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References 479

Downloaded from https://onlinelibrary.wiley.com/doi/ by Universität Bern, Wiley Online Library on [22/08/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License

https://t.me/medicina_free

31 Juel J, Olesen SS, Olesen AE etal. Study protocol for a

randomised, doubletrial of S-

ketamine for pain treatment in patients with

blinded, placebo- controlled, clinical

chronic pancreatitis (RESET trial). BMJ Open 2015;5(3):e007087.

32 Duggan SN, Smyth ND, O’Sullivan M, Feehan S, Ridgway

PF, Conlon KC. The prevalence of malnutrition and

soluble vitamin deficiencies in chronic pancreatitis.

fatNutr Clin Pract 2014;29(3):348–354.

33 Ni Chonchubhair HM, Bashir Y, Dobson M, Ryan BM,

Duggan SN, Conlon KC. The prevalence of small intestinal bacterial overgrowth in non-

surgical patients with chronic pancreatitis and pancreatic exocrine insufficiency (PEI). Pancreatology 2018;18(4):379–385.

34 Chowdhury RS, Forsmark CE, Davis RH, Toskes PP, Verne

GN. Prevalence of gastroparesis in patients with small duct chronic pancreatitis. Pancreas 2003;26(3):235–238.

35 DiMagno MJ, Forsmark CE. Chronic pancreatitis and

small intestinal bacterial overgrowth. Pancreatology 2018;18(4):360–362.

36 Fasullo M, Omer E, Kaspar M. Sarcopenia in chronic

pancreatitis -

- prevalence, diagnosis, mechanisms and potential therapies. Curr Gastroenterol Rep 2022;24(4):53–63.

37 Dominguez- Munoz JE, Phillips M. Nutritional therapy in

chronic pancreatitis. Gastroenterol Clin North Am 2018;47(1):95–106.

38 Walkowiak J, Witmanowski H, Strzykala K etal. Inhibition of

endogenous pancreatic enzyme secretion by oral pancreatic enzyme treatment. Eur J Clin Invest 2003;33(1):65–69.

39 Winstead NS, Wilcox CM. Clinical trials of pancreatic

enzyme replacement for painful chronic pancreatitis—

review. Pancreatology 2009;9(4):344–350.

40 de la Iglesia- Garcia D, Huang W, Szatmary P etal. Efficacy

of pancreatic enzyme replacement therapy in chronic pancreatitis: systematic review and meta- analysis. Gut 2017;66(8):1354–1355.

41 Burton F, Alkaade S, Collins D etal. Use and perceived

effectiveness of non-

analgesic medical therapies for chronic pancreatitis in the United States. Aliment Pharmacol Ther 2011;33(1):149–159.

42 Forsmark CE, Tang G, Xu H, Tuft M, Hughes SJ, Yadav D.

The use of pancreatic enzyme replacement therapy in

patients with a diagnosis of chronic pancreatitis and pancreatic cancer in the US is infrequent and inconsistent. Aliment Pharmacol Ther 2020;51(10):958–967.

43 Duggan SN, Smyth ND, Murphy A, Macnaughton D,

O’Keefe SJ, Conlon KC. High prevalence of osteoporosis in patients with chronic pancreatitis: a systematic review and

analysis. Clin Gastroenterol Hepatol

meta2014;12(2):219–228.

44 Duggan SN, O’Sullivan M, Hamilton S, Feehan SM,

Ridgway PF, Conlon KC. Patients with chronic pancreatitis are at increased risk for osteoporosis. Pancreas 2012;41(7):1119–1124.

45 Hart PA, Yadav D, Li L etal. High prevalence of osteopathy

in chronic pancreatitis: a cross-

sectional analysis from the PROCEED study. Clin Gastroenterol Hepatol 2022;20(9):2005–2013.

Shalimar, Midha S, Hasan A, Dhingra R, Garg PK.

Long-

term pain relief with optimized medical treatment

including antioxidants and step-

up interventional therapy in patients with chronic pancreatitis. J Gastroenterol Hepatol 2017;32(1):270–277.

47 Ahmed Ali U, Jens S, Busch OR etal. Antioxidants for pain

in chronic pancreatitis. Cochrane Database Syst Rev 2014(8):CD008945.

48 Wang L, Hong PJ, May C etal. Medical cannabis or

cannabinoids for chronic nonpain: a systematic review and meta-

cancer and cancer related

analysis of randomised

clinical trials. BMJ 2021;374:n1034.

49 de Vries M, van Rijckevorsel DCM, Vissers KCP etal.

Tetrahydrocannabinol does not reduce pain in patients with chronic abdominal pain in a phase 2 placebocontrolled study. Clin Gastroenterol Hepatol 2017;15(7):1079–1086.e4.

50 Barlowe TS, Koliani- Pace JL, Smith KD, Gordon SR,

Gardner TB. Effects of medical cannabis on use of opioids and hospital visits by patients with painful chronic pancreatitis. Clin Gastroenterol Hepatol 2019;17(12):2608–2609.e1.

51 Shah I, Bocchino R, Yakah W etal. Evaluating outcomes

and misuse in opioid-

dependent chronic pancreatitis using a state- mandated monitoring system. Dig Dis Sci 2022;67(12):5493–5499.

480

https://t.me/medicina_free

Pancreatic Cancer Risks inChronic Pancreatitis

Patrick Maisonneuve1 and Albert B. Lowenfels

Unit of Clinical Epidemiology, IEO European Institute of Oncology IRCCS, Milan, Italy

Department of Family Medicine, NewYork Medical College, Valhalla, NY, USA

Introduction

In the late nineteenth century, the German pathologist Rudolf Virchow proposed that there was a close link between inflammation and cancer, based on cellular studies made possible by microscopy. Since then it has been observed that inflammatory diseases such as esophagitis, gastritis, and colitis sometimes precede the development of cancer in these organs. Throughout the twentieth century, anecdotal reports of pancreatitis preceding pancreatic cancer have emerged. These isolated reports suggested a possible link between chronic pancreatitis and pancreatic cancer and eventually led to a large retrospective cohort analysis conducted near the end of the twentieth century. In this chapter, we review and summarize the evidence linking chronic pancreatitis and pancreatic cancer.

Descriptive Findings

Acute pancreatitis, chronic pancreatitis, and pancreatic cancer are the three most common pancreatic diseases. How does their incidence compare? Acute pancreatitis is one of the commonest gastrointestinal disorders and has an estimated incidence of about 13–45/100,000 per year [1]. The incidences of chronic pancreatitis and pancreatic cancer are similar to each other, with agestandardized incidence rates of around 10/100,000 peryear.

Figure61.1 illustrates the relationship between these three diseases and the potential pathways for progression from acute to chronic pancreatitis and, in some patients, to pancreatic cancer. In patients with gallstonerelated pancreatitis, cholecystectomy performed on a

timely basis eliminates the major source for gallstones and precludes additional attacks. However, acute pancreatitis also develops from many other causes, and if the cause is heavy drinking, smoking, autoimmunity, or a

Acute pancreatitis

(non-gallstone)

(25)

Acute pancreatitis

(gallstone)

(15)

Figure61.1 Incidence rates for pancreatic diseases in the United

States. Numbers inside circles indicate incidence rates per 100,000 population. The arrow indicates the progression from benign to malignant disease. Note the small overlap between the circles representing chronic pancreatitis and pancreatic cancer. Source: Yadav and Lowenfels 2013[1]. With permission of Elsevier.

Recurrent

acute pancreatitis

(10)

Chronic

pancreatitis

(8)

Pancreatic

cancer

(13)

The Pancreas: An Integrated Textbook of Basic Science, Medicine, and Surgery, Fourth Edition. Edited by Hans G. Beger, Markus W. Büchler, RalphH. Hruban, Julia Mayerle, John P. Neoptolemos, Tooru Shimosegawa, Andrew L. Warshaw, David C. Whitcomb, and Yupei Zhao. © 2023 John Wiley & Sons Ltd. Published 2023 by John Wiley & Sons Ltd. Companion website: www.wiley.com/go/beger/thepancreas4e

Measuring theStrength ofthe Pancreatitis–Pancreatic Cancer Association 481

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genetic disorder, recurrent attacks of acute pancreatitis (recurrent pancreatitis) may occur and disease progression may then lead to chronic pancreatitis. Of patients who develop chronic pancreatitis, a small proportion will develop pancreatic cancer. The average age at diagnosis of chronic pancreatitis in patients with alcoholrelated disease is about 45–55 years, approximately a decade earlier than the average age of onset of pancreatic cancer. This time sequence indicates that the direction of causality is compatible with a progression from benign to malignant disease.

Other than age, what are some of the other similarities and differences between chronic pancreatitis and pancreatic cancer? For both diseases, smoking and obesity are recognized risk factors, whereas heavy drinking, which is strongly linked to chronic pancreatitis, is associated only with a modest increased risk for pancreatic cancer[2]. Both diseases are also more frequent in black than in white populations, and diabetes frequently accompanies both diseases.

Measuring theStrength ofthe Pancreatitis–Pancreatic Cancer Association

After initial reports from single centers by Ammann and coworkers in 1984 [3] and Rocca and coworkers in 1987[4] who described the gradual increase of pancreatic calcifications and pancreatic dysfunction with increasing duration of the disease and suggested an increased risk of pancreatic, as well as extrapancreatic cancer, in patients with chronic pancreatitis, Lowenfels and coworkers conducted the first multicenter cohort study. Among 2015 patients with well- documented chronic pancreatitis from six countries followed up for a minimum of 5 years after the diagnosis of chronic pancreatitis, the risk of pancreatic cancer was 14.4 (95% Cl:

8.5–22.8) times higher than that in the background population. The risk was similar in all study countries and in patients with either alcoholic or nonalcohol pancreatitis [5]. Over a followcumulative incidence of pancreatic cancer was 4%. This implies that chronic pancreatitis, although a strong risk factor, explains only a small proportion of the total burden of pancreatic cancer. Also in contrast to the 29 patients who died from pancreatic cancer, 137 patients in the group died from other types of cancers. Because of lifestyle factors such as smoking and heavy alcohol drinking, most cancer deaths in patients with chronic pancreatitis will be from nonpancreatic cancer.

Since publication of this report, several additional studies have looked at the relationship between chronic pancreatitis and pancreatic cancer[6–29]. Raimondi and coworkers published an initial meta- analysis in 2010

up period of up to 20 years, the

based on 18 additional studies[30] with a pooled relative risk (RR) of 13.3 (95% CI: 6.1–29) for well- defined chronic pancreatitis. In 2014, Tong and coworkers published a systematic review of epidemiologic studies linking pancreatitis and pancreatic cancer[31]. This report contained 14 case- control studies and 3 cohort studies and found a pooled odds ratio of 7.1 (95% CI: 6.4–7.8). As in the previous meta- analysis, the results were stronger in cohort studies than in case- control studies. In a large pooled analysis of 10 case- control studies, Duell and coworkers reported a nearly threefold increased risk of pancreatic cancer in patients where there was a minimum of 2 years separating the diagnosis of pancreatitis from pancreatic cancer[10] More recent reviews and meta- analyses were performed by Kirkegard and coworkers [32] and Ghandi and coworkers [33]. Based on these reports and more recent studies, we prepared an updated meta- analysis of 26 studies, stratified by broad type of chronic pancreatitis (Fig. 61.2). The pooled risk estimates are as follows: RR = 12.0 (95% CI:

7.7–18.7) for 19 studies in patients with definite chronic pancreatitis[3,5–22], RR = 69 (95% CI: 56–85) for three studies in patients with hereditary pancreatitis[23–25], RR = 109 (95% CI: 56–211) for two studies in patients with tropical pancreatitis or similar forms of idiopathic pancreatitis from India[26–27]. For two studies comparing the risk of pancreatic cancer in SPINK1- related pancreatitis compared to idiopathic pancreatitis, the pooled RR = 20.3 (95% CI: 9.1–45.3)[28–29].

Among recent major representative studies, a nationwide report from Denmark provides further evidence for a strong link between pancreatitis and pancreatic cancer[16]. In this follow- up study of nearly 12,000 patients with chronic pancreatitis and nearly 120,000 matched controls the authors found a 6.9- fold increased risk of death from pancreatic cancer in pancreatitis patients compared with the control population. Again, the risk of pancreatic cancer was similar in patients with either alcoholic or nonalcoholic pancreatitis. Based on an electronic medical record system, Hao and coworkers[18] examined data from 1656 patients with chronic pancreatitis from Shanghai Hospital, China and confirmed a markedly increased risk of pancreatic cancer (SIR 95% CI: 12.5–30.9) especially in heavy smokers. More recently, Munigala and coworkers[21] performed a retrospective study of US Veterans Administration identifying as many as 21,785 patients with chronic pancreatitis, of whom 226 developed pancreatic cancer 2 years after chronic pancreatitis (HR = 4.28; 95% CI: 3.74–4.89). The risk was consistent and sustained beyond 5 years and 10 years of follow- up. Finally, Vujasinovic and coworkers assessed the cumulative incidence of pancreatic cancer in 581 patients with definite chronic pancreatitis from Karolinska University Hospital, Stockholm, Sweden[34]. Excluding patients diagnosed with pancreatic cancer

= 20.2;

Pancreatic Cancer Risks inChronic Pancreatitis

Chronic Pancreatitis

Rocca Lowenfels Bansal Karlson Talamini Malka Duell Goldacre Pedrazzoli Wang Wu Ueda Bang Hirano Hao Zheng Jeon Munigala Han

Random effects model

Heterogeneity:

Hereditary Pancreatitis

Lowenfels Howe Rebours

Random effects model

Heterogeneity:

Tropical Pancreatitis

Chari Midha

Random effects model

Heterogeneity:

Random effects model

Heterogeneity:

Spink1/PRSS1/CFTR VS idiopathic CP

Hamoir Muller

20.3 (9.1–45.3)

1 Relative risk (95% CI) 200

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482

1987 1993 1995 1997 1999 2002 2006 2008 2008 2011 2012 2013 2014 2014 2017 2019 2020 2021 2022

I2 = 95%, P = 0.01

1997 5 3.0 ( 23.0–105.0)

2004 67.0 ( 50.0– 82.0) 2008 87.0 ( 42.0–114.0)

Figure61.2 Meta- analysis showing study- specific and summary risk estimates with 95% confidence intervals for the association between

different types of pancreatitis and pancreatic cancer.

within 2 years from the diagnosis of chronic pancreatitis,

I2 = 0%, p = 0.51

1994 100.0 ( 37.0–218.0)

2016 121.0 ( 39.7–295.9)

I2 = 0%, p = 0.78

2013 26.5 ( 8.6– 61.9)

2019 12.0 ( 3.0– 47.8)

I2 = 0%, p = 0.36

the incidence rate of pancreatic cancer was 0.2% annually, a rate similar to that observed in the initial multicenter study by Lowenfels and coworkers [5] and the latest Veterans Administration study[21] (Fig.61.3).

Discussion

Reviewing the evidence accumulated over several decades reveals a strong link between chronic pancreatitis and pancreatic cancer. Clinicians must still be aware of reverse causality because one symptom of pancreatic cancer can be sudden onset of pancreatitis in the absence of known risk factors. However, the evidence from several long- term

74.1 ( 22.2–267.0)

16.5 ( 11.1– 23.7)

2.2 ( 1.4– 3.5)

7.6 ( 6.0– 9.7)

18.5 ( 10.0– 30.0)

26.7 ( 7.3– 68.3)

6.0 ( 1.7– 21.0)

27.0 ( 21.4– 33.8)

2.9 ( 0.4– 10.6)

27.2 ( 7.4– 69.6)

28.3 ( 9.1– 87.6)

11.8 ( 7.1– 18.4)

6.9 ( 5.6– 8.6)

3.7 ( 0.4– 12.5)

20.2 ( 12.5– 30.9)

68.1 ( 35.2–119.0)

12.0 ( 8.8– 16.0)

4.3 ( 3.7– 4.9)

3.9 ( 2.7– 5.5)

12.0 (7.7–18.7)

69.0 (55.8–85.3)

109 (55.9–211)

follow- up studies with exclusion of early- onset pancreatic cancer confirms the pancreatitis–pancreatic cancer link. The findings of this relationship in the pancreas agrees with information from other organs, and confirms Virchow’s nineteenth- century hypothesis. As yet we do not have a full understanding of the mechanisms underlying the transformation from a nonmalignant disease to cancer.

All the reports indicate that the cumulative risk of pancreatic cancer in patients with long- standing confirmed chronic pancreatitis is low— probably less than 5%. This implies that until we develop noninvasive screening procedures with greater sensitivity and specificity than are currently available, screening patients with chronic pancreatitis is not likely to be rewarding.

Discussion 483

Lo V Munig

12,074

–

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Vujasinovic et al., 2020 Karolinska University Hospital

[6 Pacas, 5.9 years follow-up]

Cumulative incidence of pancreatic cancer (%)

Lowenfels et al., 1993 Multicenter cohort [29 Pacas, 7.4 years follow-up]

Munigala et al., 2021 US veterans [226 Pacas, 5.5 years follow-up]

5101 Years after Diagnosis of Pancreatitis

atients at risk

wenfels

ujasinovic

ala

Figure61.3 Cumulative incidence of pancreatic cancer in patients with chronic pancreatitis from three selected cohort studies[5,21,34].

1,552

581

21,765

1,160

303

Hereditary pancreatitis due to inherited PRSS1 mutations is a rare inherited autosomal dominant genetic disorder that causes early- onset pancreatitis characterized by recurrent attacks eventually leading to chronic pancreatitis. As with other risk factors, such as smoking, long duration of exposure increases the risk of cancer. Because patients with this type of pancreatitis have about a 70% lifetime risk of developing pancreatic cancer, already in 2001, minimally invasive imaging screening with endoscopic ultrasound (EUS), multiphasic helical computed tomography (CT) or magnetic resonance imaging/magnetic resonance cholangiopancreatography (MRI/MRCP) have been proposed for patients with the hereditary pancreatitis phenotype, beginning at the age of 40 years[35]. Recent international consensus guidelines recommend surveillance in affected individuals with hereditary pancreatitis due to inherited PRSS1 mutations, but estimate that the risk of pancreatic cancer in patients with chronic pancreatitis associated with SPINK1 or other germline mutations including those ofCFTR, CTRC, CPA1, and CEL is not high enough to justify surveillance[36].

599

103

2,949

244

–

What are fruitful areas for additional research that might benefit patients with underlying pancreatitis? Pancreatic cysts are now being detected with increasing frequency and we need to be able to identify or confirm subgroups of these patients who have an increased risk of pancreatic cancer[37].

Pancreatic cancer can mimic nonmalignant disease such as autoimmune pancreatitis, leading in some patients to unnecessary pancreatic surgery[38,39]. We need to develop biological tests and/or biomarkers that can reliably distinguish between chronic pancreatitis and pancreatic cancer. Finally, collecting and storing biologic samples from patients with well- documented chronic pancreatitis will help us improve our understanding of the gradual transition of pancreatitis to pancreatic cancer.

The irreversible pathologic changes characteristic of chronic pancreatitis make this disease difficult to treat and the progressive cellular disruption of glandular and ductal tissues leads eventually, in some patients, to pancreatic cancer. Efforts to reduce lifestyle factors such as smoking and alcohol drinking in patients with recurrent

Pancreatic Cancer Risks inChronic Pancreatitis

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484

bouts of acute pancreatitis offer an opportunity to reduce the burden of this disabling disease and prevent the occurrence of pancreatic cancer[2]. Advising all patients with CP to lead a healthy lifestyle aimed at avoiding risk

References

1 Yadav D, Lowenfels AB. The epidemiology of pancreatitis

and pancreatic cancer. Gastroenterology 2013;144(6): 1252–1261.

2 Alsamarrai A, Das SL, Windsor JA, Petrov MS. Factors that

affect risk for pancreatic disease in the general population: a systematic review and metastudies. Clin Gastroenterol Hepatol 2014;12:1635–1644.

3 Ammann RW, Akovbiantz A, Largiader F, Schueler G.

Course and outcome of chronic pancreatitis. Longitudinal study of a mixed medicalGastroenterology 1984;86:820–828.

4 Rocca G, Gaia E, Iuliano R etal. Increased incidence of

cancer in chronic pancreatitis. J Clin Gastroenterol 1987;9:175–179.

5 Lowenfels AB, Maisonneuve P, Cavallini G etal. Pancreatitis

and the risk of pancreatic cancer. International Pancreatitis Study Group. N Engl J Med 1993;328:1433–1437.

6 Bansal P, Sonnenberg A. Pancreatitis is a risk factor for

pancreatic cancer. Gastroenterology 1995;109:247–251.

7 Karlson BM, Ekbom A, Josefsson S, McLaughlin JK,

Fraumeni JF, Jr., Nyrén O. The risk of pancreatic cancer following pancreatitis: an association due to confounding? Gastroenterology 1997;113:587–592.

8 Talamini G, Falconi M, Bassi C etal. Incidence of cancer in

the course of chronic pancreatitis. Am J Gastroenterol 1999;94:1253–1260.

9 Malka D, Hammel P, Maire F etal. Risk of pancreatic

adenocarcinoma in chronic pancreatitis. Gut 2002;51:849–852.

10 Duell EJ, Lucenteforte E, Olson SH etal. Pancreatitis and

pancreatic cancer risk: a pooled analysis in the International Pancreatic Cancer Case- Control Consortium (PanC4). Ann Oncol 2012;23:2964–2970.

11 Goldacre MJ, Wotton CJ, Yeates D, Seagroatt V, Collier J.

Liver cirrhosis, other liver diseases, pancreatitis and subsequent cancer: record linkage study. Eur J Gastroenterol Hepatol 2008;20:384–392.

12 Pedrazzoli S, Pasquali C, Guzzinati S, Berselli M, Sperti C.

Survival rates and cause of death in 174 patients with chronic pancreatitis. J Gastrointest Surg 2008;12:1930–1937.

13 Wang W, Liao Z, Li G etal. Incidence of pancreatic cancer

in Chinese patients with chronic pancreatitis. Pancreatology 2011;11:16–23.

14 Wu Q, Chen G, Wu WM etal. Metabolic syndrome

components and risk factors for pancreatic adenocarcinoma: a case- control study in China. Digestion 2012;86:294–301.

analysis of prospective cohort

surgical series of 245 patients.

factors for progression of CP and pancreatic cancer was specifically emphasized in the recent international consensus guidelines on surveillance for pancreatic cancer in chronic pancreatitis[36].

15 Ueda J, Tanaka M, Ohtsuka T, Tokunaga S, Shimosegawa

T; Research Committee of Intractable Diseases of the Pancreas. Surgery for chronic pancreatitis decreases the risk for pancreatic cancer: a multicenter retrospective analysis. Surgery 2013;153:357–364.

16 Bang UC, Benfield T, Hyldstrup L, Bendtsen F, Beck

Jensen JE. Mortality, cancer, and comorbidities associated with chronic pancreatitis: a Danish nationwide matchedcohort study. Gastroenterology 2014;146:989–994.

17 Hirano K, Tada M, Sasahira N etal. Incidence of

malignancies in patients with IgG4-

related disease. Intern

Med 2014;53:171–176.

18 Hao L, Zeng XP, Xin L etal. Incidence of and risk factors

for pancreatic cancer in chronic pancreatitis: a cohort of 1656 patients. Dig Liver Dis 2017;49:12491256.

19 Zheng Z, Chen Y, Tan C, Ke N, Du B, Liu X. Risk of

pancreatic cancer in patients undergoing surgery for chronic pancreatitis. BMC Surg 2019;19:83.

20 Jeon CY, Chen Q, Yu W etal. Identification of individuals

at increased risk for pancreatic cancer in a communitybased cohort of patients with suspected chronic pancreatitis. Clin Transl Gastroenterol 2020;11:e00147.

21 Munigala S, Subramaniam DS, Subramaniam DP,

Burroughs TE, Conwell DL, Sheth SG. Incidence and risk of pancreatic cancer in atients with a new diagnosis of chronic pancreatitis. Dig Dis Sci 2022;67:708–715.

22 Han M, Tran TPT, Oh JK. Chronic pancreatitis and cancer

risk in a matched cohort study using national claims data in South Korea. Sci Rep 2022;12:5545.

23 Lowenfels AB, Maisonneuve P, DiMagno EP etal.

Hereditary pancreatitis and the risk of pancreatic cancer. International Hereditary Pancreatitis Study Group. J Natl Cancer Inst 1997;89:442–446.

24 Howes N, Lerch MM, Greenhalf W etal.; European

Registry of Hereditary Pancreatitis and Pancreatic Cancer (EUROPAC). Clinical and genetic characteristics of hereditary pancreatitis in Europe. Clin Gastroenterol Hepatol 2004;2:252–261.

25 Rebours V, Boutron- Ruault MC, Schnee M etal. Risk of

pancreatic adenocarcinoma in patients with hereditary pancreatitis: a national exhaustive series. Am J Gastroenterol 2008;103:111–119.

26 Chari ST, Mohan V, Pitchumoni CS, Viswanathan M,

Madanagopalan N, Lowenfels AB. Risk of pancreatic carcinoma in tropical calcifying pancreatitis: an epidemiologic study. Pancreas 1994;9:62–66.

27 Midha S, Sreenivas V, Kabra M, Chattopadhyay TK, Joshi

YK, Garg PK. Genetically determined chronic pancreatitis

References 485

https://t.me/medicina_free

but not alcoholic pancreatitis is a strong risk factor for pancreatic cancer. Pancreas 2016;45:1478–1484.

28 Hamoir C, Pepermans X, Piessevaux H etal. Clinical and

morphological characteristics of sporadic genetically determined pancreatitis as compared to idiopathic pancreatitis: higher risk of pancreatic cancer in CFTR variants. Digestion 2013;87:229–239.

29 Muller N, Sarantitis I, Rouanet M etal. Natural history of

SPINK1 germline mutation related-

pancreatitis.

eBioMedicine 2019;48:581–591.

30 Raimondi S, Lowenfels AB, Morselli- Labate AM,

Maisonneuve P, Pezzilli R. Pancreatic cancer in chronic pancreatitis; aetiology, incidence, and early detection. Best Pract Res Clin Gastroenterol 2010;24:349–358.

31 Tong GX, Geng QQ, Chai J etal. Association between

pancreatitis and subsequent risk of pancreatic cancer: a systematic review of epidemiological studies. Asian Pac J Cancer Prev 2014;15(12):5029–5034.

32 Kirkegård J, Mortensen FV, Cronin- Fenton D. Chronic

Pancreatitis and pancreatic cancer risk: a systematic review and meta- analysis. Am J Gastroenterol 2017;112(9):1366–1372.

33 Gandhi S, de la Fuente J, Murad MH, Majumder S.

Chronic Pancreatitis is a risk factor for pancreatic cancer, and incidence increases with duration of disease: a systematic review and meta-

analysis. Clin Transl

Gastroenterol 2022;13:e00463.

34 Vujasinovic M, Dugic A, Maisonneuve P etal. Risk of

developing pancreatic cancer in patients with chronic pancreatitis. J Clin Med 2020;9:3720.

35 Ulrich CD; Consensus Committees of the European

Registry of Hereditary Pancreatic Diseases, Midwest

Center Pancreatic Study Group, International

MultiAssociation of Pancreatology. Pancreatic cancer in hereditary pancreatitis: consensus guidelines for prevention, screening and treatment. Pancreatology 2001;1:416–422.

36 Greenhalf W, Lévy P, Gress T etal., for the Working group

for the International (IAP– APA– JPS– EPC) Consensus Guidelines for Chronic Pancreatitis. International consensus guidelines on surveillance for pancreatic cancer in chronic pancreatitis. Recommendations from the working group for the international consensus guidelines for chronic pancreatitis in collaboration with the International Association of Pancreatology, the American Pancreatic Association, the Japan Pancreas Society, and European Pancreatic Club. Pancreatology 2020;20: 910–918.

37 Tamburrino D, de Pretis N, Pérez-Cuadrado-Robles E,

Uribarri-Gonzalez L et al. Identification of patients with branch-duct intraductal papillary mucinous neoplasm and very low risk of cancer: multicentre study. Br J Surg 2022;109(7):617–622.

38 Asbun HJ, Conlon K, Fernandez- Cruz L etal. When to

perform a pancreatoduodenectomy in the absence of positive histology? A consensus statement by the International Study Group of Pancreatic Surgery. Surgery 2014;155:887–892.

39 Hart PA, Zen Y, Chari ST. Recent advances in autoimmune

pancreatitis. Gastroenterology 2015;149:39–51.

486

https://t.me/medicina_free

Evidence ofEndoscopic andInterventional Treatment ofChronic Pancreatitis andPseudocysts

Jörg Schirra1, Simon Sirtl MD1, Markus M. Lerch2, and Julia Mayerle

Department of Medicine II, LMU University Hospital, Ludwig- Maximilians- University, Munich, Germany

LMU University Hospital, Munich, Germany

Indications forInterventional Endoscopic or Surgical Therapy

Belt- like upper abdominal pain is regarded as a cardinal symptom of chronic pancreatitis (CP), together with weight loss, steatorrhea, and diabetes mellitus. In the absence of causal therapeutic options, treatment is restricted to symptom control by means of enzyme replacement, pain therapy, and optimal control of endocrine insufficiency. The complexity of disease management is justified as morphology on imaging and pain level do not correlate in most patients and an impressive ductal obstruction or intraductal calcification may be associated with little pain and subtle findings on imaging may be associated with a significant loss of quality of life due to constant pain[1]. Comparative trials with sham interventions to evaluate the placebo effect or the natural course of the disease have rarely been conducted, one example being the trial by Seza et al. Between 30% and 60% of patients develop complications of their disease such as strictures of the common bile duct, inflammatory masses, pancreatic pseudocysts, or pancreatic duct strictures or ductal stones, which require interventional or surgical treatment. Chronic pancreatitis with severe pain requiring constant analgesics should be treated by interventional or surgical procedures dependent on the symptomof an inflammatory mass clearly favors a surgical resection. In the case of a dilated pancreatic duct due to strictures and/or ductal stone both endoscopic as well as surgical drainage procedures are effective. The indication of an endoscopic drainage has not been fully clarified in randomized controlled trials (RCT). Endoscopic treatment of a dominant stricture of the main pancreatic duct is often followed by pain relief in the short term [3,4].

causing pathogenic features[2]. The presence

Retrospective studies have reported long-

term pain relief in 32–68% of patients [4]. Two randomized controlled studies directly compared endoscopic procedures with resection or a surgical drainage procedure[1,5,6]. Those studies proved surgery to be superior to endoscopy with respect to long- term outcome; however, due to limitations in the study design, a reliable evidence- based assessment remains difficult under the current lack of consideration of the placebo effect, the natural course, and a possible selection bias. Nevertheless, endoscopic drainage can achieve a long- lasting complete or partial pain relief in at least one- third of patients; it is associated with lower mortality and does not impede surgery as a second- line therapy [6]. In the presence of a resectable pancreatic mass suspected to be caused by pancreatic carcinoma surgical resection should be performed. Without surgery, life expectancy for patients with pancreatic carcinoma is less than 1 year; after successful resection 20–25% of patients may survive more than 5 years[7–9]. Gastric outlet obstruction secondary to CP requires surgical or endoscopic treatment for persistent clinical symptoms. A noninterventional management supplemented by endoscopic dilatation may be sufficient for an adequate quality of life in at least 30% of cases. According to the natural course of CP further intervention will be necessary in about 30–60% of patients[10]. As there are no studies directly comparing the efficacy of pancreatic head resection, bypass surgery, and endoscopic insertion of self-

expanding metal stents (fcSEMS)[11], the decision may be taken in view of the patient’s comorbidities. Symptomatic stenosis of the common bile duct (CBD) will develop in 10–40% of cases requiring endoscopy with dilation and stent insertion. The outcome of endoscopic therapy in patients without acute inflammation of the pancreas has improved with

Treatment ofPancreatic Cysts 487

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new techniques but is still not entirely satisfactory. Stent therapy rarely resolves a stricture beyond 1 year of therapy [12], in particular in the presence of calcifications within the pancreatic head [13]. Lasting patency rates have significantly improved with the use of fcSEMS. Surgical resection should be performed if symptoms or cholestasis persist after temporary endoscopic therapy not longer than a year. For obstructive chronic painful pancreatitis with ductal dilatation of more than 5 mm, a recent trial (ESCAPE) recommended earlier surgery after a maximum of 6months of opiate pain medication without clinical improvement or preceded by 3 months of endoscopic therapy without symptom improvement[14]. Fragmentation and removal of stones within the pancreatic duct by extracorporeal shock wave lithotripsy (ESWL) have somewhat replaced surgery since its introduction in 1989. Several retrospective studies have shown ESWL as an effective and safe management option for pain relief in chronic calcifying pancreatitis with pancreatic main duct stones greater than 5 mm[15], for which ESWL followed by ERCP may be the standard of care. Intraductal lithotripsy under direct endoscopic vision is a promising technique in evolution. Interventional endoscopic options in CP will be discussed in more detail below.

Treatment ofPancreatic Cysts

According to the revised Atlanta classification a pancreatic pseudocyst is an encapsulated collection of fluid with a well- defined inflammatory wall usually outside the pancreas with minimal or no necrotic tissue content. This entity usually arises in connection with CP[16]. A walled- off necrosis (WON) is defined as a mature, encapsulated collection of pancreatic and/or peripancreatic necrosis that has developed a well- defined inflammatory wall. WON usually occurs >4 weeks after the onset of necrotizing pancreatitis[16]. The prevalence of pancreatic pseudocysts in CP ranges between 20% and 40% [17]. They occur with the highest frequency in patients with alcoholic CP (70–78%), followed by idiopathic CP patients (6–16%), and biliary pancreatitis patients (6–8%)[17,18]. Approximately 40% of the fluid collections resolve spontaneously within the first 6weeks after an acute attack of pancreatitis. In contrast, spontaneous remission of pseudocysts after 12weeks is a rare event. Complications are observed in up to two- thirds of cases encompassing pain, infection, hemorrhage, cystic rupture, or obstruction of adjacent organs such as cholestasis, gastric outlet obstruction, or vascular stenosis. A multivariate analysis showed a pseudocyst/WON size <4 cm as the only favorable factor for spontaneous resolution[19]. The increase in size of a pseudocyst/WON to

over 5 cm in diameter is associated with an increased risk of complications[20]. Asymptomatic pseudocysts >5 cm in diameter which do not resolve within 6weeks can be an indication for treatment. The aim of this intervention is to avoid possible complications that may occur later in the course of the disease, such as a cyst rupture, infection or hemorrhage, the likelihood of such complications being approximately 50%. However, symptomatic pseudocysts should undergo treatment regardless of their size.

Only limited information is available with regard to interventional therapy of pancreatic pseudocysts for pain management. Most of the data at hand are based on retrospective case series [21–24], but three systematic reviews are available[25–27]. Pain relief will be achieved in a large number of patients (about 80%). Although medical management of CP can result in pain relief, in a certain percentage of patients, interventional or surgical drainage is still the more effective form of pain management regardless of the drainage procedure.

A diagnostic needle aspiration of the cyst may be performed for suspected infection or for suspected cancer. If needle aspiration of the cyst confirms an infection, then drainage is indicated. Surgical treatment should be carried out if malignancy is suspected. In 28% of all MRI scans of the abdomen, a cystic lesion of the pancreas is discovered as an incidental finding[28] when populationbased cohorts are investigated, albeit most of these cysts are smaller than 1 cm in diameter. More than two- thirds of these lesions are dysontogenetic cysts or pancreatic pseudocysts. Of the cystic lesions that are not pancreatic pseudocysts but genuine cystic neoplasms, 30% are benign serous cystadenomas. Forty- five percent of the resected lesions are mucinous- cystic neoplasms and 25% intraductal papillary mucinous neoplasms (IPMN). Solid pseudopapillary tumors or cystic acinar cell carcinoma are rather rare entities. For the differential diagnosis of cystic tumors in asymptomatic patients, the question of a connection to the pancreatic duct (IPMN and pancreatic pseudocysts) and of the size of the cystic lesion (indication for resection in the case of IPMN or therapeutic indication for pseudocyst) is essential. Diagnostic needle aspiration of a cyst with the aid of EUS helps in differentiating between premalignant cystic neoplasms, cystic malignancies, and pseudocysts. In case the fluid analysis reveals a CEA >400 ng/mL, a variably increased or low amylase (lipase), high viscosity, mucin or epithelial cells in the cyst content, then a mucinous neoplasm must be assumed [28–30]. In addition to CEA and amylase/ lipase, low pancreatic cyst fluid glucose has been established as a marker for the differentiation of mucinous versus non- mucinous pancreatic lesions. In 609 cystic lesions examined, a systematic review showed significantly increased pooled sensitivity (91% vs. 56%; P < 0.001)

Evidence ofEndoscopic andInterventional Treatment ofChronic Pancreatitis andPseudocysts

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488

and diagnostic accuracy (94 % vs. 85 %; P < 0.001) compared to CEA alone[31].

If a connection to the pancreatic duct is excluded the final diagnosis of a mucinous cystic neoplasm (MCN) can be made. A serous cystadenoma is diagnosed in 30% of cystic lesions and virtually never turns into a malignant lesion. In this case aspiration of the cyst is negative for mucin, CEA, and amylase. Cytology reveals a glycogen- rich epithelium. Surgical, percutaneous, or endoscopic drainage of pancreatic pseudocysts demonstrate comparable results regarding technical success, efficacy, and recurrence rates [26,32]. Percutaneous drainage is associated with the risk of external fistula and may affect the patient’s quality of life. Endoscopic drainage is less prone to complications when compared to surgical procedures. A systematic review of retrospective series of endoscopic and surgical drainage showed similar morbidity (13.3% vs. 16%) and long-

term pseudocyst

recurrence (10.7% vs. 9.8%) but lower mortality (0.2% vs.

2.5%) achieved by an endoscopic drainage[33]. Therefore, the endoscopic approach should have first preference as it is less invasive and more convenient for the patient. In a recent RCT that compared endoscopic versus surgical cystogastrostomy for pancreatic pseudocyst drainage endoscopic treatment was associated with shorter hospital stays, improved physical and mental health status of the patients, and lower costs[32]. However, the decision between endoscopic and surgical drainage should take into account the cyst location and additional pathophysiological features. Surgical drainage may be the preferable therapy in hemorrhagic pseudocysts as endoscopic drainage is associated with a higher risk of bleeding. Approximately 10% of pseudocysts recur in the long term after endoscopic drainage (Table 62.1). Although initial therapy of nonhemorrhagic pseudocysts should be endoscopic drainage, surgery may follow in case of recurrence. Drainage of pseudocysts can be carried out by transgastric, transduodenal, or transpapillary routes. Transmural drainage should be done under endoscopic ultrasound (EUS) guidance to assess the pseudocyst location, size, wall, content, and adjacent blood vessels. Two RCT compared transmural drainage with and without EUS guidance[34,35]. No difference was observed in terms of morbidity and clinical outcome but technical success was higher with EUS. The success rate in 1018 published patients with transmural drainage of a pseudocyst was 87% (Table 62.1), with more recent studies reporting success rates of more than 90%. The mortality rate in larger case series involving more than 30 patients was 0.2%, the recurrence and complications rates are reported to be around 9% and 13%, respectively. Without antibiotic prophylaxis the procedure- related incidence of an infection of a pseudocyst and the risk of development of a pancreatic abscess increases[36,37]. Antibiotic

prophylaxis for transmural or transpapillary drainage of pancreatic pseudocysts is recommended in recent guidelines based on expert opinion [4,38]. Double-

pigtail stents should be used for transmural drainage of pancreatic pseudocysts because straight stents are associated with more frequent and severe complications in a retrospective study[39]. Early stent retrieval within 2weeks after cyst resolution was associated with a higher rate of recurrence in a prospective randomized trial suggesting that long- term stent placement for more than 2months may prevent recurrence without an increase of severe adverse events[40]. In its clinical guideline ESGE recommends transmural drainage of pancreatic pseudocysts by inserting at least two double- pigtail plastic stents, which should not be retrieved before at least 2months of stenting [4]. Recently, short, lumen- apposing, fully covered,

expandable metal stents (LAMS) have been devel-

selfoped for EUS- guided drainage of peripancreatic fluid collections.

In CP with advanced pancreatic ductal changes, especially with pancreaticolithiasis, a pseudocyst should be considered and treated as part of an overall therapeutic concept. For small pancreatic cysts, the tendency to regress due to persistent inflammatory stimuli is a maximum of 26%, so that even in the case of small symptomatic cysts, an interventional or surgical procedure may be considered in the individual patient context.

Due to its ease of use and the large diameter, the LAMS may make drainage of peripancreatic fluid collections more effective, particularly the endoscopic debridement of WON [41,42]. Despite initial reports on bleeding, recent meta- analyses demonstrated superior efficacy and safety compared to plastic stents in the management of peripancreatic fluid collections [43,44]. The basic question of an ideal timing for WON drainage in case of infected pancreatic necrosis has been studied in the POINTER trial. With regard to mortality and the comprehensive complication index (which includes all major complications), there was no significant difference between immediate catheter drainage (catheter drainage within 24 hours after randomization) and postponed catheter drainage (stage of walled- off necrosis, when necrotic collections were largely or fully encapsulated). However, the cohort of the later WON drainage installation (partly percutaneous, partly EUS- assisted) required fewer interventions overall, especially in terms of the number of necrosectomies required, and patients stayed in hospital for a correspondingly shorter time [45]. Of note, the median time to “immediate catheter drainage” was after a mean of 24days (median, 24days; interquartile range, 20 to 30) after onset of symptoms and postponed catheter drainage after a mean of 34days (median, 29days; interquartile range, 24 to 40) after onset of symptoms (mean difference, −10days; 95% confidence interval [CI],

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