Infl uence of the functional state of the pancreas on the pressure in the proximal duodenum in patients with chronic biliary pancreatitis and postcholecystectomy syndrome

Objective. To investigate the pressure in the proximal duodenum after intraduodenal injection of 0.1 M hydrochloric acid and sunflower oil solution in patients with chronic biliary pancreatitis and postcholecystectomy syndrome depending on the state of excitation and inhibition in the pancreas. Materials and methods. We examined 316 patients with a clinical diagnosis of chronic biliary pancreatitis and 53 patients with postcholecystectomy syndrome. The pancreatic function was assessed by the method of complex fractional gastroduodenal probing. To assess the state of excitation and inhibition processes in the pancreas, the pressure in the antrum of the stomach was measured during stimulated pancreatic secretion using an open catheter. Results. In patients with chronic biliary pancreatitis and postcholecystectomy syndrome after intraduodenal administration of 0.1 M hydrochloric acid solution and sunflower oil, 4 pressure ranges in the duodenal cavity were observed: 0 – 5, 6 – 13, 14 – 18 and 19 – 42 mm Hg. After intraduodenal injection of 0.1 M hydrochloric acid solution among patients with chronic biliary pancreatitis at a pressure in the antrum of the stomach of 0 – 5 mm Hg. statistically significantly increased the proportion of patients with a pressure of 6 – 13 mm Hg (48.09%) and decreased the proportion of patients with a pressure of 19 – 42 mm Hg. (19.85%) in the duodenal cavity compared to the corresponding figures for unstable pressure in the antrum – 35.59 and 30.51% (p < 0.05) and for pressure in the antrum of the stomach 6 – 9 mm Hg – 32 and 36% (p < 0.025). Among patients with postcholecystectomy syndrome with a pressure in the antrum of the stomach of 0 – 5 mm Hg, the proportion of patients with a pressure of 6 – 13 mm Hg increased statistically significantly (52.94%) and the proportion of patients with a pressure of 19 – 42 mm Hg (11.76%) decreased compared with the corresponding figures for unstable pressure in the antrum – 19.35 and 51.61% (p < 0.01). After intraduodenal administration of sunflower oil among patients with chronic biliary pancreatitis with a pressure in the antrum of the stomach of 0 – 5 mm Hg, the proportion of patients with a pressure of 14 – 18 mm Hg increased statistically significantly (47.33%) and decreased the proportion of patients with a pressure of 19 – 42 mm Hg (40.46%) compared with the corresponding figures for unstable pressure in the antrum – 32.2 and 64.41% (p < 0.01), 6 – 9 mm Hg – 36 and 64% (p < 0.01) and 10 and above mm Hg – 17.65 and 82.35% (p < 0.025). Conclusions. The pressure in the proximal duodenum after administration of 0.1 M hydrochloric acid solution and sunflower oil depends on the state of the excitation process in the pancreas: the pressure in the range of 0 – 5 and 6 – 13 mm Hg after administration of 0.1 M hydrochloric acid solution and 6 – 13 and 14 – 18 mm Hg after administration of sunflower oil indicates normal or reduced pancreatic excitability, pressure in the range of 14 – 18 and 19 – 42 mm Hg after administration of 0.1 M hydrochloric acid solution and 19 – 42 mm Hg after administration of sunflower oil – increased pancreatic excitability.

In patients with functional dyspepsia, the duodenal mucosa (DM) is hypersensitive to hydrochloric acid (HCl) and lipids, but the pathogenesis of these disorders has not been investigated [1][2][3].The reason for the increased sensitivity of the duodenal mucosa to HCl may be an increase in the duration of contact of HCl with the mucosa due to hypokinesia of the proximal part of the duodenum [4].Previously, we have obtained data that the secretion of pancreatic juice and bile in healthy volunteers with chronic biliary pancreatitis (CBP) and chronic pancreatitis (CP) begins only after reaching a pressure in the cavity of the proximal part of the duodenum of 14-18 mm Hg.Taking into account these data, 4 pressure ranges were identified that characterise the readiness of the pancreas (PG) for secretion: at rest (0 -5 mm Hg), basal (6 -13 mm Hg), threshold secretory (14 -18 mm Hg) and secretory .We also found

GENERAL PROBLEMS OF SURGERY
The Ukrainian Journal of Clinical Surgery that in patients with IBD and CP, the relationship between the increase in duodenal pressure and the secretion of pancreatic secretion was lost -the secretion of each portion of pancreatic secretion could be preceded by several increases in duodenal pressure.This suggests that the functional state of the pancreas affects the pressure in the proximal duodenum, and this effect is not necessarily related to the presence of pancreatic secretion.It is interesting to find out whether the functional state of the pancreas affects the pressure in the duodenal cavity during the latent period (LP) of pancreatic secretion.
The aim of the study was to investigate the pressure in the proximal part of the duodenum after intraduodenal injection of 0.1 M HCl solution and sunflower oil (SO) in patients with chronic biliary disease and postcholecystectomy syndrome (PCS), depending on the state of excitation and inhibition in the pancreas.

Materials and methods
We examined 316 patients with a clinical diagnosis of CBD (190 women and 126 men), whose average age was (34.3 ± 11.13) years, and 53 patients with PCaE (40 women and 13 men), whose average age was (53.68 ± 7.43) years.
The pancreatic function was assessed by the method of complex fractional gastroduodenal probing, modified in our clinic (copyright certificate No. 942711, 1982).As a stimulator of pancreatic secretion, 30 ml of 0.1 M HCl solution was used.To assess the state of excitation and inhibition in the pancreas, the pressure in the antrum of the stomach (AS) was measured during stimulated pancreatic secretion using an open catheter (multichannel pressure meter manufactured by Saturn, Ukraine).The pressure in the AS in the range of 0 -5 mm Hg indicated the balance of excitation and inhibition in the pancreas, 6 -9 mm Hg -the limiting tension of the inhibition process, 10 mm Hg and above -the failure of the inhibition process, unstable pressure (a combination of two or three types of pressure) -an imbalance of excitation and inhibition due to the weakness of the inhibition process.The volume of stimulated pancreatic secretion of 181 -260 ml was considered normal.
The study was performed in the morning on an empty stomach with a probe consisting of two linked duodenal probes (gastric end 10 cm above the oleum).After insertion of the gastric end of the probe in the area of the AS and the olive in the middle third of the descending part of the duodenum, the basal portion of the duodenal contents was collected every 5 min for 20 min, and in case of longer secretion -until it stopped.Then, 30 ml of 0.1 M HCl solution was injected into the duodenal cavity and the pressure was measured until the onset of stimulated PZ secretion.After its onset, the secretion was collected in the same way every 5 min.After the end of pancreatic secretion, 20 ml of SO was injected into the duodenal cavity and the pressure was measured until the onset of gallbladder contraction.The pressure was measured and the secretion was collected through one channel.The pressure in the ABG was recorded continuously, except for short-term shutdowns for gastric contents sampling.The maximum pressure values recorded in the duodenal cavity during the first 2 min after the start of the injection of 0.1 M HCl and SO solution were taken into account.
The statistical significance of the differences in the indicators was assessed using the non-parametric criterion 2 , and the Yates and Bonferroni corrections were applied.

Results
Measurement of the pressure in the proximal part of the duodenum after administration of 0.1 M HCl solution, depending on the type of pressure in the duodenum during

Note.
UJCS. 2024 May/June; 91(3) The Ukrainian Journal of Clinical Surgery stimulated pancreatic secretion in patients with IBD and PSC (Table 1), showed that among patients with IBD with a duodenal pressure of 0 -5 mm Hg. there was an increase in the proportion of patients with RV pressure of 6 -13 mm Hg compared with the corresponding figures for unstable AS pressure (p < 0.05) and 6 -9 mm Hg (p < 0.025) and a decrease in the proportion of patients with RV pressure of 19 -42 mm Hg compared with the corresponding figure for unstable AS pressure (p < 0.05).Among patients with PCES, the proportion of patients with a LVAD pressure of 0 -5 mm Hg increased and the proportion of patients with a LVAD pressure of 6 -13 mm Hg decreased compared with the corresponding indicators in unstable LVAD pressure (p < 0.01).
According to the results of measuring the pressure in the proximal part of the duodenum after SO administration, depending on the type of pressure in the duodenum during stimulated pancreatic secretion in patients with CBP (Table 2), at a pressure in the duodenum of 0 -5 mm Hg, the proportion of patients with a duodenal pressure of 14 -18 mm Hg increased and the proportion of patients with a duodenal pressure of 19 -42 mm Hg decreased.There were no statistically significant differences between the proportion of patients with an unstable (p < 0.01), 6 -9 (p < 0.01) and 10 and above (p < 0.025) mm Hg in the pressure in the AS.
The results obtained indicate differences between the response of the duodenum to intraduodenal injection of 0.1 M HCl solution in patients with IBD and PCES at a pressure in the AS of 0-5 mm Hg and its other types.These differences are not related to the influence of the gallbladder, as patients with PCES do not have it, so it can be assumed that they are due to the functional state of the pancreas.Given that we are talking about the pressure in the duodenum during stimulated pancreatic secretion as an indicator of the state of inhibition in the pancreas, it can be assumed that the pressure in the duodenal cavity in response to the introduction of 0.1 M HCl solution indicates the state of excitation in the pancreas.According to the results of the study, in patients with CBP and PCES with balanced processes of excitation and inhibition of the pancreas, the pressure in the duodenum was more often observed at 6-13 mm Hg, which is probably a normal reaction to the intraduodenal injection of 0.1 M HCl solution.In patients with CBP and PCES with a weakened process of inhibition in the pancreas, the ductal pressure of 19-42 mm Hg was observed more often, which probably indicates increased excitability of the pancreas.At the same time, in patients with CBP with a weakened pro-

The Ukrainian Journal of Clinical Surgery
cess of inhibition in the pancreas, the frequency of pressure in the pancreas of 6 -13 and 19 -42 mm Hg was the same.This fact suggests that a pressure of 6-13 mm Hg in the duodenum may indicate not only normal but also reduced excitability of the pancreas, since the imbalance of excitation and inhibition in the pancreas is characterised by not only increased but also reduced excitability.
Interesting results were obtained in patients with IBD at a pressure in the AVC of 6-9 mm Hg.We consider this type of pressure in the AVC as a sign of the limiting tension of the inhibition process in the pancreas.This conclusion was made on the basis of the results obtained earlier [6], according to which impaired gallbladder motility and common bile duct sphincter function equally affect the frequency of pressure in the ABD of 6-9 and 0-5 mm Hg.According to the results of this study, the frequency of pressure in the duodenum of 6 -13 and 19 -42 mm Hg was statistically significantly different at the pressure in the AS of 6 -9 and 0 -5 mm Hg and was identical at the pressure in the AS of 6 -9 mm Hg and unstable.Since the limiting stress of the inhibition process in the pancreas should be accompanied by very strong excitation, the high frequency of the pressure in the IPC of 19 -42 mm Hg at the pressure in the AS of 6 -9 mm Hg does not contradict the assumption that this type of pressure in the AS indicates increased excitability of the pancreas.The frequency of 14-18 and 19-42 mm Hg pressure in the RCA at 0-5 and 10 and above mm Hg was not statistically significantly different, but at 10 and above mm Hg RCA pressure, the pressure in the RCA was observed more often (47.06%)than the pressure of 19-42 mm Hg (29.41%).On this basis, it can be assumed that the pressure in the WPC of 14 -18 mm Hg also indicates increased excitability of the pancreas.
Measurement of the indicators of pressure in the RV after the administration of SO in patients with CBP showed that the differences between the proportions of patients with different indicators of pressure in the RV at the pressure in the AS of 0 -5 mm Hg and other types of its pressure remained, but their ratio changed due to a significant decrease in the proportion of patients with a pressure in the RV of 6 -13 mm Hg (0 -12.21%, depending on the type of pressure in the AS).Most likely, this is a consequence of different properties of stimuli and the pressure in the RCA of 6 -13 mm Hg after the injection of 0.1 M HCl solution is analogous to the pressure in the RCA of 6 -13 and 14 -18 mm Hg after the injection of SO and indicates normal or reduced excitability of the RCA.Accordingly, the analogue of the pressure in the RPE after injection of 0.1 M HCl solution is 14 -18 and 19 -42 mm Hg, the pressure in the RPE after SO injection is 19 -42 mm Hg, which indicates increased excitability of the RPE.
At the same time, according to Tables 1 and 2, in some patients in the pancreas, the state of increased excitability changed to a state of normal or decreased excitability and vice versa.Therefore, we studied the pressure in the proximal part of the duodenum after SO administration depending on the pressure in the proximal part of the duodenum after the administration of 0.1 M HCl solution and the type of pressure in the AVC during stimulated pancreatic secretion (Table 3).
According to Table 3, the proportion of patients with changes in pancreatic excitability is much higher than expected.The highest proportion of patients was found to be those with preserved increased excitability of the pancreas -72.22 -80.56%.With an AS pressure of 0 -5 mm Hg and a RV pressure after administration of 0.1 M HCl solution of 6 -13 mm Hg, the proportion of patients with a RV pressure after SO administration of 14 -18 mm Hg was higher (55.56%), and the proportion of patients with a RV pressure after CO administration of 19 -42 mm Hg was lower (25.4%)than the corresponding figures for unstable AS pressure -42.86 and 54.76% (p < 0.05).Thus, the latter indicators indicate a higher probability of the transition of the pancreas to a state of increased excitability, which is a sign of instability and confirms the assumption that the pressure in the ductus arteriosus of 6-13 mm Hg after the introduction of 0.1 M HCl solution with unstable pressure in the AS indicates a reduced pancreatic excitability.However, in both cases, the proportion of patients with increased excitability was less than the similar proportion of patients with RV pressure after injection of 0.1 M HCl solution of 19-42 mm Hg. -55.56 and 25.4% and 26.92 and 73.08%, respectively (p < 0.005), 42.86 and 54.76% and 19.44 and 80.56%, respectively (p < 0.05), which indicates sufficient stability of the balance of excitation and inhibition in the RV in these patients.At other types of pressure in AS, no statistically significant differences between the studied parameters were found, which can be explained by the instability of the balance of the corresponding processes in the pineal gland.
The results obtained indicate that during the period from the beginning of the administration of 0.1 M HCl solution to the beginning of the administration of SO, i.e. during the LP of pancreatic secretion or during secretion, a significant number of patients with CBP change the balance of excitation and inhibition in the pancreas.At a pressure in the AS of 0-5 mm Hg, 48.85% of patients with CBP with increased excitability of the pancreas during LP restored the balance of excitation and inhibition, which can be explained by increased inhibition.A similar process occurred in 100% of patients with CVD with an AS pressure of 6-9 mm Hg, if the pressure in the duodenum of 6-13 mm Hg in these patients is interpreted as a sign of reduced excitability of the pancreas.In patients with unstable AS pressure during the LP of pancreatic secretion, the balance between the processes of excitation and inhibition was not restored, but this does not exclude the increase in the process of inhibition in these patients.

The Ukrainian Journal of Clinical Surgery
The volume of stimulated pancreatic secretion in patients with IBD depending on the pressure in the proximal part of the duodenum after the administration of 0.1 M HCl and SO solution and the type of pressure in the AS.

The Ukrainian Journal of Clinical Surgery
Since the consequence of restoring equilibrium by increasing inhibition should be a decrease in the volume of pancreatic secretion, the volume of stimulated pancreatic secretion in patients with CBP was studied depending on the pressure in the duodenum after the introduction of 0.1 M HCl and CO solution and the type of pressure in the AS (see Figure).This indicator was studied in groups of 5 patients or more (see Table 3).
In patients with AS pressure of 0 -5 mm Hg, in whom the excitability of the pancreas was normal both before and after the onset of secretion, a normosecretory reaction prevailed, whereas in patients with increased pancreatic excitability before the onset of secretion, a hyposecretory reaction prevailed (see Figure , A).This is consistent with the assumption that the balance of excitation and inhibition in the pancreas is restored by enhancing the inhibition process.In patients with AS pressure of 0 -5 mm Hg, who had increased excitability of the pancreas after the end of secretion (see Figure , B), the normosecretory reaction prevailed only at the pressure in the ductus arteriosus of 19 -42 mm Hg, while at the pressure in the ductus arteriosus of 6 -13 and 14 -18 mm Hg the hyposecretory reaction prevailed.Based on the fact that in patients whose excitability of the pancreas did not change, but during the period of secretion the balance of excitation and inhibition processes was restored, it can be assumed that these patients had a slight imbalance, so the increase in inhibition was not accompanied by a pronounced hyposecretory reaction.If there was normal excitability of the pancreas before and during secretion, which increased after the end of secretion, it is most likely that the imbalance of excitation and inhibition was pronounced.However, due to a significant increase in the inhibition process and the resulting pronounced hyposecretory reaction during the secretion period, the balance was restored, as in patients with a pancreatic pressure of 14-18 mm Hg.Thus, it can be concluded that a strong inhibition process in the pancreas is inherent not only in patients with a stable balance of excitation and inhibition processes, but also in patients with a stable imbalance of these processes, and a sign of this is the dominance of normosecretory states.
In patients with unstable AVP pressure (see Figure , C, D), normosecretion prevailed both in the case of a stable balance of excitation and inhibition processes and in their stable imbalance, whereas hyposecretion appeared in the case of transition of increased pituitary excitability to decreased excitability and vice versa.This confirms the assumption that the process of inhibition in the secretion of LP is enhanced in patients with an imbalance of excitation and inhibition.
In patients with a pressure in the AS of 6-9 mm Hg (see Figure , E), with a pressure in the duodenum of 6-13 mm Hg before the onset of secretion and 14-18 mm Hg after its completion, hyposecretion prevailed.This means that before the onset of secretion, the pancreas was in a state of reduced excitability, but during LP secretion, the balance of excitation and inhibition processes was restored and maintained after its completion.At the same time, in patients with increased pancreatic excitability before the onset of secretion, a normosecretory reaction prevailed, whereas in patients with increased pancreatic excitability after the end of secretion (see Figure , F), a hyposecretory reaction was observed.This can be explained by the fact that in patients with the limiting tension of the inhibition process, the state of normal pancreatic excitability is unstable and quickly changes to a state of reduced or increased excitability, but there are patients with stable slightly increased pancreatic excitability, which is characterised by a strong inhibition process.In patients with an AS pressure of 0-5 mm Hg, in whom the duodenal pressure before and after secretion was 6-13 mm Hg (see Figure , G), a hyposecretory reaction prevailed.This confirms the correctness of the conclusion that the analogue of the 6-13 mm Hg pressure in the RPE after the injection of 0.1 M HCl solution is the pressure in the RPE of 14-18 mm Hg after the injection of SO, and such a significant increase in inhibition is unstable.In patients with disruption of the process of inhibition in the pancreas before and after secretion, its increased excitability was observed (see Figure , H).The presence of a pronounced hypo-and hypersecretory reaction without a normosecretory reaction confirms the correctness of the conclusion that a strong inhibition process is characterised by a normosecretory reaction.

Discussion
The results of the study indicate that under the influence of 0.1 M HCl solution during the LP of pancreatic secretion, the balance of excitation and inhibition processes in the pancreas is restored or the degree of their imbalance is reduced due to the enhancement of the inhibition process.This suggests that for the normal functioning of the inhibition process in the pancreas, periodic short-term strong excitation is required, and a similar process occurs during the brain phase of gastric secretion [7].At the same time, a strong inhibition process before the introduction of 0.1 M HCl solution was observed in 41.22% of patients with a pressure in the AS of 0-5 mm Hg, in 39.83% of patients with unstable ICA pressure and in 20% of patients with ICA pressure of 6-9 mm Hg.Therefore, it can be assumed that the necessary conditions for the functioning of the inhibition process in the pancreas are created during phase III of the interdigestive migratory complex and this is sufficient for a balanced system or a system with a slight imbalance of excitation and inhibition processes.If the imbalance is pronounced, the necessary additional excitation is created during the brain phase of gastric and pancreatic secretion.
The results of the study suggest that physiological gastric secretion contributes to the preservation of normal pancre-UJCS.2024 May/June; 91(3) The Ukrainian Journal of Clinical Surgery atic secretory function in patients with an imbalance of excitation and inhibition in the pancreas by enhancing the inhibition process, which protects the excitation process from overload.It is possible that increased gastric secretion in patients with CP [8] is due to a violation of the third phase of the interdigestive migratory complex [9], which creates an additional burden on the gastric component.It can be assumed that Pylorus affects not only the motor function of the stomach and duodenum, but also the secretory function of the stomach, increasing acid secretion in the case of a decrease in the functional activity of the Pylorus.This may be the reason for the existence of two clinical variants of functional dyspepsia [10], as well as for the reduced effectiveness of acid-suppressive therapy [11], but these assumptions require further investigation.

Conclusions
1.The pressure in the WPC cavity after injection of 0.1 M HCl and CO solution depends on the state of the excitation process in the PZ.
2. The pressure in the duodenal cavity after injection of 0.1 M HCl solution in the range of 0 -5 and 6 -13 mm Hg indicates normal or reduced excitability of the pancreas, in the range of 14 -18 and 19 -42 mm Hg -increased excitability of the pancreas.
3. The pressure in the duodenal cavity after SO administration in the range of 6 -13 and 14 -18 mm Hg indicates normal or reduced excitability of the pancreas, in the range of 19 -42 mm Hg -increased excitability of the pancreas.
4. During the LP of pineal gland secretion, after the introduction of 30 ml of 0.1 M HCl solution, the balance of excitation and inhibition processes in the pineal gland is completely or partially restored due to the enhancement of the inhibition process.A similar process occurs during the third phase of the inter-herbaceous migratory complex.If this imbalance persists, the necessary additional excitation is created during the brain phase of gastric pancreatic secretion.
Funding.There were no external sources of funding or support.No honoraria or other compensation was paid.
Author contributions.All authors contributed equally to this work.
Conflict of interest.The authors who participated in this study have declared that they have no conflicts of interest regarding this manuscript.
Consent for publication.All authors have read and approved the final version of the manuscript.All authors have agreed to the publication of this manuscript.
Ethical aspects.All procedures performed in the study with the involvement of patients complied with ethical standards for clinical practice and the Declaration of Helsinki, 1964, as amended.