)
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) gene