Obesity as a risk factor for severe acute pancreatitis patients
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1 Wien Klin Wochenschr (2014) 126: DOI /s Oesity s risk fctor for severe cute pncretitis ptients Jn Ktuchov Jurj Boer Pvol Hrulk Alexnder Hudk Toms Gjdzik Rstislv Klnin Jozef Rdonk Received: 28 July 2013 / Accepted: 15 Jnury 2014 / Pulished online: 13 Ferury 2014 Springer-Verlg Wien 2014 Summry Bckground Oesity plys n importnt role in incresing the risks of crdiovsculr diseses, metolic diseses, nd deth. Controversy persists concerning the degrees to which oesity influences mortlity nd moridity in severe cute pncretitis. Mterils nd methods Between 2008 nd 2012, the findings of 384 consecutive cute pncretitis ptients were nlyzed in prospective tril. Rnson s scores, Acute Physiology And Chronic Evlution II scores, nd computed tomogrphy severity indexes were clculted. Ptients were ctegorized y ody mss index (BMI) nd wist circumference for the nlysis. The im of this study ws to investigte the influence of oesity on locl nd systemic complictions s well s on mortlity in severe cute pncretitis ptients. Results Severe cute pncretitis ws confirmed in 91 (23.7 %) ptients. Locl nd systemic complictions were recorded in 64 (16.7 %) nd 51 (13.3 %) ptients, respectively. Oesity clculted y BMI ws identified s significnt risk fctor for locl nd systemic complictions (p < 0.02 nd p < 0.03, respectively). Moreover, in this study, oesity ws lso ctegorized y wist circumference nd ws confirmed s risk fctor (p < 0.01). The overll mortlity rte ws 2.4 %, i.e., nine ptients died. This study indictes tht oesity cn hve sttisticlly significnt influence on the mortlity of severe cute pncretitis ptients. Conclusions The presence of oesity hs negtive impct on the survivl rte of severe cute pncretitis ptients. Oese ptients hve higher incidence of Assoc. Prof. J. Ktuchov, MD, PhD ( ) Prof. J. Boer, MD, PhD Asst. Prof. P. Hrulk, MD A. Hudk, MD T. Gjdzik, MD R. Klnin, MD Prof. J. Rdonk, MD, PhD First Deprtment of Surgery, University Hospitl Košice, Tr. SNP 1, Košice, Slovki e-mil: jn.ktuchov@upjs.sk locl nd systemic complictions. Oesity seems to e negtive prognostic fctor in severe cute pncretitis ptients. Keywords Severe cute pncretitis Oesity Body mss index Wist circumference Locl nd systemic complictions Mortlity Adiposits ls Risikofktor ei Ptienten mit schwerer kuter Pnkretitis Zusmmenfssung Grundlgen Die Adiposits spielt eine wichtige Rolle ls Risikofktor für krdiovskuläre Erkrnkungen, Stoffwechselerkrnkungen und Tod. Kontroverse Meinungen estehen drüer, in welchem Ausmß die Adiposits die Mortlität und Moridität ei schwerer kuter Pnkretitis eeinflussen Mteril und Methoden In einer prospektiven Studie von 2008 is 2012 wurden die Ergenisse von 384 Ptienten mit kuter Pnkretitis nlysiert. Die Rnson Scores, die physiologischen kuten und chronischen Evlution II Scores und die Schweregrd Indices in der Computertomogrphie wurden errechnet. Die Ptienten wurden entsprechend ihrer BMI und Tillenumfänge für die Studie ktegorisiert. Ziel der Studie wr es, den Einfluss der Adiposits uf lokle und systemische Kompliktionen sowie uf die Mortlität von Ptienten mit schwerer kuter Pnkretitis zu erforschen. Ergenisse Eine schwere Pnkretitis wurde ei 91 (23,7 %) der Ptienten estätigt. Lokle und systemische Kompliktionen trten ei 64 (16,7 %) eziehungsweise 51 (13,3 %) der Ptienten uf. Die nch dem BMI errechnete Adiposits stellte sich ls signifiknter Risikofktor für lokle und systemische Kompliktionen (p < 0,02 zw. p < 0,003) herus. Auch die nch Hüftumfng erechnete Adiposits estätigte sich ls signifiknter Risikofktor Oesity s risk fctor for severe cute pncretitis ptients 223
2 (p < 0,01). Die Gesmt Mortlität etrug 2,4 % (9 Ptienten verstren), woei die Adiposits einen sttistisch signifiknten Einfluss uf die Mortlität in unserer Studie zu hen scheint. Schlussfolgerungen Ds Vorliegen einer Adiposits ht einen negtiven Einfluss uf die Üerleensrte von Ptienten mit einer schweren kuten Pnkretitis. Adipöse Ptienten hen eine höhere Inzidenz von loklen und systemischen Kompliktionen. Adiposits scheint ein negtiver prognostischer Fktor ei schwerer kuter Pnkretitis zu sein. Schlüsselwörter Pnkretitis (kute, schwere) Adiposits Body mss Index Hüftumfng Kompliktionen (lokle und systemische) Mortlität Introduction Acute pncretitis (AP) is n inflmmtory condition the clinicl course of which vries from cute interstitil edemtous pncretitis (IEP) to severe cute pncretitis (SAP), the most severe form with serious complictions tht pose risk of deth. According to the Atlnt clssifiction, SAP occurs in pproximtely 25 % of ll ptients with AP nd is ssocited with % mortlity [1 3]. IEP usully resolves without mjor consequences, wheres SAP is ssocited with considerle moridity nd mortlity [4]. SAP is defined y the presence of persistent orgn filure (orgn filure tht persists for more thn 2 dys) nd/or the presence of pncretic necrosis, pncretic nd peripncretic scesses, pseudocysts, nd intr-dominl leeding. The deth of AP ptients is often connected with t lest one orgn [1, 4]. Dignosis is sed on clinicl presenttion, lortory indictes, nd imging studies, wheres the illness severity cn e ssessed y the clinicl scoring systems, such s the Rnson, Glsgow, or Acute Physiology nd Chronic Helth Evlution (APACHE) II criteri, or y rdiologicl ssessments, such s the computed tomogrphy severity index [4 6]. The prediction of the clinicl course of SAP t the time of dignosis remins uncler. With the incresing prevlence of oesity, there is ccumulting evidence tht oese ptients with SAP might exhiit worse outcomes in comprison with ptients with norml ody mss index (BMI) [7, 8]. Conversely, severl uthors hve filed to confirm these findings nd reported no differences etween oese nd non-oese ptients [9, 10]. BMI is the sic method used to determine oesity. BMI is mesure otined y dividing the ptient s weight (in kilogrms) y the squre of his/her height (in meters); oesity is defined s BMI > 30 kg/m 2. The method is sed on the presumption tht person s excess weight predominntly consists of ft. The dvntge of this method is its simplicity in ppliction, the lck of complicted procedures needed for mesurement, s well s the fct tht it hs een glolly ccepted. Wist mesurements > 94 cm for men or > 80 cm for women give n indiction of viscerl ft mss [11]. Mterils nd methods Between Jnury 2008 nd Decemer 2012, 384 consecutive AP ptients were nlyzed in the prospective tril. Confirmtions of the AP dignosis included the presence of dominl pin chrcteristic of AP, serum mylse nd/or lipse more thn three times the upper norml limit, nd the chrcteristic findings for AP on computed tomogrphy scn. The severity of AP ws defined in ccordnce with the Atlnt criteri [1, 3]. The locl complictions included necrosis, pncretic nd peripncretic scesses, pseudocysts, nd intr-dominl leeding. The systemic complictions presented s n orgn filure (crdiovsculr, respirtory, nd renl), disseminted intrvsculr cogultions, nd shock. Renl filure, respirtory filure, nd crdiovsculr collpse were defined s the need for hemodilysis, n rteril oxygen concentrtion < 60 mmhg, nd systolic lood pressure < 60 mmhg, respectively. The exclusion criteri included dignosis of chronic pncretitis, recent trums, nd the surgicl interventions responsile for the development of AP. The etiology of AP ws clssified s lcoholic, iliry, nd other, ccording to detiled history; lortory prmeters nd dominl ultrsonogrphy findings were otined for this purpose. To determine oesity, the BMI ws mesured in ll ptients, nd oesity ws dignosed when the BMI ws > 30 kg/m 2. A wist circumference (WC) > 94 cm for men or > 80 cm for women ws n indiction of viscerl ft mss. The im of the present study ws to investigte the reltionship etween the BMI, WC, nd the presence of locl nd systemic complictions for SAP ptients. The mortlity comprison etween oese nd non-oese ptients ws performed. Fisher s exct test, Person chi-squre test, nd the Mnn Whitney tests were used for dt nlysis. The vlue p < 0.05 ws considered sttisticlly significnt. Results During 5-yer period, 384 ptients in totl were dmitted with dignosis of AP. According to the Atlnt criteri, 91 of the 384 ptients were confirmed to hve dignosis of SAP. The remining 293 ptients were clssified s hving IEP. The ptients clinicl nd demogrphic chrcteristics re summrized in Tle 1. Using the BMI index, oesity seems to e risk fctor to develop SAP. The WC mesurement in womn nd men suggested sttisticlly significnt influence of WC on the presence of SAP, with p = nd 0.002, respectively. Systemic complictions (renl, respirtory, nd crdiovsculr) nd locl complictions (pncretic necro- 224 Oesity s risk fctor for severe cute pncretitis ptients
3 Tle 1 Chrcteristics of ptients with interstitil edemtous pncretitis (IEP) nd severe cute pncretitis (SAP) [n (%)] Vrile IEP SAP p-vlue n = 293 (76.3) n = 91 (23.7) Age, yer ± ± /139 56/ (52.5/47.5) (61.5/38.5) 149/121/23 55/34/ (lcohol/stone/other) (50.8/41.2/8) (60.4/37.3/2.7) BMI, kg/m ± ± WC, cm Femle ± ± Mle 87.8 ± ± Rnson s score 1.10 (0 4) 3.51 (0 8) APACHE II score 4.02 (0 14) (0 27) CT severity index score 1.37 (0 4) 3.19 (0 9) BMI ody mss index, WC wist circumference, APACHE II Acute Physiology And Chronic Helth Evlution II, CT computed tomogrphy Tle 2 Comprison of the non-oese group nd the oese group of SAP ptients with respect to BMI [n (%)] Vrile BMI, kg/m 2 p-vlue < n = 43 (47.2) n = 48 (52.8) Age, yer ± ± /13 26/ (69.7/20.3) (54.2/45.8) 24/17/2 31/17/ (lcohol/stone/other) (55.8/39.5/4.7) (64.5/35.5/0) Rnson s score 3.13 (1 8) 3.31 (1 7) APACHE II score (0 23) (4 27) CT severity index score 3.18 (0 8) 3.20 (2 10) Outcome Locl complictions 25 (58.1) 39 (81.2) Systemic complictions 19 (44.1) 32 (66.7) Deth 1 (2.3) 8 (16.6) SAP severe cute pncretitis, BMI ody mss index, APACHE II Acute Physiology And Chronic Helth Evlution II, CT computed tomogrphy sis, infection, scess, nd pseudocyst) occurred in 64 (16.7 %) nd 51 (13.3 %) ptients, respectively. The influence of oesity on the presence of locl nd systemic complictions is descried in Tles 2 nd 3 in more detil. Moreover, we determined tht oesity is negtive prognostic fctor for survivl in SAP ptients. According to the BMI nd WC, this study confirms tht oesity is significnt risk fctor for the development of SAP, with p = nd 0.001, respectively (Tle 4). Tle 3 Comprison of the non-oese group nd the oese group of SAP ptients with respect to the WC [n (%)] Vrile WC, cm () p-vlue Discussion < 95/80 95/80 n = 49 (53.8) n = 42 (46.2) Age, yer ± ± /17 24/ (65.3/34.7) (57.1/42.9) 28/19/2 26/16/ (lcohol/stone/other) (57.2/38.7/4.1) (61.9/38.1/0) Rnson s score 3.16 (0 8) 3.26 (0 8) APACHE II score (0 23) (2 27) CT severity index score 3.08 (0 8) 3.26 (2 8) Outcome Locl complictions 29 (59.1) 35 (83.3) Systemic complictions 21 (42.8) 30 (71.4) Deth 1 (2.1) 8 (19.1) SAP severe cute pncretitis, WC wist circumference, APACHE II Acute Physiology And Chronic Helth Evlution II, CT computed tomogrphy In AP ptients, oesity promotes the development of vrious complictions through severl mechnisms. Oese ptients exhiit n incresed ccumultion of peripncretic ft. The risk of pncretic infection is proportionl to the mount of pncretic necrosis, nd oese ptients exhiit microcircultory chnges tht my led to incresed ischemic tissue. The ltter lso tends to fvor the development of infection of the pncres [12]. Severl investigtions [13 15] hve reported tht oesity is ssocited with low-grde inflmmtory sttus under norml circumstnces. For oese AP ptients, oesity increses the inflmmtory response to pncretic injury y upregulting proinflmmtory meditors. The cytokines produced in the dipose tissue, known s dipokines, include visftin, leptin, resistin, nd dipsin [16, 17], which ply n importnt role in the pthogenesis of multisystem orgn filure [15]. The dysregultion etween inflmmtory nd nti-inflmmtory meditors excertes the systemic inflmmtory response nd results in worse or even ftl outcomes for oese AP ptients [15]. Furthermore, oesity tends to restrict the movements of the chest wll nd diphrgm. This restriction cuses reduced inspirtory cpcity nd modifies oth the expirtory reserve volume nd the residul functionl cpcity, incresing the physiologicl pulmonry rteriovenous shunt nd leding to hypoxemi. Thus, respirtory filure is the most common systemic compliction in oese ptients with AP. Such hypoxemi predisposes the ptient to deficient tissue oxygention, ggrvting the consequences of the excessive inflmmtory response tht occurs in severe pncretitis, fcilitting the occurrence of multiorgn filure nd susequent deth [12]. Oesity s risk fctor for severe cute pncretitis ptients 225
4 Tle 4 The influence of oesity on the development of SAP, locl nd systemic complictions, nd deth with respect to BMI nd WC [n (%)] BMI, kg/m 2 WC, cm () < p-vlue < 95/80 95/80 p-vlue n = 384 n = 384 AP 235 (61.1) 149 (38.9) (67.9) 123 (32.1) SAP 43 (18.2) 48 (32.2) 49 (18.7) 42 (34.1) Complictions Locl 25 (10.2) 39 (26.2) (11.1) 35 (28.4) Systemic 19 (8.1) 32 (21.5) (8.1) 30 (24.4) Deth 1 (0.4) 8 (5.3) (0.4) 8 (6.5) SAP severe cute pncretitis, BMI ody mss index, WC wist circumference, AP cute pncretitis In the recent study y Go et l. [18], BMI t dmission ws reported to reflect the severity of AP nd to e potentil reference prmeter for prognosis evlution. Our study demonstrted tht in group of ptients with BMI > 30 kg/m 2 (149 ptients), SAP occurred in 48 ptients (32.2 %). However, in group of ptients with BMI < 30 kg/m 2 (235 ptients), we dignosed SAP in only 43 ptients (18.2 %). The unique influence of viscerl dipose tissue on the development of SAP ws investigted y Yshim et l. [8]. The uthors reported tht the impct of oesity on SAP using BMI nd WC hd significnce of p = nd 0.004, respectively. Petrov [19] suggested tht dominl rther thn whole-ody ft is key plyer in AP. A iologicl interction etween dominl diposity nd disturnces in glucose nd lipid metolism is likely to increse the risk of developing AP. Chen et l. [15] confirmed tht oesity is definite prognostic fctor for AP, nd the dominl ft distriution my e etter predictor of its severity. In the present study, we report tht oesity increses the incidence of SAP. Moreover, our study indictes tht WC (n indictor of viscerl ft mss) exerts stronger influence on SAP thn does BMI (p = versus 0.002). In recent met-nlysis written y Hong et l. [20], the uthors oserved tht oesity is not only ssocited with n incresed risk of developing AP ut tht it lso represents poor prognostic fctor for AP ptients. Our study oserved higher incidence of locl nd systemic complictions in oese SAP ptients, which in non-oese ptients hd significnce of p = 0.02 nd 0.03 (using BMI) nd p = 0.02 nd 0.01 (using WC), respectively. Mrtinez et l. [12] pointed tht oesity is lso good predictor of mortlity in AP. In met-nlysis, the uthors recommended BMI clcultions in ptients with AP, nd the use of the APACHE-O score s n initil prognostic fctor with high negtive prognostic vlue to predict, to decide which ptients must e monitored for the development of orgn filure. We confirmed tht oesity is high risk fctor for mortlity in SAP ptients [using oth the BMI (p = 0.03) s well s the WC mesurements (p = 0.01)]. In the study y Wng et l. [21], the erly trnsfer of overweight nd oese SAP ptients to specilized centers ws recommended. Conclusions Oesity seems to e significnt risk fctor for the presence of locl nd systemic complictions, s well s for mortlity in SAP ptients. For SAP ptients, the risk posed y oesity is relted not only to the totl mount of ody ft ut lso to its loction. The viscerl ft mss is n ccurte predictor of SAP. For these resons, we recommend to clculte the BMI nd WC in AP ptients. Disclosure The uthors confirm tht the mnuscript is not under simultneous considertion y ny other puliction. All procedures were in ccordnce with the ethicl stndrds of the responsile committee on humn experimenttion (institutionl nd ntionl) nd with the Helsinki Declrtion of 1975, s revised in Informed consent ws otined from ll ptients efore inclusion in the study. There is no commercil ssocition tht might pose conflict of interest. The customry listing of sources of support nd institutionl ffilitions t the end of the mnuscript is proper nd does not imply conflict of interest. Conflict of interest The uthors declre tht there re no ctul or potentil conflicts of interest in reltion to this rticle. References 1. Büchler MW, Gloor B, Müller CA, et l. Acute necrotizing pncretitis: tretment strtegy ccording to the sttus of infection. Ann Surg. 2000;232(5): Mitchell RM, Byrne MF, Billie J. Pncretitis. Lncet. 2003;361(9367): Srr MG revision of the Atlnt clssifiction of cute pncretitis. Pol Arch Med Wewn. 2013;123(3): Bnks PA, Bollen TL, Dervenis C, et l. Clssifiction of cute pncretitis 2012: revision of the Atlnt clssifiction nd definitions y internl consensus. Gut. 2013;62: Oesity s risk fctor for severe cute pncretitis ptients
5 5. Thoeni RF. The revised Atlnt clssifiction of cute pncretitis: its importnce for the rdiologist nd its effect on tretment. Rdiology. 2012;262(3): Zheer A, Singh VK, Qureshi RQ, et l. The revised Atlnt clssifiction for cute pncretitis: updtes in imging terminology nd guidelines. Adom Imging. 2013;38(1): Dvis PJ, Eltwill KM, Au-Wswl B, et l. Effect of oesity nd decompressive lprotomy on mortlity in cute pncretitis requiring intensive cre unit dmission. World J Surg. 2013;37(2): Yshim Y, Isym H, Tsujino T, et l. A lrge volume of viscerl dipose tissue leds to severe cute pncretitis. J Gstroenterol. 2011;46(10): Frosrd JL, Lescuyer P, Pstor CM. Experimentl evidence of oesity s risk fctor for severe cute pncretitis. World J Gstroenterol. 2009;15(42): De Wele B, Vnmierlo B, Vn Nieuwennhove Y, et l. Impct of ody overweight nd clss I, II nd III oesity on the outcome of cute iliry pncretitis. Pncres. 2006;32(4): Pu YF, He HB, Zho ZG, et l. [Evlution of viscerl dipose in dominl oesity nd its clinicl ppliction]. Zhonghu Yi Xue Z Zhi. 2008;88(34): Mrtínez J, Johnson CD, Sánchez-Pyá J, et l. Oesity is definitive risk fctor of severity nd mortlity in cute pncretitis: n updted met-nlysis. Pncretology. 2006;6(3): Lee YH, Prtley RE. The evolving role of inflmmtion in oesity nd the metolic syndrome. Curr Di Rep. 2005;5(1): Fin JN, Mdn AK, Hiler ML, et l. Comprison of the relese of dipokines y dipose tissue, dipose tissue mtrix, nd dipocytes from viscerl nd sucutneous dominl dipose tissues of oese humns. Endocrinology. 2004;145(5): Chen SM, Xiong GS, WU SM. Is oesity n indictor of complictions nd mortlity in cute pncretitis? An updted met-nlysis. J Dig Dis. 2012;13(5): Lyon CJ, Lw RE, Hsueh WA. Minireview: diposity, inflmmtion, nd therogenesis. Endocrinology. 2003;144(6): Fntuzzi G. Adipose tissue, dipokines, nd inflmmtion. J Allergy Clin Immunol. 2005;115(5): Go H, Wng L, Yo P. Reltionship of ody mss index, lood glucose nd serum tricylglycerol with severity of cute pncretitis. Chin J Gstroenterol. 2012;17(1): Petrov MS. Adominl ft: key plyer in metolic cute pncretitis. Am J Gstroenterol. 2013;108(1): Hong S, Qiwen B, Ying J, et l. Body mss index nd the risk nd prognosis of cute pncretitis: met-nlysis. Eur J Gstroenterol Heptol. 2011;23(12): Wng S, Li S, Feng Q, et l. Overweight is n dditionl prognostic fctor in cute pncretitis: met-nlysis. Pncretology. 2011;11(2):92 8. Oesity s risk fctor for severe cute pncretitis ptients 227
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