Weight loss

December 29, 2003

Serum Complex of Trypsin-2 and a 1-antitrypsin: A New Sensitive Marker of

Acute Pancreatitis

Johan Hedström, M.D*., Jari Leinonen, M.Sc., and Ulf-Håkan Stenman, M.D.

Departmetnt of Clinical Chemistry, Helsinki University Central Hospital,

Helsinki, Finland

Introduction: Pathological intrapancreatic activation of trypsinogen to

trypsin occurs in acute pancreatitis (AP). When reaching blood, trypsin-2

forms a complex with a1-antitrypsin (AAT). The trypsin-2-AAT complex can be

specifically measured by a recently developed double antibody sandwich

assay.

Purpose: To estimate the diagnostic and prognostic accuracy of serum

determinations of trypsin-2-AAT in AP. Serum CRP, amylase and trypsinogen-2

were used as reference methods.

Design: A retrospective study on consecutive patients during March 1992 to

November 1993.

Setting: Patients treated for AP and other acute abdominal disorders at the

Second Department of Surgery at Helsinki University Central Hospital.

Methods: 110 patients with AP and 66 patients with acute abdominal diseases

of extrapancreatic origin were studied. The final diagnosis of AP was based

in findings of upper abdominal pain accompanied by the typical appearance of

AP in ultrasonography or computed tomography (CT). Based on the clinical

course, AP was classified as mild (n=82) or severe (n=28). Trypinogen-2 and

trypsin-2-AAT were determined by time- resolved immunofluorometric assays

(IFMA). The upper reference limit was 12 µg/L. The ability of various tests

to differentiate between mild and severe AP and nonpnacreatic disease was

estimated on the basis of sensitivity and specificity at clinically relevant

cut-off levels and the validity of the test was further evaluated by

receiver-operating characteristic (ROC) curve analysis.

Results: At admission, all patients with AP had clearly elevated values of

trypsin-2-AAT (= 32 µ g/L), whereas only 5% of the controls had such values.

In AP, trypsinogen-2 and trypsin-2-AAT increased earlier than CRP and

remained elevated longer than amylase. There was also less overlapping

between patients with AP and controls for trypsin-2-AAT than for the other

markers. Time course profiles of trypsin-2-AAT showed that in severe cases

it mostly peaked in the initial sample and slowly decreased during the next

days. In patients with mild AP the peak was mostly observed in the second

day. Of the markers studied, trypsin-2-AAT showed the best accuracy (largest

area under the ROC curve) both in differentiating AP from controls and mild

from severe disease. At presentation, trypsin-2-AAT differentiated between

mild and severe AP much more accurately than CRP, AUC being 0.82 and 0.73,

respectively.

Conclusion: Of the markers studied, trypsin-2-AAT displayed the best

accuracy for differentiating between AP and extrapancreatic disease as well

as for predicting a severe course of the disease at presentation. If

available on automated instrumentation and on emergency basis, the assay

could markedly improve the diagnosis of this common and potentially lethal

disease.

Weight Loss

> Hi all. I've posted before but to catch up, my doctor thinks i MAY

> have chronic pancreatitis but cannot give me a definite diagnosis.

> In the meantime, I have been sick for a year, cannot work, have

> regular pain, and malabsorption. So I've lost 25 pounds just this

> year. I cannot seem tot olerate any fat whatsoever. My dietician

> suggested some things but i also can't tolerate very big portions (2

> pieces of toast fill me up) and get headaches from the very sugary

> Boost drinks she suggested. Does anyone have any suggestions on how

> to put some weight on? It's very hard since I'm 5'10 " and now only

> 108 pounds. Feeling horrible AND continuously losing weight is so

> hard to deal with.

> Also, anyone else have trouble getting diagnosed? I go to a very

> good specialist in philly...I just know it's sometimes hard to get a

> diagnosis.

> Thanks so much and Happy Holidays to all of you.

> Sincerely,

>

December 29, 2003

VASCULAR COMPLICATIONS OF PANCREATITIS : RADIOLOGICAL DIAGNOSIS AND

TREATMENT

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VASCULAR COMPLICATIONS OF PANCREATITIS : RADIOLOGICAL DIAGNOSIS AND TREATMENT

Sundeep J Punamiya

Associate Consultant and Head of Department, Vascular and Interventional

Radiology, Bombay Hospital, Mumbai.

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INTRODUCTION

Involvement of the blood vessels around the pancreas is a frequently occurring

event in pancreatitis, seen in at least 10% of the patients suffering from the

disease. [1] There are many mechanisms by which the pancreatic and

peripancreatic vessels can get involved. The proteolytic enzymes released during

the episode of pancreatitis can directly erode the numerous arteries in and

around the pancreas, resulting in haemorrhage or formation of a pseudoaneurysm.

Alternatively, the inflammatory mass may compress or thrombose the adjacent

splenic or superior mesenteric vein. [2]

Arterial complications

The splenic artery, because of its contiguity with the pancreas, is the vessel

most commonly involved in pancreatitis. However, virtually all of the pancreatic

and peripancreatic vessels can be affected. The gastroduodenal and

pancreatico-duodenal arteries are frequently involved, while the left gastric,

hepatic and small intra-pancreatic branches are less often implicated.

Pancreatic enzymes can produce enzymatic necrosis of the arterial wall,

resulting in free haemorrhage or formation of a pseudoaneurysm. The

pseudoaneurysm may develop within a pancreatic pseudocyst, or in some cases, the

pseudoaneurysm may rupture into the adjacent pseudocyst; in either case the

haemorrhage will be confined to the pseudocyst cavity. Once formed, the

pseudoaneurysm has a tendency to enlarge and ultimately ruptures into the upper

gastrointestinal tract, colon, abdominal cavity, or rarely, the pancreatic duct.

[1] Rupture into the aorta, portal vein and venous tributaries have also been

reported.

Encasement of major arteries is also frequently seen in pancreatic disease.

However, thrombosis of these arteries is not a prominent feature. When it

occurs, arterial thrombosis could lead to splenic or bowel infarction.

Venous complications

Unlike arterial thrombosis, thrombosis of the splenic vein is much more

common, being reported in [8] .5-45% of patients with pancreatitis. [3]

Thrombosis involving the portal and superior mesenteric veins is rare and if

present, should raise the suspicion of either a septic stage of severe

necrotising pancreatitis or a pancreatic head malignancy.

CLINICAL PRESENTATION AND DIAGNOSIS

Early recognition of bleeding in patients with pancreatitis is essential for

successful management and reduction of mortality. The presenting features are

usually a combination of gastrointestinal bleeding, vague recurrent upper

abdominal pain, pulsatile abdominal lump and splenomegaly. Pulsatility or rapid

enlargement of a pre-existing pseudocyst should alert the clinician about

bleeding into the pseudocyst. If the patient has undergone an abdominal surgery,

such as necrosectomy, the bleeding may appear within the abdominal drains.

Unusually, the patient may present with blood loss anaemia due to long-standing

occult bleeding from a pseudoaneurysm into the gastrointestinal tract. the

patient manifests as a GI bleed, endoscopy is often the first investigation to

rule out bleeding from other sources e.g. peptic ulcer disease, gastritis,

Mallory-Weiss tears and varices. Occasionally it may permit diagnosis of

pancreatic bleeding (haemosuccus pancreaticus) and rarely may reveal the site of

the erosion of the pseudocyst directly into the GI tract.

Ultrasonography is generally asked for when a pre-existing pseudocyst has

rapidly enlarged in size, suggesting bleeding into the cavity. If the

enlargement is indeed due to haemorrhage into the pseudocyst, the USG confirms

rapid enlargement of the cystic mass, with a sudden change in its internal

echogenicity. [4] When these collections are studied after a week, the cystic

mass shows solid tissue or septations. [5] Occasionally it is impossible to

distinguish between pseudoaneurysms and pseudocysts on routine USG examination.

With the advent of Doppler, however, it is now possible to detect blood flow

within the haemorrhagic pseudocyst.

Computed tomography (CT) produces excellent opacification of the arteries and

veins surrounding the pancreas and is an invaluable modality for identifying

these vascular complications. [6] , [7] The finding of a focal collection of

fluid with increased attenuation (more than 30 HU) or an interim increase in the

attenuation values of the fluid within a previously demonstrated pseudocyst, is

diagnostic of acute bleeding into the pseudocyst. A dynamic, contrast-enhanced

spiral CT scan can diagnose pseudoaneurysm by demonstrating contrast pooling in

the collection (Figs. 1A, 1B). CT is also the procedure of choice in diagnosing

splenic vein thrombosis (Fig. 2).

Fig 1A Fig 1B Fig 1C

Plain CT of the abdomen revealing a collection in the pancreatic bed

After injecting contrast, there is opacification of a pseudoaneurysm within the

collection. Cleliac angiogram confirming large pseudoaneurysm arising from the

splenic artery

A 56 year old female , presented with persistent pain in the left

hypochondrium 6 months after initial episode of pancreatitis.

Angiography provides the most detailed evaluation of vascular involvement and

may diagnose the site and source of bleeding, indicated by erosive arterial

changes or pseudoaneurysm formation (Fig. 1C). On occasion, there may be

multiple small pseudoaneurysms or encasement of the intra-pancreatic arteries

(Fig. 3A). Rarely, frank extravasation of contrast from the artery or

pseudoaneurysm is seen (Fig. 3B). In addition, it can evaluate the portal venous

system, for detection of splenic vein thrombosis and confirmation of associated

generalised portal hypertension due to liver disease. No intervention, be it

surgical or percutaneous, is carried out without angiographic mapping of the

arterial patho-anatomy.

MANAGEMENT

Haemorrhage from pancreatic and peripancreatic vessels is severe and, until

recently, had been associated with mortality rates approaching and exceeding

50%, primarily because of delayed diagnosis and extreme conservative treatment.

[2] , [8] Prompt diagnosis and an aggressive interventional approach has helped

in reducing the mortality. Surgical management has been the mainstay in treating

these vascular complications. However, the past decade or so has seen a rapid

acceptance of angiographic techniques to control the bleed in these patients,

with a success rate ranging from 78-100%. [1] , [9-14] Angiographic control

involves placement of embolic material, e.g. steel coils, selectively into the

artery that is either bleeding or fostering the pseudoaneurysm.

Fig 2 : 46 year old male, 4 weeks after an attack of pancreatitis.

Contrast enhanced CT revealing an acute panmcreatic collection, with thrombosis

of the underlying splenic vein

The success rates of transcatheter embolisation have varied over the years,

with the initial reports citing a fair number of rebleeds. As the past decade

progressed, the success rates began to show a great deal of improvement, being

attributed to betterment of catheter and embolic material technology and to the

improvement in technical expertise. The earliest problems associated with

transcatheter control of bleeding in pancreatitis was inability to reach the

small and tortuous target vessels with the large calibre catheters that were

available. Micro-catheters, primarily designed for use for embolisation in the

cerebral vessels, were then adapted for visceral arteries. It was with the aid

of these catheters that even the small intra pancreatic arteries could be

catheterised and embolic material delivered .

Along with this development, came an understanding about the techniques

involved in successful embolisation in pancreatitis. Due to thegood collateral

circulation around the pancreas, it is essential to occlude the artery proximal

and distal to the arterial pathology, failing which the artery can refill and

the bleeding will not cease. If the vessel is severely involved and can be

closed only upstream or downstream, one could use additional liquid embolic

material such as glue for effective embolisation. [15] Embolisation can be a

time-consuming process, especially if there are a number of efferent arteries

originating from the pseudoaneurysm or there are many collateral circulations

coming from the adjacent arteries. The expertise of the interventional

radiologist plays an important role in suspecting this potential problem and

addressing it immediately.

CONCLUSION

Vascular complications of pancreatitis although uncommon, are usually

life-threatening. Clinical suspicion, corroborated with judicious use of

imaging, can bring about a prompt diagnosis and prevent morbidity that is

usually associated with these complications. Immediate efficacy of arterial

embolisation is undeniable and the procedure is rapidly being accepted as the

first line of treatment, wherever the expertise of the interventional

radiologist is available.

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