The History of Cystic Fibrosis by Dr James Littlewood OBE

Edited and produced by Daniel Peckham

 

Some of the following references to case reports do not appear in the main text.

 

1982 Abdul-Karim FW, King TA, Dahms BB, Gauderer MWL, Boat TF. Carcinoma of extrahepatic biliary system in an adult with cystic fibrosis. Gastroenterology 1982; 82:758-762. [PubMed]

 

1986 Tedesco FJ, Brown R, Schuman BM. pancreatic carcinoma in a patient with cystic fibrosis. Gastrointest Endosc 1986; 32:25-26.[PubMed]

 

1987  Siraganian PA, Miller RW, Swender PT. Cystic fibrosis and ileal carcinoma. Lancet 1987; 2(8568):1158,. [PubMed]

 

1988 McKintosh JC, Schoumacher RA, Tiller RE. pancreatic adenocarcinoma in a patient with cystic fibrosis. Am J Med 1988; 85:592.[PubMed] <

 

1993 Sheldon CD, Hodson ME, Carpenter LM, Swerdlow AJ. A cohort study of cystic fibrosis and malignancy. Brit J Cancer 1993; 68:1025-8.  [PubMed]
A cohort of 412 patients first attending a cystic fibrosis (CF) clinic between 1961 and 1989 were followed up to 30 June 1989. The number of malignancies observed in the cohort was compared with the number expected based on the age, sex and calendar-year-specific cancer registration rates for England and Wales. Four CF patients were diagnosed as having malignancies before 30 June 1989. The tumors were: adenocarcinoma of the terminal ileum; adenocarcinoma of the pancreas, testicular teratoma, and B-cell lymphoma. This compares with 0.89 malignancies expected on the basis of rates in England and Wales (Standardised Registration Ratio = 452; 95% confidence interval 122-1150, P = 0.03). The single case of adenocarcinoma of the terminal ileum contrasts with less than 0.001 expected (P = 0.003) and that of the pancreas with 0.007 expected (P = 0.01). A further adenocarcinoma of the pancreas was diagnosed 2 years after the end of the study period. The two cases of pancreatic cancer compare with 0.008 expected (P = 0.0001) during the period to mid 1991.

 

On the basis of the present findings and previous case reports in the literature, adenocarcinoma of the pancreas and adenocarcinoma of the terminal ileum may be associated with cystic fibrosis.

This is an early paper from the world's largest adult CF centre at the Royal Brompton in London suggesting that there may be an association between CF and malignancy - an association later confirmed and particularly associated with CF patients who had received organ transplants. Many of the reports are of isolated case reports.

 

1994 Tsongalis GJ, Faber G, Dalldorf FG, Friedman KJ, Sillverman LM, Yankaskas JR. Association of pancreatic adenocarcinoma, mild lung disease, and delta f508 mutation in a cystic fibrosis patient. Clin Chem 1994; 40:1972-4.[PubMed]

The fifth case of adenocarcinoma of the pancreas to be reported in a person with CF and the first with molecular data.

 

2003 Maisonneuve P, FitzSimmons SC, Neglia JP, Campbell PW 3rd, Lowenfels AB. Cancer risk in non-tansplanted and transplanted cystic fibrosis patients: a 10-year study. J Nat Cancer Instit 2003; 95:381-387.[PubMed]
The aim of the study was to assess the risk of cancer in nontransplanted and transplanted CF patients. The authors followed 28,858 patients whose data were reported to the Cystic Fibrosis Foundation patient registry from 1990 through 1999 and compared the number of cancers observed in transplanted and nontransplanted patients to the number expected from population-based cancer incidence data. All statistical tests were two-sided.
In 202 999 person-years of observation of nontransplanted CF patients, 75 cancers were observed, but 69.7 were expected (standardized incidence ratio [SIR] = 1.1, 95% confidence interval [CI] = 0.8 to 1.4). Twenty-three digestive tract tumors were observed, but 4.5 were expected (SIR = 5.1, 95% CI = 3.2 to 7.6). More cancers than expected were observed of the small bowel, colon, and biliary tract but not of the stomach or rectum. They found that the deficit of non-digestive tract tumors was not statistically significant (52 observed versus 65.2 expected; SIR = 0.80, 95% CI = 0.6 to 1.0; P =.055). In 2725 person-years of observation of 1063 transplanted patients, 13 cancers were observed, but 2.05 were expected (SIR = 6.3, 95% CI = 3.4 to 10.8), and more digestive tract tumors (four observed versus 0.19 expected; SIR = 21.2, 95% CI = 5.8 to 54.2) and lymphomas (seven observed versus 0.16 expected; SIR = 44.0, 95% CI = 17.7 to 90.7) were observed than expected.


The authors observed an increased risk of digestive tract cancers among adult CF patients, particularly of the small bowel, colon, and biliary tract. This increased risk appeared to be more pronounced in patients who had had an organ transplantation.

 

2004 McKeon D, Day A, Parmar J, Alexander G, Bilton D. Hepatocellular carcinoma in association with cirrhosis in a patient with cystic fibrosis. J Cyst Fibros 2004; 3:193-195.[PubMed]
Cystic fibrosis liver disease (CFLD) occurs in 37% of patients with CF. To date and to the best of our knowledge, there has not been a documented case of hepatocellular carcinoma in association with cirrhosis and CF. A 32-year-old lady with cystic fibrosis (CF) had ultrasound lesions consistent with hepatocellular carcinoma, confirmed on histology. She was also pregnant at the time of diagnosis. Her tumour was considered too large for resection and liver transplantation and she was referred to a national centre for laser ablative therapy.


The authors are concerned that with the increased life expectancy of patients with CF and the chronic nature of CFLD that this may be an increasingly recognised complication amongst the CF adult population. Therefore, they have changed their practice to more intense surveillance of patients with established CFLD to incorporate biannual ultrasound imaging of the hepatic system and yearly serum concentration measurements of alpha-fetoprotein.

 

2005 Oermann CM, Al-Salmi Q, Seilheimer DK, Finegold M, Tatevian N. Mucinous cystadenocarcinoma of the pancreas in an adolescent with cystic fibrosis.  Pediatr Devel Pathol 2005; 8:391-396. [PubMed]

The tumour developed within a pancreatic cyst that had been identified 13 years before resection and highlights the premalignant potential of pancreatic cysts in this at-risk population.

 

2005 Kelleher T, Staunton M, O'Mahaony S, McCormick PA. Advanced hepatocellular carcinoma associated with cystic fibrosis. Eur J Gastroenterol Hepatol 2005; 17 1123-1124. [PubMed]

An 18 year old female with CF presented with advanced hepatocellular carcinoma with no prior clinical evidence of liver disease.

 

2007 Ibele AR, Koplin SA, Slaughenhoupt BL, Kryger JV, Friedl A, Lund DP. Colonic adenocarcinoma in a 13-year old with cystic fibrosis. J Pediatr Surg 2007; 42:E1-3. [PubMed]

A 13-year-old boy with CF presented with pneumaturia secondary to a colonic adenocarcinoma.

 

2008 Lees AN, Reid DW. Management dilemma; a woman with cystic fibrosis and severe lung disease presenting with colonic carcinoma: a case report.J Med Case Rep.J Med Case Rep 2008; 2:384. [PubMed]

A 41-year-old Caucasian woman with cystic fibrosis and severe lung disease who had been considered for lung transplantation, who presented with rectal bleeding and was found to have a Stage I adenocarcinoma of the sigmoid colon. After considerable discussion as to the operative risks, she underwent a laparoscopic resection and remains relatively well 1 year postoperatively with no recurrence.

 

2010 Healy F, Mulloy E, Peirce TH, Mahony MJ. Co-morbidity in a cystic fibrosis population attneding a regional clinic. Irish Med J 2010; 103:313-314.  [PubMed]
Pulmonary disease remains the major cause of morbidity in patients with cystic fibrosis (CF). However, of 115 patients attending a regional CF clinic there were 16 cases (14%) with co-morbid conditions. Of this group, 4 of 115 patients (3.5%) had renal problems including both structural and functional defects and 4 (3.5%) had neurological disorders, 3 of which were types of epilepsy. Notably, 3 of 115 patients (2.6%) had different forms of neoplasia, all of which required significant surgical and/or chemotherapeutic intervention. There is now increasing evidence of the association between digestive tract malignancy and CF, which further complicates management of these already complex cases.

Additional suggestion that there is an increased incidence of malignancy in people with CF from an unselected large group of patients at Dr Mike Mahony's CF centre in Limerick in the West of Ireland

 

2011 Meyer KC, Francois ML, Thomas HK, Radford KL, Hawes DS, Mack TL, Cornwell RD, Maloney JD, De Oliveira NC. Colon cancer in lung transplant recipients with CF: increased risk and results of screening. J Cyst Fibros 2011; 10:366-369. [PubMed].
A study to determine the incidence of colon cancer in lung transplant recipients with cystic fibrosis (CF) and review screening colonoscopic findings in other recipients with CF. A retrospective chart review was performed for all patients with CF transplanted at the University of Wisconsin Hospital and Clinics (January 1994 through December 2010).
Four of 70 transplant recipients with CF developed fatal colon carcinoma following transplantation, and the cancer was advanced in all 4 recipients (age 31, 44, 44, 64 years) at the time of diagnosis. In contrast, only one of 287 recipients transplanted for non-CF indications developed colon cancer. Of all recipients with CF who did not develop colon cancer, 20 recipients underwent screening colonoscopy at 1 to 12 years following transplantation. Seven (35%) of the screened transplant recipients (ages 36, 38, 40, 41, 43, 49, 51 years) had colonic polyps in locations ranging from cecum to sigmoid colon and up to 3 cm in diameter.

The authors concluded that in contrast to non-CF recipients, patients with CF displayed a significant incidence of colon cancer (4 of 70 recipients; 5.7%) with onset ranging from 246 days to 9.3 years post-transplant, which may be due to a combination of their underlying genetic disorder plus intense, sustained immunosuppression following lung transplantation. Colonoscopic screening may identify patients with pre-malignant colonic lesions and prevent progression to colonic malignancy.

 

 

2014 Gory I. Brown G. Wilson J. Kemp W. Paul E. Roberts SK. Increased risk of colorectal neoplasia in adult patients with cystic fibrosis: a matched case-control study. Scand J Gastroenterol 2014; 49:1230-6. [PubMed].
A matched case-control study of adult CF patients in Melbourne undergoing colonoscopy in a 5-year period from 2007 to 2012. Controls were matched in a 2:1 ratio for age, gender, and colonoscopy indication. A total of 50 patients with CF who underwent colonoscopy were identified. Among CF patients, there were 5 (10%) cases with colorectal cancer (CRC), 1 (2%) with ileal adenocarcinoma, 13 (26%) with adenomas, and 16 (32%) with advanced adenomas. In contrast in controls there was 1 (1%) case with CRC, 11 (11%) with adenomas, and 6 (6%) with advanced adenomas.
Compared to controls, CF was associated with a 10-fold increased risk of CRC, threefold increased risk of adenomas and sevenfold increased risk of advanced adenomas.
The authors suggest that CF patients are at significantly increased risk of CRC compared to age, sex, and colonoscopy-indication matched controls. They suggest that consideration should be given to the introduction of a CRC surveillance program in the CF population.
 
Further evidence supporting previous studies reporting an increased risk of colorectal carcinoma in adults with CF.