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Small and Large Bowel: Systematic Review and
Meta-Analysis
Dig Dis Received: January 8, 2021
Accepted: February 10, 2021
DOI: 10.1159/000515219 Published online: February 15, 2021
Management of Chronic Diarrhea in
Primary Care: The Gastroenterologists’
Advice
Heinz F. Hammer
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University Graz, Graz,
Austria
Keywords the treatment options in patients with chronic diarrhea? Key
NET · Celiac disease · Inflammatory bowel diseases · Messages: Acute diarrhea is usually of infectious origin with
Treatment · Diagnosis the main treatment goal of preventing water and electrolyte
disturbances. Chronic diarrhea is usually not of infectious
origin and may be the symptom of a large number of gastro-
Abstract intestinal and general diseases or drug side effects. In undi-
Background: Chronic diarrhea is defined as more than 3 agnosed or intractable diarrhea, the question shall be raised
bowel movements per day, or loose stools, or stool weight whether the appropriate tests have been performed and in-
>200 g/day for at least 4 weeks. Accompanying symptoms terpreted correctly. © 2021 The Author(s).
may include urgency, abdominal pain, or cramps. Summary: Published by S. Karger AG, Basel
A number of causes have to be considered, including inflam-
matory, neoplastic, malabsorptive, infective, vascular, and
functional gastrointestinal diseases. Other causes include Introduction
food intolerances, side effects of drugs, or postsurgical con-
ditions. Diarrhea may also be symptom of a systemic disease, Chronic diarrhea is defined as more than 3 bowel
like diabetes or hyperthyroidism. Special patient groups, like movements or loose stools for at least 4 weeks [1, 2]. Pop-
the very elderly and immunocompromised patients, pose ulation-based studies have suggested a prevalence of
special challenges. This review follows a question-answer chronic diarrhea in the USA between 14 and 18% [3].
style and addresses questions raised on the intersection of Symptoms which may accompany chronic diarrhea may
primary and secondary care. What do you mean by diarrhea? include urgency, abdominal pain, or cramps with bowel
Why is it important to distinguish between acute or chronic movements. Several conditions may be responsible for
diarrhea? How shall the patient with chronic diarrhea be ap- chronic diarrhea, including inflammatory [4], neoplastic
proached? How can history and physical exam help? How [5], malabsorptive [6–8], infective [9, 10], and functional
can routine laboratory tests help in categorizing diarrhea? gastrointestinal diseases [11]. Other causes include food
Which additional laboratory tests may be helpful? How to intolerances [12, 13], side effects of drugs like magnesium
proceed in undiagnosed or intractable diarrhea? What are [14] or promotility drugs [15], or postsurgical [6, 16] con-
karger@karger.com © 2021 The Author(s). Correspondence to:
www.karger.com/ddi Published by S. Karger AG, Basel Heinz F. Hammer, heinz.hammer @ medunigraz.at
This is an Open Access article licensed under the Creative Commons
Attribution-NonCommercial-4.0 International License (CC BY-NC)
(http://www.karger.com/Services/OpenAccessLicense), applicable to
the online version of the article only. Usage and distribution for com-
mercial purposes requires written permission.ditions. Diarrhea may also be a symptom of a systemic Table 1. Medications and toxins to be considered as a cause of
disease, like diabetes [17, 18] or hyperthyroidism [19]. diarrhea (modified after [42])
Special patient groups, like the very elderly and the im-
Acid-reducing drugs and antacids
munocompromised patients pose special challenges in Anti-arrhythmics
the diagnosis and treatment of chronic diarrhea [10]. Antibiotics
Chronic diarrhea may result in a multitude of clinical Antihypertensives (beta-blockers)
and social problems for the patients. The most frequent Antineoplastic drugs
causes of diarrhea are functional [11] and have neither Antiretroviral drugs
Colchicine
life-threatening consequences nor are they sign of a se- Heavy metals
vere underlying disease, although chronic diarrhea may Herbal products
severely inflict on quality of life [20–23], due to interfer- NSAID
ence of diarrhea, fecal urgency, or fecal incontinence with Prostaglandin analogs
Theophylline
normal daily activities. In a proportion of patients, chron- Vitamin and mineral supplements
ic diarrhea is symptom of a disease, like in inflammatory
bowel diseases (IBD); and in these patients, other symp- NSAID, nonsteroidal anti-inflammatory drug.
toms, like blood loss or abdominal pain, may have more
clinical relevance than diarrhea [4]. In a small minority,
chronic diarrhea can be life-threatening, due to excessive
fluid and electrolyte losses, for example, in some endo- and stool weight (recent travel or an immunocompromised state may re- Table 2. Likely causes of diarrhea in well-defined patient groups or
quire consideration. Clinically, systemic complications clinical settings (modified after [42])
due to dehydration, electrolyte disturbances, and rarely
Travelers
sepsis or Guillain-Barre syndrome may require attention Bacterial infections (mostly acute diarrhea)
[31]. Diarrhea may become clinically relevant as a nurs- Protozoal infections (ameba and giardia lamblia)
ing problem [32] or it may develop into a nuisance (e.g., Tropical sprue
in travel). Epidemics
Treatment of acute diarrhea is usually symptomatic, Bacterial infection
Viral infections
including, but not restricted to, oral or intravenous water Rare causes
and electrolyte replacement or of the underlying patho- Diabetic patients
gen. Symptomatic treatments with, among others, loper- Autonomic neuropathy
amide or the enkephalinase inhibitor racecadotril (100 Drug side effects (acarbose and metformin)
Fructose malabsorption
mg up to 3 times daily) may be useful [30]. Associated diseases: celiac, pancreatic insufficiency, and SIBO
Chronic diarrhea in developed countries is commonly Immunodeficiency
the symptom of a large number of noninfectious intesti- Opportunistic infections
nal and extraintestinal diseases [2, 33] although there are Drug side effects
a few infectious causes that have to be considered, like Lymphoma
Institutionalized persons
Clostridioides difficile [27], or Giardia lamblia, ameba or Clostridioides difficile
other pathogens in people having returned from travel Drug side effects
into the subtropic regions [34]. Chronic diarrhea may be Fecal impaction with overflow diarrhea
accompanied by malabsorption and by a variety of symp- Ischemic colitis
toms of the underlying cause of diarrhea. The prognosis Tube feeding
usually depends on the underlying disease, and the treat- SIBO, small intestinal bacterial overgrowth.
ment is directed against the underlying disease, if possi-
ble, or shall be symptomatic [2].
How Should the Patient with Chronic Diarrhea Be physicians toward further diagnostics in patients with ab-
Approached? dominal symptoms [35]. These alarm symptoms are
With a large differential diagnosis of potential causes blood in stool, awakening by symptoms, unintended
of diarrhea, the clinical challenge is not to overdo or re- weight loss, family history of gastrointestinal cancer, or
peat diagnostic tests in the face of the frequently occur- symptom onset after the age of 50 years. However, posi-
ring functional causes of diarrhea and at the same time, tive predictive values for each of these alarm symptoms
not to overlook diseases which demand specific treat- for any of the above named relevant diseases are below
ments or may be dangerous and therefore must not be 10% so that patients should not be alarmed too much if
overlooked to prevent complications or delayed damage. one of these red flags are noticed [35]. In contrast, alarm
The clinically important questions related to this are as symptoms may occur in functional diarrhea or IBS with
follows: a frequency of up to 18% for blood in stool, up to 51% for
1. Is symptomatic therapy appropriate to start with? awakening because of symptoms, up to 33% for uninten-
2. For how long may symptomatic treatment be given tional weight loss, and 40% for symptom onset beyond
and how to follow up on it? the age of 50 years. Furthermore, up to 20% of patients
3. How may the tests which are available in primary care with functional diarrhea or IBS may have a positive fam-
practice help? ily history of gastrointestinal cancer [35]. Therefore,
4. For which patient is a referral for further information alarm symptoms do not exclude a functional cause of di-
required? arrhea. History shall also focus on medications and toxins
associated with diarrhea (Table 1) and in identifying like-
How Can History and Physical Examination Help? ly causes of diarrhea in well-defined patient groups (Ta-
Alarm symptoms, also called red flag symptoms, may ble 2).
be helpful in identifying patients with abdominal symp- Physical exam of the abdomen may reveal localized
toms who have a risk of relevant diseases like GI cancer, tenderness or masses which shall direct attention away
IBD, or malabsorptive diseases and therefore may guide from functional causes of diarrhea and serve as an argu-
Chronic Diarrhea Dig Dis 3
DOI: 10.1159/000515219ment for further diagnostic evaluations. Measurement of The presence of calprotectin in feces is directly pro-
blood pressure and heart rate and inspection of mucous portional to neutrophil migration to the gastrointestinal
membranes may help to detect anemia or dehydration. tract. It is very sensitive for inflammation but not specific
regarding the cause of inflammation [40]. Only markedly
How Can Routine Laboratory Tests Help? elevated calprotectin levels are indicative of IBD, whereas
Laboratory tests which are commonly available to pri- less pronounced elevations may also occur in diarrhea-
mary care may be helpful in detecting the presence of ac- predominant IBS. A recent study (upper limit of normal
companying symptoms or complications of diarrhea. De- for fecal calprotectin was 50 μg/g feces) has demonstrated
tection of accompanying symptoms may guide the direc- a mean calprotectin concentration in IBS of approximate-
tion of the further diagnostic evaluations. These are the ly 100 μg/g feces with individual values up to 800, where-
detection of bleeding through decreased red cell counts as mean concentrations in IBS where approximately
and fecal occult blood, detection of inflammatory pro- 1,000 μg/g [41]. Elevated calprotectin levels shall be fur-
cesses by elevated white blood cell counts, elevated plate- ther evaluated by colonoscopy.
let counts in Crohn’s disease, sedimentation rate or CRP, Fecal elastase concentrations below 100 μg/g feces
or signs of malabsorption (of iron or vitamin B12 or vita- have a sensitivity of 54% for mild and 95% for severe exo-
min K) through altered mean corpuscular volume or he- crine pancreatic insufficiency and a specificity between
moglobin content of the erythrocytes and increased pro- 79 and 96% [42]. Low levels shall be further evaluated by
thrombin time. Fluid and electrolyte losses may be as- CT scan of the pancreas in order to demonstrate signs of
sessed with serum creatinine, serum Na and K chronic pancreatitis and to exclude pancreatic duct ob-
concentrations, and urinary volume and concentration. struction due to tumor of the papilla or the pancreatic
In the case of abdominal pain, serum amylase or lipase, head.
urinary analysis, and cholestasis parameters may be of ad-
ditional help. How to Proceed in Undiagnosed or Intractable
Diarrhea?
Which Additional Laboratory Tests May Be Helpful? Some patients with chronic diarrhea may return to pri-
Some specialized laboratory tests may be used by pri- mary care after specialized diagnostic evaluations with
mary care physicians in their further diagnostic evalua- undiagnosed or intractable diarrhea. These are patients
tions. Samples for these tests can be collected in the phy- not having responded to seemingly appropriate treat-
sician’s office to be sent to specialized laboratories for ment with diet, probiotics, adstringents, opioids, and oth-
analysis. These tests are the analysis of serum samples for ers. In these patients, commonly most appropriate tests
tissue transglutaminase for the diagnosis of celiac disease have been performed, including laboratory tests of serum
in malabsorption and of chromogranin A (CgA) for the and stool, endoscopic evaluations of the upper and lower
diagnosis of rare neuroendocrine tumors in the case of GI tract, ultrasound, and radiographic examinations.
watery diarrhea. Fecal samples can be sent for analysis of Clinical challenges in undiagnosed or intractable diar-
calprotectin if IBD is suspected, elastase if exocrine pan- rhea may include that:
creatic insufficiency is suspected, and Clostridioides dif- 1. no pathology or disease has been identified,
ficile if there is a history of antibiotic use. 2. pathology has been identified but its clinical role re-
Sensitivity of immunoglobulin A-tissue transgluta- mains uncertain,
minase for the detection of celiac disease ranges between 3. results of clinical testing may have led into a wrong
78 and 100%, with a specificity between 90 and 100% [36]. direction,
Positive serology should be supported by histology ob- 4. treatment has been ineffective or inappropriate, and
tained from the duodenum. 5. expectations on establishing a diagnosis or curing the
Sensitivity of CgA in patients with secreting neuroen- disease have been too enthusiastic.
docrine tumors of all locations is around 70% and is 80– In these patients, the following questions must be
100% for carcinoid tumors [37]. Falsely elevated CgA lev- raised and appropriately dealt with:
els may occur in renal insufficiency, atrophic gastritis, 1. Have the appropriate tests been performed and inter-
heart insufficiency, and proton-pump inhibitor treat- preted correctly?
ment. Positive results shall be further evaluated by neuro- 2. Which test results must be reevaluated?
endocrine tumor search tests, like octreotide scintigraphy 3. Are additional tests worth doing?
or positron emission tomography-CT scanning [38, 39]. 4. Are tests leading down the wrong alley?
4 Dig Dis Hammer
DOI: 10.1159/000515219Table 3. Treatment options in chronic diarrhea (modified after [42])
Drug class Mode of action and indication Agent Dose
Opiates (mu opiate Inhibition of motility, proabsorptive, and Loperamide 2–4 mg 4 times daily
receptor selective) symptomatic treatment for most cases of chronic
diarrhea Morphine 2–20 mg 4 times daily
Diphenoxylate 2.5–5 mg 4 times daily
Codeine 15–60 mg 4 times daily
Tincture of opium 2–20 drops 4 times daily
Alpha-2 adrenergic Proabsorptive, diabetic diarrhea, VIPoma, and Clonidine 0.1–0.3 mg 3 times daily
agonist autonomic neuropathy
Somatostatin analog Proabsorptive, hormonal antagonist, Octreotide 50–250 μg 3 times daily
neuroendocrine tumors, fistulas, and small bowel (subcutaneously)
resections
NSAID Inhibition of prostaglandin synthesis, inoperable, Indomethacin 25 mg 3 times daily
villous adenoma, radiation proctitis, and medullary
carcinoma
Antibiotics Small bowel bacterial overgrowth (intermittent Metronidazole, rifaximin,
treatment), C. difficile quinolones, and vancomycin
Bile acid-binding Binding of bile acids and bacterial toxins, ileal Cholestyramine 4 g 1 to 4 times daily
resin disease, and postcholecystectomy diarrhea
Colesevelam 625 mg up to 6 times
daily
Colestipol 4 g 1 to 4 times daily
Fiber supplements Water binding Calcium polycarbophil 5–10 g daily
Psyllium 10–20 g daily
NSAID, nonsteroidal anti-inflammatory drug.
5. Shall treatments beyond the routine be considered? What Are the Pharmacological Treatment Options in
6. Does the patient or do I have wrong expectations of Patients with Chronic Diarrhea?
healing? Table 3 lists pharmacological treatment options for
7. What is the real problem and how can the patient’s chronic diarrhea, many of them for symptomatic treat-
quality of life be improved by measures other than ment. The symptomatic treatment options shall not delay
medical treatment? attention from various additional causal treatment options,
In a highly specialized center, the most common diag- like diet in celiac disease or lactose intolerance, or treat-
nostic categories of 193 patients with undiagnosed or dif- ments directed against the underlying cause of diarrhea.
ficult-to-manage chronic diarrhea where “low fecal stool
weight” syndromes (IBS, hyperdefecation, and fecal in-
continence) in 21%, idiopathic secretory diarrhea in 20%, Conclusion
postsurgical (vagotomy, gastrectomy, cholecystectomy,
and intestinal resection) in 20%, microscopic colitis (lym- Acute diarrhea is usually of infectious origin with the
phocytic and collagenous) in 15%, and “small bowel dys- main treatment goal of preventing water and electrolyte
function” (small intestinal bacterial overgrowth, carbohy- disturbances. In acute diarrhea, signs of potentially inva-
drate malabsorption, diabetes mellitus, motility disorders, sive bacterial pathogens (fever and bloody stools) shall be
strongyloides, sprue, and spruelike illnesses) in 11% [2]. observed because these may require antibiotics. In chron-
Chronic Diarrhea Dig Dis 5
DOI: 10.1159/000515219ic diarrhea, which is usually not of infectious origin, it is Conflict of Interest Statement
important to identify the underlying cause. Loperamide
The authors have no conflicts of interest to disclose.
may be used to decrease stool frequency and improve
quality of life. In undiagnosed or intractable diarrhea, the
question shall be raised whether the appropriate tests Funding Sources
have been performed and interpreted correctly. Some test
results may need to be reevaluated. There was no funding received for research, preparation, and
writing of this manuscript.
Statement of Ethics
Author Contributions
Not applicable.
H.H. performed the literature search, collated the information,
and wrote the manuscript.
References
1 Hammer HF. Chronic diarrheal disorders. Neurogastroenterol Motil. 2020; 32(12): surreptitious ingestion of laxatives and di-
Preface. Gastroenterol Clin North Am. 2012; e13934. uretics. Am J Dig Dis. 1977;22(4):280–92.
41(3):ix–x. 13 Hammer J, Sonyi M, Engeber KM, Riedl G, 21 Kacere RD, Srivatsa SS, Tremaine WJ, Ebnet
2 Fine KD, Schiller LR. AGA technical review Luong S, Hammer HF. Carbohydrate-in- LE, Batts KP. Chronic diarrhea due to surrep-
on the evaluation and management of chron- duced gastrointestinal symptoms: develop- titious use of bisacodyl: case reports and
ic diarrhea. Gastroenterology. 1999; 116(6): ment and validation of a test-specific symp- methods for detection. Mayo Clin Proc. 1993;
1464–86. tom questionnaire for an adult population, 68(4):355–7.
3 Talley NJ, Zinsmeister AR, Van Dyke C, the adult carbohydrate perception question- 22 Stepan VM, Hammer HF, Krejs GJ. Hyperka-
Melton LJ. Epidemiology of colonic symp- naire. Eur J Gastroenterol Hepatol. 2020; 32: laemia and diarrhoea in a patient with surrep-
toms and the irritable bowel syndrome. Gas- 171–7. titious ingestion of potassium sparing diuret-
troenterology. 1991;101(4):927–34. 14 Hammer HF, Santa Ana CA, Schiller LR, ics. Eur J Gastroenterol Hepatol. 1997; 9(10):
4 Wenzl HH. Diarrhea in chronic inflammato- Fordtran JS. Studies of osmotic diarrhea in- 1001–4.
ry bowel diseases. Gastroenterol Clin North duced in normal subjects by ingestion of poly- 23 Arasaradnam RP, Brown S, Forbes A, Fox
Am. 2012;41(3):651–75. ethylene glycol and lactulose. J Clin Invest. MR, Hungin P, Kelman L, et al. Guidelines for
5 Fabian E, Kump P, Krejs GJ. Diarrhea caused 1989;84(4):1056–62. the investigation of chronic diarrhoea in
by circulating agents. Gastroenterol Clin 15 Pohl D, Fried M, Lawrance D, Beck E, Ham- adults: British society of gastroenterology, 3rd
North Am. 2012;41(3):603–10. mer HF. Multicentre, non-interventional edition. Gut. 2018;67(8):1380–99.
6 Hammer HF, Fine KD, Santa Ana CA, Porter study of the efficacy and tolerability of lina- 24 Steffer KJ, Santa Ana CA, Cole JA, Fordtran
JL, Schiller LR, Fordtran JS. Carbohydrate clotide in the treatment of irritable bowel syn- JS. The practical value of comprehensive stool
malabsorption. Its measurement and its con- drome with constipation in primary, second- analysis in detecting the cause of idiopathic
tribution to diarrhea. J Clin Invest. 1990; ary and tertiary centres: the Alpine study. chronic diarrhea. Gastroenterol Clin North
86(6):1936–44. BMJ Open. 2019;9(12):e025627. Am. 2012;41(3):539–60.
7 Hammer HF. Pancreatic exocrine insufficien- 16 Hammer HF. Medical complications of bar- 25 Langner C. Colorectal normal histology and
cy: diagnostic evaluation and replacement iatric surgery: focus on malabsorption and histopathologic findings in patients with
therapy with pancreatic enzymes. Dig Dis. dumping syndrome. Dig Dis. 2012; 30(2): chronic diarrhea. Gastroenterol Clin North
2010;28(2):339–43. 182–6. Am. 2012;41(3):561–80.
8 Hammer HF, Hammer J. Diarrhea caused by 17 Valdovinos MA, Camilleri M, Zimmerman 26 Evans KE, Sanders DS. Celiac disease. Gastro-
carbohydrate malabsorption. Gastroenterol BR. Chronic diarrhea in diabetes mellitus: enterol Clin North Am. 2012;41(3):639–50.
Clin North Am. 2012;41(3):611–27. mechanisms and an approach to diagnosis 27 Hogenauer C, Hammer HF, Krejs GJ, Reis-
9 Scaldaferri F, Pizzoferrato M, Pecere S, Forte and treatment. Mayo Clin Proc. 1993; 68(7): inger EC. Mechanisms and management of
F, Gasbarrini A. Bacterial flora as a cause or 691–702. antibiotic-associated diarrhea. Clin Infect
treatment of chronic diarrhea. Gastroenterol 18 Zhao Q, Hong D, Zheng D, Xiao Y, Wu B. Dis. 1998;27(4):702–10.
Clin North Am. 2012;41(3):581–602. Risk of diarrhea in patients with type 2 diabe- 28 Sonyi M, Keller J, Fox M, Hammer HF. Devel-
10 Krones E, Högenauer C. Diarrhea in the im- tes mellitus treated with sitagliptin: a meta- opment of a multinational clinical practice
munocompromised patient. Gastroenterol analysis of 30 randomized clinical trials. Drug guideline: a practical structured procedure.
Clin North Am. 2012;41(3):677–701. Des Devel Ther. 2014;8:2283–94. Dig Dis. 2020. doi: 10.1159/000511007.
11 Tack J. Functional diarrhea. Gastroenterol 19 Bricker LA, Such F, Loehrke ME, Kavanaugh 29 Wenzl HH, Fine KD, Schiller LR, Fordtran JS.
Clin North Am. 2012;41(3):629–37. K. Intractable diarrhea in hyperthyroidism: Determinants of decreased fecal consistency
12 Hammer J, Memaran N, Huber WD, Ham- management with beta-adrenergic blockade. in patients with diarrhea. Gastroenterology.
mer K. Development and validation of the Endocr Pract. 2001;7(1):28–31. 1995;108(6):1729–38.
paediatric carbohydrate perception question- 20 Krejs GJ, Walsh JH, Morawski SG, Fordtran 30 Riddle MS, DuPont HL, Connor BA. ACG clin-
naire (pCPQ), an instrument for the assess- JS. Intractable diarrhea. Intestinal perfusion ical guideline: diagnosis, treatment, and pre-
ment of carbohydrate-induced gastrointesti- studies and plasma VIP concentrations in pa- vention of acute diarrheal infections in adults.
nal symptoms in the paediatric population. tients with pancreatic cholera syndrome and Am J Gastroenterol. 2016;111(5):602–22.
6 Dig Dis Hammer
DOI: 10.1159/00051521931 Ropper AH. Campylobacter diarrhea and 36 Al-Toma A, Volta U, Auricchio R, Castillejo 40 Tibble J, Teahon K, Thjodleifsson B, Roseth
Guillain-Barré syndrome. Arch Neurol. 1988; G, Sanders DS, Cellier C, et al. European so- A, Sigthorsson G, Bridger S, et al. A simple
45(6):655–6. ciety for the study of coeliac disease (ESsCD) method for assessing intestinal inflammation
32 Pather P, Hines S. Best practice nursing care guideline for coeliac disease and other gluten- in Crohn's disease. Gut. 2000;47(4):506–13.
for ICU patients with incontinence-associat- related disorders. United European Gastro- 41 Melchior C, Aziz M, Aubry T, Gourcerol G,
ed dermatitis and skin complications result- enterol J. 2019;7(5):583–613. Quillard M, Zalar A, et al. Does calprotectin
ing from faecal incontinence and diarrhoea. 37 Ferrari L, Seregni E, Bajetta E, Martinetti A, level identify a subgroup among patients suf-
Int J Evid Based Healthc. 2016;14(1):15–23. Bombardieri E. The biological characteristics fering from irritable bowel syndrome? Results
33 Fine KD, Seidel RH, Do K. The prevalence, of chromogranin A and its role as a circulating of a prospective study. United European Gas-
anatomic distribution, and diagnosis of co- marker in neuroendocrine tumours. Antican- troenterol J. 2017;5(2):261–9.
lonic causes of chronic diarrhea. Gastrointest cer Res. 1999;19(4C):3415–27. 42 Chronic Pancreatitis German Society of Di-
Endosc. 2000;51(3):318–26. 38 Lipp RW, Hammer HF, Passath A, Dobnig H, gestive and Metabolic Diseases, Hoffmeister
34 Libman M, Catmat . Summary of the commit- Ramschak-Schwarzer S, Stiegler C, et al. Pri- A, Mayerle J, Beglinger C, Büchler MW, Bu-
tee to advise on tropical medicine and travel mary and follow-up studies of patients with fler P, et al. [S3-Consensus guidelines on def-
(CATMAT) statement on travellers' diarrhea. carcinoid metastases using indium 111 oc- inition, etiology, diagnosis and medical, en-
Can Commun Dis Rep. 2015;41(11):272–84. treotide–rational use of sandostatin. Acta doscopic and surgical management of chron-
35 Whitehead WE, Palsson OS, Feld AD, Levy Med Austriaca. 1993;20(1–2):42–4. ic pancreatitis German Society of Digestive
RL, VON Korff M, Turner MJ, et al. Utility of 39 Bauckneht M, Albano D, Annunziata S, Santo and Metabolic Diseases (DGVS)]. Z Gastro-
red flag symptom exclusions in the diagnosis G, Guglielmo P, Franellizzi V, et al. Soma- enterol. 2012;50(11):1176–224.
of irritable bowel syndrome. Aliment Phar- tostatin receptor PET/CT imaging for the de-
macol Ther. 2006;24(1):137–46. tection and staging of pancreatic NET: a sys-
tematic review and meta-analysis. Diagnos-
tics. 2020;10(8):598.
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