Clinical Case Summary

A 45-year-old woman was founded with a raised serum alpha-fetoprotein (AFP) level of 89 ng/ml ( normal range < 8ug/L ) when taking a routine physical examination. During the following year, the serum AFP concentration level was gradually rising, up to 6353 ng/ml. There was no significant loss of weight or loss of appetite, and she denied having any feeling of bloating or abdominal pain.
Although the serum AFP concentration level was abnormally high, the cancer antigen (CA)125, cancer antigen (CA)199, carcinoembryonic antigen (CEA), PIVKA-II, AFP-L3, β-HCG levels were all within normal limits at each check. There was no abnormal findings in the hepatobiliary systems except the modest increased bilirubin (within 2 times). Hepatitis A, hepatitis C, hepatitis E antibody screen was negative. The result of HBV markers were: HBsAg(-), HBsAb(+), HBeAb(-), HBeAb(-), HBcAb(+), While HBV DNA quantification was less than 5.00E+2 IU/ml. Moreover, there was no significant abnormality concerning autoimmune liver disease. During the one-year follow up, several imaging examinations were performed,including abdominal ultrasonography, enhanced computer tomography (CT) , magnetic resonance imaging (MRI) and PET-CT. However, there was no evidence of liver lesion or tumour on all of them, even the PET scan.To check for hepatoid adenocarcinoma, gastroscopy, colonscopy, enhanced chest CT enhanced abdomen CT, and thyroid ultrasound were performed. Nevertheless, no suspicious lesion was found.
One year later, a 2.8×2.6 cm mass was detected in the left lobe of liver in a surveillance ultrasound scan. She underwent laparoscopic hepatocarcinoma resection, and the mass was confirmed moderately differentiated hepatocellular carcinoma by pathology. After surgery, AFP levels took 3 months to normalize.
From this case, we found that a gradual rise elevation in AFP were positive predictors for tumor development, especially hepatocellular carcinoma.

Introduction

The number of epidemiological population-based studies on unclassified inflammatory bowel disease (IBD-U) patients are very limited. The present study is a continuation of the Veszprem IBD population based cohort with a follow-up of the incidence and disease course of IBD-U since 1977.

Aims & Methods

Our aim was to evaluate incidence, prevalence, disease course, time to biological therapy and surgery rates in a prospective population-based database of incident IBD-U patients diagnosed between 1977 and 2018, with follow-up until 2020. Both in-hospital and outpatient records were collected. The source of age- and gender-specific demographic data was derived from the Hungarian Central Statistical Office. Medical therapy, time to first biological therapy, disease progression, and colectomy was registered.

Results

Data of 119 incident IBD-U patients were analyzed (male/female: 55/64; median age at diagnosis: 34 years(y) (IQR: 24-47)). Adjusted mean incidence rate was 0.76 (CI95%: 0.63-0.9) /10⁵ person-years in the total study period, and 0.96 (CI95%: 0.79-1.16) /10⁵ person-years between 1990-2018. Disease extent at diagnosis was proctitis in 7.6%, one-sided colitis (left-sided colitis, or isolated right-sided colitis) in 36.1%, and extensive (pancolitis) in 56.3%. The probability of progression in colonic disease extent was 6.7% (SE:2.3) at 3 years, 10.3% (SE:2.8) at 5 years and 15.3% (SE:3.4) at 10 years. The probability of developing terminal ileitis, thus disease classification change – Crohn’s disease was 2.6% (SE:1.5) at 5 years and 3.5% (SE:1.7) at 10 years. Perianal disease developed in 5% (n=6) of all patients during the total follow-up. The probability of receiving biological therapy in patients diagnosed after the year 2000 (n=62), was 15.5% (SE:4.8) at 5 years, and 19.4% (SE:5.3) at 10 years. The overall resective surgery rate was 16.8% at the end of follow-up. Segment resection was performed in 5.0% of the patients, and 11.8% underwent subtotal- or total colectomy. The cumulative probability of resective surgery was 7.6% (SE:2.4) at 1 year, 9.3% (SE:2.7) at 5 years, 13.5% (SE:3.3) at 10 years, and 18.5% (SE:3.9) at 20 years. ​

Conclusion

Initial disease phenotype was severe in most cases of IBD-U and colonic progression is substantial over time. Disease classification change to Crohn’s disease with development of terminal ileitis or perianal disease was low. High rates of biological therapy and surgery are suggestive of a severe disease course of IBD-U.

Clinical Case Summary

Introduction: Cronkhite-Canada syndrome (CCS) is a rare non-hereditary gastrointestinal polyposis syndrome. We illustrate a case with clinical presentation of dysgeusia, chronic diarrhoea and weight loss, and endoscopic features mimicking inflammatory bowel disease (IBD).
Case: Our patient is a 58-year-old Chinese lady who presented with dysgeusia, vomiting, loose stools, hair loss, peripheral numbness and weight loss. Examination revealed xerosis, onycholysis, periorbital hyperpigmentation and alopecia. (Fig. 1) Gastroscopy showed diffuse gastric mucosal hyperaemia, oedema and nodular changes (Fig. 2A). Helicobacter pylori was negative. Colonoscopy revealed a confluent pan-colonic circumferential nodular colitis (Fig. 3A) Histology showed features reminiscent of IBD with mild ileitis and continuous diffuse crypt architectural changes, cryptitis and crypt abscess formation (Fig. 4A-C). The final diagnosis was CCS based on the constellation of clinical and endoscopic features. She received high dose steroid therapy and mesalamine with significant improvement. However, upon tapering of her prednisolone to 15mg once daily, recrudescence occurred. Prednisolone was escalated with a more gradual taper with resultant improvement. At 4 months of treatment, the patient achieved clinical response with improvement of appetite, weight gain, diarrhoea and normalization of serum albumin. Repeat OGD showed gastric hyperplastic polyps (Fig. 4C) and colonoscopy showed improvement of confluent nodular and circumferential colitis (Fig. 2B and 3B). The severity of activity improved but features of chronicity remained on her colonic biopsies histologically (Fig. 5A-C).
Conclusion: The optimum treatment of CCS is currently unknown with no consensus guidelines. The mainstay of treatment remains as steroid therapy and nutritional support with clinical and endoscopic remission as therapeutic goals. Recurrences are not uncommon but often respond to corticosteroid retreatment as in our patient.

References

1. Kopáčová M, Urban O, Cyrany J, et al. Cronkhite-Canada Syndrome: Review of the Literature. Gastroenterology Research and Practice. 2013;2013:e856873. doi:10.1155/2013/856873
2. Watanabe C, Komoto S, Tomita K, et al. Endoscopic and clinical evaluation of treatment and prognosis of Cronkhite–Canada syndrome: a Japanese nationwide survey. J Gastroenterol. 2016;51:327-336. doi:10.1007/s00535-015-1107-7
3. Goto. Cronkhite-Canada syndrome: epidemiological study of 110 cases reported in Japan. Nihon Geka Hokan, vol. 64, no. 1, pp. 3–14, 1995
4. Mao E, Hyder S, Laskiewicz L, Taliano R, DeNucci T. A Rare Case of Cronkhite-Canada Syndrome: 1558. Official journal of the American College of Gastroenterology | ACG. 2017;112:S851.
5. Mao EJ, Hyder SM, DeNucci TD, Fine S. A Successful Steroid-Sparing Approach in Cronkhite-Canada Syndrome. ACG Case Rep J. 2019;6(3):e00055. doi:10.14309/crj.0000000000000055
6. Hewett DG, Kaltenbach T, Sano Y et al. Validation of a simple classification system for endoscopic diagnosis of small colorectal polyps using narrow-band imaging. Gastroenterology. 2012 Sep;143(3):599-607.e1. doi: 10.1053/j.gastro.2012.05.006. Epub 2012 May 15.
7. Schulte S, Kütting F, Mertens J, et al. Case report of patient with a Cronkhite-Canada syndrome: sustained remission after treatment with corticosteroids and mesalazine. BMC Gastroenterology. 2019;19(1):36. doi:10.1186/s12876-019-0944-x

Introduction

The undetermined pancreatic cystic neoplasms represent 20-30% of the total number of pancreatic cystic lesions(PCL). The diagnostic accuracy of endoscopic ultrasound (EUS) morphology is 51%. Endoscopic ultrasound-guided fine-needle aspiration(EUS-FNA) should be performed for differentiating between mucinous and non-mucinous pancreatic cysts when the characterization of the cyst cannot be made on the basis of non invasive imaging techniques.

Aims & Methods

Our aim was to assess the utility of the Neutrophil gelatinase-associated lipocalin(Ngal) concentration alone or combined with glucose level in cyst fluid obtained by EUS with EUS-FNA for discriminating between mucinous and non-mucinous PCL's.
This prospective study was performed between april 2018 and may 2020 at one tertiary referral hospital and included 63 patients , 30 with undetermined pancreatic cysts (group A) and the controlled group was represented by 33 patients with pancreatic pseudocysts after acute pancreatitis drained by EUS (group B). The patients from group A underwent EUS-FNA for liquid analysis and the patients from group B had liquid collection during the drainage of pseudocysts. The final diagnosis was based on surgery or EUS results (morphology, cytology, glucose and carcinoembryonic antigen(CEA) intracystic level) or on imaging during follow-up (24 month). We performed sandwich enzyme-linked immunosorbent assays (ELISA) for cystic and serum Ngal determination and measured glucose levels by a hand glucometer.

Results

The final diagnosis was pseudocyst in 33 patients, serous cystadenoma in 6, mucinous cystadenoma in 3, intraductal papillary mucinous neoplasms in 19 patients, and ductal adenocarcinoma in 2 patients. The cystic fluid analysis of these patients showed that the mean Ngal value for the serous cystic adenomas was 336ng/dl, 728ng/dl for the mucinous lesions and 1116ng/dl for the pseudocysts. The intracystic Ngal concentration (cut-off ≥ 500 and ≤ 800ng/dl) had diagnsotic sensitivity 70.8%, and specificity 92.3% for mucinous cysts. Serum Ngal concentration had no diagnostic contribution. The cystic glucose levels (cut-off ≤ 22mg/dl) had sensitivity 83.3% and specificity 82.1% for mucinous lesions. Combined glucose(cut-off ≤ 22mg/dl) and Ngal(cut-off ≥ 500 and ≤ 800ng/dl ) testing showed sensitivity of 58,3 and specificity 100% for mucinous cysts. Wheras either positive Ngal (cut-off ≥ 500 and ≤ 800ng/dl) or glucose (cut-off ≤ 22mg/dl) testing showed sensitivity 95.8% and specificity 74.4%.

Conclusion

Pancreatic cyst fluid NGAL concentration alone and combined with glucose level appeared to be useful in discriminating mucinous cysts.

References

State‑of‑the‑Art Update of Pancreatic Cysts -Andrew Canakis · Linda S. Lee2 Digestive Diseases and Sciences (2022) 67:1573–1587

Disclosure

Nothing to disclouse

Introduction

The quality of colonoscopy is influenced by patient and operator factors. Studies investigating operator attentional fatigue on adenoma detection rate (ADR) have yielded conflicting results.

Aims & Methods

This study aims to compare ADR, polyp detection rate (PDR) and sessile serrated lesion detection rate (SSLDR) and complication rates between elective colonoscopies performed early and late in the list, across multiple operators (n>15), over 10 years, in a tertiary Brisbane (Australia) hospital.
A retrospective study was conducted on elective colonoscopies performed between 2012 and 2022 at The Prince Charles Hospital. ‘Early procedures’ are defined as procedures starting in the first hour of the first procedure starting and ‘late procedures’ are defined as procedures starting within the last hour of the last procedure starting. This pre-defined early and late procedures were used as surrogate markers for operator fatigue, accounting for a possible non-linear relationship between time and onset of fatigue, as well as the variation in number of colonoscopies performed every hour. Timing and the order of colonoscopy were used as alternative surrogates, in a secondary analysis.
Logistic regression was performed on all categorical outcome variables, and Poisson regression was modelled on continuous outcome variables, due to their non-linear distribution. Multivariate analysis included all potential confounding variables related to outcomes of interest. Statistical significance was defined as a P-value less than 0.05. Statistical analyses were performed using the SAS® statistical software (SAS Institute Inc, USA).
Exclusion included; surveillance for IBD and elective ESD.

Results

In total, 15 proceduralist (11 gastroenterologists, 4 surgeons) performed 39, 206 elective colonoscopies from 2012 to 2022. The baseline characteristics of patients, year and procedure sessions are similarly distributed between the early and late groups.
Multivariant analysis found significant associations between late procedures and lower adenoma detection rates, polyp detection rates and SSL detection rates. After adjusting for age, gender, proceduralist, year, morning or afternoon procedure, and bowel preparation quality, PDR, ADR and SDR remain 20-28% lower in late colonoscopies compared with early ones. We also found that age, gender, proceduralist, year and bowel preparation independently affected ADR in multivariant analysis. However, morning or afternoon ADRs did not significantly differ after adjusting for other variables. Proceduralist were found to be the only additional significant variable for SDR in multivariant analysis. There was no significant association between timing of procedures and major adverse events.

Conclusion

This is the largest single-centre study on operator fatigue and its effect on colonoscopy quality. Although the minimum standards for ADR was achieved, ‘late procedures’ have statistically significant lower ADR, PDR and SSLDR compared to ‘early procedures’. There was no difference in the complication rates between ‘early procedures’ and ‘late procedures’.
This study highlights the detrimental effect of fatigue in later procedures affecting the quality of colonoscopies and may be applicable in principal to other procedural based clinical work. Importantly, this may or perhaps will or is having an impact on patient safety, satisfaction, outcomes and clinical KPI’s for the operators and hospital administrators.

Disclosure

None

Introduction

Urgency is not an IBD Patient Reported Outcome (PRO) in the STRIDE II but it has been assessed at baseline and as an outcome measure in recent pivotal RCTs with newer biologicals and targeted synthetic small molecules in both Crohn’s disease CD) and ulcerative colitis (UC). However, although it is reasonable to assume that UC patients or CD patients with rectal involvement may complain for severe urgency, urgency has been assessed even in patients with Crohn’s ileitis (iCD).

Aims & Methods

The aim of this study was to assess whether urgency is reported by iCD patients with flares or quiescent disease in a Real-World (RW) setting. This prospective, pilot, RW study included CD patients with solely L1 phenotype. L1 location was documented by ileocolonoscopy, histology and, imaging (MRE, US, or capsule endoscopy). Patients with colonic and/or rectal disease, perianal involvement and complicated ileal disease were excluded. Patients were interviewed by office visits during disease flare [HBI>5, CRP <5mg/dl, faecal calprotectin (FC)>250μg/g faecal tissue and SES-CD for terminal ileum >3 if colonoscopy was performed within a month prior to the visit) and during clinical remission (HBI<5, CRP <5mf/dl and FC <200μg/g and ileal SES-CD=0, in a recent ileocolonoscopy). The presence of and severity of urgency was recorded by a Symptom Rating Score of 0-10 (absent to very severe). The presence and severity of abdominal pain, the number and consistency of stools, nocturnal stools, blood and/or mucus in the stools, and the feeling of inadequate evacuation were sought by a structed questionnaire.

Results

During a 15-month period, 85 iCD patients [45 males, median age (range) 33 (18-65) years, median (range) disease duration 9 (0.6-25) years] were enrolled in the study. Patients were receiving a wide range of treatments, including anti-TNF agents (n=35), ustekinumab (N=25), vedolizumab (N=5), azathioprine (n=10), budesonide (n=5) and mesalazine (n=15). Fifty patients had a flare, 65 were in remissionand 30 patients were interviewed sequentially in flare and remission of disease. All patients in disease flare reported abnormal classical PROs of CD. Moderate to severe urgency [median score 5, range 4-8] was reported by 5/50 (10%) patients with disease flare, 8/65 (12%) patients with disease remission and 2/30 (6.5%) patients who were interviewed during flare and remission of disease. 3/50 patients with urgency during a flare of CD did not report urgency during disease remission. Six of the 8 patients who were interviewed only with iCD in remission and reported urgency had concurrently typical Irritable Bowel Symptoms (IBS, abdominal pain relieved by defecation, alternating diarrhoea/constipation, inadequate bowel emptying).

Conclusion

This prospective, pilot, real-world study shows that the reliability of urgency as classical PRO in patients with iCD is questioned and raises doubts whether urgency should be included in the spectrum of PROs for patients with iCD both in RCTs and in RW studies. Validation of the terminology in different ethnic languages may also pose additional barriers in patient understanding and reporting the symptom in the presence of additional IBS-type symptoms. Large studies are needed to assess if urgency is present in patients with iCD and how reliably is reported especially in multinational RCTs.

Disclosure

Dr GJ Mantzaris: Research grants: AbbVie, Genesis, Merck Sharp & Dohme, Takeda; advisor/speaker: AbbVie, Aenorasis, Dr Falk, Ferring, Hospira, Janssen, Merck Sharp & Dohme, MYLAN, Pfizer, Takeda, Vianex.
Dr A Loukou: Nothing to declare