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Upper jejunal motility after pancreatoduodenectomy according to the type of anastomosis, pancreaticojejunal or pancreaticogastric
Upper Jejunal Motility after Pancreatoduodenectomy According to the Type of Anastomosis, Pancreaticojejunal or Pancreaticogastric Isabelle Le Blanc-Louvry, MD, Philippe Ducrotte´, MD, PhD, Christophe Peillon, MD, PhD, Jacques Testart, MD, PhD, Philippe Denis, MD, PhD, Francis Michot, MD, PhD, and Paul Tenie`re, MD, PhD
and mean area under the postprandial curve was higher (p < 0.01) than in asymptomatic patients. Propagated clusters of contractions were only found in symptomatic patients and in the afferent limb.
Background: The goal of this study was to compare upper jejunal motor patterns after Billroth II pancreatoduodenectomy according to the type of pancreatic anastomosis (pancreaticojejunostomy [PJA] or pancreaticogastrostomy [PGA]) and the presence or absence of postoperative symptoms.
Conclusions: Pancreatoduodenectomy is associated with significant motor disturbances, mainly slower phase III and a reduced fed pattern, in the upper jejunum, at least during the first 3 postoperative months. Few motor differences were observed between PGA and PJA pancreatic anastomosis. A lesser occurrence of postsurgical motor anomalies does not appear to be an argument for preferring PGA to PJA. (J Am Coll Surg 1999; 188:261–270. © 1999 by the American College of Surgeons)
Study Design: Manometric recordings during fasting and after a 750-kcal meal were performed in the afferent limb in 12 patients (7 PJA, 5 PGA) and in the efferent limb in 15 other patients (7 PJA, 8 PGA) with a postoperative delay of 15 6 6 days and 3.9 6 2.2 months respectively. Patient data were compared to those of 20 healthy controls. Results: During fasting, the 2 main abnormal findings were a higher incidence (p < 0.05) and a slower migration velocity (p < 0.01) of incomplete phase III by comparison with that recorded in controls. No difference for phase III was observed between the 2 surgical procedures regardless of recording site. Trimebutine, 100 mg intravenously, induced a phase III in 89% (24 of 27) of the patients. Delay of motor response varied from 5 to 10 minutes without difference between the recording site; it was less than 2 minutes in 100% of controls. Trimebutine-induced phase III showed similar propagation abnormalities to the spontaneous phase III. Duration of the fed pattern (p < 0.001) and motor index (p < 0.001) were significantly lower than in controls after the meal, in both limbs, whatever the type of anastomosis. Differences between the 2 surgical procedures were a slower migration velocity of phase III (p < 0.01) and a lower postmeal motor index (p < 0.05) in the efferent limb after PJA than after PGA. Nine of 27 patients were symptomatic. In these 9 patients, mean phase III migration velocity was slower (p < 0.001),
In about 30% to 40% of patients, pancreatoduodenectomy according to Whipple’s procedure is complicated by symptoms suggesting delayed gastric emptying or a dumping syndrome that severely impairs quality of life.1,2 After gastric and small bowel surgery, postoperative symptoms have been related to motor disturbances, such as interrupted or retrograde phase III or low postprandial activity.3 After pancreatoduodenectomy, an animal study has shown motor anomalies both in the afferent and efferent limbs.4 The single study in humans has confirmed anomalies of phase III in the efferent limb (low amplitude and frequency, interrupted propagation in 70% of the patients), and decreased amplitude of postprandial activity.5 After pancreatoduodenectomy, gastrointestinal and pancreatic continuity can be restored by performing either a pancreaticojejunostomy (PJA) or a pancreaticogastrostomy (PGA). Short surgical series suggest that functional results are better after PGA than after PJA.6 The aim of this study was to describe jejunal motor patterns after pancreatoduodenectomy in both types of anastomosis, PJA or PGA, in symp-
Received August 20, 1998; Revised October 15, 1998; Accepted November 4, 1998. From the Digestive Tract Research Group (Le Blanc, Ducrotte´, Denis, Michot, Tenie`re) and the Department of Vascular Surgery (Peillon, Testart), Rouen University Hospital, Rouen, France. Correspondence address: Isabelle Le Blanc, MD, Service de Chirurgie Digestive, Pavillon Derocque, Hoˆpital Charles Nicolle, 76031 Rouen Cedex, France. © 1999 by the American College of Surgeons Published by Elsevier Science Inc.
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Table 1. Postoperative Symptoms and Weight Evolution in the 27 Patients
Postoperative symptoms No symptoms Symptoms Epigastric fullness Nausea, vomiting Dumping Bloating Diarrhea Weight (kg) Before surgery After surgery
Pancreaticojejunal anastomosis (n 5 14)
Pancreaticogastric anastomosis (n 5 13)
9 5 2 5 0 0 0
9 4 1 3 0 0 1
69 6 18 72 6 16
73 6 22 72 6 24
Weight values are mean 6 SEM.
tomatic and asymptomatic patients, to determine whether postoperative motor disturbances are less frequent with PGA. METHODS Patients. Twenty-seven patients, 16 men and 11 women, were enrolled in this prospective study. PJA was performed from January 1, 1995 until January 8, 1996 and PGA from January 8, 1996 until January 12, 1997 by the same surgeons. Therefore, in 14 patients, gastrointestinal continuity was restored by PJA; in the 13 others, the anastomosis was PGA. In 20 of 27 patients, surgery was indicated for a resectable carcinoma of the head of the pancreas. In 10 patients, continuity was restored by PJA and in 10 by PGA. In all 20 patients, surgery was a potentially curative procedure. In the remaining 7 patients (4 PJA, 3 PGA) surgery was performed for chronic pancreatitis complicated by pain unrelieved by medical treatment, without possibility of derivation of the Wirsung duct. Antalgic medication was always stopped at least 10 days before the manometric study. Age of the patients (mean 6 SEM) was 59 6 12 years and 54 6 9 years in PJA and PGA groups respectively. No significant weight modification was observed between the pre- and postoperative periods (Table 1). Patients were regarded as symptomatic if they had symptoms occurring at least 5 days a week, requiring daily treatment with prokinetic drugs or transit modifiers, and observed at the time of the manometric recording session. Nine patients in each group were symptomatic and complained of at least one of the following symptoms (Table 1): epigastric fullness, nausea, vomiting, diarrhea. All the patients
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considered symptomatic at the time of the recording session remained symptomatic at least at the followup visits scheduled during the 6-month period following the study. Return of bowel function with gas emission was effective between 2 to 4 days after the surgical procedure and observed in all patients before the recording session. Manometric data obtained from the patient group were compared with those from 20 healthy volunteers, 10 men and 10 women, aged 20 to 56. This group also had duodenojejunal motor recordings that were obtained with the same manometric technique as in the patient group. Surgical procedure. In all cases, the proximal portion of the gastric antrum was not involved in the resection and no truncal vagotomy was performed. In PJA, the remaining pancreas was sutured terminolaterally to the proximal part of the jejunum, the biliary and pancreatic anastomoses were distant from 10 cm and the gastrojejunal anastomosis was 60 cm aborad (Fig. 1). In PGA, the remaining pancreas was sutured terminolaterally to the posterior face of the gastric remnant (Fig. 1). Technique of manometric recording. Jejunal manometry was performed with a tube assembly consisting of 4 polyvinyl catheters (0.8 mm internal diameter) with side holes 10 cm apart. Sensors were located at 5, 15, 25, and 35 cm from a rubber bag fixed to the tip and containing 2 mL of mercury to facilitate positioning. Radiopaque markers were inserted near the side hole to facilitate fluoroscopic control of the entire assembly. Recording lumens were perfused with degasified distilled water (0.5 mL/min) from a pressurized reservoir. At this infusion rate, the delay for pressure rise is 0.5 second for 102 mmHg. Pressure values from transducers (Gould Statham P23 ID, Oxnard, CA) were numbered with a frequency of 5 Hz per channel to be stored in the hard disk of an IBM/PC computer. Study design. Two different protocols were used in this study. None of the patients participated in both protocols. In protocol 1, studies were performed during the early postoperative period with a mean interval of 15 6 6 days between surgery and recording to analyze motility of the jejunum used for the biliary intestinal anastomosis in both surgical procedures (Fig. 1). This portion of jejunum will now be referred to as the afferent limb in the manuscript. In this protocol, the manometric probe was inserted during the surgical procedure at least in the first 50 cm of the afferent
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Figure 1. Surgical procedures and site of the manometric probe. (A) Pancreaticojejunal anastomosis—protocol 1: probe in the afferent limb. (B) Pancreaticojejunal anastomosis—protocol 2: probe in the efferent limb. (C) Pancreaticogastric anastomosis—protocol 1: probe in the afferent limb. (D) Pancreaticogastric anastomosis—protocol 2: probe in the efferent limb.
limb. This protocol was performed in 7 patients with PJA and in 5 patients with PGA anastomosis. In symptomatic patients who had received medication liable to affect motility, administration was stopped 1 week before the recording session. The aim of protocol 2, which had 15 other patients, was to record efferent limb motor activity after both surgical procedures. Fasting subjects were intubated between 9:00 a.m. and 10:00 a.m. Under fluoroscopic control the manometric probe was pushed into the efferent limb and its position was considered correct when at least 3 of the 4 sideholes were in the efferent limb (Fig. 1). The position of the probe in the efferent limb was always obtained before beginning the recording session. Studies were performed with a mean delay between surgery and recording of 3.9 6 1.2 months (mean 6 SEM) in PJA group (7 patients) and 2.9 6 0.7 months in PGA group (8 patients) (NS). In patients operated on for a pancre-
atic carcinoma, no sign of tumor recurrence was observed at the time of the study. In protocol 1, recordings were performed over a period of 4 to 7 hours in fasting subjects, and for 3 hours after a 750-kcal meal (carbohydrates, 46%; lipids, 36%; proteins, 18%). In protocol 2, recordings were done for at least 5 hours and were performed first in fasting subjects during the first 2 hours then in the 3 hours following the same 750kcal meal as in protocol 1. At the end of the manometric session, an intravenous injection of 100 mg trimebutine, known to induce a phase III in healthy volunteers,7 was systematically given. This study design was approved by the Ethics Committee of Haute Normandie (France) and all patients and healthy volunteers gave their informed consent. Analysis of the tracings. Analysis was visual for the interdigestive period, the postmeal period, and
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Table 2. Interdigestive Manometric Patterns Type of surgery
Afferent limb
Efferent limb
Pancreaticojejunal anastomosis Lack of phase III Normal phase III only Incomplete phase III Retrograde phase III Pancreaticogastric anastomosis Lack of phase III Normal phase III only Incomplete phase III Retrograde phase III
(n 5 7) 0 4 3 1 (n 5 5) 0 3 2 0
(n 5 7) 3 2 2 0 (n 5 8) 1 5 2 0
the response to trimebutine. Visual analysis was performed by 2 observers used to analyze small bowel manometry (ILB, PD). One observer (PD) was unaware of the type of surgical procedure, either PJA or PGA, when performing the analysis. During the interdigestive period, the aims of this visual analysis were to recognize phase IIIs to calculate their characteristics, and to analyze their propagation. A burst of motor activity was considered phase III according to previously published criteria.8 Briefly, phase III was defined as burst of contractions, aborally propagated and lasting at least 3 minutes at the maximum frequency (11–12 cycles per min21 in the jejunum). The frequency (number of phase IIIs per hour), duration, amplitude, and migration velocity were determined as previously described.9 Propagation was defined according to the 3 following modes: complete when the bursts of regular contractions were recorded successively at least by the 4 probe sensors, incomplete when the propagation was observed on the proximal but not the more distal sensors, retrograde when the propagation was aborad-orad on more than 2 sideholes. Analysis of the postprandial motor activity was both visual and computerized. Computerized analysis was performed using a previously validated software (2ERL, LOMATECH, Rennes, France).9 Postprandial motor parameters were calculated either on the period of time elapsed from the beginning of the meal to the return of a phase III or on the 3 postprandial hours in case of no reappearance of the phase III. The software analyzed the digital recording with the following successive steps: elimination of pressure waves related to respiration; detection of contraction waves; and calculation of the area under curve (AUC, mmHg/min), the number of contraction waves (NW), the wave amplitude (mmHg), and the percentage of recording time occupied by motor activity.9 All these parameters were automatically calcu-
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lated at each level of recording on each successive half hour of the postprandial period. The aim of the visual analysis was detection of propagating clustered contractions (PCCs) defined as repetitive phasic contractions at slow wave frequency (10–12/min), propagated, preceded, and followed by a period of quiescence.10 Statistical analysis. Except for phase III, parameters were calculated as means of the values recorded by all sensors, either in the afferent or the efferent limb. Student’s t-test and Wilcoxon nonparametric test were used to compare quantitative data, and chisquare test was used for the analysis of qualitative parameters. Correlation between 2 quantitative values was verified by the Spearman’s test. RESULTS Motility of the afferent limb (12 patients). During the interdigestive period, in the PJA group (7 patients), phase III was recorded in all 7 patients. Propagation was normal in only 4 patients. In the remaining 3 phase III was incomplete and propagated over less than 30 cm (Table 2). In the PGA group (5 patients), phase III was recorded in all 5 patients but was normally propagated in only 3 patients (Table 2). Therefore, a complete propagation was significantly less frequent in patients than in controls (7 of 12 versus 19 of 20, p , 0.02). In patients, phase III was more frequent (p , 0.05), had a lower amplitude (p , 0.05), and a slower migration velocity (p , 0.01) (Fig. 2) than in controls. Phase III duration was the only characteristic not different between patients and controls (Fig. 2). After the meal, phase III returned before the third postprandial hour more frequently in patients than in controls (10 of 12 versus 1 of 20, p , 0.001), in 6 of 7 PJA patients and in 4 of 5 PGA patients (NS) (Table 3). During this postprandial period, mean 30minute AUC was significantly lower than in controls (p , 0.001), without any difference between PGA and PJA groups (Fig. 3). As in controls, NW (Fig. 3) was positively correlated with AUC (r 5 0.66, p , 0.02). In 2 PJA patients and 1 PGA patient, PCCs were observed (Fig. 4). Motility of the efferent limb (15 patients). Phase III was recorded in 12 patients but was normally propagated in only 7 patients (Table 2). Comparison with phase III recorded in healthy volunteers shows a slower migration velocity (p , 0.01) and a longer duration (p , 0.05) in patients (Fig. 2). After PJA, the migration velocity was slower (p , 0.05)
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than after PGA, when duration and amplitude were not different. After the meal, phase III returned within the 3 postprandial hours more frequently than in controls (10 of 15 patients versus 1 of 20 controls, p , 0.001), in 3 of 7 PJA patients and in 7 of 8 PGA patients (NS) (Table 3). During this postprandial period, mean 30-minute AUC was significantly lower than in controls (p , 0.001) and AUC was lower after PJA than after PGA (64 6 13 versus 103 6 18 mmHg/min, p , 0.05) (Fig. 3). As in the afferent limb, NW was correlated with AUC (r 5 0.61, p , 0.01) (Fig. 3). No PCC was observed in any patient in the efferent limb. Response to 100 mg intravenous trimebutine. In each healthy volunteer, trimebutine induced a phase III having the same characteristics as spontaneous phase III, in the 2 minutes following the injection. In the PJA group, trimebutine induced a motor response in 12 of 14 patients, in particular, in all 7 patients recorded in the afferent limb. Trimebutineinduced phase III had a similar propagation, complete or not, as a spontaneous phase III, without any difference between afferent and efferent limbs. In 2 patients, trimebutine induced a phase III when none was noted during the interdigestive recording. The delay of motor response after intravenous injection was not different between afferent and efferent limb (8.1 6 1.7 minutes versus 10.0 6 2.0 minutes). Trimebutine-induced phase III was of higher amplitude than the spontaneous one (p , 0.05) and not different from that in healthy controls (Fig. 5). Duration and velocity of phase III induced by trimebutine was not different from spontaneous phase III (Fig. 5). In the PGA group, trimebutine induced a motor response in all patients except 1 in whom recordings were performed only in the efferent limb. In 1 patient, trimebutine induced a phase III, but none was recorded during the interdigestive recording. On the other hand, the patient who failed to respond to trimebutine had spontaneous phase III. The delay for the motor response after intravenous injection was not different from those of the PJA group (5.1 6 1.2 minutes in the afferent limb, and 6.2 6 1.3 minutes in the efferent limb). Trimebutine-induced phase III was of higher amplitude than the spontaneous one (p , 0.05) and not different from that of healthy controls (Fig. 5). The number, delay, and characteristics of the trimebutine-induced phase III were not
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Figure 2. Characteristics of phase III. (A) Phase III number per hour21; (B) phase III amplitude (mmHg); (C) migration velocity (cm per min2); (D) phase III duration (min). *p , 0.05 versus controls, †p , 0.05 versus group PGA, ‡p , 0.05 versus efferent. Values are mean 6 SEM. PGA, pancreaticogastric anastomosis; PJA, pancreaticojejunal anastomosis.
different between the 2 groups, both on the afferent and efferent limb (Fig. 5). Comparison between symptomatic and asymptomatic patients. Nine of the 27 patients (33%) were symptomatic, 5 of 14 patients with PJA and 4 of 13 in patients with PGA (Table 1). All reported an epi-
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Table 3. Postprandial Manometric Patterns Duration (min) of phase III interruption after the meal Pancreaticojejunal anastomosis Number of patients with a duration . 180 , 180 (mean duration) Pancreaticogastric anastomosis Number of patients with a duration . 180 , 180 (mean duration) Controls Number of patients with a duration . 180 (mean duration) , 180
Afferent limb Total (n 5 7)
Efferent limb
Symptomatic Asymptomatic (n 5 2)
Total
Symptomatic Asymptomatic
(n 5 5)
(n 5 7)
(n 5 3)
1 0 6 (56 6 19*) 2 (66 6 19*) (n 5 5) (n 5 2)
1 4 (51 6 15*) (n 5 3)
4 3 3 (115 6 15*) 0 (n 5 8) (n 5 2)
1 3 (115 6 15) (n 5 6)
1 1 4 (64 6 14*) 1 (43*) n 5 20
0 3 (72 6 18*)
1 7 (74 6 16*)
1 5 (79 6 14*)
0 2 (51 6 1*)
(n 5 4)
19 (419 6 15) 1 (155)
*p , 0.001 vs controls. Values are means 6 SEM.
gastric fullness or nausea and vomiting. A slower migration velocity in the symptomatic patients, without difference between afferent and efferent limb (Table 4), was the only motor difference during fasting between symptomatic and asymptomatic patients. After the meal, symptomatic patients had a
Figure 3. Mean postprandial values of area under the curve and number waves per 30 min period. (A) Postprandial AUC (mmHg per min) per 30 min period; (B) number waves per 30 min period. *p , 0.001 versus controls, †p , 0.05 versus group PGA. Values are mean 6 SEM. AUC, area under curve; PGA, pancreaticogastric anastomosis; PJA, pancreaticojejunal anastomosis.
higher (p , 0.05) postprandial AUC in the efferent limb (Fig. 6), but the same duration of the fed pattern (Table 3). PCCs were more frequent in the symptomatic than in the asymptomatic patients; they were recorded only in the afferent limb, in 3 of the 4 symptomatic patients (2 PJA, 1 PGA), and never in the asymptomatic patients. DISCUSSION In humans, motor disturbances are frequent after supramesocolic surgical procedures.3 The absence of information on jejunal motility after pancreaticoduodenectomy was the basis of this study with a comparison between PGA and PJA anastomosis. Before this study, we speculated that motor patterns would be different between the two types of anastomosis because of the arrival site of biliary and pancreatic secretions and the mixing with the luminal content, which differ between the two procedures. Luminal factors are known to influence motor patterns.11 Moreover, electromyographic studies in animals have demonstrated that the digestive reconstruction mode after pancreaticoduodenectomy influences postoperative motility with a disturbed phase III propagation and a lack of fed pattern more frequent after Billroth II than Billroth I gastrointestinal anastomosis.4 Our study demonstrated, both in early and later postoperative periods, that none of the 27 patients had jejunal motility that could be considered normal. In this study, recordings were never performed before
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Figure 4. Example of propagated clusters of contractions (PPCs) recorded during postoperative period in an afferent limb. PPCs were defined as repetitive propagated phasic contractions at 10–12 cycles/min21, preceded and followed by a period of quiescence.11
the sixth postoperative day to avoid considering acute motor changes, only related to the postoperative ileus12 as chronic motor disturbances. During the interdigestive period, pancreaticoduodenectomy disturbed the amplitude, migration velocity, and mode of propagation of the phase III in the jejunum by comparison with a control group. After PGA, motor disturbances were less pronounced than after PJA, with phase III characteristics more similar than those in controls, and postmeal motor activity reduced less in only the efferent limb. Interdigestive motility disturbances were not uniform in our series. Therefore, in both groups, the 2 main abnormal features concerning phase III were disturbed incidence and slow propagation. Frequent, slowly propagated, and often incomplete phase III was the main anomaly found. Animal studies have shown that duodenectomy disturbed jejunal fasting motor activity, increased the number, and decreased the migration velocity of phase III.13 A slow migration velocity has previously been reported in dogs after Whipple’s procedure with a PJA.4 The study design does not permit us to explain these motor changes. However, several mechanisms could be involved in these interdigestive jejunal motor changes. Intestinal fasting motor activity is controlled by a sophisticated neural network, the enteric nervous system, which itself is influenced by extrinsic nerves and circulating hormones. When the head of the pancreas is resected, the surgical procedure interrupts the intrinsic circuitry and removes the duodenum where the pacemaker controlling the motor activity of the bowel has been located.14 Extrinsic denervation of the jejunum was shown
to increase phase III frequency, to shorten the propagation and to slow intestinal transit in dogs.15 However, vagus and mesenteric vasculonervous connections were always carefully preserved during the
Figure 5. Characteristics of phase III after trimebutine. White bar, spontaneous phase III; black bar, phase III after trimebutine; hatched bar, controls. * p , 0.02 versus controls, † p , 0.05 versus spontaneous phase III. Values are mean 6 SEM. PGA, pancreaticogastric anastomosis; PJA, pancreaticojejunal anastomosis.
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Table 4. Phase III Characteristics in Symptomatic and Asymptomatic Patients Patients Afferent limb PJA Symptomatic (n 5 2) Asymptomatic (n 5 5) PGA Symptomatic (n 5 2) Asymptomatic (n 5 3) Efferent limb PJA Symptomatic (n 5 3) Asymptomatic (n 5 4) PGA Symptomatic (n 5 2) Asymptomatic (n 5 6)
Migration velocity (cm/min)
Duration (min)
Amplitude (mmHg)
1.5 6 0.1 3.3 6 0.2
5.5 6 0.3 6.3 6 0.4
25 6 2 23 6 2
1.4 6 0.1 5.0 6 0.3
3.7 6 0.2 4.6 6 0.3
24 6 3 21 6 2
1.7 6 0.1 2.1 6 0.2
8.7 6 0.5 8.0 6 0.4
28 6 3 24 6 2
1.1 6 0.1 5.5 6 0.3
8.5 6 0.3 6.0 6 0.4
35 6 3 31 6 3
PGA, pancreaticogastric anastomosis; PJA, pancreaticojejunal anastomosis.
surgical procedure in our study to maintain small bowel vitality; the hypothesis of motor disturbances related to extrinsic lesions therefore appears unlikely. Surgical procedure also disturbs circulating hormones, and after duodenectomy motilin levels decrease dramatically.13 This hormonal change must be
Figure 6. Postprandial values of area under the curve and number waves per 30 minute period in symptomatic and asymptomatic patients. White bar, asymptomatic; gray bar, symptomatic; black bar, controls. (A) Postprandial area under the curve per 30 min (mmHg per min); (B) number waves per 30 min. *p , 0.05 versus asymptomatic patients. PGA, pancreaticogastric anastomosis; PJA, pancreaticojejunal anastomosis.
taken into account even if motilin effects on jejunal phase III have been less extensively studied than those on antral phase III.16 The more disturbed phase III activity after PJA than after PGA anastomosis in the efferent limb emphasizes the role of luminal content on motility. Among the anatomic changes after pancreaticoduodenectomy, a difference in the arrival site of biliary and pancreatic secretions is the only anatomic difference between the 2 surgical procedures, with a different mixing in the luminal content. This could explain the differences of motor patterns that we observed between the 2 surgical procedures. Bile has a direct stimulating effect on duodenal migrating activity,17 correlated with the doses and the rate of intraluminal flow.18 The motor effect of bile could be the reason for the high phase III incidence found in the afferent limb. At variance, few patients had no phase III during the recording session. The great variability in the incidence of the phase III is well recognized19 and the relatively short duration of fasting recordings could have overestimated the absence of phase III. However, in most of the patients without spontaneous phase III, the lack of response to 100 mg intravenous trimebutine was an argument to not consider this absence of phase III as a methodologic artefact. In most patients, fed motor pattern was disturbed, both reduced in amplitude in 27 patients and significantly shorter than in controls, with a return of phase III before the third postprandial hour in 22 of the 27 patients. Postprandial motor results confirm animal data that have shown the absence of fed pattern after a pancreaticoduodenectomy with digestive
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continuity restored with PJA.4 The same hypothesis that applies to interdigestive motor changes can be evoked to explain motor anomalies recorded during the fed period. Duodenectomy abolished the suppressive effect of a meal on cyclic fasting motility;13 postsurgical nervous damages could shorten and reduce fed pattern because a short fed pattern has been reported in humans after vagotomy,20,21 but no extrinsic lesions were created during the surgical procedure in our study. The secretion of gastrin, cholecystokinin, or insulin, all hormones involved in the onset of a fed pattern, has been shown to significantly decrease after pancreaticoduodenectomy,2,22,23 and Simpson and colleagues22 have shown that insulin secretion is more severely disturbed after PGA than PJA. Fed pattern anomalies could also be explained by an impaired nutrient absorption; duration and importance of postprandial motor activity are related to the absorption rate of the nutrients24 and to postprandial blood concentrations of nutrients.25 After pancreatoduodenectomy, absorption is often impaired.26 In both types of anastomosis, bile arrives 60 cm orad the gastrojejunal anastomosis and an asynchronism between arrival of the meal in the jejunal lumen and bile secretion appears possible.27 Synchronization between arrival of the meal and pancreatic enzyme secretion is theorically better after PGA than PJA, providing better mixing conditions of nutrients with pancreatic secretion, a better digestion, and improved absorption. This improved synchronization could be one of the reasons why a more significant fed pattern was observed after PGA than PJA in the efferent limb. However, in PGA, pancreatic enzymes are secreted directly into the stomach and gastric chloric acid and the lack of enteropeptidases are both well recognized factors preventing activation of pancreatic enzymes. A better digestion after PGA than PJA remains to be demonstrated. Interpretation of PPCs is difficult. Their onset in the afferent limb only in symptomatic patients is noteworthy. Repetitive clusters of phasic pressure waves are suggestive of partial mechanical obstruction, particularly when the clusters have a very prominent tonic component.28 This was not the case in our study. Therefore, it is difficult to affirm that these patterns were related to a partial mechanical obstruction. The last finding of this study was the absence of major differences in the motor patterns between the 9 symptomatic and the 18 asymptomatic patients. The main differences were a slower phase III migration velocity, a higher postprandial AUC, and more frequent PCCs in the afferent limb in symptomatic
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patients. It seems difficult to explain postoperative symptoms by these subtle motor jejunal differences even if they could impair transit of the luminal content; the efferent limb after pancreaticoduodenostomy in our symptomatic patients could in fact be in a state of greater contraction less likely to empty than in asymptomatic patients. Symptoms could also be related to motor changes in other digestive areas, mainly the stomach, although Pastorino and associates5 did not report major motor anomalies on the gastric remnant after pancreatoduodenectomy. Another explanation is that symptoms are rather related to sensitive visceral postsurgical disturbances; visceral hyperalgesia often plays a major role in symptoms arising from the digestive tract.29 In conclusion, this study suggests the high prevalence of upper small bowel motor disturbances after pancreatoduodenectomy, both in the early and later postoperative periods, whatever the surgical indication (chronic pancreatitis or carcinoma). Although we could not exclude a type II error because of the relative small number of patients and the rather irregular degree of motor patterns, very few differences were observed between the 2 types of pancreatic anastomosis in comparison with a control group. Fewer postsurgical motor changes do not appear to be an argument for preferring PGA to PJA. Acknowledgment: The authors thank Mr Richard Medeiros for his advice in editing this manuscript. References 1. Yeo CJ, Barry MK, Sauter PK, et al. Erythromycin accelerates gastric emptying after pancreaticoduodenostomy. A prospective, randomized, placebo-controlled trial. Ann Surg 1993;8:237–238. 2. McLeod RS, Taylor BR, O’Connor BI, et al. Quality of life, nutritional status, and gastro-intestinal hormone profile following the Whipple procedure. Am J Surg 1995;169:179–183. 3. Van der Mijle HC, Beekhuis H, Bleichrodt RP, Kleibeuker JH. Transit disorders of the gastric remnant and Roux en Y gastrojejunostomy: relation to symptomatology and vagotomy. Br J Surg 1993;80:60–64. 4. Shiota M. Clinical and experimental study on reconstruction after pancreatectomy: myoelectric activity of small intestine after pancreatoduodenectomy. J Jpn Surg Soc 1988;89:1241–1251. 5. Pastorino G, Ermili F, Zappatore F, et al. Multiparametric evaluation of functional outcome after pylorus-preserving duodenopancreatectomy. Hepato Gastroenterol 1995;42:62–67. 6. Millbourn E. Pancreatico-gastrostomy in pancreatico-duodenal resection for carcinoma of the head of the pancreas or the papilla of vater. Acta Chir Scandinav 1958;116:12–27. 7. Chaussade S, Grandjouan S, Couturier D, et al. Induction of Phase III of the migrating motor complex in human small intestine by trimebutine. Eur J Clin Pharmacol 1987;32:615–618. 8. Kellow JE, Borody TJ, Phillips SF, et al. Human interdigestive motility: variations in patterns from esophagus to colon. Gastroenterology 1986;91:386–395. 9. Riachi G, Ducrotte´ P, Guedon C, et al. Duodenojejunal motility after oral and enteral nutrition in humans: a comparative study. J Parenter Enteral Nutr 1996;20:150–155.
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10. Wilson P, Pardikis G, Hinder RA, et al. Prolonged ambulatory antroduodenal manometry in humans. Dig Dis Sci 1994;89: 1489–1495. 11. Wood JD. Neurophysiological theory of intestinal motility. Jpn J Smooth Muscle Res 1987;23:143–186. 12. Schippers E, Holscher AH, Bollschweiler E, Siewert JR. Return of interdigestive motor complex after abdominal surgery. End of post-operative ileus? Dig Dis Sci 1991;36:621–626. 13. Tanaka M, Sarr MG. Total duodenectomy: effect on canine gastrointestinal motility. J Surg Res 1987;42:483–493. 14. Wingate DL. Complex clocks. Dig Dis Sci 1983;28:1133–1140. 15. Johnson CP, Sarna SK, Cowles VE, et al. Motor activity and transit in the autonomically denervated jejunum. Am J Surg 1994;167: 80–88. 16. Pinnington J, Wingate DL. The effects of motilin on the periodic myoelectric spike activity in intact and transected canine small intestine. J Physiol 1983;337:471–478. 17. Owyang C, Achem Karam S, Funakoshi A, Vinik AI. Pancreaticobiliary secretion stimulates motilin release and initiates the interdigestive complex in man. Clin Res 1982;30:287–294. 18. Radymska-Wawrzyniak K, Bobowiec R, Studzinski T. Effects of bile and bile acids on spontaneous motor activity of the small and large rabbit intestine in vitro. Polskie Archiwum Weteynaryjne 1989;29:43–56. 19. Dooley CP, Di Lorenzo C, Valenzuela JE. Variability of migrating motor complex in humans. Dig Dis Sci 1992;37:723–728. 20. Thompson DG, Ritchie HD, Wingate DL. Patterns of small intestinal motility in duodenal ulcer patients before and after vagotomy. Gut 1982;23:517–523.
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21. Sarr MG, Kelly KA. Myoelectric activity on the autotransplanted canine jejunoileum. Gastroenterology 1981;81:303–310. 22. Simpson KW, Johnstone JMS, Bell PRF, Morton DB. Pancreatic function following partial pancreatectomy and anastomosis of the pancreatic duct to the stomach or duodenum in dogs. Res Vet Sci 1992;52:97–104. 23. Tangoku A, Nishikawa M, Adachi A, Suzuki T. Plasma gastrin and cholecystokinin response after pylorus preserving duodenopancreatectomy with Billroth I type reconstruction. Ann Surg 1990;214:56–60. 24. Shang JC, Sava P, Angel F, et al. Influence de l’absorption intestinale sur la motricite´ de l’intestin greˆle-Etude e´lectromyographique chez le chien. Gastroenterol Clin Biol 1981;5:490–496. 25. Guedon C, Ducrotte´ P, Chayvialle JA, et al. Effects of intravenous and intraduodenal fat on jejunal motility and on plasma cholecystokinin in man. Dig Dis Sci 1988;33:558–564. 26. Pain JA, Knight MJ. Pancreaticogastrostomy: the preferred operation for pain relief in chronic pancreatitis. Br J Surg 1988;75: 220–222. 27. Kotoura Y, Takahashi T, Ishikawa Y, et al. Hepatobiliary and gastro-intestinal imaging after pancreaticoduodenectomy—a comparative study on Billroth I and Billroth II reconstructions. Jpn J Surg 1990;20:294–299. 28. Malagelada JR, Camillari M, Stanghellini V. Manometric diagnosis of gastrointestinal motor disorders. New York: Thieme Inc, 1986. 29. Meyer EA, Gebhart GF. Basic and clinical aspects of visceral hyperalgesia. Gastroenterology 1994;107:271–293.
and mean area under the postprandial curve was higher (p < 0.01) than in asymptomatic patients. Propagated clusters of contractions were only found in symptomatic patients and in the afferent limb.
Background: The goal of this study was to compare upper jejunal motor patterns after Billroth II pancreatoduodenectomy according to the type of pancreatic anastomosis (pancreaticojejunostomy [PJA] or pancreaticogastrostomy [PGA]) and the presence or absence of postoperative symptoms.
Conclusions: Pancreatoduodenectomy is associated with significant motor disturbances, mainly slower phase III and a reduced fed pattern, in the upper jejunum, at least during the first 3 postoperative months. Few motor differences were observed between PGA and PJA pancreatic anastomosis. A lesser occurrence of postsurgical motor anomalies does not appear to be an argument for preferring PGA to PJA. (J Am Coll Surg 1999; 188:261–270. © 1999 by the American College of Surgeons)
Study Design: Manometric recordings during fasting and after a 750-kcal meal were performed in the afferent limb in 12 patients (7 PJA, 5 PGA) and in the efferent limb in 15 other patients (7 PJA, 8 PGA) with a postoperative delay of 15 6 6 days and 3.9 6 2.2 months respectively. Patient data were compared to those of 20 healthy controls. Results: During fasting, the 2 main abnormal findings were a higher incidence (p < 0.05) and a slower migration velocity (p < 0.01) of incomplete phase III by comparison with that recorded in controls. No difference for phase III was observed between the 2 surgical procedures regardless of recording site. Trimebutine, 100 mg intravenously, induced a phase III in 89% (24 of 27) of the patients. Delay of motor response varied from 5 to 10 minutes without difference between the recording site; it was less than 2 minutes in 100% of controls. Trimebutine-induced phase III showed similar propagation abnormalities to the spontaneous phase III. Duration of the fed pattern (p < 0.001) and motor index (p < 0.001) were significantly lower than in controls after the meal, in both limbs, whatever the type of anastomosis. Differences between the 2 surgical procedures were a slower migration velocity of phase III (p < 0.01) and a lower postmeal motor index (p < 0.05) in the efferent limb after PJA than after PGA. Nine of 27 patients were symptomatic. In these 9 patients, mean phase III migration velocity was slower (p < 0.001),
In about 30% to 40% of patients, pancreatoduodenectomy according to Whipple’s procedure is complicated by symptoms suggesting delayed gastric emptying or a dumping syndrome that severely impairs quality of life.1,2 After gastric and small bowel surgery, postoperative symptoms have been related to motor disturbances, such as interrupted or retrograde phase III or low postprandial activity.3 After pancreatoduodenectomy, an animal study has shown motor anomalies both in the afferent and efferent limbs.4 The single study in humans has confirmed anomalies of phase III in the efferent limb (low amplitude and frequency, interrupted propagation in 70% of the patients), and decreased amplitude of postprandial activity.5 After pancreatoduodenectomy, gastrointestinal and pancreatic continuity can be restored by performing either a pancreaticojejunostomy (PJA) or a pancreaticogastrostomy (PGA). Short surgical series suggest that functional results are better after PGA than after PJA.6 The aim of this study was to describe jejunal motor patterns after pancreatoduodenectomy in both types of anastomosis, PJA or PGA, in symp-
Received August 20, 1998; Revised October 15, 1998; Accepted November 4, 1998. From the Digestive Tract Research Group (Le Blanc, Ducrotte´, Denis, Michot, Tenie`re) and the Department of Vascular Surgery (Peillon, Testart), Rouen University Hospital, Rouen, France. Correspondence address: Isabelle Le Blanc, MD, Service de Chirurgie Digestive, Pavillon Derocque, Hoˆpital Charles Nicolle, 76031 Rouen Cedex, France. © 1999 by the American College of Surgeons Published by Elsevier Science Inc.
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Table 1. Postoperative Symptoms and Weight Evolution in the 27 Patients
Postoperative symptoms No symptoms Symptoms Epigastric fullness Nausea, vomiting Dumping Bloating Diarrhea Weight (kg) Before surgery After surgery
Pancreaticojejunal anastomosis (n 5 14)
Pancreaticogastric anastomosis (n 5 13)
9 5 2 5 0 0 0
9 4 1 3 0 0 1
69 6 18 72 6 16
73 6 22 72 6 24
Weight values are mean 6 SEM.
tomatic and asymptomatic patients, to determine whether postoperative motor disturbances are less frequent with PGA. METHODS Patients. Twenty-seven patients, 16 men and 11 women, were enrolled in this prospective study. PJA was performed from January 1, 1995 until January 8, 1996 and PGA from January 8, 1996 until January 12, 1997 by the same surgeons. Therefore, in 14 patients, gastrointestinal continuity was restored by PJA; in the 13 others, the anastomosis was PGA. In 20 of 27 patients, surgery was indicated for a resectable carcinoma of the head of the pancreas. In 10 patients, continuity was restored by PJA and in 10 by PGA. In all 20 patients, surgery was a potentially curative procedure. In the remaining 7 patients (4 PJA, 3 PGA) surgery was performed for chronic pancreatitis complicated by pain unrelieved by medical treatment, without possibility of derivation of the Wirsung duct. Antalgic medication was always stopped at least 10 days before the manometric study. Age of the patients (mean 6 SEM) was 59 6 12 years and 54 6 9 years in PJA and PGA groups respectively. No significant weight modification was observed between the pre- and postoperative periods (Table 1). Patients were regarded as symptomatic if they had symptoms occurring at least 5 days a week, requiring daily treatment with prokinetic drugs or transit modifiers, and observed at the time of the manometric recording session. Nine patients in each group were symptomatic and complained of at least one of the following symptoms (Table 1): epigastric fullness, nausea, vomiting, diarrhea. All the patients
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considered symptomatic at the time of the recording session remained symptomatic at least at the followup visits scheduled during the 6-month period following the study. Return of bowel function with gas emission was effective between 2 to 4 days after the surgical procedure and observed in all patients before the recording session. Manometric data obtained from the patient group were compared with those from 20 healthy volunteers, 10 men and 10 women, aged 20 to 56. This group also had duodenojejunal motor recordings that were obtained with the same manometric technique as in the patient group. Surgical procedure. In all cases, the proximal portion of the gastric antrum was not involved in the resection and no truncal vagotomy was performed. In PJA, the remaining pancreas was sutured terminolaterally to the proximal part of the jejunum, the biliary and pancreatic anastomoses were distant from 10 cm and the gastrojejunal anastomosis was 60 cm aborad (Fig. 1). In PGA, the remaining pancreas was sutured terminolaterally to the posterior face of the gastric remnant (Fig. 1). Technique of manometric recording. Jejunal manometry was performed with a tube assembly consisting of 4 polyvinyl catheters (0.8 mm internal diameter) with side holes 10 cm apart. Sensors were located at 5, 15, 25, and 35 cm from a rubber bag fixed to the tip and containing 2 mL of mercury to facilitate positioning. Radiopaque markers were inserted near the side hole to facilitate fluoroscopic control of the entire assembly. Recording lumens were perfused with degasified distilled water (0.5 mL/min) from a pressurized reservoir. At this infusion rate, the delay for pressure rise is 0.5 second for 102 mmHg. Pressure values from transducers (Gould Statham P23 ID, Oxnard, CA) were numbered with a frequency of 5 Hz per channel to be stored in the hard disk of an IBM/PC computer. Study design. Two different protocols were used in this study. None of the patients participated in both protocols. In protocol 1, studies were performed during the early postoperative period with a mean interval of 15 6 6 days between surgery and recording to analyze motility of the jejunum used for the biliary intestinal anastomosis in both surgical procedures (Fig. 1). This portion of jejunum will now be referred to as the afferent limb in the manuscript. In this protocol, the manometric probe was inserted during the surgical procedure at least in the first 50 cm of the afferent
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Figure 1. Surgical procedures and site of the manometric probe. (A) Pancreaticojejunal anastomosis—protocol 1: probe in the afferent limb. (B) Pancreaticojejunal anastomosis—protocol 2: probe in the efferent limb. (C) Pancreaticogastric anastomosis—protocol 1: probe in the afferent limb. (D) Pancreaticogastric anastomosis—protocol 2: probe in the efferent limb.
limb. This protocol was performed in 7 patients with PJA and in 5 patients with PGA anastomosis. In symptomatic patients who had received medication liable to affect motility, administration was stopped 1 week before the recording session. The aim of protocol 2, which had 15 other patients, was to record efferent limb motor activity after both surgical procedures. Fasting subjects were intubated between 9:00 a.m. and 10:00 a.m. Under fluoroscopic control the manometric probe was pushed into the efferent limb and its position was considered correct when at least 3 of the 4 sideholes were in the efferent limb (Fig. 1). The position of the probe in the efferent limb was always obtained before beginning the recording session. Studies were performed with a mean delay between surgery and recording of 3.9 6 1.2 months (mean 6 SEM) in PJA group (7 patients) and 2.9 6 0.7 months in PGA group (8 patients) (NS). In patients operated on for a pancre-
atic carcinoma, no sign of tumor recurrence was observed at the time of the study. In protocol 1, recordings were performed over a period of 4 to 7 hours in fasting subjects, and for 3 hours after a 750-kcal meal (carbohydrates, 46%; lipids, 36%; proteins, 18%). In protocol 2, recordings were done for at least 5 hours and were performed first in fasting subjects during the first 2 hours then in the 3 hours following the same 750kcal meal as in protocol 1. At the end of the manometric session, an intravenous injection of 100 mg trimebutine, known to induce a phase III in healthy volunteers,7 was systematically given. This study design was approved by the Ethics Committee of Haute Normandie (France) and all patients and healthy volunteers gave their informed consent. Analysis of the tracings. Analysis was visual for the interdigestive period, the postmeal period, and
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Table 2. Interdigestive Manometric Patterns Type of surgery
Afferent limb
Efferent limb
Pancreaticojejunal anastomosis Lack of phase III Normal phase III only Incomplete phase III Retrograde phase III Pancreaticogastric anastomosis Lack of phase III Normal phase III only Incomplete phase III Retrograde phase III
(n 5 7) 0 4 3 1 (n 5 5) 0 3 2 0
(n 5 7) 3 2 2 0 (n 5 8) 1 5 2 0
the response to trimebutine. Visual analysis was performed by 2 observers used to analyze small bowel manometry (ILB, PD). One observer (PD) was unaware of the type of surgical procedure, either PJA or PGA, when performing the analysis. During the interdigestive period, the aims of this visual analysis were to recognize phase IIIs to calculate their characteristics, and to analyze their propagation. A burst of motor activity was considered phase III according to previously published criteria.8 Briefly, phase III was defined as burst of contractions, aborally propagated and lasting at least 3 minutes at the maximum frequency (11–12 cycles per min21 in the jejunum). The frequency (number of phase IIIs per hour), duration, amplitude, and migration velocity were determined as previously described.9 Propagation was defined according to the 3 following modes: complete when the bursts of regular contractions were recorded successively at least by the 4 probe sensors, incomplete when the propagation was observed on the proximal but not the more distal sensors, retrograde when the propagation was aborad-orad on more than 2 sideholes. Analysis of the postprandial motor activity was both visual and computerized. Computerized analysis was performed using a previously validated software (2ERL, LOMATECH, Rennes, France).9 Postprandial motor parameters were calculated either on the period of time elapsed from the beginning of the meal to the return of a phase III or on the 3 postprandial hours in case of no reappearance of the phase III. The software analyzed the digital recording with the following successive steps: elimination of pressure waves related to respiration; detection of contraction waves; and calculation of the area under curve (AUC, mmHg/min), the number of contraction waves (NW), the wave amplitude (mmHg), and the percentage of recording time occupied by motor activity.9 All these parameters were automatically calcu-
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lated at each level of recording on each successive half hour of the postprandial period. The aim of the visual analysis was detection of propagating clustered contractions (PCCs) defined as repetitive phasic contractions at slow wave frequency (10–12/min), propagated, preceded, and followed by a period of quiescence.10 Statistical analysis. Except for phase III, parameters were calculated as means of the values recorded by all sensors, either in the afferent or the efferent limb. Student’s t-test and Wilcoxon nonparametric test were used to compare quantitative data, and chisquare test was used for the analysis of qualitative parameters. Correlation between 2 quantitative values was verified by the Spearman’s test. RESULTS Motility of the afferent limb (12 patients). During the interdigestive period, in the PJA group (7 patients), phase III was recorded in all 7 patients. Propagation was normal in only 4 patients. In the remaining 3 phase III was incomplete and propagated over less than 30 cm (Table 2). In the PGA group (5 patients), phase III was recorded in all 5 patients but was normally propagated in only 3 patients (Table 2). Therefore, a complete propagation was significantly less frequent in patients than in controls (7 of 12 versus 19 of 20, p , 0.02). In patients, phase III was more frequent (p , 0.05), had a lower amplitude (p , 0.05), and a slower migration velocity (p , 0.01) (Fig. 2) than in controls. Phase III duration was the only characteristic not different between patients and controls (Fig. 2). After the meal, phase III returned before the third postprandial hour more frequently in patients than in controls (10 of 12 versus 1 of 20, p , 0.001), in 6 of 7 PJA patients and in 4 of 5 PGA patients (NS) (Table 3). During this postprandial period, mean 30minute AUC was significantly lower than in controls (p , 0.001), without any difference between PGA and PJA groups (Fig. 3). As in controls, NW (Fig. 3) was positively correlated with AUC (r 5 0.66, p , 0.02). In 2 PJA patients and 1 PGA patient, PCCs were observed (Fig. 4). Motility of the efferent limb (15 patients). Phase III was recorded in 12 patients but was normally propagated in only 7 patients (Table 2). Comparison with phase III recorded in healthy volunteers shows a slower migration velocity (p , 0.01) and a longer duration (p , 0.05) in patients (Fig. 2). After PJA, the migration velocity was slower (p , 0.05)
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than after PGA, when duration and amplitude were not different. After the meal, phase III returned within the 3 postprandial hours more frequently than in controls (10 of 15 patients versus 1 of 20 controls, p , 0.001), in 3 of 7 PJA patients and in 7 of 8 PGA patients (NS) (Table 3). During this postprandial period, mean 30-minute AUC was significantly lower than in controls (p , 0.001) and AUC was lower after PJA than after PGA (64 6 13 versus 103 6 18 mmHg/min, p , 0.05) (Fig. 3). As in the afferent limb, NW was correlated with AUC (r 5 0.61, p , 0.01) (Fig. 3). No PCC was observed in any patient in the efferent limb. Response to 100 mg intravenous trimebutine. In each healthy volunteer, trimebutine induced a phase III having the same characteristics as spontaneous phase III, in the 2 minutes following the injection. In the PJA group, trimebutine induced a motor response in 12 of 14 patients, in particular, in all 7 patients recorded in the afferent limb. Trimebutineinduced phase III had a similar propagation, complete or not, as a spontaneous phase III, without any difference between afferent and efferent limbs. In 2 patients, trimebutine induced a phase III when none was noted during the interdigestive recording. The delay of motor response after intravenous injection was not different between afferent and efferent limb (8.1 6 1.7 minutes versus 10.0 6 2.0 minutes). Trimebutine-induced phase III was of higher amplitude than the spontaneous one (p , 0.05) and not different from that in healthy controls (Fig. 5). Duration and velocity of phase III induced by trimebutine was not different from spontaneous phase III (Fig. 5). In the PGA group, trimebutine induced a motor response in all patients except 1 in whom recordings were performed only in the efferent limb. In 1 patient, trimebutine induced a phase III, but none was recorded during the interdigestive recording. On the other hand, the patient who failed to respond to trimebutine had spontaneous phase III. The delay for the motor response after intravenous injection was not different from those of the PJA group (5.1 6 1.2 minutes in the afferent limb, and 6.2 6 1.3 minutes in the efferent limb). Trimebutine-induced phase III was of higher amplitude than the spontaneous one (p , 0.05) and not different from that of healthy controls (Fig. 5). The number, delay, and characteristics of the trimebutine-induced phase III were not
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Figure 2. Characteristics of phase III. (A) Phase III number per hour21; (B) phase III amplitude (mmHg); (C) migration velocity (cm per min2); (D) phase III duration (min). *p , 0.05 versus controls, †p , 0.05 versus group PGA, ‡p , 0.05 versus efferent. Values are mean 6 SEM. PGA, pancreaticogastric anastomosis; PJA, pancreaticojejunal anastomosis.
different between the 2 groups, both on the afferent and efferent limb (Fig. 5). Comparison between symptomatic and asymptomatic patients. Nine of the 27 patients (33%) were symptomatic, 5 of 14 patients with PJA and 4 of 13 in patients with PGA (Table 1). All reported an epi-
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Table 3. Postprandial Manometric Patterns Duration (min) of phase III interruption after the meal Pancreaticojejunal anastomosis Number of patients with a duration . 180 , 180 (mean duration) Pancreaticogastric anastomosis Number of patients with a duration . 180 , 180 (mean duration) Controls Number of patients with a duration . 180 (mean duration) , 180
Afferent limb Total (n 5 7)
Efferent limb
Symptomatic Asymptomatic (n 5 2)
Total
Symptomatic Asymptomatic
(n 5 5)
(n 5 7)
(n 5 3)
1 0 6 (56 6 19*) 2 (66 6 19*) (n 5 5) (n 5 2)
1 4 (51 6 15*) (n 5 3)
4 3 3 (115 6 15*) 0 (n 5 8) (n 5 2)
1 3 (115 6 15) (n 5 6)
1 1 4 (64 6 14*) 1 (43*) n 5 20
0 3 (72 6 18*)
1 7 (74 6 16*)
1 5 (79 6 14*)
0 2 (51 6 1*)
(n 5 4)
19 (419 6 15) 1 (155)
*p , 0.001 vs controls. Values are means 6 SEM.
gastric fullness or nausea and vomiting. A slower migration velocity in the symptomatic patients, without difference between afferent and efferent limb (Table 4), was the only motor difference during fasting between symptomatic and asymptomatic patients. After the meal, symptomatic patients had a
Figure 3. Mean postprandial values of area under the curve and number waves per 30 min period. (A) Postprandial AUC (mmHg per min) per 30 min period; (B) number waves per 30 min period. *p , 0.001 versus controls, †p , 0.05 versus group PGA. Values are mean 6 SEM. AUC, area under curve; PGA, pancreaticogastric anastomosis; PJA, pancreaticojejunal anastomosis.
higher (p , 0.05) postprandial AUC in the efferent limb (Fig. 6), but the same duration of the fed pattern (Table 3). PCCs were more frequent in the symptomatic than in the asymptomatic patients; they were recorded only in the afferent limb, in 3 of the 4 symptomatic patients (2 PJA, 1 PGA), and never in the asymptomatic patients. DISCUSSION In humans, motor disturbances are frequent after supramesocolic surgical procedures.3 The absence of information on jejunal motility after pancreaticoduodenectomy was the basis of this study with a comparison between PGA and PJA anastomosis. Before this study, we speculated that motor patterns would be different between the two types of anastomosis because of the arrival site of biliary and pancreatic secretions and the mixing with the luminal content, which differ between the two procedures. Luminal factors are known to influence motor patterns.11 Moreover, electromyographic studies in animals have demonstrated that the digestive reconstruction mode after pancreaticoduodenectomy influences postoperative motility with a disturbed phase III propagation and a lack of fed pattern more frequent after Billroth II than Billroth I gastrointestinal anastomosis.4 Our study demonstrated, both in early and later postoperative periods, that none of the 27 patients had jejunal motility that could be considered normal. In this study, recordings were never performed before
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Figure 4. Example of propagated clusters of contractions (PPCs) recorded during postoperative period in an afferent limb. PPCs were defined as repetitive propagated phasic contractions at 10–12 cycles/min21, preceded and followed by a period of quiescence.11
the sixth postoperative day to avoid considering acute motor changes, only related to the postoperative ileus12 as chronic motor disturbances. During the interdigestive period, pancreaticoduodenectomy disturbed the amplitude, migration velocity, and mode of propagation of the phase III in the jejunum by comparison with a control group. After PGA, motor disturbances were less pronounced than after PJA, with phase III characteristics more similar than those in controls, and postmeal motor activity reduced less in only the efferent limb. Interdigestive motility disturbances were not uniform in our series. Therefore, in both groups, the 2 main abnormal features concerning phase III were disturbed incidence and slow propagation. Frequent, slowly propagated, and often incomplete phase III was the main anomaly found. Animal studies have shown that duodenectomy disturbed jejunal fasting motor activity, increased the number, and decreased the migration velocity of phase III.13 A slow migration velocity has previously been reported in dogs after Whipple’s procedure with a PJA.4 The study design does not permit us to explain these motor changes. However, several mechanisms could be involved in these interdigestive jejunal motor changes. Intestinal fasting motor activity is controlled by a sophisticated neural network, the enteric nervous system, which itself is influenced by extrinsic nerves and circulating hormones. When the head of the pancreas is resected, the surgical procedure interrupts the intrinsic circuitry and removes the duodenum where the pacemaker controlling the motor activity of the bowel has been located.14 Extrinsic denervation of the jejunum was shown
to increase phase III frequency, to shorten the propagation and to slow intestinal transit in dogs.15 However, vagus and mesenteric vasculonervous connections were always carefully preserved during the
Figure 5. Characteristics of phase III after trimebutine. White bar, spontaneous phase III; black bar, phase III after trimebutine; hatched bar, controls. * p , 0.02 versus controls, † p , 0.05 versus spontaneous phase III. Values are mean 6 SEM. PGA, pancreaticogastric anastomosis; PJA, pancreaticojejunal anastomosis.
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Table 4. Phase III Characteristics in Symptomatic and Asymptomatic Patients Patients Afferent limb PJA Symptomatic (n 5 2) Asymptomatic (n 5 5) PGA Symptomatic (n 5 2) Asymptomatic (n 5 3) Efferent limb PJA Symptomatic (n 5 3) Asymptomatic (n 5 4) PGA Symptomatic (n 5 2) Asymptomatic (n 5 6)
Migration velocity (cm/min)
Duration (min)
Amplitude (mmHg)
1.5 6 0.1 3.3 6 0.2
5.5 6 0.3 6.3 6 0.4
25 6 2 23 6 2
1.4 6 0.1 5.0 6 0.3
3.7 6 0.2 4.6 6 0.3
24 6 3 21 6 2
1.7 6 0.1 2.1 6 0.2
8.7 6 0.5 8.0 6 0.4
28 6 3 24 6 2
1.1 6 0.1 5.5 6 0.3
8.5 6 0.3 6.0 6 0.4
35 6 3 31 6 3
PGA, pancreaticogastric anastomosis; PJA, pancreaticojejunal anastomosis.
surgical procedure in our study to maintain small bowel vitality; the hypothesis of motor disturbances related to extrinsic lesions therefore appears unlikely. Surgical procedure also disturbs circulating hormones, and after duodenectomy motilin levels decrease dramatically.13 This hormonal change must be
Figure 6. Postprandial values of area under the curve and number waves per 30 minute period in symptomatic and asymptomatic patients. White bar, asymptomatic; gray bar, symptomatic; black bar, controls. (A) Postprandial area under the curve per 30 min (mmHg per min); (B) number waves per 30 min. *p , 0.05 versus asymptomatic patients. PGA, pancreaticogastric anastomosis; PJA, pancreaticojejunal anastomosis.
taken into account even if motilin effects on jejunal phase III have been less extensively studied than those on antral phase III.16 The more disturbed phase III activity after PJA than after PGA anastomosis in the efferent limb emphasizes the role of luminal content on motility. Among the anatomic changes after pancreaticoduodenectomy, a difference in the arrival site of biliary and pancreatic secretions is the only anatomic difference between the 2 surgical procedures, with a different mixing in the luminal content. This could explain the differences of motor patterns that we observed between the 2 surgical procedures. Bile has a direct stimulating effect on duodenal migrating activity,17 correlated with the doses and the rate of intraluminal flow.18 The motor effect of bile could be the reason for the high phase III incidence found in the afferent limb. At variance, few patients had no phase III during the recording session. The great variability in the incidence of the phase III is well recognized19 and the relatively short duration of fasting recordings could have overestimated the absence of phase III. However, in most of the patients without spontaneous phase III, the lack of response to 100 mg intravenous trimebutine was an argument to not consider this absence of phase III as a methodologic artefact. In most patients, fed motor pattern was disturbed, both reduced in amplitude in 27 patients and significantly shorter than in controls, with a return of phase III before the third postprandial hour in 22 of the 27 patients. Postprandial motor results confirm animal data that have shown the absence of fed pattern after a pancreaticoduodenectomy with digestive
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continuity restored with PJA.4 The same hypothesis that applies to interdigestive motor changes can be evoked to explain motor anomalies recorded during the fed period. Duodenectomy abolished the suppressive effect of a meal on cyclic fasting motility;13 postsurgical nervous damages could shorten and reduce fed pattern because a short fed pattern has been reported in humans after vagotomy,20,21 but no extrinsic lesions were created during the surgical procedure in our study. The secretion of gastrin, cholecystokinin, or insulin, all hormones involved in the onset of a fed pattern, has been shown to significantly decrease after pancreaticoduodenectomy,2,22,23 and Simpson and colleagues22 have shown that insulin secretion is more severely disturbed after PGA than PJA. Fed pattern anomalies could also be explained by an impaired nutrient absorption; duration and importance of postprandial motor activity are related to the absorption rate of the nutrients24 and to postprandial blood concentrations of nutrients.25 After pancreatoduodenectomy, absorption is often impaired.26 In both types of anastomosis, bile arrives 60 cm orad the gastrojejunal anastomosis and an asynchronism between arrival of the meal in the jejunal lumen and bile secretion appears possible.27 Synchronization between arrival of the meal and pancreatic enzyme secretion is theorically better after PGA than PJA, providing better mixing conditions of nutrients with pancreatic secretion, a better digestion, and improved absorption. This improved synchronization could be one of the reasons why a more significant fed pattern was observed after PGA than PJA in the efferent limb. However, in PGA, pancreatic enzymes are secreted directly into the stomach and gastric chloric acid and the lack of enteropeptidases are both well recognized factors preventing activation of pancreatic enzymes. A better digestion after PGA than PJA remains to be demonstrated. Interpretation of PPCs is difficult. Their onset in the afferent limb only in symptomatic patients is noteworthy. Repetitive clusters of phasic pressure waves are suggestive of partial mechanical obstruction, particularly when the clusters have a very prominent tonic component.28 This was not the case in our study. Therefore, it is difficult to affirm that these patterns were related to a partial mechanical obstruction. The last finding of this study was the absence of major differences in the motor patterns between the 9 symptomatic and the 18 asymptomatic patients. The main differences were a slower phase III migration velocity, a higher postprandial AUC, and more frequent PCCs in the afferent limb in symptomatic
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patients. It seems difficult to explain postoperative symptoms by these subtle motor jejunal differences even if they could impair transit of the luminal content; the efferent limb after pancreaticoduodenostomy in our symptomatic patients could in fact be in a state of greater contraction less likely to empty than in asymptomatic patients. Symptoms could also be related to motor changes in other digestive areas, mainly the stomach, although Pastorino and associates5 did not report major motor anomalies on the gastric remnant after pancreatoduodenectomy. Another explanation is that symptoms are rather related to sensitive visceral postsurgical disturbances; visceral hyperalgesia often plays a major role in symptoms arising from the digestive tract.29 In conclusion, this study suggests the high prevalence of upper small bowel motor disturbances after pancreatoduodenectomy, both in the early and later postoperative periods, whatever the surgical indication (chronic pancreatitis or carcinoma). Although we could not exclude a type II error because of the relative small number of patients and the rather irregular degree of motor patterns, very few differences were observed between the 2 types of pancreatic anastomosis in comparison with a control group. Fewer postsurgical motor changes do not appear to be an argument for preferring PGA to PJA. Acknowledgment: The authors thank Mr Richard Medeiros for his advice in editing this manuscript. References 1. Yeo CJ, Barry MK, Sauter PK, et al. Erythromycin accelerates gastric emptying after pancreaticoduodenostomy. A prospective, randomized, placebo-controlled trial. Ann Surg 1993;8:237–238. 2. McLeod RS, Taylor BR, O’Connor BI, et al. Quality of life, nutritional status, and gastro-intestinal hormone profile following the Whipple procedure. Am J Surg 1995;169:179–183. 3. Van der Mijle HC, Beekhuis H, Bleichrodt RP, Kleibeuker JH. Transit disorders of the gastric remnant and Roux en Y gastrojejunostomy: relation to symptomatology and vagotomy. Br J Surg 1993;80:60–64. 4. Shiota M. Clinical and experimental study on reconstruction after pancreatectomy: myoelectric activity of small intestine after pancreatoduodenectomy. J Jpn Surg Soc 1988;89:1241–1251. 5. Pastorino G, Ermili F, Zappatore F, et al. Multiparametric evaluation of functional outcome after pylorus-preserving duodenopancreatectomy. Hepato Gastroenterol 1995;42:62–67. 6. Millbourn E. Pancreatico-gastrostomy in pancreatico-duodenal resection for carcinoma of the head of the pancreas or the papilla of vater. Acta Chir Scandinav 1958;116:12–27. 7. Chaussade S, Grandjouan S, Couturier D, et al. Induction of Phase III of the migrating motor complex in human small intestine by trimebutine. Eur J Clin Pharmacol 1987;32:615–618. 8. Kellow JE, Borody TJ, Phillips SF, et al. Human interdigestive motility: variations in patterns from esophagus to colon. Gastroenterology 1986;91:386–395. 9. Riachi G, Ducrotte´ P, Guedon C, et al. Duodenojejunal motility after oral and enteral nutrition in humans: a comparative study. J Parenter Enteral Nutr 1996;20:150–155.
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Le Blanc et al
Small Bowel Motility after Pancreatoduodenectomy
10. Wilson P, Pardikis G, Hinder RA, et al. Prolonged ambulatory antroduodenal manometry in humans. Dig Dis Sci 1994;89: 1489–1495. 11. Wood JD. Neurophysiological theory of intestinal motility. Jpn J Smooth Muscle Res 1987;23:143–186. 12. Schippers E, Holscher AH, Bollschweiler E, Siewert JR. Return of interdigestive motor complex after abdominal surgery. End of post-operative ileus? Dig Dis Sci 1991;36:621–626. 13. Tanaka M, Sarr MG. Total duodenectomy: effect on canine gastrointestinal motility. J Surg Res 1987;42:483–493. 14. Wingate DL. Complex clocks. Dig Dis Sci 1983;28:1133–1140. 15. Johnson CP, Sarna SK, Cowles VE, et al. Motor activity and transit in the autonomically denervated jejunum. Am J Surg 1994;167: 80–88. 16. Pinnington J, Wingate DL. The effects of motilin on the periodic myoelectric spike activity in intact and transected canine small intestine. J Physiol 1983;337:471–478. 17. Owyang C, Achem Karam S, Funakoshi A, Vinik AI. Pancreaticobiliary secretion stimulates motilin release and initiates the interdigestive complex in man. Clin Res 1982;30:287–294. 18. Radymska-Wawrzyniak K, Bobowiec R, Studzinski T. Effects of bile and bile acids on spontaneous motor activity of the small and large rabbit intestine in vitro. Polskie Archiwum Weteynaryjne 1989;29:43–56. 19. Dooley CP, Di Lorenzo C, Valenzuela JE. Variability of migrating motor complex in humans. Dig Dis Sci 1992;37:723–728. 20. Thompson DG, Ritchie HD, Wingate DL. Patterns of small intestinal motility in duodenal ulcer patients before and after vagotomy. Gut 1982;23:517–523.
J Am Coll Surg
21. Sarr MG, Kelly KA. Myoelectric activity on the autotransplanted canine jejunoileum. Gastroenterology 1981;81:303–310. 22. Simpson KW, Johnstone JMS, Bell PRF, Morton DB. Pancreatic function following partial pancreatectomy and anastomosis of the pancreatic duct to the stomach or duodenum in dogs. Res Vet Sci 1992;52:97–104. 23. Tangoku A, Nishikawa M, Adachi A, Suzuki T. Plasma gastrin and cholecystokinin response after pylorus preserving duodenopancreatectomy with Billroth I type reconstruction. Ann Surg 1990;214:56–60. 24. Shang JC, Sava P, Angel F, et al. Influence de l’absorption intestinale sur la motricite´ de l’intestin greˆle-Etude e´lectromyographique chez le chien. Gastroenterol Clin Biol 1981;5:490–496. 25. Guedon C, Ducrotte´ P, Chayvialle JA, et al. Effects of intravenous and intraduodenal fat on jejunal motility and on plasma cholecystokinin in man. Dig Dis Sci 1988;33:558–564. 26. Pain JA, Knight MJ. Pancreaticogastrostomy: the preferred operation for pain relief in chronic pancreatitis. Br J Surg 1988;75: 220–222. 27. Kotoura Y, Takahashi T, Ishikawa Y, et al. Hepatobiliary and gastro-intestinal imaging after pancreaticoduodenectomy—a comparative study on Billroth I and Billroth II reconstructions. Jpn J Surg 1990;20:294–299. 28. Malagelada JR, Camillari M, Stanghellini V. Manometric diagnosis of gastrointestinal motor disorders. New York: Thieme Inc, 1986. 29. Meyer EA, Gebhart GF. Basic and clinical aspects of visceral hyperalgesia. Gastroenterology 1994;107:271–293.