)
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)|
|
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|
|
| cervical esophagus cancer |
|
|
|
| upper thoracic esophagus cancer |
|
|
|
| midthoracic esophagus cancer |
|
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| 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.|
|
|
|
|
| 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 |
or cancer-testis
antigens.
Use of autologous tumor vaccine in preventing recurrence of hepatocellular
carcinomaref
(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
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
(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 lymphadenopathies
New 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.
(accuracy of up to 90% with a cut-off value of 200 units/ml) and CA50
> CEA
> AFP)
(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
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)
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.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 or ...
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)
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.
(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.
pancreatic failure,
steatorrhea,
and anemia
("bowel cocktail" of gentamycin, metronidazole and cholestyramine),
stomatitis
intertropica / tropical stomatitis, and megaloblastic
anemia due to folic acid deficiency
is common. Administration of antibiotics (especially tetracycline)
and folic acid usually results in remission
deficiency
=> sideropenic anemia,
glossitis,
aphtae,koilonychia
=> megaloblastic anemia,
fatigue, cheilosis, glossitis
=> pernicious
anemia
=> follicular hyperkeratosis, dark blindness,
Ca2+ and Mg2+ => bone pain, paraesthesia, tetanus,osteoporosis,
osteomalacia
=> inner or outer hemorrhages
=> pica
and acrodermatitis
enteropathica
in IBS has not been clearly defined. Some studies have shown improvements
in pain and flatulence in response to probiotic
administration, whilst others have shown no symptomatic improvement. It
is possible that the future role of probiotics in IBS will lie in prevention,
rather than cure
can usually tolerate jejunal feeding.
This treatment allows most patients with a jejunostomy and > 1 m functioning
jejunum remaining to manage without parenteral support)
to induce structural jejunal adaptation have been given in high doses to
patients with a jejunostomy
and do marginally increase the daily energy absorption.
from mural thrombosis in an infarcted left ventricle or left atrium fibrillation
from mitral stenosis (50%; fast onset => massive
intestinal infarction => death)
(25%; slow onset => side circulations) : formation of a clot in an artery
or arteriole of the mesentery (usually within 2 cm of the begininnig of
the superior mesenteric artery) is the end result of atherosclerotic
stenosis (history of intestinal angina)
ingestion
(e.g from acute drop in cardiac output (arrhythmias, AMI)) => splanchnic
circle vasoconstriction to increase perfusion pressure in vital organs
(brain, heart, kidneys, lungs); risk of intestinal gangrene is high because
the subtlety of clinical and radiological (collapsed vena cava) signs often
delays diagnosis
(pheochromocytoma
or rupture of ingested cocaineovules
in carriers),
surgery or necropsy, lack of vasculitis or embolism at histologyref.
(5%, affecting younger patients with no apparent underlying disease) :
due to
(e.g. polycythemia vera)
associated with hepatic cirrhosis,
or to extrinsic compression of the venous system secondary to a tumour
mass or trauma).
and short bowel syndrome), leukocytosis,
metabolic acidosis, hyperamylasemia, hypoxemia, bacteremia (portal vein
air (PVA)), hyperphosphaturia, CPK-BB > 20 ng/ml, LDH, hyperazotemia, hypercreatininema;
alkaline phosphatase increases only in massive necrosis
: vasospasms, dishomogeneous filling, delayed vein contrastography, alternance
of dilated and constricted regions,
abdominal distention, and abdominal tenderness
/atherosclerosis/advanced
age/hypercoagulability
detects pneumatosis cystoides
intestinalis or intestinorum / intestinal emphysema or pneumatosis
: the presence of thin-walled, gas-containing cysts in the intestinal wall
either subserosally or submucosally
=> edema in intestinal loop walls and air in peripheral intrahepatic portal
branches(normally
the SMA come soff ther aorta at an oblique angle and is easily visualized
on a lateral film) =>
=> heparin
=> aorta-superior mesenteric artery (SMA) bypass
drip => correct hypoperfusion
(21%). 25% of patients were under anticoagulant drugs or had a hemostatic
blood disorder.
=> type 2 acquired von Willebrand's
disease / von Willebrand's syndrome
(loss of the large multimers, which are required to maintain hemostasis
in high flow conditions, such as occur in angiodysplastic arteriovenous
malformations) => bleeding from previously latent IA.
has been shown to improve the hematological abnormalities, and this is
paralleled by clinical improvements. Valve replacement appears to offer
the best hope of long-term resolution of the bleeding, and should be considered
in most cases, particularly in those in whom the AS is symptomatic. In
those patients deemed unfit for surgery in whom no bleeding point can be
identified, recurrent blood transfusions may offer some symptomatic relief.
In patients with Heyde's syndrome antibiotic prophylaxis should be considered
before colonoscopy. to prevent infective endocarditis
=> melena (10%) => Therapy
: self-limited in 80%, severe and requiring blood transfusion in 3%; 5%
require urgent colectomy. Relapse in 25-30%. Endoscopic treatment (laser
coagulation) and drug therapy (s.c. somatostatin or octreotide)
are valid alternatives in inoperable or non-resectable cases.
))
in which there is more rapid desquamation of mucosal epithelial cells
infection. Duodenitis associated with gastric
metaplasia is observed in 85% patients
(PILs) (uncommon):
involvement of mucosa and submucosa
(lymphomatous polyposis)
(most commonly) occur most often in the ileum.
(more rarely)
(more rarely)
is rare, and the duodenum is the second least common site for carcinoid
tumors, which are seen with decreasing frequency from the first to the
third part of the duodenum. The tumors usually are slow growing and benign.
An association with Zollinger-Ellison
syndrome has been described.
: incidence of tumors increases with proximity to the cecum. Small-bowel
carcinoids are multiple in number in 15-35% of cases. Liver
metastases and carcinoid syndrome occur in 25-30%. The tumor often
infiltrates the mesentery, provoking an intense fibrotic reaction that
results in kinking of the bowel segments, which may cause intestinal obstruction.
A finding of kinking of the small-bowel loops is considered the hallmark
of a carcinoid tumor on a small bowel barium series.
.(>
38°C in peritonitis)
(90%; 12,000-20,000/ml (lower down to normality
if immunosuppressed); 20,000-30,000/ml if perforated;
when > 30,000/ml another diagnosis should be
suspected (hemolytic-uremic
syndrome (HUS),
Schonlein-Henoch
purpura)
with high-frequency probe with graded palpation for differential diagnosis
with other regional diseases (acute
salpingitis,
torsion of ovarian
cyst,
urinary
tract infections (UTI)).
ECD may show appendicular hyperemia. Appendix is seen only if has edematous
walls or contains purulent, uncompressable, anechogenic material, or by
contrst if periappendicular fluid collections occur : eventually echography
may detect the appendicular plate occupying whole pelvis.
for differential diagnosis with right basal lobar pneumonia
: target sign if diagnosis is not clear
(suprapubic pain, nausea and vomiting, no fever or leukocytosis, cystic
mass palpated at digital vaginal exploration and seen at echography)
(adenoviruses, also cervical lymphadenitis, tonsillitis, vomiting, fever,
pain varying with postural changes; serous fluid collection in Douglas'
cavity seen at echography)(expecially
in females, high fever, dysuria, nycturia, hematuria, leukocytosis > 15,000/ml),
gastroenteritis
(Yersinia enterocolitica
=> mesenteric
lymphadenitis;
watery diarrha, abdominal distension, clustering, fever, tachycardia, tachypnea,
objective eexamination and abdomen X-rays), Schonlein-Henoch
purpura
(vasculitis and intestinal hemorrhage preceed by 48 hrs diffuse petechias,
rectorrhage or hematuria in 50%, increased scrotal volume due to intravaginal
hemorrhages, ileocecal invagination or intestinal perforation), right basal
lobar pneumonia)
reduce the risk of gangrene, perforation, postoperatory infections of wound,
and doesn't mask the systemic effects of disease => appendicectomy
(late complications : intestinal
occlusions due to adherences (50% if perforated, 5% if not perforated;
60% within 2 years); female sterility due to salpingitis in perforated
appendicitis). Untreated appendicitis is limited by the appendicular
plate, which has beniogn prognosis. If an abscess forms, CT- or echo-assisted
paracentesis may resolve
.
.
Tumors frequently have an extraluminal component and often metastasize.
A carcinoid tumor is an occasional incidental finding on histologic examination
of a removed appendix.
of the dilated ending to prevent exclusion of the distal ending => recanalization
at age 2-6 months
(myxedema megacolon) : abdominal distention, flatulence,
and constipation
(in addition to Hirschsprung disease, some patients with mutations at EDNRB
have associated syndromes, such as abnormal pigmentation, with white spots
in the skin and hair, and hearing loss. Defects in the EDNRB signaling
pathway also play a part in other major diseases, including cancer, hypertension
and cardiovascular disorders)
(sensitivity = 90%) : reflex is physiologically absent in the first
10-20 days of extrauterine life
and colotomy with upstream decompression in severe forms and definitive
surgery after 2-4 months of age (when P > 4 kg) if good conditions and
definitive irrigations
(pull-through)
(no enteroclysm nor endoscopy to prevent perforations) shows colonic
dilatation > 6 cm in the transverse colon
suction,
antibiotics, steroids (CsA ?) and fluids for 24-48 hrs =>
: this form may appear alone or with dilatation of other parts of the digestive
tract, it frequently occurs in association with megaesophagus.
Stasis is the most common symptom, it may lead to cronic or acute obstruction
with faecal impaction, or even torsion of the sigmoid colon. Although the
pathophysiology is the same, differences occur due to individual physiological
and anatomical characteristics of the colon in relation to the esophagus.
Motility disorder however is observed as follows. In megas caused by Chagas
disease, the sigmoid colon and the rectum present increased motility with
or without associated megaesophagus. The movements are independent in the
healthy individual and syncronic in the patient with Chagas disease. The
use of pentagastrin in megacolon did not present any response because the
neural communication between the hormone and the muscle cell is lost. The
intra luminal stimuli in the esophagus determine, in the healthy individual,
rectal contraction through the mioenteric plexus. Despite its frequency
in megacolon, faecal impaction rarely causes acute colonic obstruction
due to the colon characteristc of retaining large amounts of feces. Association
with megaesophagus in the advanced phases of the disease, may cause difficulty
to prioritize treatment in severe cases. If we correct the megaesophagus
first, we may, due to the postoperative ileus, facilitate acute obstruction
caused by faecal impaction and normal feeding. Operating on the megacolon
first, the upper tract obstruction (esophageal) and the malnutrition remains.,
anticoagulant or antiplatelet drugs. They require surgery only after 2-3
relapses./US
if vomiting, broad-spectrum antibacterials
(aminoglycosides, metronidazole + third generation cephalosporin or clindamycin
for > 7 days; if resistant => clindamycin), fluids (to compensate sequestration),
percutaneous
drainage of abscesses under local anesthesia with 2-ways catheter :
and sonography on day 7 => remove drain when criteria for catheter removal
are met
scan with dilute Hypaque injection into cavity and attempt further drainage
=>
and requires colostomy
),
clinically resembling toxic megacolon from
fulminant ulcerative
colitis.,
characterized by abdominal cramping and watery diarrhea that progresses
to bloody diarrhea after one or two days; it is generally self-limited
but may be complicated by hemolytic-uremic
syndrome..ref
can occur in isolation or with diffuse or multiple involvement of the adjacent
and unrelated diseased sites (ascending colon and appendix in childrenref).
The majority of cases are associated with other diseases, the most common
being rectal adenocarcinomaref1,
ref2,
ref3,
very rarely tubular adenomaref.abuse..
is offered to patients who fail dietary therapy
may be considered
and vitamin deficiency.
to
the abdominal region, marked by tenesmus, pain,
rectal bleeding, diarrhea, and telangiectasis
which may progress to malabsorption, ulceration, and partial or complete
obstruction,
but the ulceration is often longitudinal or deep, the disease is often
segmental, stricture formation is common, and fistulas, particularly in
the perineum, are a frequent complication.
of chronic
renal failure (CRF))
in the sigmoid colon or rectum, sometimes preneoplastic. It may be sessile
or pedunculated and solitary or multiple.
(mutation carrier) (70%)
(large and small intestines)
(large and small intestines, stomach)
(large intestines, stomach)
or indomethacin
induce the activity of spermidine/spermine
N-1-acetyltransferase (SSAT), which is involved in polyamine catabolism
and export. It is expecially effective in patients with A316G SNP between
2 binding sites for c-MYC
in the ODC promoter
of colon
gene from the patient's mother. Patients who have polyps are 3 times more
likely to have LOI, while patients with a personal history of CRC are 22
times more likely to have LOI. Among healthy patients with no family history
of cancer, about 10% have the LOI marker. Mice engineered to have a double
dose of IGF2
develop more so-called precursor cells within the lining of the colon than
normal mice. When these mice also carried the APC colon-cancer-causing
genetic mutation, they developed twice as many tumors as those with normal
IGF2 levels. In the mice -- as well as in about 30% of colon cancer patients
and 10% of the general population -- the extra IGF2 stems not from a genetic
problem, or mutation, but an "epigenetic" problem that improperly turns
on the copy of the IGF2 gene that should remain off.(it
seems to be a more important risk factor than presumptively cancer-promoting
diets. Although mutagens are present in foods and feces at low concentrations,
there is little evidence that the adverse effects of diet on alimentary
cancers in the West are caused by food-borne carcinogens that can be identified
and eliminated from the food chain. It seems more plausible that the Western
gut becomes vulnerable to neoplasia because of adverse metabolic factors,
such as pro-inflammatory agents produced by adipose tissue, and because
of low intakes of anticarcinogens from plant foods. The chronic use of
aspirin and other nonsteroidal anti-inflammatory drugs significantly reduces
the risk of colorectal and esophageal cancers, perhaps by inhibiting the
expression of the pro-inflammatory enzymes in precancerous tissues. Both
diseases are also less common among consumers of diets rich in fruits and
vegetables, which harbor a huge variety of biologically active secondary
metabolites such as glucosinolates and flavonoids, which may act synergistically
in the human diet.)
in drinking water,
Escherichia
coli,
Salmonella
typhimurium) and a serine protease (that is associated with the type
I gel collagen used for the invasion assay and is also found in normal
gut tissue), stimulate cancer cell invasion and motility by modulating
the activities of THO-faimly GTPases. Tumor biopsies from colon cancer
patients are able to generate the proinvasive peptide when supplied with
the synthetic 33-mer b-casein precursor, demonstrating
that the necessary enzymes are present in the human colonref.
at 0.625 mg plus medroxyprogesterone
acetate
at 2.5 mg decreases risk of CRCr in postmenopausal women with an intact
uterus and between 50 and 79 years of age. Among women who developed colorectal
cancers, however, those using the hormone therapy had more advanced cancer
at diagnosis than those using placebo
: 75% in the ascending colon; 0.3% of colonic tumors
requires differential diagnosis with polyposis
tumor suppressor gene or b-catenin
activation causes CIN (rarely preexisting) => polyp / class I or early
adenoma => activation of K-Ras 2
or BRAF
=> class II or intermediate adenoma => loss of the SMAD4, TGF-b
or DCC
tumor suppressor gene => class III or late adenoma => loss of TP53
=> carcinoma => other mutations => metastases
genes such as MLH1,
MSH2
/ HNPCC,
and MSH6.
The mutator phenotype is dominant over the CpG island methylator phenotype
(CIMP) in CRC, and although methylation in MLH1 can induce MSI, it seems
that acquisition of the mutator phenotype is still the important event
: the frequence of methylated loci reflects a normal distribution, characteristic
of random events, whereas the frequency of MSI mutations reflects a bi-modal
distribution expected if the CIMP phenotype occurred at a specific stage
in tumour progression and was then instrumental in causing a significant
increase in methylation. DNMT1,
DNMT3b,
FAT,
LMX1A,
and DUX4
are other hypermethylated tumour suppressor genes. 15-hydroxyprostaglandin
dehydrogenase (15-HPGD),
a COX-2 oncogene antagonist, is a TGF-b-induced
suppressor of human gastrointestinal cancersref.
Other tumors have loss of the TGF-b signal,
so that there is no 15-HPGD.
CK2 exerts its anti-apoptosis effect within a structure called DISC (death-inducing
signaling complex). The DISC is a large jumble of proteins that interact
with each other after TRAIL binds to the outer cell membrane. Blocking
CK2 with DRB made the cells very sensitive to TRAIL. Because DRB can also
interfere with other cellular reactions, the researchers blocked CK2 using
short hairpin RNA (sh RNA)ref
and CEA
> TPA
> TK;
CCSP-2
may indicate bleeding from ulcers, polyps, cancer or other diseases
has 99% sensitivity in detecting polyps
in various positions to allow air movement-assisted
virtual
colonoscopy
: both endoscopic and virtual colonoscopy detect > 90% of polyps > 8 mm
in diameter in asymptomatic adults aged 5-79, but one of the malignant
growths found by the virtual technique was missed by the conventional methodref.
Human observers detect 39-58% of polyps without computer-aided detection
(CAD); 75% of the missed polyps were later identified by the human observers
with the help of the CAD system. 77% of the computer's false-positives
were easily (and appropriately) dismissed by the human readers-assisted
virtual
colonoscopy,
84% of CRC recurrences can be detected using only the patient's serum.
concentrations are higher among CRC cases than controls (median CRP, 2.44
vs 1.94 mg/L; P = .01). The highest concentration is found in persons
who subsequently developed colon cancer vs matched controls (median CRP,
2.69 vs 1.97 mg/L; P<.001) but among rectal cancer cases, CRP
concentrations are not significantly different from controls (median CRP,
1.79 vs 1.81 mg/L; P = .32). The risk of CRC is higher in persons
in the highest vs lowest quartile of CRP (OR, 2.55; 95% confidence interval
[CI], 1.34-4.88; P for trend = .002). In nonsmokers, the corresponding
association is stronger (OR, 3.51; 95% CI, 1.64-7.51; P for trend<.001).
A 1-SD increase in log CRP (1.02 mg/L) is associated with an increased
risk of colon cancer after adjusting for potential confounders and excluding
cases occurring within 2 years of baseline (OR, 1.35; 95% CI, 1.05-1.74)
or excluding those with late-stage colon cancer at the time of diagnosis
(OR, 1.38; 95% CI, 0.99-1.91)ref
(expecially from rectal carcinomas), abdomen, osteolytic
bone metastases,
local relapse|
|
|
|
|
||
| A | I | Tis | N0 | M0 | A |
| T1T2 | N0 | M0 | B1 | ||
| B | II | T3T4a | N0 | M0 | B2 |
| T4b | N0 | M0 | B3 | ||
| C | III | T1T2 | N1N2N3 | M0 | C1 |
| T3T4a | N1N2N3 | M0 | C2 | ||
| T4b | N1N2N3 | M0 | C3 | ||
| D | IV | any T | any N | M1 | D |
/folinic
acid
for 6 months. 5-FU/levamisole
for 12 months may also be considered, although at least 1 trial has shown
this to be inferior in survival to 6 months of 5-FU plus high-dose leucovorin
- irinotecan
- capecitabine
– oxaliplatin,
ovaries)
+ bolus IFL (5-FU/leucovorin/irinotecan)
+ irinotecan)
+ oxaliplatin)
to the primary tumor to palliate bleeding, obstruction, or pain. Palliative
radiation therapy may also be targeted to other sites of metastases for
similar indications.)
: colectomy
+ lymphadenectomy
(at least 8-12 lymph nodes)
(425 mg/m2/d IV days 1-5) + leucovorin
(20 mg/m2/d IV days 1-5) for 6 months (repeat q28d x 6 cycles)
if high-grade T3 or N1; LV5FU2 is less toxic than monthly
FUFOL
and no statistically significant difference could be detected in disease-free
or overall survival between the 2 schedules. FU-based adjuvant chemotherapy
for stage II or III colon cancer is associated with in improvement in 5-year
disease-free survival from 55% to 67% and an increase in 5-year overall
survival from 64% to 71% in the pooled analysis. An online
calculator predicts survival.
(425 mg/m2/d IV days 1-5) + folinic
acid
(20 mg/m2/d IV days 1-5). Repeat q28d x 6 cycles
(500 mg/m2/d IV weekly x 6) + folinic
acid
(500 mg/m2/d IV weekly x 6). Repeat q8w x 4 cycles.
(85 mg/m2 IV day 1) + 5-FU
(400 mg/m2/day IV days 1-2; 600 mg/m2/day CI
over 22 h, days 1-2) + leucovorin
(200 mg/m2/day IV days 1-2) (FOLFOX4) is the first
combination to demonstrate significant superiority over 5 fluorouracil
and leucovorin in adjuvant treatment of colorectal cancer. Repeat q14d
x 12 cycles/leucovorin/irinotecan)
- not used, excess mortality from increased toxicity/leucovorin/irinotecan))
1250 mg/m2 BID x 14 days. Repeat q21d x 8 cycles.,
oxaliplatin,
ralitrexed,
capecitabine.
DakoCytomation
in Copenhagen, Denmark, makes EGFR-pharmDx that determines if a colon tumor
overexpresses
EGFR.
:,
which allows diagnosis 8.5 months before and reduces mortality by 10%.
(P =.005) were statistically significant predictors of death (The Serological
Markers TIMP-1, PAI-1, MASP-2 and CRP Are Independent Predictors of Colorectal
Cancer-Specific Death. Abstract 5723).
exposure (sometimes accompanying malignant
pleural mesothelioma).
The median time from first exposure to symptoms was 33.5 (range, 16 to
53) years-guided
biopsy. Pleural changes suggesting asbestosis combined with CT
findings and high CA-125levels
can suggest, but are not diagnostic of, mesothelioma.
(median dose 250 mg/m2) has activity in 25% of patients, and
a single postoperative intraperitoneal dwell of fluorouracil and paclitaxel)
has resulted in a median survival of 50 to 60 months. Favorable outcome
is associated with age, tumor biology (selection of patients with a history
of previous debulking), lack of invasive tumor growth, and minimal residual
disease after tumor resection. Mesothelial cells are known to contain high
levels of carboxylesterase, a key enzyme in the activation of Irinotecan
(CPT-11)
to SN-38.
arising as small nodules scattered throughout the peritoneal surfaces,
occurring exclusively in women of reproductive age and appearing very similar
to low-grade leiomyosarcoma or metastatic carcinoma but usually regressing
spontaneously following menopause,
e.g. ...
or a ruptured mucocele of the appendix
in early stages after i.v. contrast agent injection in upper limb
or laparoscopy
is the most useful modality in diagnosis and follow-up of peritoneal tumors,
no
peritonitis, obtuseness
,
or when the tissues around the opening into the peritoneal cavity act as
valves, allowing air to enter but not to escaperef
perforation
and diagnosis (diagnostic pneumoperitoneum).
demonstrates a focal area of moderately increased echogenicity in the omental
fat in the right abdomen (a previously described finding in omental infarction)
,
LRTI) > adults (ascitis due to chronic hepatopathies); females > males
(36.4%)
(27.4%)
(34%)
(25.3%)
(15.4%)
,
urinary catheterism, ABG
(dangerous in anaesthesia !) due to ascitis and intraluminal gastrointestinal
secretions (estimate loss with expected urinary volume for age and body
mass, nasogastric aspiration and vomiting; if urinary volume remains below
expected, increase fluid administration : do not administer diuretics suspecting
renal failure !) with expansion of volemia, and, if persisting, bicarbonate
(side effect : poor clearance)
(due to hyperfusion => hyperlactacidemia; vomiting, intralumenal sequestration,
oliguria, and acid resorption from peritoneal exudate, partially balanced
by respiratory alkalosis
due to hyperventilation) and electrolyte disorders (negative prognostic
factor if new-onset)
(third-generation cephalosporin or clindamycin + metronidazole + aminoglycoside
or aztreonam) for > 7 days)
(for differential diagnosis with lower lobar pneumonia and mandatory for
anesthesia)
in orthostatic and left lateral decubitus (hydroaereal levels, free air
in intestinal perforation, pancreatolithiasis
in reacutization of chronic calcifying pancreatitis, urolithiasis)
: the patient does not need to be moved, easily repeatable, but operator-dependant
and difficult due to meteorism; cannot investigate retroperitoneum and
pelvis, but often sees free air in intestinal
perforation
: requires contrast agent, assess functionality with i.v., p.o., or i.r.
(e.g. it also assess asymptomatic acute thrombosis of renal artery),
TPN,
fluids,
antibacterials,
CT,
ERCP
=> surgery required only for septic necrosis; percutaneous drainage in
retroperitoneal and peripancreatic areas to look for anaerobes)
if symptoms > 3 days => laparoscopic appendicectomy
(expecially if obese (higher risk of surgical wound infections) or fertile
female)
ulcer
can be heard in cases of intestinal perforation with gas in the peritoneal
cavity.
detects air ...
(below liver and under diaphragm (more evident at right as at left the
gastric boil may cover it)) (aereal sick)
(medical therapy => surgery for acute complications)
([b-hCG]urine, transabdominal
echography (TAE),
laparoscopy/surgery) => rupture of uterine tube => metrorrhage.
Antibacterials
=> surgery (immediate surgery in previously appendicectomized feamles)
or endometritis
(rare)
(not modified by posture),
PAN
(tubercular peritonitis) : no evidence of gastrointestinal or pulmonary
hot-spots
puncturing once (CLP[1]) or twice (CLP[2]) the ligated cecum : the number
of punctures in CLP do not significantly change survival rate. Continuously
low amounts of bacteria and cytokines are found in CLP mice at any point
of time. 24 hours after CLP surgery, the ligated cecum is covered by adhesive
small bowel loops. CLP reveals a model of intra-abdominal abscess formation
with sustained and minor signs of systemic inflammation.
of the mesocolonrefpneumoretroperitoneum : the presence of air or gas in the retroperitoneal space retroperitoneal fibrosis (RPF) / Ormond's disease : deposition of an often asymmetric fibrous plaque in the retroperitoneal space at the level of L4-L5, of thickness varyin from some mm to 6-12 cm, reaching the external border of psoas muscles (that are rarely involved), inglobating ureter(s) and large blood vessels.
Epidemiology : retroperitoneal fibrosis occurs most commonly in the fifth and sixth decades with a 2:1 male-female predominance.
Aetiology :Symptoms & signs : dull, non-colicky pain in the back, flank, or abdomen (90%), and often causing blockage of the ureters, with resultant hydronephrosis
- idiopathic (66% : autoimmune?)
- mediastinal tuberculous adenopathy
- methysergide
- primary or metastatic malignancy in the retroperitoneum (8%) : sarcomas are the most common primary tumors, but non-Hodgkin and Hodgkin lymphomas
- peritoneal dialysis
Laboratory examinations : normal in 25% of patients, but 55% of patients will have an elevated blood urea nitrogen. Diagnosis is most commonly suggested by intravenous pyelography. The combination of medial deviation of the ureter, hydroureteronephrosis, and extrinsic ureteral compression at abdominal X-rays are highly suggestive of retroperitoneal fibrosis. CT
Therapy : identify and deal with potential causative agents, relieve the ureteral obstruction, and reverse the inflammatory-fibrotic process. Renal obstruction may need to be relieved acutely, either by retrograde ureteral stents or by percutaneous nephrostomy tubes. Long-term resolution of ureteral obstruction most frequently has been accomplished by operative freeing of the ureters from the fibrosis (ureterolysis) and displacing them laterally or within the peritoneal cavity. Although renal function is improved in more than 90% of cases so treated, in as many as one-third of patients, ureteral obstruction recurs on the ipsilateral or contralateral side.
Prognosis for patients with nonmalignant retroperitoneal fibrosis is good. Survivals of 86-100% for several years have been reported.desmoid tumor
,
scimitar
sacrum
assessed with MRI,
no longer with Wangensteen-Rice invertogram 12-24 hours after birth,
when swallowed air has reached rectum and can act as a natural contrast
agent; puborectal muscular flonde) and the sex :
).
If surgery involves sphincters it may lead to fecal
incontinence.
.
,
transrectal
ultrasonography
or anorectal manometry
are suitable procedures that may be used to detect
the causative disorder. Histopathological features of SRUS are characteristic
and pathognomonic, nevertheless the endoscopic and clinical presentations
may be confusing. The lesions may mimic other rectal pathologies and lead
to wrong diagnosis.
can be done to assess for inappropriate puborectalis contraction and occult
rectal mucosal prolapse,
an effective behavioural treatment for the majority of patients (improved
extrinsic innervation => increased rectal mucosal blood flow)
rectopexy:
most rectal carcinoids are asymptomatic and discovered incidentally during
proctoscopy and/or sigmoidoscopy. Carcinoids represent 1.3% of rectal tumors.
They are usually benign and seldom metastasize to the regional lymph nodes
or the liver. Rarely, Liver metastasesdoes
occur (1%), causing carcinoid syndrome. However, as in other tumors, metastases
are correlated directly with the size of the tumor : the incidence of metastases
increase sharply in tumors larger than 2 cm.(70%
of neoplasms are localized in sigma and rectum). Weekly controls to verify
progression
(tumor staging accuracy = 75-94%; lymph nodes staging accuracy = 57-71%)
(tumor staging accuracy = 77-83%; lymph nodes staging accuracy = 60%)
for staging (tumor staging accuracy = 66-93%; lymph nodes staging accuracy
= 61-83% : lymph nodes may not be visible, hyperechoic, hypoechoic, or
wiith mixed echo pattern) :
and anastomosis can be performed when sufficient distal rectum is available
to allow a conventional anastomosis or colo-anal anastomosis.
for lesions too distal to permit RAR
or other resection with or without perioperative external
beam radiotherapy (EBRT)
+ 5-FU.
There are no randomized trials comparing local excision with or without
postoperative chemoradiation treatments to wide surgical resection (LAR
and APR). One prospective multicenter phase II study and several larger
retrospective series suggest that well-staged patients with small (<4
cm) tumors with good histologic prognostic features (well- to moderately-differentiated
adenocarcinomas), mobile, and no lymphatic, venous, or perineural invasion,
treated with full-thickness local excision that results in negative margins
may have outcomes equivalent to APR or LARwith the selective post-operative
use chemoradiation therapy. Endoscopic ultrasound studies have been helpful
in defining these patients.
compared to those treated with radiation alone. Standard treatment options:
with colorectal or coloanal reanastomosis when feasible, followed by chemotherapy
and postoperative radiation therapy, preferably through participation in
a clinical trial.
with adjuvant chemotherapy and postoperative radiation therapy, preferably
through participation in a clinical trial.
and chemotherapy in highly selected patients, IORT has resulted in improved
local control in a single institution experience.-based
chemotherapy for stage II and III rectal cancer was established by a series
of prospective, randomized clinical trials. Subsequent studies have attempted
to increase the survival benefit by improving radiation sensitization,
and by identifying the optimal chemotherapeutic agents and delivery systems
infusion with central venous catheter 225 mg/m2 for 5-6 weeks)
(gold standard) : decreases relapses, increases overall survival)
after selection on TNM : it may allow conservative surgery (preserving
anal sphincters => no colonostomy !), downstaging in 70-80%, negativization
of pTNM in 10-29%, resecability of T4 tumor in 70-80%, conservation
in 75-89%
(85%), mostly non keratizing, but prognosis is the same for keratizing
and non keratizing types+
individuals should undergo screening annualy while HIV- homosexual men
should be screened every 2-3 years with anal pap smear
+ chemotherapy (cisplatin
or mitomycin C) for 3 months until deciding on surgery :
has 5-yr OS = 38-71% (78% if 1-2 cm, 55% if 3-5 cm), with associated mortality
= 3-6% and local recurrence up to 40%. Surgery is the primary treatment
and results in cure in approximately 45% of all patients
(successful in 50%)
+
resection vs. LE
can delineate the hematoma and localize it to the abdominal wall in almost
all cases.
.
bowel and rectal diseases affecting homosexual
males and others who engage in frequent anal intercourse; it is caused
by a wide variety of infectious agents.
and subcutis)ref.
and the external
oblique muscle
of the abdomen, just superior to the ilium (iliac crest)
(12th rib) in front, thelateral border of latissimus
dorsi muscle
behind (spinal and lumbar squared muscles), lower border of the inferior
posterior serratus muscle
above, and the posterior border of internal
oblique muscle
below,
erector spinae, and internal
oblique muscle,
and overlapped by the latissimus
dorsi muscle
and the external
oblique muscle,
with the thoracolumbar fascia as its floor. When present it is sometimes
a site through which abscesses point or hernias occur
= external
or lateral inguinal fovea,
and passes down obliquely through the inguinal
canal,
lateral to the inferior epigastric artery fold
.
Strangulation is rare. Content may be prevesical adipose tissue, urinary
bladder or vesical diverticulum
(corresponding to Hesselbach trigonum) placed medially to inferior epigastric
artery and laterally to the conjoined tendon of rectus and external oblique
muscles, where the only support is the fascia trasversalis. Usually smaller
than the indirect hernias as contained by the fascia trasversalis and the
aponeurosis of the external oblique muscle. Eventually associated to homolateral
external oblique hernia. In inveterated hernias the inner and outer inguinal
rings come nearer allowing the exploring finger to reach the abdominal
cavity. Content : urinary bladder (supravesical hernia). Strangulation
is rare : the relationship of the collar with the epigastric vessels is
important during surgical reduction
or cyst of spermatic cord-epididymusref(below
Fallopio's inguinal ligament). Palpation of femoral vein => palpation of
hernia during coughing. Often they appear red due to trasudation of serum
from large omentum.
is regularly find laterally to the hernial sac. Sometimes the sliding peritoneal
sac carries down part of the urinary bladder or its diverticulum, together
with perivesical fat. The content usually consists of omentum and/or intestinal
loops.
scan will usually confirm the diagnosis.
: opening of hernia sac => reduction of content back into abdominal cavity
=> removal or deepening of the hernia sac => plastic suture of inguinal
abdominal wall +/- reenforcing synthetic mesh
,
Streptococcus
spp.,
Escherichia
spp.,
and Proteus spp.
and Prevotella spp.