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

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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).

Smith 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 Smith 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.

 

Table 1

AUTHOR
TOTAL NO. OF CF PATIENTS
TOTAL NO. WITH GOR
NO. WHO HAD SURGERY

MORTALITY

Roz et al 1989l
110(2mth -17yr)
7
2
0
Olsen et al 1987 *
210
-
5
0
Gross et al 1985
189(30-48mths)
4
4
1
Vinocur et al 1985
40(1mth - 2yr)
8
5
0
Bendig et al 1982
Not specified
7
4
0

Studies looking at the outcome of CF patients with GOR treated with Nissen Fundoplication
*Study looking at Surgery in CF therefore total number with condition not mentioned.

 

Table 2

Author
Total No. With MI
Simple MI treated successfully with GGE
Complicated
MI

1 Year Survival for simple MI

1 Year Survival for complicated MI
Rescorla et a
60
10/25
35
92%
89%
Mushtaq et al
51
11/28
23
100%
96%
Docherty et al
53
26/44
9
81%
75%

 

Review articles looking at the survival of patients with meconium ileus (MI) and the success of treatment of simple MI with gastrograffin enemas (GCE)

 

References

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