The General Surgical Complications of Cystic Fibrosis

[Guest guest]

Hi,

this one is not made for anxious parents, LOL. It mentions problems

that CAN arise when you have CF and explains them very well. It

doesn't mean that your child will automatiacally suffer from all

those complications.

Peace

Torsten

The General Surgical Complications of Cystic Fibrosis

R.Winterborn AFRCSI

J.Torkington FRCS

J.Harvey MPhil FRCS

Department of Surgery

University Hospital of Wales and Llandough Hospital NHS Trust

Llandough Hospital

Vale of Glamorgan

CF64 2XX

Address for correspondence: Mr J Harvey, Department of Surgery,

Llandough Hospital, Penlan Road, Vale of Glamorgan, CF64 2XX. Tel

02920 711711. Fax 02920 71

Introduction Methods Gastro Oesophageal Reflux Meconium Ileus

DIOS Appendiceal Disease

Intussusception Colonic Strictures Rectal Prolapse Pancreatic

Complications Biliary Disease

Liver and Bile Duct Disease Vascular Access Summary References

Previous Page

Introduction

Cystic Fibrosis (CF) is the most common inherited disorder with an

incidence in the United Kingdom of approximately 1:2000 live births

(1). It is a disease characterised by exocrine dysfunction with

obstructive lesions throughout multiple organ systems and disturbance

of electrolyte and mucus secretion. The majority of patients

initially present with malabsorption and chronic obstructive

pulmonary disease although a diverse variety of presenting symptoms

have been reported. Patients with CF can now expect to live well into

the 4th and 5th decades with 80% surviving past their twentieth

birthday(2).

The main factors contributing to increased survival are:

1) Better recognition of complications and treatment.

2) Antibiotic use

3) Pancreatic enzyme supplements

4) Improved management of specific conditions e.g. Meconium Ileus

5) Improved General Anaesthesia in Children

6) Organ Transplantation

With this increased survival it is likely that an increasing number

of patients will present to adult surgeons with complications of

their disease. Furthermore, gastrointestinal symptoms may often be

the presenting feature, with the diagnosis of CF only first being

established in 2% of cases over the age of 18 years(2).

This article aims to describe the various complications of CF which

are likely to present to the general surgeon and to highlight some of

the pitfalls in diagnosis, investigation and management.

Methods

A literature search was performed using PubMed and Medline from 1966-

July 2000, employing keywords related to cystic fibrosis and its

complications and possible surgical interventions. All articles

retrieved were assessed for their relevance to the practice of a non-

specialist general surgeon and reviewed.

Gastro-oesophageal Reflux Disease

Gastro-oesophageal Reflux (GOR) is a relatively recently identified

complication of CF and the reported incidence varies from 6.4% to 20%

3,4. It may occur at any age but tends to present early in life and

improve with time.

The suggested mechanisms for the onset of GOR include inappropriate

relaxation of the gastro-oesophageal sphincter5, and crucially to the

patient with CF, periodic increases in intra-abdominal pressure with

coughing which overcomes the normal anti-reflux mechanisms6.

The symptoms associated with GOR include abdominal pain, vomiting ,

dysphagia, failure to thrive and intractable respiratory symptoms. In

view of the respiratory complications associated with GOR it is of

particular importance that the diagnosis is considered early in

patients with CF and treated appropriately.

A study of the medical management of GOR using cisapride in infants

and newborns showed that it was effective in 8/10 patients7. Other

methods used particularly in infants include improved posture and

thickened feeds, with H2 blockers and alkali's normally reserved for

oesophagitis8.

The surgical management of GOR is indicated in those patients in whom:

1) Medical management has failed

2) Vomiting is sufficient enough to interfere with weight gain

3) Oesophageal stricture has formed

Nissen fundoplication is the operation of choice and may be performed

with or without gastrostomy insertion. The number of CF patients

requiring operative intervention varies from 29% to 63% (3,4). A

review of five papers shows that of the 20 patients (2mths-18yrs) who

underwent fundoplication, one died as a direct result of surgery;

this was 6 days post operatively with meconium ileus equivalent

obstruction, the remaining patients all had good symptomatic relief

(3,4,9,10,11).(Table 1)

There are a number of complications of long standing GOR which are

now being recognised. These relate to both the increased life

expectancy of CF patients and also the lack of perception of GOR as a

cause of abdominal pain in the older population. A study by Bendig et

al (11) showed that in a series of 7 patients aged 8-31 years, 3 had

oesophageal strictures all requiring regular balloon dilatation for

symptomatic relief, 2 out of these 3 went onto have Nissen

Fundoplication, however surgery failed to improve symptoms in one

patient and only improved symptoms for 2 years in the other. The

third of the 3 with a stricture had advanced lung disease and thus no

further intervention was undertaken. Of the remaining 4 patients, 2

had oesophagitis associated with their GOR both of whom underwent

successful Nissen Fundoplication. Only one reference12 described

Laporoscopic Nissen Fundoplication in children. In a series of 27

patients aged 7.2 +/-4.5 years only 2 had CF. A recent paper by

Hassall et al (13) describes 2 adult CF patients with Barretts

oesophagus. They both had known GOR which had been well controlled.

An exacerbation of their symptoms prompted further investigation with

endoscopy and Barretts oesophagus was confirmed. In both cases the

symptoms settled with omeprazole.

In summary GOR is known to be associated with CF and may exacerbate

the respiratory problems of the disease. In view of this relationship

it is important that the diagnosis is considered in infants

presenting with vomiting, failure to thrive and recurrent pneumonia's

and in the older CF population those who present with abdominal pain,

dysphagia or GI bleeding.

In the majority of cases it can be medically managed with concurrent

administration of high dose antibiotics for chest infections. Surgery

should not be ruled out if clinically indicated. GOR is not a benign

diagnosis and should be treated as aggressively as is necessary to

remove symptoms, improve quality of life and prevent further

complications.

Meconium Ileus

Meconium Ileus (MI) is the earliest clinical manifestation of CF and

occurs in approximately 10-15% of neonates with CF2, although one

study has reported an incidence as high as 27% (14).

It was first described by Landsteiner in 1905 and occurs due to the

increased viscidity of the meconium associated with its high protein

and low carbohydrate content (15). The most common presentation is

abdominal distension with or without bilious vomiting and a failure

or delay in passing meconium after birth. Occasionally it is

diagnosed prenatally on ultrasound scans.

MI can be categorised as either simple or complicated. Complicated MI

includes those with volvulus, atresia, perforation or giant cystic

peritonitis. Survival at one year is similar for simple MI (81 -

100%) and for complicated MI (75 - 96%)(14,16,17). (TABLE 2)

The initial management and investigation of a neonate with abdominal

distension and other features of obstruction includes fluid

resuscitation, nasogastric tube insertion and antibiotic

administration. Abdominal x-ray is likely to show several loops of

dilated small bowel without air-fluid levels; and possibly a soap

bubble appearance in the right lower quadrant, the so-called

Neuhauser sign (18). Complicated cases may present with greater bowel

dilatation and air-fluid levels. Perforation or giant cystic meconium

peritonitis calcifications are often noted. Most babies then undergo

barium enema to confirm the diagnosis.

Prior to 1969 MI was managed with surgery alone and carried a high

mortality rate, but since the publication of Noblett's report on the

use of gastrograffin enemas (GGE) in the treatment of simple MI, non-

operative management has become increasingly important19. Success

rates vary as can be seen from Table 2. The iatrogenic perforation

rate is approximately 5% (14). All neonates with complicated and

those with 2 unsuccessful GGE require operative intervention.

The surgical management options of MI are varied and include :

1) Enterotomy/appendicectomy with irrigation

2) Enterostomy with/out resection

3) Resection with primary anastomosis

Rescorla et al advocate enterotomy and irrigation for simple MI after

unsuccessful GGE, resection, distal irrigation and primary

anastamosis for atresia/volvulus, and debridement, resection and

temporary enterostomy with closure approximately 4-6 weeks later for

perforations and peritonitis (17).

Docherty et al also advocate enterotomy and irrigation for simple MI

as they had a 20% leak rate with Bishop-Koop (End-to-distal side

ileal anastomosis with a distal end ileostomy which allows post-

operative irrigation of the meconium pellets) or Santulli (Side-to-

end anastomosis with a proximal enterostomy after resection of the

dilated segment of bowel) ileostomies. These used to be recommendeed

as they provided a safe means of enteral feeding prior to the advent

of total parenteral nutrition16.

Mushtaq et al performed 7 resection and primary anastamoses and 10

divided ileostomy/jejunostomy with or without resection. They showed

a significant reduction in initial hospital stay for those who had

primary anastamosis as opposed to stoma formation in both the

patients with complicated and uncomplicated MI (26 and 47 days

respectively p<0.02)(14).

The operation mortality has decreased dramatically since the 1960's

when rates were as high as 50-60%20. The current survival rates are

shown in Table 2. Infants with CF who present with MI and survive

beyond 6 months have the same prognosis as any patient with CF

although they are at greater risk of developing Distal Intestinal

Obstruction Syndrome (DIOS) in later life(17).

Distal Intestinal Obstruction Syndrome

Distal Intestinal Obstruction Syndrome (DIOS) or Meconium Ileus

Equivalent is characterised by repeated episodes of partial or

complete intestinal obstruction in later life. The incidence has

vbeen reported to range from 2.1-47% (21,22) of CF patients and is

probably related to inadequate doses of pancreatic enzymes

particularly as the individual's growth leads to a relative decrease

in the number of enzyme capsules/Kg body weight (22). It may present

with a right iliac fossa mass and can be difficult to distinguish

from appendicitis, intussusception, volvulus, Crohns disease,

fistulae, neoplasm's or ovarian conditions.

Interestingly, the incidence of DIOS is increased after lung

transplantation. Minkes et al identified a 10% incidence of

obstruction with in a short time of transplantation(23).

They cited a number of possible factors including -

1) Prolonged bed rest

2) Use of azathioprine (impairs motility)

3) History of previous abdominal symptoms

4) Conditions surrounding surgery e.g.. Dehydration, General

anaesthesia, analgesics

DIOS can normally be managed conservatively. Treatment involves

rehydration and the use of oral gastrograffin or N-acetylcysteine.

However, in the above series of 70 lung transplant patients the 7 who

developed DIOS were managed surgically. Five patients had

preoperative hypaque enemas which did not relieve the obstruction and

it was felt that all of the patients were too ill to safely undergo

further attempts at non-operative management. The authors suggest a

pre-transplant regimen of bowel washouts and if possible peri-

operative prophylactic N-acetylcysteine in order to prevent post

operative DIOS. A high index of suspicion should be maintained at all

times in this population of patients.

Appendiceal Disease

Appendiceal disease was once thought to be rare in CF patients

however in a retrospective review of 1220 CF patients by Coughlin et

al, 60 patients underwent appendicectomy, 19 for acute appendicitis

giving an incidence of 1.5%(24). The mean age at presentation was 15

years and 15 of the 19 patients with confirmed acute appendicitis had

classical symptoms. Of these 15, 12 patients had perforated

appendicitis. The remaining 4 had varying symptoms including a 7 year

old with painless haematuria, a 10 year old with rectal bleeding,

chronic abdominal pain, raised white cell count and negative Meckels

scan. Two further patients presented with right upper quadrant pain.

The group of patients who had perforated presented 3 -12 days after

the onset of symptom. Postoperative complications only occurred in

the group that had perforated.

Fourteen of the total sixty patients who had appendicectomies had

mucoid distension of the appendix presenting with either intermittent

right iliac fossa pain or intermittent intussusception. The remaining

27 cases were incidental removal of a normal appendix during another

operation (24).

Mucus distension of the appendix is a distinct syndrome in patients

with CF and should not be forgotten as a possible cause of pain.

Appendiceal disease is another of the presentations which is

increasing in frequency due to the increased life expectancy of CF

patients, however the often chronic abdominal pain seen in patients

with CF is often ignored both by the patient and the doctor meaning

that when a patient has right lower quadrant pain presentation to

hospital is late and therefore perforation is more likely.

In this series the group mortality was zero and there was low

morbidity suggesting that a more aggressive approach should be taken

in CF patients suspected as having appendicitis.

Appendiceal abscesses are another entity occurring in CF patients

which are often diagnosed late, due to confusion with DIOS and a

right iliac fossa mass. There have been numerous case reports of

patients with chronic appendiceal abscesses. The age range varied

from 5 -25 years old in one report from the USA of 5 patients whose

symptom duration prior to diagnosis ranged from weeks to 18 months

(25).

et al (26) suggest that in view of the difficulty in diagnosing

this condition CF patients with severe colicky abdominal pain should

undergo:

1) Contrast enema to exclude intussusception. This may also relieve

obstruction in DIOS or reduce the intussusception.

2) Where there is no result from the enema, treatment with balanced

electrolyte lavage up to 10 litres should be instituted.

3) If this is unsuccessful then an USS or CT should be performed to

look for other causes.

4) If the scans are negative (2) should be repeated and if the mass

or symptoms persist laparotomy should be performed.

This is a useful protocol for CF patients particularly in view of the

vast possible pathologies ranging from fairly benign DIOS to

appendiceal abscesses through to malignant causes.

Intussusception

Intussusception occurs in approximately 1% of the cystic fibrosis

population despite its rarity after the age of 2 in the general

population27. It is thought to be related to faecal overloading such

that the adherence of a faecal bolus acts as a lead point2.

Intussusception in the older age group may be related to a relatively

hypotonic colon (2). The incidence may now be decreasing with the use

of pancreatic enzymes (28). A number of case reports have described

intussusception in children ranging from 4.5 to 12 years of age (29,

30). The protocol suggested by et al (26) is useful in

diagnosing patients with right iliac fossa pain. Reduction is often

successful with hydrostatic enema, however in the older children

progression to laparotomy is more likely. Intussusception can lead to

intemittent abdominal pain in adults as illustrated by a case in an

18 year old was described by Webb et al (28). He presented with acute

abdominal pain, constipation and episodic vomiting. No formal

diagnosis was made and he was treated conservatively. Examination was

unremarkable apart from a fullness in the epigastric region. The only

positive investigative finding was a mass with a target or bulls eye

appearance ontransverse ultrasonogram. This seemed to decrease in

size over a few days and his symptoms settled. A week or so later the

severe pain recurred and a laparotomy was performed. This showed an

ileocolic intussussception which was resected. Although he had been

on 2-3 pancrease tablets he was converted to Creon and it was felt

that insufficient pancreatic supplements and abnormal intestinal

mucous was probably the cause. A more recent case describes a 41/2

year old boy who developed an appendiceal mucocoele and recurrent

intussusceptions, despite appendicectomy the intussuscpetions

recurred and an ileocolic resection was necessary (29).

It is hoped that the incidence of intussusception should decrease

with the advent of microspheres - these have a protective coating

protecting them from acid inactivation in the stomach and allowing

them to pass to the less acid environment of the duodenum and jejunum

where the enzymes are released at pH 5.5 - for pancreatic

supplementation, but it should not be forgotten as a cause of

abdominal symptoms in CF patients both young and old.

Colonic Strictures

Colonic strictures are becoming an increasingly recognised in

patients with CF. There are many rare causes including lymphoma,

Crohn's disease, ulcerative colitis, TB and pericolic abscesses,

however with the use of pancreatic enzyme supplements and the

increased life span of patients the most common cause is high

strength pancreatic supplements. A case control study published by

Fitzsimmons et al compared (29) patients who underwent surgery for

fibrosing colonopathy from 1990-94 with 105 controls. The mean daily

dose of pancreatic enzymes supplements taken by the patients with

strictures from 6-24 months prior to surgery was significantly

greater than that of the controls, 50,046 Units Lipase/Kg compared

with 18,985 Units Lipase/Kg. The shortest duration of therapy was 12

months suggesting that it is a chronic process. They concluded that

the relative risk of developing a stricture is 10.9 with a daily

intake of 24-50,000 Units/Kg compared with 199.5 with an intake

greater than 50,000 Units/Kg (31). This study led to a Food and Drug

Administration investigation and the recommendation that no more than

10,000 Units/Kg should be given.

The reasons postulated for stricture formation include pressure

induced ischaemic necrosis due to alterations in the composition of

bowel mucus, high strength enzymes becoming embedded in the retained

faecal matter in the caecum causing pressure damage to the bowel

mucosa with penetration into submucosal tissue and a fibrotic

reaction. These are further exacerbated by slow transit times,

constipation, DIOS and previous surgery (32).

With regard to diagnosis and treatment, King et al published a report

of 5 children aged 2-13.4 years who presented with a 2-6 weeks

history of abdominal pain which was initially treated as DIOS.

Radiological investigations were performed as the patients did not

improve and this revealed marked bowel wall thickening and dilatation

of the ascending colon with a normal terminal ileum on ultrasound

scanning and a stricture on contrast enema. All 5 underwent right

hemicolectomies and the only child who developed further symptoms and

a second stricture remained on high dose enzymes post surgery (33).

Colonic strictures should therefore be considered in those patients

particularly older patients who present with abdominal pain and are

diagnosed as having DIOS but who do not respond to medical management.

Other Causes of Bowel Obstruction

Clearly patients with CF can present with the most common causes of

bowel obstruction such as adhesions and hernias. The commoner

conditions peculiar to CF have already been discussed however, a few

cases of unusual causes of obstruction have been described. These

include a child who had partial obstruction of the ascending colon

secondary to diverticulitis (34), and two adult women with CF who

developed colonic cancer, both aged 31 years old (35). The first of

the cases of colonic cancer presented with symptoms similar to DIOS

and in view of her young age a diagnosis of cancer was not initially

suspected; but she was eventually diagnosed with a mid-transverse

colonic cancer with regional lymph node metastases. The second case

also had mid-transverse colonic cancer and despite a long history of

chronic pulmonary and similar disorders CF was not diagnosed until

she was 36 years old.

The incidence of gastrointestinal malignancies is significantly

increased in CF patients and with their increased life expectancy

should be borne in mind as a possible diagnosis in an older patient

presenting with obstructing symptoms (35).

A final unusual case is described of an 8 year old girl who presented

with abdominal pain, anorexia, pyrexia, weight loss and vomiting. As

a neonate she had presented with MI secondary to jejunal atresia;

ileal volvulus and perforation with meconium peritonitis with pseudo

cyst formation. The affected bowel was resected and she had an end to

end anastomosis from which she made a good recovery. Investigation of

her symptoms showed a lobulated mass partially obstructing the second

part of the duodenum on GI series and duodenal obstruction on

endoscopy. At laparotomy there was a large inflammatory mass in the

right upper quadrant with a fistula from the anterior aspect of the

ascending colon to the distal jejunum, this was found to be secondary

to a pedunculated polyp which was also causing luminal obstruction.

She had multiple polyps in the ascending colon and hepatic flexure.

These were found to be inflammatory in nature. The author suggested

that the polyps may have formed secondary to chronic irritation of

the already hyperplastic mucosa. They felt that the fistula probably

formed due to erosion of the polyp through a stercoral duodenal ulcer

(36).

Rectal Prolapse

Rectal prolapse (RP) is a common complication of CF. Its incidence

varies from 18.5% - 22% 37, 38. It usually presents during the first

3 years of life and resolves with the institution of pancreatic

enzymes; however there are reports of RP in patients up to 35 years

old37. Rectal prolapse can be the presenting feature of CF and in one

series 11% of the infants presenting with RP had CF22. The factors

responsible for the increased incidence of RP in CF include increased

frequency of bowel movements, poor muscle tone, malnutrition and

increased intra-abdominal pressure due to coughing (38).

In a review of 605 CF patients - 112 of whom had RP ; 38 out of 40

who had less than 5 episodes did not have treatment. In 48 out of 112

patients, RP was diagnosed prior to CF and of the 29 patients who

were still having recurrences after the diagnosis of CF, 21 had

immediate cessation when enzyme supplements were started. Fourteen

patients continued to have RP up to the age of 35. Surgical treatment

was undertaken in 10 patients, all whom were less than 15 years old,

where the indications were extremely frequent prolapses, pain and

general inconvenience. A sling procedure was the most commonly

performed operation, this is a modified Thiersch technique. Under

general anaesthesia, 1-3 strands of Mersilene encased silastic are

placed perianally beneath the external sphincter through four

radially placed stab incisions 2cm from the anal verge. The suture is

cut to allow it to approximate the Silastic portion when tied. The

anal opening is constricted between a Hegar No. 8 and 10 dilator. The

skin is closed with subcuticular 5-0 chromic catgut. The sling is

removed under sedation 2-3 yrs later.

Of these 10, 2 required early removal due to infection, 1 had a

single recurrence following removal, 1 continued to have RP and 1 had

a different procedure and this was associated with the formation of

an anal abscess due to a retained stitch. Many older patients managed

themselves with abdominal, perineal and gluteal muscle control and

those children who had RP many years before diagnosis of CF probably

had learned the sensation of RP and in some way used their gluteal,

abdominal and perineal muscles to prevent RP or to effect immediate

reduction following the passage of stool (37).

In summary RP is a common feature of CF and may be a presenting

symptom. Therefore it is advised that all children with unexplained

RP should be tested for CF. Surgery is seldom required and with

conservative management the episodes eventually become less frequent

and usually stop altogether.

Pancreatic complications

Pancreatitis is a well known complication of CF particularly in those

patients who have residual pancreatic function. It tends to occur in

older CF patients and consequently is becoming a more common problem.

A series of 2000 CF patients showed an incidence of 0.5% with 9/10 of

those affected being adolescents or young adults. The diagnosis of CF

was retrospective in 2 of these cases (39). In cases of acute or

relapsing pancreatitis, CF should be considered as a diagnosis even

if there are no other features of the disease. Masaryk et al describe

2 young adult males who presented with acute pancreatitis in their

early 20's and were found to have CF. The first patient had a sister

with CF and his only other feature of the disease was recurrent colds

and a productive cough. The second patient had no cause for his

pancreatitis but ERCP showed a tortuous dilated pancreatic duct with

irregular ectatic side branches in the head of the gland and

obstruction of the distal duct. Sweat testing showed a high

concentration chloride and semen analysis showed azoospermia. CF was

diagnosed and he underwent a laparotomy which showed a fibrotic,

thickened pancreas; particularly distally. The proximal duct was

dilated and a Roux - en - Y pancreatectomy was performed in order to

improve pancreatic drainage. He was discharged 14 days later and

remained symptom free 1 year post surgery (40).

Pancreatitis is not the only pancreatic complication of CF. A case on

intrapancreatic common bile duct compression leading to jaundice has

been reported (41). The 29 year old man had a 4 year history of

recurrent obstructive jaundice. ERCP confirmed the above diagnosis

and a choledochojejunostomy was performed in order to try to improve

drainage. Unfortunately the patient died of overwhelming sepsis. The

finding at autopsy were analogous to those of chronic pancreatitis.

One can thus predict that with the increased laying down of fat and

fibrous tissue in the pancreas of CF patients with increasing age,

the incidence of jaundice may well increase (41). Since the surgical

management of obstruction secondary to intrapancreatic common bile

duct compression differs from obstructive jaundice secondary to

gallstones it is recommended that ERCP be performed in all CF

patients presenting with obstructive jaundice.

The other pancreatic complication reported in the literature is that

of diffuse microcystic enlargement of the pancreas in a 9 year old

whose abdominal pain radiated to the back and woke him from sleep.

Imaging showed a large pancreas and feature consistent with

pancreatitis however the amylase remained in the normal range. His

symptoms persisted and the pancreas continued to enlarge to the point

that it became palpable and tender. He also developed hypoglycaemic

seizures and his previously diagnosed Diabetes became very difficult

to control. Laparotomy revealed a swollen lobulated pancreas and a

total pancreatectomy, cholecystectomy and jejunoduodenostomy was

performed. He had no postoperative complications and no further

abdominal pain or seizures (42).

Despite the fact that 85% of patients with CF have almost complete

loss of pancreatic function, these are important pancreatic

complications that can cause abdominal pain and may require surgical

intervention.

Biliary Disease

Gallbladder disease is a common problem in patients with CF and once

again an increased incidence has been noted due to longer survival of

patients with the disease. The most prevalent abnormalities are non-

functioning gallbladders (30%), micro gallbladders (8-30%) and

gallstones (4-30%).

The underlying pathophysiology is not well understood but a number of

theories have been postulated. These include:

1) Abnormal bile acid metabolism leading to bile high in cholesterol

content.

2) Biliary stasis due to gallbladder abnormalities and/or impaired

gallbladder motility.

3) Increased viscidity of mucus (43).

The diagnosis of gallbladder disease in patients with CF is often

delayed as the presenting symptoms are often indistinguishable from

the malabsorption syndrome seen in patients with the disease. There

are few studies which discuss the management of gallbladder disease

and in particular the role of laparoscopic surgery. Snyder et al

performed a retrospective study of 20 patients with CF who underwent

surgery for gallbladder disease form 1973-86. The average age of

diagnosis was 21 years (3 - 43 years). The average delay between on

set of symptoms and diagnosis was 7.4 months (1 day-1080 days).

The operative findings included gallstones in 17, acalculous

cholecystitis in 3, empyema in 1, micro gallbladder in 6 and small

cystic or common bile ducts in 4. Two patients had common bile duct

exploration and one patient had roux -Y choledochojejunostomy. All

the patients gained relief of symptoms that could be related to the

biliary tract. There was one peri-operative death in a patient who

developed pseudomonas pneumonia and developed a pneumothorax and

respiratory failure (44).

A further study by Stern et al reported an incidence of symptomatic

gallbladder disease of 3.6%. The age range was 4-34 years and in 2 of

these patients cholecystectomy preceded the diagnosis of CF. Fifteen

patients had surgery for cholelithiasis, 11 of which had unequivocal

relief of symptoms. Five patients did not undergo surgery due to

advanced pulmonary disease and were treated with oral analgesia and

none of them developed cholangitis. The other 4 patients had a

variety of conditions including acute cholangitis, atonic gallbladder

and cholangiocarcinoma. They had no immediate post operative

complications and interestingly 2 of the patients had improved

pulmonary function post surgery, suggesting that the chronic pain had

cause splinting of the diaphragm and impaired expansion of the right

lung base (45).

These 2 studies demonstrate the importance of early diagnosis and

treatment of biliary symptoms. Unfortunately there have been no

studies to look at the benefits of Laparoscopic surgery in CF

patients although a number of case reports have shown good results

(46, 47).

The importance of preoperative pulmonary work up is highlighted in

both papers as is the observation that the longer the biliary disease

was left undiagnosed the older was the patient by the time surgery is

considered and therefore the worse the pulmonary function. Another

important note to come out of Sterns' study is that patients who

present with biliary symptoms in childhood or adolescence should have

a sweat test to rule out CF.

Biliary disease in CF patients is probably one of the most relevant

problems for general surgical consultants, however we can be

reassured that early surgery in this patient population is

successful, relatively safe and carries with it a number of benefits

to the patient.

Liver and Common Bile Duct Disease

Although abnormalities of Liver function tests and ultrasound scan

are relatively common in CF, problems in this area rarely cause pain.

The incidence of liver disease varies from 20-50% of cases although

only 5% develop cirrhosis and 2% progress to clinically apparent

liver disease48. It has been postulated that common bile duct

stenosis may be a cause of progression of liver disease and this may

be altered with surgical intervention49. A study by Gaskin et al

looked into the incidence of common bile duct stenosis. They

performed hepatobiliary scintigraphy scans (injection of intravenous

technetium-99m diisopropyl iminodiacetic acid) on 50/61 patients with

CF and hepatomegaly, abnormal liver function tests (LFTs) or both and

31/92 without the above abnormalities. The patients were aged between

4-19. There was evidence of biliary tract obstruction in 96% of the

patients with clinical and/or biochemical liver disease. Those

without abnormalities had normal excretion of the tracer. Recurrent

abdominal pain was a more predominant feature in those with abnormal

LFTs/hepatomegaly (34/92). Only 8/92 without abnormalities had pain.

The majority of patients localised their pain to the right upper

quadrant and it was colicky in nature and often precipitated by food.

Many of the patients had been given a diagnosis of intermittent DIOS.

Surgery was performed on 14 of 48 patients with common bile duct

obstruction. Preoperatively 13 had right upper quadrant pain and 1

had vague epigastric discomfort with nausea and vomiting. Nine

patients with functioning gallbladders had cholecystojejunostomies

and 5 with micro gallbladders had choledochojejunostomy performed.

All the patients gained symptomatic relief post surgery and the

biliary scan returned to normal in 12/14 cases. It is clearly

important to consider the diagnosis of liver disease in patients

complaining of right upper quadrant pain similar to biliary colic and

to act if necessary (49).

The worsening of liver cirrhosis secondary to common bile duct

stenosis has its own complications including portal hypertension and

the associated variceal bleeding and splenomegaly (50). A study of

the management of 44 patients with portal hypertension showed that

the mean age of diagnosis of liver cirrhosis was 9 years old. 86% of

these children developed oesophageal varices and then 50% of these

bled in the early second decade. Eleven patients who had

uncontrollable bleeding went on to have elective portosytemic

shunting, allowing prolonged post operative survival up to 15 years.

None of these patients had severe pulmonary or hepatic dysfunction51.

The initial management of patients presenting with bleeds should

follow the principles of A, B, C followed by endoscopy and injection

sclerotherapy. The newer endoscopic techniques such as injection of

tissue adhesives, thrombin and /or banding ligation may replace

sclerotherapy. Drugs such as Somatostatin and Octreotide may be used

as adjuncts although there use has not been evaluated in children.

Splenectomy can be considered in those patients who suffer severe

pain and elevation of the diaphragm leading to dyspnoea due to

splenomegaly.

A study by Louis et al showed that of 6 patients who underwent

partial splenectomy 3 had post operative rupture of the scar but no

pulmonary decompensation and with a follow up of 2.5-7 years none had

increased risk of infection52. The benefits included correction of

hypersplenism, decreased oesophageal varices and stability of hepatic

function. These procedures may increase survival or delay the need

for by a few more years whilst waiting for liver transplantation.

Vascular access procedures

The implantation of vascular access devices is one of the most common

procedures performed on CF patients. They are accepted as a safe and

effective method of providing long term intravenous therapy.

Deerojanawong et al published a report on the incidence and type of

complications associated with these devices. They found that out of a

total 57 Totally Implantable Venous Access Devices (TIVADs) implanted

in 44 patients, 21 had devices inserted without complications.

The most common complications observed were:

1) Mechanical complications (53%) - Median duration of catheter

insertion before complication was 592 days, the most common problem

being occlusion. Catheter removed in 18 cases.

2) Symptomatic venous thrombosis (9%) - These were treated with

either streptokinase or local tissue plasminogen activator infusions

and heparinisation. All devices were eventually removed and the

patients received anticoagulation therapy.

3) Infections (32%) - catheter removed in 5 cases. Median duration of

insertion prior to infection was 437 days. There were 13 episodes of

site infection.

In total 23 devices were removed because of complications. 6 were

replaced without complication, 9 were replaced with further

complication and 8 were not replaced.

Ten of the 16 patients with functioning devices at the time of the

review underwent doppler ultrasound investigation and 2 patients

showed evidence of early thrombus.

Despite the above complications the authors admit that TIVADs are a

useful technique in gaining access in CF patients who require

frequent antibiotics and have poor peripheral intravenous access

(53). Attention to preoperative preparation, meticulous surgical

technique, patient education may reduce complications as may the

cautious use of prophylactic anticoagulation.

Summary

CF used to be thought of as a paediatric disease but with development

of sophisticated treatment regimens using a variety of powerful

antibiotics, pancreatic enzyme supplementation and organ

transplantation CF patients are more likely than ever to present to

the general surgeon. There is often anxiety surrounding the operative

management of these patients, who have multiple organ disease and in

particular poor pulmonary function. However with a good preoperative

assessment and preparation most CF patients do well post operatively

and benefit from surgical intervention for the many conditions

discussed in this article. Indeed surgical treatment can in turn lead

to an improvement in lung function and quality of life e.g. in GOR

and cholecystectomy.