-oxosteroid
5b-reductase (SRD5B1; AKR1D1)
,
pruritis,
dark urine, light stools, and elevated alkaline phosphatase
and conjugated
bilirubin and in which the course is prolonged compared to
that of other
forms
,
diarrhoea, nausea, profound fatigue, meningitis,
myoarthralgia, neutropenia
with lymphocytopenia),
both conjugated and unconjugated hyperbilirubinemia). Liver
pain
due to distension of Glisson's capsule => acute liver
failure (ALF)
or acute-on-chronic liver failure (AoCLF)
(usually)ref1,
ref2,
ref3,
ref4,
ref5,
ref6
and cryptococcosis
are not ruled out by the negative fungal stain on the
liver-biopsy specimen.
for washings (assessment of internal bleedings, food
remnants or eventually
also gastoresistant cachets) : late insertion may cause
traumatic gastrorrhage
if encephalopathy grade III-IV
to correct coagulation, heated in hot air ovens at 70-80°C
for 20 minutes
(in hot water at the transfusional centers or in hospital),
then freezed
to 37°C
to maintain MAP > 100 mmHg (if oliguria occurs in absence
of diarrhea,
vomiting, or NGT)
if prothrombin activity < 40-70% in acute forms
if bilirubinemia > 30 mg/dl or intoxications (in the case
of amanitine
poisoning plasmapheresis preserves renal function but not
liver function)
can be used to induce CYPs in drug intoxications
(10-3 %)
(~
1 %)
(1÷2 % : asymptomatic or flu-like and anicteric)
(30 %)
(1÷2 %; 20 % in pregnants)
(7 %)
=> hematemesis,
melena;
hypoglycemia;
hepatic
encephalopathy
(HE)
=> 70÷95 % lethality within 2 days-8 weeks.
and balloon-like cells.
,
CCl4,
paracetamol,
halothane,
chlorpromazine,
oxyphenacetin, isoniazid,
dantrolene,
6-n-propylthiouracil,
papaverine,
benzarone, sulfonamides
assumption => alcoholic
hepatitis
(an evolution of nonalcoholic
fatty
liver disease (NAFLD)); clinically it is generally
asymptomatic
or mild, but fibrosis or cirrhosis may result. The
presence of severe
fibrosis in patients with NASH has been noted in 15 to 50%
of patients
when cirrhosis has been documented and in up to 25% of
patients at the
time of diagnosis. Most recently, NASH has been proposed as
a possible
cause of cryptogenic cirrhosis (CC).
(familial hepatitis)|
|
|
|
|
|
| none | 0 | 0 | 0 | 0 |
| portal (few) | 1 | 1 | 1 | 1 |
| portal (most) | 1 | 1 | 1 | 2 |
| periportal +/- rare portal-portal septa | 2 | 1 | 2 | 2 |
| few bridges or septa | 3 | 2 | 3 | 3 |
| numerous bridges or septa | 3 | 3 | 3 | 4 |
| incomplete cirrhosis | 4 | 4 | 4 | 5 |
| cirrhosis, definite or probable | 4 | 4 | 4 | 6 |
from centrolobular vein (high PO2, low MEOS
and cyt P450)
==> portal space (low PO2, high MEOS and
cyt P450) (porta
vein, biliary capillary, hepatic artery). Necrosis is often
zonal:
induce Ito fat(vitamin A)-storing cells to become
myofibroblasts
: the latters, together with fibroblasts and dedifferentiated
hepatocytes,
produce fibrous collagen branches, entrapping necrotic
hepatocytes into regenerative
nodules (region of localized proliferation of
hepatocytes and underlying
stroma arising in response to liver injury)and
hepatomegaly
without
liver pain.
(normoglycemia in diabetes)/MRI.
In advanced stages, ascites, jaundice,
portal
hypertension,
and CNS disorders, which may end in hepatic coma, become
prominent
chronic hepatitis => micronodular liver
steatofibrosis (centrolobular=>portal)
or tertiary
syphilis.;
the malaria is probably not an etiologic factor.,
abdominal
pain, steatorrhea, and
hepatosplenomegaly.
among Indians)
or 6-thioguanine,
actinomycin D, dacarbazine,
cytosine
arabinoside,
mithramycin, indicine N-oxide, and chemotherapy
combinations)ref1,
ref2)
prior to HSCT
=> graft-versus-host
disease
(GvHD)
is the most common cause of SOS : the incidence of SOS
varies because of
differences in the liver toxicity of conditioning
regimens. The incidence
is highest in regimens that contain CY in combination
with TBI or BU or
BCNU/etoposide. At a center, the overall incidence of
SOS among patients
with hematological malignancy conditioned with CY 120
mg/kg/TBI 12–13.2
Gy is 38% (7% severe) and among patients with MDS
conditioned with targeted
BU 16 mg/kg/CY 120 mg/kg, 12% (2% severe). There is
no sinusoidal liver
toxicity from nonmyeloablative fludarabine plus
low-dose TBI. The substitution
of fludarabine for cyclophosphamide, that is, a
BU/fludarabine regimen,
results in less liver toxicity than BU/CY. The frequency
and severity of
SOS have fallen dramatically over the last decade.
However, some current
patients come to transplant at high risk for fatal SOS
because of pre-existing
inflammatory or fibrotic liver disease.
pharmacokinetics and sinusoidal liver injury :
cyclophosphamide (CY) is
common to conditioning regimens with the highest
incidence of fatal SOS.
The metabolism of CY is highly variable; patients who
generate a greater
quantity of toxic metabolites are more likely to
develop severe SOS following
conditioning with CY and total body irradiation (TBI)ref.
The endothelial cell toxin generated by CY metabolism
is acrolein (a metabolite
formed simultaneously along with phosphoramide
mustard). The mechanisms
behind variability of CY metabolism from patient to
patient are not known;
current research focuses on the hepatocyte transporter
ABCC2 and availability
of intracellular reduced glutathione (GSH). When
patients conditioned with
CY 120 mg/kg and TBI were placed in rank order
according to their exposure
to the CY metabolite carboxyethyl phosphoramide
mustard (CEPM), those in
the highest quartile of CEPM exposure were 5.9 times
more likely to die
of non-relapse causes than those in the lowest
quartileref.
Neither relapse nor engraftment bore any relation to
variation in CY metabolism,
suggesting that CY doses can be reduced in the CY/TBI
regimen to prevent
toxicity without jeopardizing engraftment or relapse.
In a Phase I TBI/CY
protocol doses of CY were adjusted according to each
patient’s metabolism.
Using a target AUCCEPM exposure of 325 µM.h, the mean
total dose
of CY was 86 mg/kg, but with a wide dosing range
(54–120 mg/kg). Engraftment
was not affected and there were no cases of severe
SOS.
doses used in transplantation (10–16 Gy) are less than
the dose that causes
radiation-induced liver disease. In combination with
CY, however, there
is synergism, with irradiation doses 13.2 Gy
causing more severe
SOSref.
An irradiation dose of 10 Gy in the CY/TBI regimen
causes less liver injury
than does 12 Gy
in sinusoidal injury : a relationship between busulfan
(BU) exposure following
oral dosing and liver toxicity has been reported, but
this relationship
disappears among cohorts of adults with chronic
myelogenous leukemia (CML)
in chronic phase and children with acute leukemia. BU
contributes to liver
injury by inducing oxidative stress and reducing
glutathione levels in
hepatocytesref.
More importantly, BU profoundly alters CY metabolism,
such that exposure
to 4-hydroxyCY and CEPM (a reporter molecule for liver
toxicity) is increased
by > 80% and > 35%, respectively. The regimen
CY/BU is less toxic than
BU/CY, with a lower frequency of SOS, suggesting that
BU predisposes patients
to CY toxicityref.
Many centers now dose oral BU according to its
metabolism or give BU intravenously
to assure less variability in BU exposure, but liver
toxicity following
BU/CY persists despite these BU dosing improvements.,
melphalan,
and thioTEPA
leads to fatal SOS in ~4% of patients,
carboplatin,
or cytarabine,
a conjugate of anti-CD33 and calicheamicin, causes
hepatic sinusoidal injury
by a different mechanism, as it appears to deliver
toxin to CD33+
cells
residing in hepatic sinusoids (AML cells, Kupffer
cells, possibly stellate
cells). The toxicity is characterized by intense
deposition of collagen
in hepatic sinusoids and a clinical picture similar
to that of SOS following
myeloablative conditioning regimensref1,
ref2.
SOS develops in 10–90% of patients who receive
gemtuzumab ozogamicin that
is given either in close proximity to a
myeloablative conditioning regimen
(particularly if conditioning starts within 3.5
months of gemtuzumab ozogamicin
exposure) or given for relapse of AML after
transplantref1,
ref2,
ref3.
: one explanation for the rounding up of sinusoidal
endothelial cells is
activity of matrix metalloproteinases (MMPs) in
degrading extracellular
matrix. Increased MMP activity on the ablumenal side
of sinusoidal endothelial
cells allows them to detach from the space of Disseref.
Inhibition of MMP activity completely prevents SOS in
animalsref.
MMP expression and activity are regulated by redox
status and can be suppressed
by GSH and N-acetylcysteine. Thus, the
protective effect of GSH
and N-acetylcysteine may in part be due to inhibition
of MMP activity.
: in an animal model, hepatic vein nitric oxide
decreases in parallel with
changes in sinusoidal flowref.
Inhibition of nitric oxide brings on severe SOS caused
by a sub-toxic dose
of toxin, whereas nitric oxide precursors prevent
morphological changes
and "clinical features" of SOSref.
due to renal sodium retention, and weight gain, at
an average of
day +1 after CY-based transplant. Patients then develop hyperbilirubinemia
and
jaundice,
usually before day +20. A syndrome of "late VOD"
may develop
after conditioning with some BU-containing regimens, where
signs of liver
disease are first recognized after day +30.
requiring large volumes of crystalloid, followed by
renal insufficiency
and sepsis-related cholestasis
and sepsis syndrome. SOS commonly co-exists with
cholestatic liver disease.
has anti-thrombotic, anti-ischemic, and thrombolytic
properties. In treatment
of patients with SOS, the dose range is 25–40
mg/kg/day for 14 days or
longer. The mechanism for complete resolution of
severe SOS in ~50% of
patients who receive defibrotide for severe SOS is
unknownref.
Hypotension during infusion has been reported.
and heparin
infusions effect improvement in < 30% of patients
with severe SOS, but
never in patients with either renal or pulmonary
failure. Thrombolytic
therapy is further limited by the risk of fatal
intracerebral and pulmonary
bleeding.
100 mg/kg improved in 3 casesref,
but a subsequent prospective randomized study on 160
patients showed that
NAC does not improve liver toxicity after ASCTref.
Prophylaxis with NAC therapy is safe and does not
impair the myeloablative
effect of busulfan during conditioning prior to HSCTref
or activated
protein
C
are ineffective. Improvement has been reported after
therapy with PGE1,
prednisone,
topical nitrate,
and vitamin E + glutamine therapy. Inhibition of
collagen production by
stellate cells is a logical but unproven approach.
: transhepatic shunts have been placed in patients
with SOS to reduce portal
pressure and mobilize ascites, but this has no
effect on either serum bilirubin
levels or patient outcomes. TIPS may lead to acute
respiratory distress
syndrome.
for intractable ascites are unsuccessful
for severe SOS. Liver transplant should be
considered when severe SOS develops
in a patient with a condition with a favorable
outcome (for example, CML
in chronic phase). Artificial liver support may be
useful as a bridge to
transplant.|
|
|
|
|
| weight gain (% increase) | 7.0 ± 3.5 % | 10.1 ± 5.3% | 15.5 ± 9.2% |
| maximum bilirubin (mg/dL) | 4.7 ± 2.9 | 7.9 ± 6.6 | 26.0 ± 15.2 |
| peripheral edema | 23% | 70% | 85% |
| ascites | 5% | 16% | 48% |
| day 100 mortality (all causes) | 3% | 20% | 98% |
,
and, eventually, portal
hypertension
and liver failure. Onset may be acute with death occurring
within days
in cases of complete occlusion; more often there is a
chronic course with
survival for months or years
.
It is characterized by scarring about the central veins of
the hepatic
lobules.
toxicosis-treated
patients
after withdrawl of the drug..
In the late stages, portal
hypertension
with ascites, evidence of collateral
circulation,
hematemesis,
splenomegaly, and edema may be seen
,
in a child who is otherwise healthy, and progresses to biliary
cirrhosis and portal
hypertension
as a hepatotoxin.
ingestion. In the early stages, liver enlargement may
reflect fatty infiltration
of liver cells (fatty cirrhosis), with necrosis and
inflammation
due to acute alcohol injury; progressive fibrosis
extending from portal
areas separates uniform small regeneration nodules;
reactive biliary
proliferation and lymphocytes within septa
=> hepatocyte necrosis,
in which fibrosis surrounds parasites or ova trapped in
branches of the
portal vein..
(hepatorenal syndrome)
due to decreased protein catabolism to urea =>
(50÷70% of cirrhosis mortality),
pectoral
alopecia, atrophy of the testes with gynecomastia
in males, hirsutism,
menstrual disorders such as menorrhagia or hypomenorrhea
in women (due to decreased catabolism of minor sexual
hormones), sterility,
and decreased libido. It results from abnormally high
estrogenic activity
due to failure of the liver to inactivate the circulating
estrogens.,
digital
clubbing
/ digital hippocratism,
opsiuria
(Gilbert's sign), chronic liver failure (CLF)
,
CT)
(rarely used due to hemorrhage risk !). A DNA
sequencer/fragment analyzer
that generate profiles of serum protein N-glycans of liver
disease patients
yields a biomarker that distinguishes compensated cirrhotic
from noncirrhotic
chronic liver disease patients, with 79% sensitivity and 86%
specificity
(100% sensitivity and specificity for decompensated cirrhosis)ref.
(to detect varices)|
|
|
|
|
| ascitis |
|
|
|
| encephalopathy |
|
|
|
| [albumin]plasma [g/dL] |
|
|
|
| prothrombin activity |
|
|
|
| bilirubinemia [mg/dL] |
|
|
|
| esophageal varices |
receptors limits progression of experimental liver fibrosis.
During the
course of chronic hepatitis C, daily cannabis use is an
independent predictor
of fibrosis progression. Overall, these results suggest that
endocannabinoids
may drive both CB2-mediated antifibrogenic effects
and CB2-independent
profibrogenic effects. CB1
receptors were highly induced in human cirrhotic samples and
in liver fibrogenic
cells. Treatment with the CB1 receptor antagonist SR141716A
decreased the
wound-healing response to acute liver injury and inhibited
progression
of fibrosis in three models of chronic liver injury. Similar
changes were
seen in Cnr1-/- mice as compared to wild-type mice.
Genetic
or pharmacological inactivation of CB1 receptors
decreased fibrogenesis
by lowering hepatic TGF-b1
and reducing
accumulation of fibrogenic cells in the liver after apoptosis
and growth
inhibition of hepatic myofibroblastsref.
and serum a-fetoprotein
(AFP)
levels (to detect progressive increases rather absolute values)
for early
diagnosis of eventual HCC
infection.
It may be associated with polycystic
kidney
disease (PKD)
(no signal at ECD allows differential diagnosis with liver
metastases), hypodense at CT(peripheral
=>
central contrast enhancement), RBC
blood pool scintigraphy,
MRI
(hypointense in T1wi, highly hyperintense in T2wi)
,
CT
(detects central scar), isointense at MRI
(central scar is hypointense in T1wi and hyperintense in
T2wi), positive
99mTc-sulfur
colloid scintigraphy
:
a benign circumscribed tumor of the liver, usually in the
right lobe; growth
is in a sheetlike fashion and it may be highly vascular and
with areas
of necrosis. Women are affected more often than men and use
of ERT
has been implicated in some cases,
hypodense at CT
(dyshomogenous only when contains blood lakes), isointense at
MRI,
negative 99mTc-sulfur colloid scintigraphy due to
lack of Kuppfer
cells
: a rare, benign tumor of the liver in infants, generally
multicentric,
composed of anastomosing vascular channels lined with
thick endothelial
cells; it may be associated with disseminated
hemangiomatosis, and death
often occurs as the result of congestive heart failure.
occurring in infants and young children and consisting
chiefly of embryonic
hepatic tissue. Production of hCG
may result in precocious pubertyref
expression may cause severe gynecomastiaref
infection : HBxAg can inactivate several tumor
suppressors such as TP53,
p21, and pRB. Osteopontin
acts as both a diagnostic marker and a potential
therapeutic target for
metastatic HCC. At present, 50-70% of all cases of HCC
in the developoing
world occur in HBsAg+ patients . Furthermore,
30-50% of patients
with cirrhosis in the developing world are also HBsAg+.
(50%) in regions with a relativey low prevalence of HBV
infection (for
example, Italy, the USA, and Japan). In China and
Africa, HCV is associated
with < 5% of cases of HCC.
The risk of HCC is increased 59.4-fold in individuals
who have been exposed
to aflatoxin and have chronic hepatitis infection
compared with those that
have been exposed to neither chemical nor viruses.
: cirrhosis is superimposed on varying degrees of
hepatic fibrosis related
to Th deposition in only 21.1% of cases
in Japanese patients
activity, but the opposite is also true. A peptide containig
amino acids
26-44 of Arf that was modified to improve cellular uptake is
sufficient
to bind FOXM1B, target it to the nucleolus and inhibit its
transcriptional
activity without casing cellular toxicityref.
Loss of DLC-2
tumor suppressor.
,
hepatomegaly,
right hypochondrial and epigastric pain due to distension of
Glisson's
capsule, weight loss, hemoperitoneum,
and
other symptoms of the presence of an abdominal mass. Its high
mortality
rate is mainly a result of intra-hepatic metastases.
|
|
|
|
| tumor size |
|
|
| ascites |
|
|
| serum albumin |
|
|
| serum total bilirubin |
|
|
|
|
|
|
|
|
|
|
|
| 0 | single tumor |
|
normal bilirubin no portal hypertension |
|
early HCC | radical cure | hepatic
segmentectomy
or liver
transplantation |
| 0 | single tumor |
|
normal bilirubin and portal hypertension |
|
|||
| 0 | single tumor |
|
abnormal bilirubin and portal hypertension |
|
liver
transplantation |
||
| 0 | <= 3 tumors all < 3 cm |
|
Child-Pugh score A or B |
|
|||
| 0 | large multinodular (> 3 nodules or multiple nodules with largest >= 3 cm) |
|
Child-Pugh score A or B |
|
intermediate HCC | palliative | TAE/TACE,
new agents |
| 1 or 2 | vascular invasion or extrahepatic spread |
|
Child-Pugh score A or B |
|
advanced HCC | palliative | new agents (investigational) |
| 3 or 4 | any |
|
Child-Pugh score C |
|
end-stage HCC | symptomatic | supportive |
: satellite metastases, hypo- or isodense nodule with
poorly defined borders
and peripheral hypodense halo, calcifications (10%), early
and dyshomogeneous
contrast enhancement, neoplastic thrombosis (33%) and
intranodular arterovenous
shunts
: iso- or hyperechogenic nodule (hypoechogenic when
smal-sized) similar
to regeneration nodules; ECD detects high-rate flow within
nodules and
intrahepatic and suprahepatic neoplastic thrombosis
(hypointense in T1wi and hyperintense in T2wi; central
scar is hypointense
in both T1wi and T2wi; higher sensitivity than CT in
identification of
pseudocapsule, internal imaging and vascular invasion)]serum)
tumour-suppressor gene resulting in a loss of function]plasma
is found in 50% of patients with HCC in China
is no longer practiced due to false negatives
(mistakes in sampling,
HCC foci in dysplastic nodule, wrong interpretation) and
risk of peritoneal
seeding (metastases can restart growing after
immunosuppressive therapy
following
liver
transplantation)
: resecting only specific liver segments is especially
useful in patients
with HCC : 50-75% of these patients have underlying
liver cirrhosis and
poor liver reserve. The surgical challenge in these
patients is to resect
enough liver to allow complete tumor resection while
retaining all possible
non-tumorous liver to prevent further loss of liver
function. In support
of the benefit of resections along segmental boundaries,
MacIntosh has
reported an operative mortality of 0-16% with segment
based resections
compared to mortalities of 20-60% in patients receiving
traditional lobectomies
or non-segment based wedge resections.
: severe shortage of liver donors
accompanied by neoadjuvant or adjuvant chemotherapyin
alternative
to surgical portosystemic
shunt
or 5-FU
did not yield any survival benefit for patients with
unresectable HCCref
:|
|
dose (mg/m2body surface/d) | route of administration | days of use |
| cisplatin
(Platinol) |
20 | IV drip | days 1-4 |
| IFN-a2a |
|
|
|
| doxorubicin
(Adriamycin) |
40 | IV injection | day 1 |
| 5-FU |
400 | IV drip | days 1-4 |
ref
(80% sensitivity) and positive ECD
or breast
cancer
(sensitivity = 85-90%) : dyshomogeneous hypodense nodule;
early contrast
enhancement at periphery
: dyshomogenous nodule hypointense in T1wi and
hyperintense in T2wi (25%
has peripheral hyperintense halo in T2wi) but differential
diagnosis with
primary tumor is impaired
is practiced only in 25% of patients with colorectal
carcinoma (CRC) and patients with endocrine
carcinoids (without limits).Intraoperative
ultrasound is used at this point to identify nonpalpable
lesions and delineate
vascular anatomy. Just 25% (85% in cirrhotics) of liver
tissue is enough
to maintan functions. Occult intrahepatic metastasis was
always found to
be located within 10 mm from the edge of the tumor
(biliary tract, portal
vein or suprahepatic vein invasion, microsatellite lesion)
=> all liver
metastases should be resected with at least 1 cm
tumor-free margin. Median
survival ranged from 28 to 46 months. The 5-year OS =
24-38%. Many surgeons
consider 4 or more tumors in the liver to be a
contraindication for surgical
resection before. But more and more authors think that the
number was not
a limitation in liver resection of CRC liver metastases
with the use of
new techniques. The follow-up showed that there was no
significant difference
in the mortality, morbidity and 5-year OS between patients
whose lesions
> 4 and those < 4 : surgical debulking also allows
reconstitution of
antitumor immunity. Contraindications are locations near
vessels of at
the centre of liver
with liquid nitrogen (-196°C) is < 4 lesions < 5 cm
in diameter.
General anesthesia as probes are quite large.
(460 kHz) accompanied by neoadjuvant or adjuvant
chemotherapy
(hepatic arterial infusion (HAI))
cannot be used as metastases have not a capsule and ethanol
would extravasate into surrounding healthy parenchyma
(30%)
(20%),
biliary
diseases, diverticular
disease,
Crohn's
disease,
tumors with cancer abscess, and ethanol-addicted.
Sources :
|
|
|
|
|
| portal circulation | right lobe | intraabdominal infections | polymicrobial, Gram+ and - |
| arterial circulation | single lobe | systemic infections | Staphylococcus
aureus |
| biliary tract | multiple in both lobes | ascending cholangitis, biliary tract obstruction | |
| cryptogenetic | right lobes | unknown |
Bacteroides
fragilis
(anaerobes) |
| primary hepatic | traumatized or tumor area | intestinal infections | Gram - bacteria |
into the portal circulation in chronic amebiasis (amebic
hepatitis)
or sensitization to antigens => thrombosis => necrosis
=> dissemination;
amebic abscesses may also involve lungs, spleen, and brain.
They occur
in 1-25% of patients with amebic dysenteria. Male-to-female
ratio = 10:1,
in age 40-60. Right-to-left lobe ratio = 10:1. Bacterial
superinfection
of cyst content may occur during percutaneous or open surgical
drainage.
Serology has sensitivity > 98%, while the research of
amebic cyst and trophozoites
in stools is positive only in 15% of patients, and content
culture has
poor sensitivity. Therapy :
metronidazole
(> hemetine and chloroquine), percutaneous or laparotomic
closed drainage
=bacterial superinfection=> open drainage
(hypodense nodule with irregular borders and peripheral
capsular halo,
hyperdense after contrast enhancement; eventually containing
sepimentations,
semisolid vegetations, gas due to anaerobe bacteria, fluid
levels of different
densities, hydroaereal levels)
may miss the abscess : hypoechogenic, dyshomogenous,
sepimentations,(round
with net borders and pure liwquid echostructure; thick
sepimentatations
in aged echinococcal cysts prevent cyst imaging but detection
of parietal
calcifications indicates inactive disease)
in patients with meteorism or obese and for preoperative
assessment of
echinococcal cysts (< 20 HU; no contrast enhancement)
(the most common type),
alcoholic liver disease
(up to 33%). Age >45, BMI > 30, AST/ALT >1, and
diabetes are all associated
with increased risk for development of significant
fibrosis. Inflammatory
activity when present may reflect the combined effects of
oxidative stress,
subsequent lipid peroxidation, and abnormal cytokine
expression, especially
increased TNF,
starvation
(may also be associated with necroinflammatory activity),
chronic
pancreatitis, or protracted
congestive
heart
failure
(less common)
(AFLP) is a syndrome that occurs late in pregnancy
and is often associated
with jaundice and hepatic failure. The liver is typically
small. AFLP is
more common when the mother is carrying a male fetus and may
be associated
with a deficiency of long-chain-3-hydroxy acyl COH
dehydrogenase. AFLP
usually necessitates termination of pregnancy due to the
risk of rapid
and fatal deterioration. Preeclampsia or the syndrome of
hemolysis, elevated
liver enzymes, and low platelet count (HELLP), which may
complicate eclampsia,
presents in a similar fashion and progresses to severe liver
dysfunction,
though typically with a normal size liver. Aminotransferase
elevations
are typically modest in all of these conditions (generally
<500). If
diagnosed in time, the disease usually resolves with
termination of the
pregnancy. Recurrence in subsequent pregnancies is rare.,
excessive doses of tetracycline,
nucleoside analogues (combination of lactic acidosis),
petrochemicals),
which results from deposition of malarial pigment.
(contrasted and ECD)
(contrast-enhanced)
(contrast-enhanced)-assisted
FNAB
(echographic probe with needle included)
from vaso-vagal reactions, extensive intraperitoneal bleeding and
hemobilia.
Mortality is extremely low, the mean in large studies being
0.001%.
and reovirus
pyelonephritis, cholangitis); hepatomegaly; intracranial
hemorrhage due
to vitamin K deficiency;
jaundice => progressive biliary cirrhosis (biliary
cirrhosis
of children / infantile liver) => portal
hypertension
=> hepatic failure
shows hypoechogenic image at hepatic hilum; occasionally
cystic dilatation
of the biliary tree; lack of gall-bladder image,
obstruction by a choledochal cyst,
arteriohepatic
dysplasia, familial progressive intrahepatic cholestasis, and
alteration
of the bile acid metabolism
(a temporizing treatment allowing the infant to develop and
grow) => liver
transplantation.
The potential for reasonable medium-term survival is present
in about one
third of infants 100 days or older coming to primary
corrective surgery.
and episodes of pancreatitis in childhood and early adulthood.
A more frequent
type combined with congenital hepatic fibrosis is usually
manifested with
bleeding from esophageal
varices consequential
to portal hypertension.
There is a high
risk association with malignant transformation to cholangiocarcinoma
of the cells of the cystic walls => carcinomatous
arteriopathy (a rare
and distinct form of pulmonary spread of solid malignant
tumors characterized
by fibrointimal proliferation of small pulmonary arteries and
arterioles
initiated by tumor emboli)),
are relatively limited and depend on the clinical presentation,
localization
of cysts in the liver, and stage of the disease
(+ fever,
vomiting and peritonitis in cholangitis)
is extremely rare. It occurs in association with other
dilatations. Because
of the risk of cholangitis and its complications, biliary
stasis, due to
dilatations from Chagas disease, is very severe. A bilioenteric
bypass
is the best solution if the symptoms of biliary stasis (pain, jaundice,
infection) exist. This is specially true if a dilatation of the
intra or
extra-hepatic biliary tree is present. The ideal bypass is an
hepaticojejunostomy
with an excluded Roux-en-Y loop of jejunum. For initial cases, a
cholecystectomy
associated with an ample papilla sphincteroplasty is performed.
(idiopathic or estrogen-induced)-mediated
induction of HMG-CoA synthetase (before age 50
females:males 2:1 ; after
age 50 females:males 3:2)
induction by insulin
(e.g. in therapy of NIDDM)
or in oral
contraceptives,
octreotide)
(including malaria and heart valvular prosthesis), alcoholic
cirrhosis
in immunocompromised hosts,
and jaundice,
a disorder often seen in eastern and southern Asia,
sometimes associated
with
(hepatobiliary distomatosis)in
immunodeficient
hosts,
and fever
and chills characteristic of intermittent cholangitis, without
neutrophilia
or vomiting
:
a small firm white nodule with multiple bile ducts imbedded
in a fibrous
stroma
cancers
infection have RR = 30
consumption (37-45%).
The majority (91.7%) of Th-related CHC is located in the
middle-peripheral
portion of the liver. In contrast, 77.8% of the
non-Th-related cases are
located in the hilar portion:
tumors arising from enterochromaffin cells within the
biliary tree are
exceptionally rare, and only 15 cases have been reported in
the world literature.
They may arise from either an intrahepatic or extrahepatic
location. Extrahepatic tumors have been reported more
frequently because
of the presentation (obstructive jaundice).
Fibrosing hilar tumor mimicking a Klatskin tumor has been
reported.
cancers
of the extrahepatic bile ducts
of the extrahepatic bile ducts
of the extrahepatic bile ucts
of the extrahepatic bile ducts
of the extrahepatic bile ucts,
cholestasis,
hepatomegaly,
palpable gallbladder, fever
and CEA
of bile duct cancer (BDC) have shown astonishingly good
results in the
reduction of cholestasis, improvement of life quality, and
potential improvement
of survival time. PDT is minimally invasive but shows a
considerable postinterventional
cholangitis rate. ref
rejection and GvHDreduce
hepatocellular
injury without decreasing lipid peroxidation in mitochondria
and microsomes, indicating that mitochondrial oxidative
stress does not
play an important role. Therefore, the major resource of
free radicals
remains unclear.
(prevents chronic cholestatic liver diseases but not fibrosis)
or massive hemolysis
and echography
detect aerobilia in
gall-bladder and biliary
ways
(it induces choledocus to become a sort of vicariant
gall-bladder)
cholangiopathyref
(which reveals the presence of clots inside the gallbladder),
computerized
tomography, angiography or surgery
of the gallbladder has the best prognosis
of the gallbladder
of the gallbladder
of the gallbladder
of the gallbladder
of the gallbladder,
nausea, palpable mass, hepatomegaly
and CEA
> AFP
> TPA
and TK
(not correctable)
following cholecystectomy
(any kind of gall-stone is detected as a posterior shadow
cone; chronic
cholestasis de to infundibular gallstone causes precipitation
of levelled
biliary slatch; dilated biliary ways are distinguished by
blood vessels
with echocolordoppler; irregular borders of gallbladder in
acute cholecystitis
due to parietal abscessualization; fluid surrounding
gallbladder in pericholecystic
flogosis = peritonitis; pus floats over bile in gallbladder
empyema; sensitivity
= 50% for gallbladder cancers and often fail to define the
nature of polypoid
lesions in the gallbladder)
(for pancreas head tumors obstructing biliary ways)
(only for gall-stones with high [Ca2+])
(toxic)
,
especially after biliary manometry)
(acute and chronic alcoholism) (15-30%), although
clinically detected pancreatitis
never develops in most persons with this risk factorref
: the incidence of pancreatitis in alcoholics is
surprisingly low (5/100,000),
indicating that in addition to the amount of alcohol
ingested unknown genetic
factorsref
affect a person's susceptibility to pancreatic injury. The
mechanism of
injury is not well understood. Excessive alcohol use as a
cause of pancreatitis
is more common among men than women (Drinking in the
United States: main
findings from the 1992 National Longitudinal Alcohol
Epidemiologic Survey
(NLAES). Vol. 6. Bethesda, Md.: National Institutes of
Health, 1998. (NIH
publication no. 99-3519); the association between alcohol
consumption and
acute pancreatitis is complex but appears to be
dose-dependent.
(1.3-3.8%) : serum triglyceride levels are usually
>11.3 mmol/L (>1000
mg/dL). Most patients with when subsequently examined,
show evidence of
an underlying derangement in lipid metabolism
(hyperchylomicronemia), probably
unrelated to pancreatitis. Patients with diabetes
mellitus
or who are on certain medications may also develop high
triglyceride levels.,
6-mercaptopurine,
sulfonamides,
estrogens,
tetracycline,
valproic
acid,
didanosine,
pentamidine,
and trimethoprim-sulfamethoxazole,
thiazide
diuretics)
either by a hypersensitivity reaction or by the generation
of a toxic metabolite,
although in some cases it is not clear which of these
mechanisms is operative
(ischemic-hypoperfusion states after cardiac surgery)
and thrombotic
thrombocytopenic
purpura (TTP)
and acute
respiratory
distress syndrome (ARDS)
as well as multiorgan failure may occur as result of this
cascade of local
as well as distant effects.
.,
septic
shock
(during 2nd-3rd week) and MOF due to
trypsin, MDF
and SLF => death.
;
peritoneal fluid collections infected by anaerobe bacteria
=> extraintestinal
air
and catheters for selective pus draining and in situ
delivery of
antibacterials
=> shock is not unusual and may result from
occurs infrequently; when present, it usually is due to
edema of the head
of the pancreas with compression of the intrapancreatic
portion of the
common bile duct
=> slimming))
(hypertriglyceridemia can precede and apparently cause
pancreatitis. Second,
the vast majority (>80%) of patients with acute
pancreatitis do not have
hypertriglyceridemia. Third, almost all patients with
pancreatitis and
hypertriglyceridemia have preexisting abnormalities in
lipoprotein metabolism.
Fourth, many of the patients with this association
have persistent hypertriglyceridemia
after recovery from pancreatitis and are prone to
recurrent episodes of
pancreatitis. Fifth, any factor (e.g., drugs or
alcohol) that causes an
abrupt increase in serum triglycerides to levels
>11 mmol/L (1000 mg/dL)
can precipitate a bout of pancreatitis that can be
associated with significant
complications and even become fulminant. To avert the
risk of triggering
pancreatitis, a fasting serum triglyceride measurement
should be obtained
before estrogen replacement therapy is begun in
postmenopausal women. Fasting
levels < 3.4 mmol/L (300 mg/dL) pose no risk,
whereas levels >8.5 mmol/L
(750 mg/dL) are associated with a high probability of
developing pancreatitis.
Finally, patients with a deficiency of apolipoprotein
CII have an increased
incidence of pancreatitis; apolipoprotein CII
activates lipoprotein lipase,
which is important in clearing chylomicrons from the
bloodstream.)),
pancreatic
lipase]plasma
and
[pancreatic amylase]urine. Values > 3-fold
above the upper
limit of the normal virtually clinch the diagnosis if
overt salivary
gland disease and gut perforation or infarction are
excluded. However,
there appears to be no definite correlation between the
severity of pancreatitis
and the degree of serum amylase elevation. After 48 to 72 h,
even with
continuing evidence of pancreatitis, total serum amylase
values tend to
return to normal. However, pancreatic isoamylase and lipase
levels may
remain elevated for 7 to 14 days. It will be recalled that
amylase elevations
in serum and urine occur in many conditions other than
pancreatitis. Serum
lipase activity increases in parallel with amylase activity,
and measurement
of both enzymes increases the diagnostic yield. An elevated
serum lipase
or trypsin value is usually diagnostic of acute
pancreatitis; these tests
are especially helpful in patients with nonpancreatic causes
of hyperamylasemia.
Markedly increased levels of peritoneal or pleural fluid
amylase [>1500
nmol/L (>5000 U/dL)] are also helpful, if present, in
establishing the
diagnosis.]plasma
12,000 to 20,000/µL occurs frequently. Patients with more
severe
disease may show hemoconcentration with hematocrit values
exceeding 50%
because of loss of plasma into the retroperitoneal space and
peritoneal
cavity
[serum bilirubin > 68 mol/L (>4.0 mg/dL)] (10-25%)
because pancreatic edema
compresses the common bile duct : however, jaundice is
transient, and serum
bilirubin levels return to normal in 4 to 7 days
and aspartate
aminotransferase (AST)
levels are also transiently elevated and parallel serum
bilirubin values.
An elevated ALT level in a patient without alcoholism who
has pancreatitis
is the single best laboratory predictor of biliary
pancreatitis; a level
of > 3 times the upper limit of normal has a positive
predictive value
of 95% for gallstone pancreatitisref.
However, the presence of normal alanine aminotransferase
levels does not
reliably rule out the diagnosisref
levels [>8.5 mol/L (>500 U/dL)] suggest a poor
prognosis
(15-20%) : serum amylase levels in these individuals are
often spuriously
normal
(25%) (arterial PO2 60 mmHg), which may herald
the onset of
ARDS
: occasionally abnormal in acute pancreatitis with
ST-segment and T-wave
abnormalities simulating myocardial ischemia.)
to as high as 50 to 55%, indicating severe inflammation
(25%) as early as the first day because of the formation of
Ca "soaps"
secondary to excessive generation of free fatty acids,
especially by pancreatic
lipase. Although earlier studies suggested that the response
of the parathyroid
gland to a decrease in serum calcium is impaired, subsequent
observations
have failed to confirm this idea. Intraperitoneal
saponification of calcium
by fatty acids in areas of fat necrosis occurs occasionally,
with large
amounts (up to 6.0 g) dissolved or suspended in ascitic
fluid. Such "soap
formation" may also be significant in patients with
pancreatitis, mild
hypocalcemia, and little or no obvious ascites.
(as a cause or as effect) is common and is due to multiple
factors, including
decreased insulin release, increased glucagon release, and
an increased
output of adrenal glucocorticoids and catecholamines,
supine and upright plain abdomen
X-rays
: although one or more radiologic abnormalities are found
in >50% of patients,
the findings are inconstant and nonspecific. The chief
value of conventional
x-rays [chest films; kidney, ureter, and bladder (KUB)
studies] in acute
pancreatitis is to help exclude other diagnoses,
especially a perforated
viscus. Upper gastrointestinal tract x-rays have been
superseded by and
...
is more sensitive than either CT or MRI for identifying
gallstones and
sludge and for detecting bile-duct dilatation, but it is
insensitive for
detecting stones in the distal bile ductref1,
ref2
scan may confirm the clinical impression of acute
pancreatitis even in
the face of normal serum amylase levels. Importantly, CT
is quite helpful
in indicating the severity of acute pancreatitis and the
risk of morbidity
and mortality. A contrast-enhanced dynamic CT (CECT) scan,
provides valuable
information on the severity and prognosis of acute
pancreatitis. In particular,
a CECT scan allows estimation of the presence and extent
of pancreatic
necrosis. Recent studies suggest that the likelihood of
prolonged pancreatitis
or a serious complication is negligible when the CT
severity index is 1
or 2 and low with scores of 3 to 6. However, patients with
scores of 7
to 10 had a 92% morbidity rate and a 17% mortality rate.
Necrosis is present
in 20 to 30% of patients. Those with necrosis have a
morbidity rate >20%,
whereas those without necrosis have a morbidity rate
<10% and a negligible
mortality rate. A few retrospective studies have raised
concern that the
use of intravenous contrast early in the course of acute
pancreatitis might
intensify pancreatic necrosis. However, since prospective
human studies
are not available, it is reasonable to reserve CECT scans
for patients
with severe pancreatitis or suspected local septic
complications.
may also identify early duct disruption that is not seen
on CTref
are useful in acute pancreatitis to evaluate the
gallbladder and biliary
tree
to decrease gastrin release from the stomach and prevent
gastric contents
from entering the duodenum. Recent controlled trials,
however, have shown
that nasogastric suction offers no clear-cut advantages in
the treatment
of mild to moderately severe acute pancreatitis. Its use,
therefore, must
be considered elective rather than mandatory
: the patient with mild to moderate pancreatitis usually
requires treatment
with intravenous fluids, fasting, and possibly nasogastric
suction for
2 to 4 days. A clear liquid diet is frequently started on
the 3d to6th
day, and a regular diet by the 5th to 7th day. The decision
to reintroduce
oral intake is usually based on the following criteria: (1)
a decrease
in or resolution of abdominal pain; (2) the patient is
hungry; and (3)
organ dysfunction, if present, has improved. Elevation of
serum amylase/lipase
or persistent inflammatory changes seen on CT scans should
not discourage
feeding a hungry asymptomatic patient. In this regard,
persistence of inflammatory
changes on CT scans or persistent elevations in serum
amylase/lipase may
not normalize for weeks to months. The use of parenteral
nutrition makes
it possible to give nutritional support to patients with
severe, acute,
or protracted pancreatitis who are unable to eat normally.
Several studies
have demonstrated that enteral feeding via a nasojejunal
tube infused distal
to the ligament of Treitz is associated with a decreased
rate of complications,
including infection, when compared to total parenteral
nutrition.,
500 mg thrice daily for 2 weeks. In addition, because
secondary infection
of necrotic pancreatic tissue (abscess, pseudocyst or
obstructed biliary
passages, ascending cholangitis complicating choledocholithiasis)
contributes to many of the late deaths from pancreatitis,
appropriate antibiotic
therapy of established infections is quite important.
infection during acute necrotizing pancreatitis is
increasing in frequency
and is associated with an increased mortality rate. In one
representatitve
trial, intraabdominal Candida infection was found in
13 of 37 cases
and was associated with a mortality rate 4-fold greater than
that associated
with intraabdominal bacterial infection alone. Given the
impact of Candida
infection on the mortality rate in acute necrotizing
pancreatitis and the
apparent benefit of prophylactic chemotherapy, these data
suggest earlier
use of fungicides.,
serine
protease inhibitors
such as aprotinin, glucocorticoids, calcitonin, nonsteroidal
anti-inflammatory
drugs (NSAIDs), and lexiplafant, a PAFR
antagonist. A recent meta-analysis of somatostatin,
ocreotide, and
the antiprotease gabexate mesilate in therapy of acute
pancreatitis suggested
(1) a reduced mortality rate but no change in complications
with octreotide,
and (2) no effect on the mortality rate but reduced
pancreatic damage with
gabexate
antagonists) in acute pancreatitis have failed to have
any therapeutic
benefit. For this and other reasons, anticholinergic drugs
are not indicated
in acute pancreatitis. In addition to nasogastric suction
and anticholinergic
drugs, other therapies designed to "rest the pancreas" by
inhibiting pancreatic
secretion have not changed the course of the disease.
Although antibiotics
have been used in the treatment of acute pancreatitis,
randomized, prospective
trials have shown no benefit from their use in acute
pancreatitis of mild
to moderate severity.,
thiazide
diuretics,
and b-blockers),
and (5) control of diabetes.Other markers that are not included in standard scoring systems should also be considered. Obesity (a body-mass index of > 30) is associated with an increase in the risk of a severe clinical course by a factor of 2 to 3ref. A hematocrit above 44% is a clear risk factor for pancreatic necrosisref, although it is a poor predictor of the severity of disease. Preliminary evidence suggests that genetic factors, such as polymorphisms in the chemokine monocyte chemotactic protein 1 (MCP-1) generef, may also predict severity, although such genetic testing is not currently used in practice. Several clinical findings — including thirst, poor urine output, progressive tachycardia, tachypnea, hypoxemia, agitation, confusion, a rising hematocrit level, and a lack of improvement in symptoms within the first 48 hours — are warning signs of impending severe disease. If such symptoms develop, admission to an intensive care unit should be considered. Intensive care may also be warranted in patients at risk for rapid deterioration in their condition, including those over the age of 55 yearsref, those who need ongoing volume resuscitation or invasive monitoring of fluid status (e.g., central venous pressure monitoring), or those with renal failure or respiratory compromiseref
The prophylactic use of antibiotics in patients with
pancreatic necrosis
is supported by the guidelines of the International
Association of Pancreatology
for the surgical management of acute pancreatitisref
and the Japanese Society of Abdominal Emergency Medicine53
but is discouraged
by an expert panel of the American Thoracic Society and
other organizationsref.
No consensus was reached by the United Kingdom Working Party
on Acute Pancreatitisref.
The last 3 organizationsref1,
ref2,
ref3
favor the use of enteral nutrition over total parenteral
nutrition in patients
with severe acute pancreatitis whenever possible.
Early intervention for gallstone pancreatitis with bile-duct
obstruction
with the use of ERCP with endoscopic sphincterotomy is
consistently recommended.
score
score is similar to Ranson's score but can be completed on
admission. The
score ranges from 0 to 8, with scores >= 3 indicating a
greater severity
of illnessref1,
ref2ref1,
ref2
(often cited, but less useful) : severe pancreatitis
indicated by a score
>= 8
> 150 mg/L|
|
|
|
|
|
|
|
| on admission | APACHE II >= 6 | 83-99 | 33-54 | 28-40 | 80-97 | 45-65 |
| APACHE II >= 8 | 68-71 | 48-67 | 30-40 | 84-87 | 53-68 | |
| APACHE II >= 10 | 52-63 | 66-81 | 32-64 | 81-89 | 63-77 | |
| IL-6 levels > 400 pg/ml | 89 | 87 | 80 | 93 | 88 | |
| at 24 hours | APACHE II >= 8 | 63 | 73 | 38 | 88 | 71 |
| CRP > 150 mg/dl | 65 | 73 | 37 | 90 | 72 | |
| PMN elastase > 300 mg/l | 93 | 99 | 97 | 98 | 98 | |
| urinary TAP > 35 nmol/l | 68 | 74 | 44 | 89 | 73 | |
| at 48 hours | APACHE II >= 8 | 56-78 | 52-64 | 30-33 | 85-88 | 58-63 |
| Ranson's score >= 3 | 75-89 | 54-71 | 37-49 | 91-96 | 62-75 | |
| modified Glasgow score >= 3 | 45-75 | 63-89 | 28-66 | 79-93 | 59-84 | |
| CRP > 150 mg/dl | 65 | 73 | 37 | 90 | 72 |
|
|
|
||||
| 0-2 | 3-4 | 5-6 | 7-8 | ||
| Ranson's score | intensive care for > 7 days and survival | 1% | 24% | 53% | NA |
| death | 3% | 16% | 40% | 100% | |
| either intensive care for > 7 days or death | 4% | 40% | 93% | 100% | |
| 0-3 | 4-6 | 7-10 | |||
| CT severity index | complications | 8% | 35% | 92% | |
| death | 3% | 6% | 17% | ||
,
and pancreatic cancer
abuse lasting > 20-25 years
=> hypercalcemia
=> pancreas
calcinosis-secreting
neoplasm (gastrinomas / Zollinger-Ellison tumour)
may be due to ectopic production of ACTH by the gastrinoma
and lactoferrin
are important markers of the disease. However, little is
known about its
actual pathogenesis. Although elevated serum IgG4
levels have
been linked to autoimmune pancreatitis, this bispecific
and functionally
monovalent antibody may merely represent a secondary
response to a yet-unidentified
primary trigger of the inflammatory process.
Autoantibodies against lactoferrin
and carbonic anhydrase II have been identified as
potential serologic markers
of autoimmune pancreatitisref1,
ref2.
Most of the organs involved in autoimmune pancreatitis
(including the lung,
biliary tree, and renal tubules) contain intracytoplasmic
carbonic anhydraseref.
Pancreatitis with histologic features similar to those
associated with
autoimmune pancreatitis in humans has been shown to
develop in neonatal
mice that have undergone thymectomy and have been
immunized with lactoferrin
or carbonic anhydrase IIref.
Although these antibodies are frequently identified in
patients with autoimmune
pancreatitis, it is unlikely that they are the primary
mechanism of this
disease. As compared with patients with other forms of
chronic pancreatitis,
those with autoimmune pancreatitis have greater numbers of
peripheral-blood
CD4+ T lymphocytes that secrete greater amounts
of IFN-g.
The administration of amylase-sensitized CD4+ T
lymphocytes
in rats can produce a model of autoimmune pancreatitisref.
|
|
|
|||
|
|
|
|
|
|
| diffusely enlarged pancreas | segmental pancreatic ductal narrowing | elevated serum IgG4 level | periductal lymphoplasmacytic infiltration or fibrosis | tubulointerstitial nephritis with immune deposits within tubular basement membranes |
| enhanced peripheral rim of hypoattenuation "halo" | focal pancreatic ductal narrowing | elevated serum IgG or gamma globulin level | obliterative phlebitis | pulmonary interstitial lymphoplasmacytic infiltration with IgG4+ plasma cells |
| low-attenuation mass in head of pancreas | diffuse pancreatic ductal narrowing | presence of ALA, ACA II, ASMA, or ANA | increased number of IgG4+ plasma cells in tissue | chronic sialoadenitis with IgG4+ plasma cells |
of the pancreas with diffuse lymph-node
involvementref
also permits differentiation between an edematous, inflamed
pancreas, which
can give rise to a palpable mass, and an actual pseudocyst.
Furthermore,
serial ultrasound studies will indicate whether a pseudocyst
has resolved.
CT complements ultrasonography in the diagnosis of pancreatic
pseudocyst,
especially when the pseudocyst is infected..
Pancreatic calculi cause hemorrhage by either migrating through
the pancreatic
parenchyma to perforate the duodenum, ulcerating the vessels of
the periductal
parenchyma, or rupturing the pancreas. The usual sign of this
complication
of chronic calcifying pancreatitis, difficult to diagnose, is
repeated
hematemesis
and sometimes pain, as in epigastric colitis. The immediate
therapy is
control of the hemorrhage. With transcatheter occlusive
techniques, radical
surgery can be postponed until it is more tolerableref.
are found in most cases, as are loss-of-function
mutations in CDKN2A
- which encodes the tumour suppressors INK4A and ARF.
Neither Kras
nor Cdkn2a mutations are sufficient : Kras
activation is
required to initiate tumorigenesis, but additional
homozygous mutation
of Cdkn2a is essential for progression to
advanced malignancyref.
Mesothelin,
Muc4,
Muc5A/C,
kallikrein
10,
transglutaminase
2, fascin,
TMPRSS3
and stratifin
are highly expressed genesref.
(4%)
of the pancreas (1%ref)
Acinar cell carcinomas are highly malignant with a
poor prognosis and a
high rate of recurrenceref
of the pancreas (by convention are assigned
grade 3),
cystic
teratoma,
enteric pancreatic cysts, lymphoepithelial cyst, cystic
lymphangioma,
cystic pseudopapillary carcinoma, necrotic sarcoma,
giant-cell tumor, mucinous
adenocarcinoma
sex hormones, pernicious anemia
use
(OR=3.4), other pesticides (OR=3.17), aniline
derivatives, formaldehyde,
dyes and organic pigments (OR = 4.8). There is some
indication of weaker
associations between K-Ras
mutations and occupational exposure to lead,
PAHs,
benzo[a]pyrene,
gasoline, nickel,
inhalatory exposure to chromium
and sedentary work. The association with chromium
compounds was stronger
for G to T transversions, a finding compatible with
experimental studies
on mutation spectra for chromium
mutations at diagnosis)
(30%) pathways|
|
|
|
|
|
|
| I | local/resectable (T1-T2, selected T3 (those with isolated involvement of the SMV, portal vein, or hepatic artery without encasement of the celiac axis or SMA), Nx; M0) | disease is confined to the pancreas and is clearly separated from surrounding blood vessels (no encasement of celiac axis or SMA, patent superior mesenteric vein confluence with portal vein (SMPV)) |
|
surgery; postoperative chemotherapy and/or radiation may also be offered | 17 months |
| II | locally advanced/unresectable (T3, NX-1, M0). Arterial enhancement (celiac axis or SMA) or venous occlusion (SMV or portal vein). No extrapancreatic disease | disease encases or compresses surrounding blood vessels, or has directly extended into adjacent structures |
|
chemotherapy (most commonly gemcitabine-based) and/or radiation. In very rare instances, cancers that respond well to initial treatment may subsequently be surgically resected. | 8-9 months |
| III | metastatic (T1-3, NX-1, M1) | evidence of extrapancreatic spread to distant organs (liver, peritoneum, and occasionally lungs, etc.) |
|
chemotherapy (most commonly gemcitabine-based); investigational trials | 4-6 months |
(72%)
=> ascitis, splenomegalia and
stomach varices due
to side shunt through brief gastric veins => hematemesis
and/or melena;
due to liver metastases
or hilar lymphadenopathiesNew
onset
of diabetes is observed in 15% to 20% of patients
(solid or cystic; retroperitoneal lymphadenomegaly, liver
metastases)
scanning with both arterial and venous timed injection is
currently the
best noninvasive technique for determining the proximity of
the primary
neoplasm to major peripancreatic vascular structures such as
the celiac
axis, superior mesenteric artery, and mesenteric venous
structures (superior
mesenteric vein, splenic vein, and portal vein).
Preservation of fat planes
around each of these vessels suggests a lack of direct
invasion by the
primary neoplasm and is consistent with resectability.|
|
|
|
| sensitivity | 0.82 (CI = 0.96-0.52) | 0.94 (CI = 1.00-0.68) |
| specificity | 0.53 (CI = 0.80-0.23) | 0.80 (CI = 0.95-0.49) |
| overall accuracy | 0.69 | 0.87 |
for neoplastic choledocus stenosis
(best reserved for the evaluation of a patient with presumed
pancreatic
cancer and obstructive jaundice in whom no mass is evident
on CT; the symptomatic
but nonjaundiced patient without an obvious pancreatic mass;
or the patient
with chronic pancreatitis in whom the development of a
pancreatic neoplasm
is suspected based on clinical determination or the
development of jaundice)
(presurgical evaluation of infiltration of inferior vena
cava and upper
mesenteric veins)
with 21G needle is useful in selected patients. The
technique is safe and
generally reliable, but is of limited value in patients in
whom surgical
exploration for attempted resection or palliation is
planned. The reason
for not using fine needle aspiration cytology or biopsy in
potentially
resectable lesions is 2-fold. First, even after repeated
sampling, a negative
result cannot exclude malignancy; in fact, it is the
smaller and more potentially
curable tumors that are most likely to be missed by the
needle. The second
concern is seeding of the tumor, either along the needle
tract or with
intraperitoneal spread. The primary indication for
percutaneous biopsy
is in unresectable cancer, based on preoperative staging,
where nonsurgical
palliation is appropriate. The results may then be used to
direct palliative
chemoradiation therapy. The technique is also useful in
patients with cancer
of the head of the pancreas in whom neoadjuvant protocols
are being considered.
Finally, percutaneous biopsy may also be useful if the CT
picture suggests
pancreatic lymphoma, which is best managed nonoperatively.
oncogene
(accuracy of up to 90% with a cut-off value of 200 units/ml)
and CA50
> CEA
> AFP
counts in peripheral blood are good markers for metastasis
detection in
pancreatic cancer patients and more accurate than other
conventional tumor
markers, especially at advanced stages of the diseaseref.)
(Whipple or Longmire-Traverso procedure) :
when this operation
is performed in cancer centers by surgeons experienced
in the procedure,
approximately 2% to 5% of patients die as a direct
result of complications
from surgery. When the operation is done in small
hospitals or by doctors
with less experience, up to 10% of patients may die as a
result of surgical
complications
: the overall poor long-term survival following the
standard Whipple operation
was the impetus for the concept of extending resection
to include total
pancreatectomy. Advocates cite eliminating multicentric
disease as well
as eradicating the spread of the disease to the distal
pancreas by ...
may result in increased postoperative surgical
complications. It appears
likely, therefore, although not indicated routinely,
that in selected patients
with advanced malnutrition, sepsis, and/or correctable
medical conditions,
or in whom a time delay prior to surgery is necessary,
preoperative biliary
drainage can be useful. 4 prospective, RCTs have been
completed in which
surgical biliary bypass was compared with nonoperative
biliary stenting
for malignant obstructive jaundice. The conclusions of
these studies are
similar, demonstrating that both techniques are equally
effective for relief
of jaundice. Nonoperative palliation, however, appears
to be associated
with lower complication rates, lower procedure-related
mortality rates,
and shorter initial periods of hospitalization.
Unfortunately, there appears
to be no advantage with respect to long-term survival.
or choledochojejunostomy.
Results of a randomized, prospective study, as well as
of a collective
review, favor the use of the bile duct for better
long-term results
without increased perioperative morbidity or mortality.
In Johns Hopkins"
series, recurrent jaundice developed in only 2% of
patients prior to death.
A gastrojejunostomy
for the treatment or prevention of gastric outlet
obstruction is the only
palliative procedure that cannot be performed
nonoperatively. According
to a review of > 8,000 patients reported in the
English-language literature
from 1965 to 1990, the creation of a gastrojejunostomy
did not increase
the operative mortality rate. Moreover, if a
gastrojejunostomy was not
performed, 13% of patients had subsequent duodenal
obstruction requiring
a gastrojejunostomy before death, and nearly one in five
of the remaining
patients died with symptoms of duodenal obstruction.
This question, namely
whether to perform a prophylactic gastrojejunostomy, was
recently addressed
by a prospective randomized study at our institution. In
this series, patients
with periampullary cancer found to be unresectable at
laparotomy were randomized
to undergo either a retrocolic gastrojejunostomy or no
gastrojejunostomy.
There was no difference in perioperative morbidity,
mortality, or postoperative
length of stay. On follow-up, however, 19% of patients
not undergoing gastrojejunostomy
developed late duodenal obstruction requiring
intervention (p<0.01).
The final major advantage of operative palliation is in
the management
of pain....
than with optimised systemic
analgesic
therapy (SAT),
but did not show improved quality of life or survival.
It alone provides
complete pain relief until death only in a few cases and
combined palliative
therapy is necessary in most of the cases. A prospective
randomized study
has demonstrated that intraoperative celiac axis
injection with 50% alcohol
can both successfully relieve pain in patients with pain
and prevent the
development of pain in patients without pain at the time
of exploration.
Celiac axis injection was not associated with
significant morbidity, mortality,
or prolonged hospital of stay. Standard pain assessment
completed until
death showed a significant reduction in both pain scores
and narcotic use.
In addition, a surprising benefit revealed by the study
was prolonged survival
in those patients undergoing chemical splanchnicectomy
who had significant
preoperative pain
50-70 Gy. If surgery is planned, preoperative treatment is
often preferred.
Postoperative treatment is often delayed for several weeks
while the patient
recovers from surgery (treatment right after surgery can
interfere with
wound healing). Radiation therapy, often combined with
chemotherapy (chemoradiation),
may be used for patients whose tumors are too widespread
to be removed
by surgery.+5-fluorouracil)
is a new approach to treating patients with cancers of the
pancreas that
is being studied at some cancer centers. With this
treatment, external
beam
radiotherapy (EBRT)
using electrons (a type of high-energy particle) is
delivered from a machine
in the operating room, while the operation is in progress.
The advantage
to this approach is that the doctors can move nearby
organs aside temporarily
and deliver a large dose of radiation to the pancreas
without doing much
damage to other organs in the area.
1500 mg/m² given over 150' infusion at a fixed dose rate
(FDR) increases
blood levels of the drug and leads to median survival of 8
months, about
3 months longer than that achieved with standard 2200
mg/m², 30' infusion.
Additionally, preliminary data have demonstrated that
gemcitabine is also
a potent radiation sensitizer of human pancreatic cancer
cells in vitro.
Temporary side effects might include nausea and vomiting,
loss of appetite,
loss of hair, and mouth sores. Because chemotherapy can
damage the blood-producing
cells of the bone marrow, patients may have low blood cell
counts. This
can increase the chance of infection (due to a shortage of
white blood
cells), bleeding or bruising after minor cuts or injuries
(due to a shortage
of blood platelets), and fatigue (due to a shortage of red
blood cells,
methotrexate,
epirubicin,
irinotecan,
cisplatin,
streptozotocin,
mitomycin,
leucovorin,
dipyridamole,
and doxorubicin
: flavopiridol
inhibitors
inhibitors improve 1-yr OS from 17% to 25%
inhibitors : marimastat
and CEA
was tested in a new orthotopic ultrasound guided
pancreatic cancer mouse
model. This model is close to the biological situation and
avoids the stress
and immunostimulation caused by laparotomy. Cells from the
syngeneic, highly
aggressive, and metastatic cell line Panc 02 were
administered orthotopically,
by ultrasound guidance, to C57bl/6 mice. MALP-2 was
administered intratumorally
or intraperitoneally and tumour growth, immune status, and
leucocyte infiltration
at the tumour site were determined. A single injection of
MALP-2 increases
median survival from 21 to 30 days. Combining chemotherapy
(gemcitabine)
with MALP-2 treatment causes further prolonged survival
(median survival
27 days with chemotherapy alone v 37 days for combined
treatment). The
life prolonging effect was paralleled by a significant
increase in cytotoxic
T cells, restoration of b2
integrin
expression on lymphocytes, and high expression of CD45RB
on Th
cells. IHC stains shows strong CTL and NK cell
infiltrationref.,
Oncophage©,
anti-gastrin
17
vaccine,
anti-VEGF
mAb-dependent
pancreatic carcinomas)
as well. The combination of chemotherapy and radiation
therapy is often
called chemoradiation. This treatment may be given before or
after surgery.
IORT
is being evaluated at certain cancer centers. During the
last decade, a
dramatic decline in operative morbidity and mortality
following pancreaticoduodenectomy
has been reported at a number of centers, with operative
mortality rates
in the range of 2% to 3% Some centers have reported large
series in excess
of 100 patients without one perioperative death. These
dramatic improvements
might be attributed to:
to the pancreatic bed (4,000-4,500 cGy) given with 2 3-day
courses of 5-FU
and followed by a weekly bolus of 5-FU for an additional 4
months; 2) intensive
therapy consisting of external
beam radiotherapy (EBRT)
to the pancreatic bed (5,040-5,760 cGy) with prophylactic
hepatic irradiation
(2,340-2,700 cGy) followed by infusional 5-FU plus leucovorin
for 5 of
7 days per week for 4 months; or 3) no therapy. All patients
who had satisfactorily
recovered from pancreaticoduodenectomy by postoperative day 60
were encouraged
to accept either standard therapy or the more intensive
regimen. In the
4-year period of this study, 174 patients underwent
pancreaticoduodenectomy
for pancreatic carcinoma. The median survival for the entire
cohort of
174 patients was 19 months, with actuarial one-, two- and
three-year survivals
of 68%, 36%, and 29%, respectively. No differences in survival
were noted
on the basis of age, gender, or race. Patients who received
either type
of adjuvant therapy had a median survival of 19.5 months and a
two-year
survival of 39%, which were significantly higher than those of
patients
who received no therapy (13.5 months, and 30%; p=0.003). Using
a Cox proportional
hazards model, a multivariate analysis determined that the use
of either
of the two adjuvant therapy protocols had a significant impact
on survival,
with both hazard ratios less than 1.0, indicating improvement
in survival
with therapy. Standard therapy appeared to be a more powerful
predictor
of survival than intensive therapy because of both the smaller
probability
value and the small hazard ratio. Based on these data and the
earlier results
from the Gastrointestinal Tumor Study Group, standard
5-FU-based chemotherapy
with external beam
radiotherapy
(EBRT)appears
to
be indicated after pancreaticoduodenectomy for adenocarcinoma
of the
pancreas. A number of clinical trials are currently underway
utilizing
preoperative chemoradiation for the treatment of pancreatic
cancer. Preliminary
results suggest that neoadjuvant therapy can be completed
without increasing
the morbidity and mortality of subsequent surgical resection.
Researchers
at MD Anderson Cancer Center have recently reported on the
multimodality
treatment of 142 consecutive patients with localized
adenocarcinoma of
the pancreatic head. A subset of 41 patients treated with
preoperative
chemoradiation and pancreaticoduode-nectomy were compared with
19 patients
who received pancreaticoduodenectomy and postoperative
adjuvant chemoradiation.
No patient who received preoperative chemoradiation
experienced a delay
in surgery because of chemoradiation toxicity, but 24% of
eligible patients
did not receive their intended postoperative chemoradiation
because of
delayed recovery following pancreaticoduodenectomy. Patients
who were treated
with rapid fractionation were reported to have significantly
shorter duration
of treatment (median 62.5 days) compared with patients who
received postoperative
chemoradiation (median 98.5 days). In early follow-up, no
patient who received
preoperative chemoradiation experienced a local recurrence,
while peritoneal
recurrence occurred in only 10% of these patients. In
contrast, local or
regional recurrence occurred in 21% of patients who received
postoperative
chemoradiation. Overall survival curves were similar for both
cohorts.
The use of neoadjuvant therapy remains controversial, with
some groups
reserving neoadjuvant therapy for patients with evidence of
locally unresectable
tumors (as defined by imaging studies or laparotomy).
or the combination of radiation therapy and chemotherapy
with 5-FU
and/or gemcitabine. At some institutions, patients with
locally unresectable
disease receive chemotherapy and radiation together and are
then reevaluated
to see if the cancer has shrunk enough to be completely
removed by surgery.
Some patients can undergo curative surgery after the
chemotherapy and radiation.
In one study of patients who were treated this way, those
with locally
advanced disease actually had a longer survival than
patients who had resectable
cancer treated first by surgery followed by chemotherapy
and/or radiation
or 5-FU
is the standard treatment strategy for these patients.
Participation in
clinical trials of new chemotherapy combinations (with or
without radiation
therapy) and new biological therapies should be considered.
Many other
drugs have also been used. These include doxorubicin,
etoposide, and streptozotocin. In general, none of these
drugs have been
able to increase the lifespan of patients with metastatic
cancer of the
pancreas. Some studies have shown, however, that after
patients with pancreatic
cancer receive chemotherapy drugs, they have fewer symptoms.
For patients
with metastatic cancer of the pancreas who have common bile
duct blockage,
placement of an endoscopic stent to relieve blockage is
generally recommended.
Whenever possible, doctors avoid any surgical treatment that
will require
a significant amount of recovery time in the hospital. The
average survival
time following diagnosis of patients with metastatic cancer
of the pancreas
is in the range of 3 to 7 months.,
used together, can help can find precancerous changes called
dysplasia
among members of high-risk families. If results of these
tests are suspicious,
prophylactic pancreatectomy (preventive removal of the
pancreas) may be
considered as an option.
oncogene, and alters regulation of cell growth. New
diagnostic tests are
often able to recognize this change in samples of pancreatic
juice collected
at the time of ERCP. For now, EUS, ERCP, and tests for K-Ras
changes are an option for people with a very strong family
history of pancreatic
cancer, but are not recommended for widespread testing of
people at average
risk who do not have any symptoms.is
rare;
most occur in the tail of the pancreas. They frequently
metastasize
to the regional lymph nodes and liver. They frequently
become calcified,
whereas islet cell tumors usually do not.
oncogeneref
,
CEA]plasma
: ileus in acute pancreatitis,
calcifications in chronic
pancreatitis
and echocolordoppler : only areas, surrounded by fatty tissue,
explores
Wirsung's duct
(pancreas is well-contrasted by peripancreatic fatty tissue; as
it is a
retroperitoneal organ, it doesn't move during respiration).
/ endoscopic
retrograde
cholangiopancreatography (ERCP)
to detect neoplastic choledocus stenosis (the dilated Wirsung's
duct contains
stationary fluid)
alone
or
in combination with the liver is highly successful in children
with
MVID, offering them a long-term perspective for the first
time. Associated
colon grafting markedly improves the outcome and quality of
life after
SbTx in patients with MVIDref1,
ref2.
from early infancy. Since these are intractable diseases, they
have been
proposed to be elective indication for early bowel
transplantation in order
to avoid complications, such as TPN-related liver disease, that
would require
a combined small bowel-liver transplant.
(29%)
/ bacteremia, chylous ascitis,
necrotizing
enterocolitis, maternal drug ingestion
(20-35%), multiple boils or cystic images (multiple dilated
loops), opaque
enema for differential diagnosis
and Fogarty's catheter to assess intestinaal patency
down to anus,
spina bifida, omphalocele
,
cloacal exstrophy, intersex state, ectopia cordis, OIES
complex (omphalocele,
exstrophy of bladder, imperforate anus, spina bifida) due to
an arrest
in median fusion of caudal embryonal hemisoma
,
umbilical granuloma after detachment of umbilical cord
(treated with silver
nitrate ointment, cryotherapy or folgoration) or sinus
of omphaloenteric canal)
(RBC
blood pool scintigraphy
for bleeding due to peptic ulcer;
false negatives
in 20%); abdomen X-rays has poor sensitivity; laparoscopic
examination
,
the first 40 cm of small bowel should be carefully
examined to look for
Meckel's
diverticulum; if found : exeresis together
with a tract of small
bowel => ileoileal anastomosis
: isolated megaduodenum is the most infrequent form of mega;
but more frequent
is its association with megaesophagus
and
megastomach.
The duodenum becomes elongated, widened, and has evident
symptomatic stasis.
Little is known about the causes of megaduodenum: if the
problem is incoordination
along the duodenum or at the level of the duodenal jejunal
junction, like
in achalasia of the lower esophageal sphincter,
the degree and kind of malabsorption depending on the site and
extent of
the resection
and gastrojejunostomy
(Norwalk gastroenteritis; 96% of nonbacterial
gastroenteritis in
the United States)
(rotavirus gastroenteritis (RGE)),
and malabsorption, depend on the site and extent of the
disorder. The stomach
is also frequently involved. The disorder is commonly
associated with intolerance
to specific foods
(2 mg for children weighing 8 to 15 kg, 4 mg for children
weighing more
than 15 kg and up to 30 kg, and 8 mg for children weighing
more than 30
kg) reduces vomiting and facilitates oral
rehydration
and may thus be well suited for use in the emergency
departmentref
alters the bowel flora and results in diarrhea
during the first 2 months of life (the most common
surgical emergency in
the neonatal intensive care unit). The incidence of
necrotizing enterocolitis
increases with decreasing birth weightref
proliferation after broad-spectrum antibacterial
therapy in adults
in babies
with intestinal resection and peritoneal drainage
are widely practiced. The standard approach to patients
with perforated
intestine, necrotic intestine, or both is surgical
resection of the involved
bowel with the creation of intestinal stomas. In a
critically ill premature
infant, this entails substantial risks. Primary peritoneal
drainage, a
minimally invasive operation, has evolved as an
alternativeref.
It involves a small abdominal incision with placement of a
drain into the
peritoneal cavity without a formal laparotomy or bowel
resection. There
is considerable controversy regarding which procedure is
preferable. Evidence
consists largely of case series from single institutionsref.
However, laparotomy and resection in very-low-birth-weight
infants with
necrotizing enterocolitis entail high morbidity and
mortality; long-term
follow-up shows that good neurodevelopmental outcomes are
rareref.
3 decades ago, pediatric surgeons, out of desperation,
began a bold experiment.
Ein and colleagues, in Toronto, reported on a case series
of 6 infants
with extremely low birth weights who were treated with a
temporizing primary-peritoneal-drainage
procedure. 3 survived, 2 of whom did not require a second
operationref.
The concept was to relieve the increased intraabdominal
pressure, drain
the infection, and allow the physiological status of the
infants to improve
before a definitive operative procedure. This initial
report was met with
skepticism or even outright hostility from surgical
colleagues but was
followed in subsequent years by several other small case
series, many of
which supported a role for primary peritoneal drainage in
the treatment
of very-low-birth-weight infantsref1,
ref2,
ref3,
ref4,
ref5.
Surprisingly, a substantial number of infants treated with
primary peritoneal
drainage survived, many without the need for a second
operation, although
neurodevelopmental outcomes remained poorref.
Despite its widespread use, the role of primary peritoneal
drainage has
continued to remain controversial. Even among those who
accept the approach,
there has been controversy regarding which subgroups of
infants are the
most likely to benefit. Available data have been limited
by bias in the
selection of patients, investigator bias in the
interpretation of the results,
or bothref.
Currently, in the absence of rigorous evidence supporting
the superiority
of one approach over the other, the care of infants
requiring surgical
intervention depends mostly on the local biases of the
treating institution
or the individual surgeon. A multicenter, randomized
clinical trial was
conducted to determine whether primary peritoneal drainage
improves survival
90 days postoperatively as compared with laparotomy and
resection for very-low-birth-weight
(< 1500 g) premature infants with perforated
necrotizing enterocolitis.
It was also assessed whether primary peritoneal drainage,
as compared with
laparotomy and resection, reduced the frequency of
dependence on total
parenteral nutrition 90 days after operation or reduced
the length of hospital
stay in surviving infants. The type of operation
performed for perforated
necrotizing enterocolitis does not influence survival
or other clinically
important early outcomes in preterm infantsref
,
passive immunization, and the use of probiotics have all
been suggested
but not proven as possible preventive methods. Emerging
strategies include
amino acid supplementation, the use of platelet-activating
factor(PAF)
antagonists or PAF-acetylhydrolase administration,
polyunsaturated fatty
acid administration, and EGF
administration
.
Antibiotic-associated hemorrhagic colitis has also been
reported after
antibiotic therapy with quinolones and cephalosporinsref1,
ref2.
In contrast to antibiotic-associated colitis induced by
C. difficile,
antibiotic-associated hemorrhagic colitis is thought to
resolve spontaneously
after cessation of antibiotic therapyref1,
ref2,
ref3.
The cause of antibiotic-associated hemorrhagic colitis
is unknown. Several
mechanisms have been suggested, including allergic
reactionref,
mucosal ischemiaref,
and infection with Klebsiella
oxytocaref1,
ref2.
This gram-negative bacterium has been found in patients
with antibiotic-associated
hemorrhagic colitis, but it is also found in stools of
healthy subjectsref.
K.
oxytoca strains isolated from patients with
antibiotic-associated hemorrhagic
colitis and half of the strains isolated from healthy
subjects have been
shown to produce a cytotoxin that is capable of inducing
cell death in
various epithelial-cell culturesref1,
ref2,
ref3,
ref4.
5 patients with antibiotic-associated hemorrhagic
colitis were described
: a K. oxytoca strain isolated from one of these
patients was used
in an animal model of antibiotic-associated hemorrhagic
colitis, which
allowed us to fulfill Koch's postulatesref.
Several case reports and small series have demonstrated
that K. oxytoca
is
present in the stool of most patients with
antibiotic-associated hemorrhagic
colitisref1,
ref2,
ref3,
ref4,
ref5,
ref6.
The prevalence of K. oxytoca among healthy
subjects is 1.6% in Austria,
as compared with 9% in Franceref,
suggesting that the prevalence varies by geographic
region. 2 case reports,
in which K. oxytoca was the presumed cause of
colitis in patients
who had not received antibiotic therapyref1,
ref2,
deserve special attention, since they suggest that K.
oxytoca may
be pathogenic even in the absence of antibiotics under
certain circumstances.
Previous studies investigating the effect of orally
administered amoxicillin–clavulanate
on fecal microflora revealed that fecal enterobacteria
that are sensitive
to amoxicillin–clavulanate may persist in the intestinal
microflora during
antibiotic therapyref1,
ref2.
This may be due to very low fecal concentrations of
amoxicillin–clavulanateref.
Cytotoxin-producing K. oxytoca strains are
present at least temporarily
in the colon of some people, in whom antibiotic therapy
can lead to overgrowth
of toxigenic K. oxytoca in the colon, owing to
selection of this
organism. Since Klebsiella is nearly always
resistant to penicillins
because it expresses a b-lactamase,
antibiotic-associated
hemorrhagic colitis is particularly seen during therapy
with penicillin
derivatives. Overgrowth of K. oxytoca in the
colon finally results
in high cytotoxin concentrations that induce mucosal
damage. NSAIDs appear
to aggravate colitis caused by potentially pathogenic
bacteria in the intestinal
lumenref1,
ref2,
ref3,
ref4,
ref5;
it is generally self-limited but may be complicated by hemolytic-uremic
syndrome..
(diphtheritic enteritis) : enteritis characterized
by the presence
of a false membrane and severe ulceration of the mucosa
beneath the membrane
(enteritis necroticans) : an inflammation of the
intestines in humans
and characterized by necrosis
(streptococcus enteritis) : primary phlegmonous
enteritis
(psorenteritis)
for
,
believed to be caused by the swallowing of large amounts
of positive sputum;
now rare due to antibiotic tuberculosis therapy
infection (colonizes only metaplastic areas)
affecting the ileum
.
and digestion are not impaired.