Pathophysiology after pancreaticoduodenectomy

Table 1 Experimental study showing the relationship between motilin and duodenectomy

Ref.	Year	Study design and model	Primary end point	Observations
Tanaka et al[74]	1987	Normal dog vs Duodenectomized dog	Phase III contraction, plasma level of motilin	All control dogs showed characteristic MMC Duodenectomized dog showed non-typical, irregular and non-cyclic pattern of contraction Duodenectomized dog showed low plasma concentration of motilin without cyclical variation
Tanaka et al[75]	1988	Normal dog vs Duodenectomized dog	Inter-digestive gastric and small intestinal MMC plasma level of motilin and Polypeptide Y	MMC was abolished in duodenectomized dogs (3 out of 4 dogs) The other dogs showed intermittent cyclic, but markedly abnormal characteristics of gastric contraction Jejunal MMC appeared with short interval Duodenectomy abolished cyclic variation of plasma motilin and polypeptide Y
Suzuki et al[76]	2001	Conscious dog vs Duodenectomized dog	Phase III contraction, plasma level of insulin, and motilin	Duodenectomy resulted in no phase III contraction in upper GI tract Duodenectomy resulted in no fluctuation of plasma motilin (low level of motilin) Exogenous administration of motilin resulted in comparable response of phased III as shown in control
Malfertheiner et al[77]	1989	Normal dog vs	Pancreatic trypsin	In duodenectomized dog
		Duodenectomized dog	GI motility plasma motilin, PPY	Trypsin secretion was not coordinated with inter-digestive motility, motilin, and PPY Inter-digestive motility was altered Plasma level of motilin and PPY were reduced, and showed no cyclic pattern
Itoh et al[78]	1976	Normal dog	GI motility plasma motilin	Gastrointestinal contractile activity in the conscious dog, Digestive states: motilin had no influence upon the motor activity Inter-digestive states: had influence upon the motor activity
Vantrappen et al[79]	1979	Human	GI motility plasma motilin level	The effect of exogenous motilin on interdigestive migrating motor complex Plasma motilin levels is one of the factor involved in the production of the activity front of the MMC in man
Sarna et al[80]	1983	Normal dog	Plasma motilin levels Migrating myoelectric complexes (MMCs)	Cause and effect relationship between plasma motilin levels and migrating myoelectric complexes Endogenous motilin does not initiate spontaneous mmcs MMC contractions release motilin

GI: Gastrointestinal.

Table 2 Incidence of delayed gastric emptying according to different gastrointestinal reconstructive methods following pancreaticoduodenectomy

Ref.	Year	Study design	Primary end point	Observations
Eshuis et al[81]	2014	In PPPD Antecolic (n = 125) vs Retrocolic (n = 121)	DGE	No differences in DGE (45 patients (36%) vs 41 (34%), absolute risk difference: 2.1% (95%CI: -9.8-14.0) No differences in need for postoperative nutritional support, other complications, hospital mortality, and median length of hospital stay
Tamandl et al[82]	2014	In PPPD, antecolic (n = 36) vs retrocolic (n = 28)	DGE	No differences in DGE (17.6% vs 23.1%, P = 0.628) No differences in length of hospital stay [13.0 (10.0-17.5) vs 12.5 (11.0-17.0) days; P = 0.446], time to regular diet [5 (5-7) d vs 5 (4-6) d, P = 0.353], and NG tube requirement [4 (3-7) d vs 3 (3-5) d, P = 0.600]
Imamura et al[83]	2014	In PPPD, antecolic (n = 58) vs vertical retrocolic (n = 58)	DGE	No difference in DGE (12.1% vs 20.7%, P = 0.316) At postoperative 6 mo, DGE was accelerated in antecolic group At postoperative 12 mo, better postoperative weight recovery in vertical retrocolic group (93.8% ± 1.2% vs 98.5 % ± 1.3%, P = 0.015)
Tani et al[84]	2014	In PD, Conventional (n = 76) vs Isolated Roux-en-Y (n = 77)	POPF/DGE	No differences in DGE and POPF POPF: conventional (34%) vs isolated Roux-en-Y (33%), P = 0.909 DGE: conventional (12%) vs isolated Roux-en-Y (15%), P = 0.609
Shimoda et al[85]	2013	In SSPPD, Billroth II (n = 52) vs Roux-en-Y (n = 49)	DGE	Lower DGE in Billroth II: (5.7% vs 30.4%, P = 0.028) Shorter hospital stay in Billroth II (31.6 ± 15.0 d vs 41.4 ± 20.5 d, P = 0.037) Significant association between POPF and DGE (P = 0.037)
Ke et al[86]	2013	In PD	DGE/POPF	No differences in DGE and POPF
		Continuous loop (n = 109) vs Roux-en-Y (n = 107)		POPF: continuous loop (17.6%) vs Roux-en-Y (15.7%), P > 0.05 DGE: continuous loop (25%) vs Roux-en-Y (23%), P > 0.05
Gangavatiker et al[87]	2011	In conventional PD and PPPD Antecolic (n = 32) vs Retrocolic (n = 36)	DGE	No difference in DGE (34.4% vs 27.8%, P = 0.6)
Kurahara et al[88]	2011	In SSPPD, Antecolic (n = 24) vs retrocolic (n = 22)	DGE	Lower incidence of DGE in the antecolic group [20.8% vs 50%, P = 0.0364, especially in the incidence of DGE grade B/C (4.2% vs 27.3%, P = 0.0234)] Significantly shorter time to full resumption of diet in antecolic group No significant difference in other postoperative complications
Chijiiwa et al[89]	2009	In PPPD, Antecolic (n = 17) vs retrocolic (n = 18)	DGE	No difference in DGE DGE: 6% vs 22%, P = 0.34

PPPD: Pylorus-preserving pancreaticoduodenectomy; DGE: Delayed gastric emptying; PD: Pancreaticoduodenectomy; POPF: Postoperative pancreatic fistula.

Table 3 Definition of postoperative pancreatic fistula

	Postoperative pancreatic fistula
Grade	A	B	C
General appearance (clinical condition)	Well	Often Well	Ill appearing, Bad
Medical or interventional approach	No	Yes or No	Yes
Postoperative radiologic finding (US/CT)	Negative	Negative or Positive	Positive
Long-time drainage (≥ 21 d)	No	Usually Yes	Yes
Reoperation	No	No	Yes
Mortality related to POPF	No	No	Possibly yes
Sign of infection	No	Yes	Yes
Sepsis	No	No	Yes
Readmission	No	Yes or No	Yes or No

US: Ultrasonography; CT: Computed tomographic scan; POPF: Postoperative pancreatic fistula.

Table 4 Recent clinical studies about fatty liver after pancreaticoduodenectomy

Ref.	Year	Patient number	Follow-up period	Definitions of NAFLD	Incidence of fatty liver, n (%)	Risk factors/observation
			(mo)
Song et al[90]	2011	228	16	When CTS-L was equal to or less than 10 HU When CTL/S was equal to or less than 0.9 HU	15 (7.8)	In multivariate analysis, Pancreatic fistula (HR = 3.332, P = 0.037) External pancreatic duct stent (HR = 4.530, P = 0.017)
Sato et al[91]	2014	110	6	Hepatic CT value of less than 40 HU	44 (40)	In multivariate analysis,
						Younger age (OR = 1.079, P = 0.002), Female (OR = 6.102, P < 0.001)
						Small remnant pancreatic volume (< 10 mL), OR = 4.109, P = 0.009
						Suspicion infection on POD7-28 (OR = 3.109, P = 0.027)
Kato et al[92]	2010	54	7.7 ± 2.1	Hepatic CT value of less than 40 HU a	20 (37.0)	In multivariate analysis,
						Pancreatic adenocarcinoma (P < 0.05)
						Pancreatic resection line (left side of SMA, SMA/PV) (P < 0.01)
						Diarrhea (P < 0.05)
Nagai et al[71]	2014	361	6	When CTL/S was equal to or less than 0.9 HU	30 (8.3)	In patients with NAFLD, CTL/S ratio was significantly improved by pancrelipase treatment
						Nutritional status by total protein, albumin, and cholesterol was significantly improved by pancrelipase treatment
						Severe diarrhea was improved
						Malnutrition after PD might be cause for postoperative NAFLD
Ito et al[93]	2014	100	NA	When CTL/S was equal to or less than 0.9 HU	12 (12)	In multivariate analysis, Blood loss (HR = 1.001, P = 0.016)
Nakagawa et al[94]	2014	104	Median 7.7 (2.5-23.6)	When CTS-L was equal to or less than 10 HU	26 (25)	In multivariate analysis, Postoperative pancreatic exocrine insufficiency (HR = 4.16, P = 0.02)
Tanaka et al[72]	2011	60	12	When CTL/S was equal to or less than 0.9 HU When CTL/S was equal to or less than 0.9 HU	14 (23)	In multivariate analysis,
						Pancreatic head cancer (OR = 12.0, P = 0.006)
						De novo NAFLD after PD was associated with body weight loss and decreases in serum levels of albumin, cholinesterase, and total cholesterol
						After administration of pancreatic enzyme, body weight and serum concentrations of albumin, cholinesterase, and total cholesterol were markedly increased
						In addition, hepatic steatosis and serum AST and ALT levels were also significantly improved by treatment
						De novo NAFLD after PD was primarily
						caused by pancreatic exocrine insufficiency

NAFLD: Non-alcoholic fatty liver disease; NA: Not available; AST: Aspartate transaminase; PD: Pancreaticoduodenectomy.