A study into the urgent endoscopy referral system for patients with suspected gastrointestinal cancer

2. A study into the urgent endoscopy referral system for patients with suspected gastrointestinal cancer Christopher Jump 3rd Year Medical Student

3. Background information With the aim of improving the detection of cancers at an early stage and therefore survival rates the 2-week referral system was introduced in 2000 by the Department of Health and was revised in 2005 by NICE This included a referral form which specified symptoms that needed to be present in order for the patient to be urgently referred to a specialist consultation or directly to endoscopy

4. Reasons the study was needed Many patient’s specimens referred as urgent to the histopathologist are not diagnosed with malignancy. This displaces ‘correctly’ referred urgent patients down the waiting list, potentially causing them a worse prognosis due to the delay of diagnosis and subsequent treatment

5. Reasons the study was needed • Each colonoscopy costs about £900 • Each oesophagogastroduodenoscopy (OGD) costs about £500-600 • Histopathology costs are about: • £67 per single biopsy site • £100 for 2 biopsy sites • £133 for 3 biopsy sites • The PCT pays for each one they refer for, so if they are not necessary it is a waste of their limited budget

6. Reasons the study was needed There are significant complications associated with all types of endoscopy, which patients are being needlessly exposed to if they are incorrectly referred E.g. Perforation, haemorrhage, infection, pain and discomfort, sedation associated (cardio-pulmonary events), etc.

7. Current evidence base • Limited number of studies investigating urgent referral for endoscopy in GI cancer patients, most of which look into therapeutic endoscopy • Many studies looking into the effectiveness of the guidelines for urgent referral to a specialist in secondary care. Have shown mixed results regarding if the guidelines are specific enough to detect early cancer presentation and their effect on the outcome of patients

8. Main aims of the study • To investigate: • The number of patients that are correctly and incorrectly referred for urgent endoscopies • The differences in outcome between the patients who were correctly and incorrectly referred

9. Method 50 patients included in the study, 25 who underwent an upper GI endoscopy and 25 who had a lower GI endoscopy between the 25th February and 17th March 2009 at Southport and Formby District General Hospital. Patients were identified by urgent histopathology referral forms. Medical records were then accessed and data collected. Urgent referrals were deemed to be correct or incorrect using ‘NICE referral for suspected cancer guidelines’. Outcomes were recorded by assessing their progress since their endoscopy.

10. Results • Mean age of 72.1 years • 25 males and 25 females in total sample • When divided: • 14 females and 11 males in upper GI group • 11 females and 14 males in lower GI group

11. Results- Source of referrals 43 (86%) of the 50 patients were referred from a GP 4 from hospital wards 1 from A&E, 1 referred by MDT, 1 surveillance

12. Results- Number of correct and incorrect referrals • 18 (36%) of 50 patients were referred in accordance with NICE guidelines • When divided: • Upper GI= 4 correct and 21 incorrect referrals • Lower GI= 14 correct and 11 incorrect referrals

13. Results- what the upper GI referrals should have been • Of the 21 incorrect referrals: • 12 should have been given an urgent outpatient referral • 5 should have been considered for an urgent outpatient referral • 4 should have been routinely referred for an outpatient appointment

14. Results- Outcomes of correct referrals • Upper GI: • 1 patient with a benign polyp, now on surveillance • 1 patient with an oesophageal ulcer and gastritis (PPI and discharged) • 1 patient with duodenitis, duodenal ulcer, gastritis and 2 gastric ulcers (PPI and discharged) • 1 patient with gastritis and duodenitis (PPI and discharged) • Lower GI: • 5 cancers; 3 died, 1 is treated palliatively and 1 had surgical excision and is now under surveillance • 2 patients with Diverticular Disease discharged • 2 patients with benign polyps discharged • 5 patients normal, discharged

15. Results-Outcome of correct referrals

16. Results-Outcome of incorrect referrals • Upper GI • 3 patients died (2 cancers, 1 unknown) • 13 patients treated for an inflammatory condition (oesophagitis, gastritis or duodenitis) with a PPI and discharged. • 2 patients normal • 2 treated for malignancy (partial gastrectomy, oesophageal stent) • 1 patient continued on surveillance for Barrett’s oesophagus

17. Results-Outcome of incorrect referrals • Lower GI: • 3 malignancies detected; 2 had successful surgical excisions, 1 treated palliatively • 3 patients had adenomatous polyps excised, now under surveillance • 2 normal patients • 1 with haemorrhoids, discharged • 2 treated for ulcerative colitis (both medication, 1 also had a colectomy)

18. What has it shown Minority (36%) of urgent referrals comply with guidelines Majority (81%) of incorrect referrals are from GPs There are considerably more upper GI than lower GI incorrect urgent referrals for endoscopy (21/25- 11/25) Minority of patients who are urgently referred for endoscopy are diagnosed with cancer (24%) The incorrect referrals detected more cancers than the correct referrals (7-5)

19. What has it shown Correct upper GI referrals detected no cancers, incorrect detected 4 Correct lower GI referrals detected 5 cancers, incorrect detected 3 Incorrect lower GI referrals had a higher curative treatment rate for cancer than correct lower GI referrals (66.7%-20%) 3 patients out of 50 had life saving surgical resection of their cancer over the 3 weeks this study observed Equates to 52 patients a year saved at an annual cost of about £718,363 for endoscopy and histopathology only

20. Conclusions The existing guidelines are not effective as originally hoped in detecting patients with gastrointestinal cancer This study suggests that for a cancer to meet the current urgent referral guidelines it has to be at a late enough stage to exhibit enough symptoms to fulfil the criteria, with the majority of the time this being too late to cure the patient Guidelines need to be reviewed and amended with the aim of detecting more cancers at an early stage Guidelines need to be made compulsory for all GPs as this is where the main problem lies

21. Limitations Symptoms in urgent referral form not specified, which meant many patients may have been eligible for urgent referral but were deemed not, as form not filled in extensively enough. E.g. ‘rectal bleeding’ but duration not specified Handwriting on some referral forms illegible so patient may have met criteria

22. Limitations Some patients had missing histology reports in their medical files so information had to be taken from consultants letter to GP, which contains less specific information Sample size in this study is not large enough to draw significant conclusions, so a possible future study could expand on these findings with more patients from a wider region

23. Thank you for listening

25. Audit of Lung Biopsies Received at Whiston Hospital Histopathology Department in 2009 Dr S Kelly Dr L Forsyth Dr S A Melmore

26. Aim To review all lung biopsies received at Whiston in 2009. To assess adequacy. Try to further differentiate the non-small cell carcinomas (NSCC) into adenocarcinoma (adenoca) and squamous cell carcinoma (SCC) on morphology, and with the aid of immunohistochemistry.

27. Background Biopsy interpretation limited by Sampling error, Sample size, Tumour heterogeneity. BTS guidelines (2001)recommend 90% adequacy with 5+ biopsies in cases of suspected malignancy.

28. Small cell carcinoma (SMCC) → chemotherapy. NSCC → surgery. New medical treatments for adenoca without squamous differentiation (folate antimetabolite chemotherapy drugs under assessment by NICE), and with EGFR-TK mutations (EGFR-TK inhibitors).

29. Immunohistochemistry (IHC) may aid further differentiation. Limitations include; inadequate sample size, crush artefact, positive staining of normal lung constituents, overlapping immunophenotypes, and previous studies conducted on resection specimens and cytology but not biopsies.

30. Immunohistochemistry Squamous cell carcinoma; CK5, p63 and 34βE12. Adenocarcinoma; CK7, CK20 and TTF1. P63 Nuclear, SCC 78-100%, adenoca 1-33%, SMCC 77%. CK 5/6 SCC 100%. TTF1 Nuclear, adenoca 68-85%, SMCC 84%, 5-21% SCC. Poorly differentiated more likely to be negative.

31. SCC H & E TTF -ve P63 +ve

32. Adenoca TTF +ve H & E P63 -ve

33. Method Telepath search for all lung biopsies in 2009. All cases reviewed by 2 consultants and 1 SpR. Number of biopsy fragments counted. Morphological diagnosis given. All carcinoma NOS, 6 adenoca and 6 SCC → TTF-1 and p63. TTF1 and p63 - ve → CK5/6 Case notes and reports from RLBUHT reviewed.

34. Results Pieces 1 2 3 45 6 Negative (9) 2 4 2 0 1 0 Suspicious (1) 0 0 1 0 0 0 Malignant (49) 4 12 17 7 5 4 Total (64) 6 16 20 7 6 4 % of total 9.4 25 31.3 11 9.4 6.3 Number of adequate = 15.7 %

35. Total 64 Inadequate 5 Negative 9 Low grade dysplasia, 1 Adenocarcinoma 9 Squamous cell carcinoma, 17 Carcinoma (NOS) 11 Small cell carcinoma 8 Metastatic or other 4

37. 83% of adenocarcinoma TTF1 + (75-85% in studies). 1 adenocarcinoma TTF1 + p63 + (1-33% literature). 100% of satisfactory biopsies of sqcc p63 +. 4 cases of carcinoma NOS TTF1 +, p63 - probably adenocarcinoma. 1 case p63 +/- , showed a positive internal control. (Patient with cerebral metastases so no resection performed).

38. TTF +ve H & E CK 5/6 -ve P63 +/-ve

39. 4 cases TTF1 - ve, p63 – ve, all internal controls for p63 + ve, and all CK5/6 – ve. 1 was small cell marker - ve on biopsy, resection showed a squamous cell carcinoma. 3 showed possible squamous morphology, no resection due to the patient’s co-morbidities, metastases or locally advanced disease.

40. Conclusion We diagnosed 5/64 cases as inadequate on H&E. Only 10/64 (15.7%) of the remaining cases contained 5+ fragments of tissue.( vs. 90%). We made a morphological diagnosis of malignancy on 49/64 cases, (9/49 had 5+ biopsies), and Differentiated type on H&E in 38/49 cases (6/38 had 5+ biopsies). 4/23 cases sent for IHC were inadequate. diagnosed on H&E as 2 x SCC, 2 x carcinoma NOS

41. Our cases are comparable with the literature for these robust IHC stains. For morphologically classic adenocarcinoma TTF1 and p63 can be used in combination to confirm the absence/presence of squamous differentiation. For poorly differentiated NSCC cells the use of TTF1 and p63 may aid further differentiation. Immunohistochemistry should be interpreted together with morphology and clinical history. Sub classification should be avoided if uncertain.

42. Limitationsinclude; small sample size, difficult morphology, variable immunohistochemical staining and interpretation, tumour heterogeneity, previous studies done on resection specimens.

43. The future As the prospect of mutational analysis on more/all of these tumours draws closer, and The use of IHC is used increasingly to choose the tumours that will benefit from treatment, Clinicians will need to be aware of The need for an adequate sample, and The impact on turnaround times will mean waiting for a delayed report, or receiving preliminary and supplementory reports.

44. Recommendations Use TTF1 and p63; to confirm squamous differentiation in morphologically diagnosed adenocarcinoma, in poorly differentiated NSCC but be aware of the limitations. Cut spare sections on all levels for IHC. Check results of subsequent resections. Comment on BTS adequacy in reports. Disseminate this information to all histopathologists and relevant clinicians.

45. Take Home Message For clinicians An adequate sample is required for accurate diagnosis, and extensive IHC and mutational testing is time consuming. For pathologists Immunohistochemistry should ALWAYS be interpreted together with morphology and clinical history.

46. Thank you Any questions?

48. Cancer Data for Outcomes NHS North West Supplier Data Report 2010/11 Desperately Seeking Your Support ‘We can only be sure to improve what we can actually measure’ – Lord Darzi Data Supply Data Quality

49. Poor SurvivalKey Questions? • Stage at Presentation • Does my population have a problem with late stage presentation? (not amenable to healthcare) • Do I know where and with whom there are delays in presentation/delays in diagnosis? • Am I able to make informed investment/disinvestment decisions? • Access to Diagnosis and Treatment • Does the population and sub-populations of my PCT access the right services at the right time?

50. March 2011 – Electronic PathPipe delimited txt files