Review for 10.1186/s12876-024-03371-z (2024)

Title: Esophageal cancers missed at upper endoscopy in Central Norway 2004 to 2021 – A
population based study
Version: 2 Date: 22 Jun 2024
Reviewer's report:
Comment 1: be consistent in British English or American English (tumour=British, esophageal
cancer=American)
Comment 2: I would advise against using too many abbreviations such as EC for esophageal
cancer, UE for upper endoscopy, BE for Barrett’s esophagus (also the abbreviation BE is not
explained in the abstract). It makes the article more difficult to read. Also, I would recommend
not using an abbreviation in your title, as this might not be found as a hit in search strategies.
Comment 3: MEC was defined as EC diagnosed 6-36 months after a non-diagnostic UE. High
proportions of MEC patients had Barrett’s esophagus (n=26, 51.0%). 36 months (3 years), is
quite a long time, is it truly a missed esophageal cancer after 36 months, or did the patient
develop the cancer in these 36 months? With Barret for instance, as these patients are more
likely to develop cancer in the first place. Also, patients with Barrett may have been more likely
to receive repeat endoscopy and therefore the changes are higher to discover a cancer. In the
discussion it is argued that after three years most malignant lesions are still small, I think this is
indeed an important part of the discussion. Small lesions upon diagnosis were then not excluded
so I think it cannot be stated that all these lesions were already present. It would be interesting to
know therefore in what TNM stage were upon diagnosis. I think this is quite crucial information
for the message of this article. In the discussion it is stated that: ‘The TNM classification of
malignant tumours evolved from edition 6 to 8 during the study period’ However, TNM stage
is not noted in the baseline table
Comment 4: reference 13 might be a bit outdated (2005), as it discusses the sensitivity of
endoscopy but the data is from 20 years ago. Most likely, techniques have improved significantly
over the course of this time.
Comment 5: I would recommend using STROBE guidelines for the method section.
Comment 6: To truly capture the missed carcinoma’s, it would be interesting to see if in
retrospect, these carcinomas were already visible. (Of course, this is only possible when
endoscopy images are saved)
Comment 7: A good recommendation might be to have closer follow-up (after e.g. 3 months)
for a specific group of patients.
Comment 8: in method and materials it is described “In addition, the medical records for the
36 months prior to the cancer diagnosis were reviewed to identify possible endoscopy reports
outside the endoscopy journal.” I think that what you are trying to describe is “In addition,
medical records up to 36 months prior to the esophageal cancer diagnosis were reviewed for
previous endoscopy reports”
Comment 9: “described as a macroscopic cancer, but not biopsied due to e.g. short life
expectancy” What group of patients does undergo a diagnostic endoscopy but then no biopsy is
taken? Why was the endoscopy performed in the first place if their life expectancy was already
so low? What it then really a diagnostic endoscopy or just for placing a stent for instance?
Comment 10: When noting the interquartile range, you note the Q1 and Q3 (so not the upper
and lower boundary). You note that the median age was 70.7 (31.1-100.4). I can hardly imagine
that the Q4 is above 100.4 years?
Comment 11: I would refer to your ‘control group’ as something other than the control group,
as this is not a separate group you are comparing with but it is in fact part of your cohort.
Comment 12: I would consider removing the malign melanoma and hemangiosarcoma from the
cohort as these are very different entities.
Comment 13: “The most common symptom at the prior endoscopy was gastrointestinal (GI)-
bleeding, followed by heartburn. There was a significantly higher proportion of patients with
alarm symptoms at diagnosis compared to at the prior endoscopy (p < 0.001) (Table 2). The most
common symptom at diagnosis was dysphagia (49.0%)” How is the most common symptom
prior to endoscopy GI bleeding? Was this defined as melena or?
Comment 14: Esophageal adenocarcinoma is among the fastest rising cancers in Western
populations [15] and early diagnosis is the most important prognostic factor. I would not repeat
this part of the introduction, start with the summation of your own results.
Comment 15: I think it is important to note in your methods how patients with e.g. Barrett's
esophagus were followed-up and after how much time. What where the guidelines in Norway
during this period?
Comment 16: seven patients were not biopsied at the endoscopy preceding cancer diagnosis.
Where these patients without BE or ulcerations? (so, was there nothing to take a biopsy from)
Or where there also patients with e.g. an ulcer but without biopsy?
Comment 17: In the discussion it is described: ‘Interestingly, others have reported that
missed upper GI cancers were most often found at the same location as previously described
abnormalities, that was either not biopsied or biopsied insufficiently’ I think this would be very
useful information, if there is any way you can find this data on your group of patients I think
it would be of great additional value.
Comment 18: I would lose the headlines in the discussion (MEC rate and definition, Factors
associated with MEC etc).
Overall, the article is well conducted and has a strong conclusion with good recommendations.