
Patterns of Pancreaticobiliary Confluence: Morphometric Analysis and Clinical Relevance in a Select Adult Population
Oliver Munene Kinoti, Paul Ochieng Odula, Pamela Mandela Idenya, Josphat Kiruka Kimani, Mohamed Abdirashid Farah, Ian Ng’ang’a Kihonge, Haron Sami Wafula, Bernard Ndung’u
Department of Human Anatomy and Medical Physiology, Faculty of Health Sciences, University of Nairobi, Nairobi, Kenya
Correspondences to: Oliver Munene Kinoti; email: olivermunene39@gmail.com
Received: 13 Jan 2026; Revised: 9 Jun 2026; Accepted: 19 Jun 2026; Available online: 14 Jul 2026
Abstract
Background
Pancreaticobiliary junction (PBJ) variants influence cannulation success during endoscopic retrograde cholangiopancreatography and are associated with pancreatitis and biliary cystic dilatation. Population-specific morphometric data remain scarce in sub-Saharan Africa, limiting the regional applicability of existing reference values.
Materials and methods
This observational cross-sectional study examined 140 postmortem adult specimens from three mortuaries after obtaining ethical approval. Junctions were classified as separate (V-type), intramural, biliopancreatic (B-P), or pancreaticobiliary (P-B) type. Common channel (CC) lengths and the common bile duct (CBD)–main pancreatic duct (MPD) angle were measured using digital Vernier calipers and a protractor.
Results
The proximal types (B-P and P-B) were most frequent (59.3%), followed by intramural (34.3%) and separate (6.4%). Mean intramural and extramural CC lengths were 2.86±1.46 mm and 8.91±4.07 mm, respectively. Older individuals (aged ≥59 years) had significantly longer distal CCs. The mean angle between the CBD and MPD was 49.4°±23.24°.
Conclusion
The PBJ exhibits considerable inter-individual variation in this population. Pre-procedural evaluation of junctional anatomy is essential to guide safe cannulation and minimize iatrogenic injury.
Key words: Pancreaticobiliary junction, Ampulla of Vater, Hepatopancreatic ampulla, Variations, Morphology
Ann Afr Surg. 2026; 23(4): **-**
DOI: http://dx.doi.org/10.4314/aas.v23i4.2
Conflicts of Interest: None
Funding: None
© 2026 Author. This work is licensed under the Creative Commons Attribution 4.0 International License.
Introduction
The hepatopancreatic ampulla of Vater is a cystic dilatation that is formed by joining the common bile duct (CBD) and the main pancreatic duct (MPD) at the pancreaticobiliary junction (PBJ) (1). The CBD and MPD junction variations are based on the length of the common channel (CC), the presence of an intraductal septum, and the presence of separate duodenal openings for the ducts (2, 3). The three main morphological types of PBJ are as follows. First, a proximal junction where the MPD opens into the CBD at a variable distance from the opening on the major duodenal papilla (MDP), forming a CC. This proximal junction can take two forms: a biliopancreatic (B-P) type, in which the CBD appears to join the MPD from the side, or a pancreaticobiliary (P-B) type, in which the MPD appears to join the CBD from the side. Second, an intramural junction where the CBD and MPD join to form a short CC within the duodenal wall. Third, a separate-type junction involves separate openings of the CBD and MPD on the papilla, separated by a septum (2, 4, 5). This classification was first systematically described by Millbourn (4) and later refined by subsequent authors, including Misra and Dwivedi, and Sherifi et al. (2, 3). Based on the available literature, the B-P type is the most frequently encountered, accounting for approximately 42–85% of all junctions depending on the population studied, followed by the intramural type (approximately 30–40%), the P-B type (15–20%), and the separate type (approximately 6%) (2, 3, 5, 6). The presence and length of a CC and the size of the angle formed between the CBD and the MPD are therefore determined by the morphological type of the PBJ.
Sex, age, and ethnic differences in morphology and morphometric measurements of the junctions are documented (2, 5-8). These differences likely reflect developmental variations rooted in both genetic background and environmental exposures during embryogenesis, though specific genomic sequences governing PBJ morphology have not yet been identified (6, 8). The B-P junction type has been implicated as a risk factor for cystic biliary dilatation primarily because the right-angled union of the CBD into the MPD promotes reflux of pancreatic juice into the biliary tract, leading to chronic inflammation, epithelial hyperplasia, and ultimately cystic dilatation of the bile duct (9-12). In contrast, the P-B junction, where the MPD joins the CBD at an acute angle, has been implicated in the causation of acute pancreatitis, as the biliopancreatic reflux in this configuration transiently raises intrapancreatic pressure and activates pancreatic enzymes within the ductal system (9, 10). The reported incidence of B-P type junction-associated cystic biliary dilatation ranges from 1.5% to 8.7% across different populations, while acute pancreatitis attributable to anomalous PBJ configurations has been reported in up to 22% of recurrent pancreatitis cases in some series (6, 9, 10). People with separate channels have also been noted to be at higher risk of gallstone disease (3, 13).
Studying the morphometry of the PBJ is important because a long CC, defined as one longer than 15 mm, has been associated with some clinical conditions, such as acute and chronic pancreatitis, hyperamylasemia, pancreatic and gallstones, choledochal cysts, and cholangiocarcinoma due to impaired functioning of the sphincter of Oddi (5, 14-18). In addition, wider angles of the junction of the CBD and MPD have been implicated in the causation of acute reflux pancreatitis (9). The configuration of the PBJ varies across populations and influences both disease susceptibility and the success of endoscopic procedures such as ERCP; hence, understanding its distribution in specific populations remains essential for improving the safety and accuracy of endoscopic and surgical procedures involving the biliary and pancreatic ducts (19). Therefore, establishing detailed region-specific anatomical and morphometric data is crucial. Despite multiple studies conducted to establish the prevalence of these patterns both regionally and internationally, local data on the variant anatomy of the PBJ from Sub-Saharan Africa and East Africa remain scarce (2, 20). The available Sub-Saharan African and East African literature on PBJ anatomy is limited primarily to a small number of cadaveric studies with modest sample sizes and variable methodology, which do not comprehensively characterize junction subtypes or provide morphometric data comparable to international series, underscoring the critical need for robust, population-specific reference data from this region (20). This study, therefore, aimed to determine the anatomical variants and morphometry of the PBJ in Kenya’s population, providing valuable evidence-based reference data that may improve clinical outcomes, guide training, and inform future anatomical and radiological research in the region.
Materials and Methods
This observational cross-sectional study using postmortem specimens was conducted in the Department of Human Anatomy at the University of Nairobi, with ethical approval granted by the Institutional Ethics and Research Committee (ethics approval reference number: UP52/02/2024). We obtained adult postmortem specimens from nairobi funeral home, university of nairobi-chiromo funeral parlour, and kenyatta national hospital farewell, with approved consent from the next of kin, from March 2024 to May 2024. With the aid of professional advice from the pathologist performing the autopsy, via visual analysis, we excluded cases with pathological processes restricted to the duodenum, pancreas, or papilla, such as papillary cancer, gastrointestinal tuberculosis, sphincter of Oddi dysfunction, ectopic ampulla or ampullae, as well as those which we could not classify due to mucosal swelling, deformity, ulcers, or surgically altered anatomy. We used convenience sampling, enrolling participants based on availability and accessibility. The sample size was calculated using the formula described by Jung (21). The estimated prevalence of the most frequent variant of the MDP segmental position was set at 91%, based on findings from a previous study (22). Substituting these values into the formula yielded a minimum required sample size of 126. This was subsequently rounded up to 150 to account for potential missing or incomplete data. Given the exploratory and descriptive nature of this study, no formal a priori stratification by age or sex was performed; however, both variables were recorded for all specimens to enable subgroup analyses. Although ethnicity was not systematically recorded as a variable, all three facilities are located within the capital city of Kenya. Because the capital serves as a highly diverse, cosmopolitan hub, the combined catchment area of these distinct institutions encompasses individuals from all walks of life. Consequently, the sample is considered broadly representative of the wider national population, naturally capturing the vast majority of ethnic and socioeconomic groups within the country.
Identification of the papilla and access to the PBJ
The peritoneal cavity was accessed via a midline incision, and the duodenum was opened along the convex margin. The major papilla was identified as a small protrusion on the medial wall. The stomach and transverse colon were reflected inferiorly to expose the hepato-duodenal ligament. The left and right hepatic ducts were subsequently exposed and followed from the porta hepatis to their junction, forming the common hepatic duct (CHD), and then to the fusion of the CHD with the cystic duct, forming the CBD. The CBD was followed into the pancreatic tissue to expose its junction with the MPD. The MPD was identified by dissecting the central region of the gland’s neck because it lies close to the surface and could be easily traced in either direction. By making an incision in the CBD close to the cystic duct entry and subsequently opening it to its termination, we established the relationship between the MPD and the terminal portion of the CBD. Likewise, the MPD was tracked from its connection with the accessory duct to its duodenal end to identify its position in generating an ampulla.
The patterns of the P-B junctions were recorded and classified into either V-type (separate), intramural (short CC), or proximal (B-P or P-B) junctions. This classification follows the widely used system described by Misra and Dwivedi (3) and subsequently adopted by multiple morphometric studies (2), as it clearly delineates the anatomical relationship between the CBD and MPD at and proximal to the duodenal wall. Using a digital Vernier caliper version CVU 200 m (precision of 0.01 mm) and a standard Trident 6-inch 180° plastic mathematical protractor, the length of the intramural and extramural CC and the angle between the MPD and the CBD were measured. The CC length was measured and recorded from the tip of the papilla to the junction of the confluence of the MPD and CBD. A 12-megapixel camera was used to take photographs. The dissections were carried out by the principal investigator of the study, together with two research assistants (senior medical students) who assisted with taking photographs and documentation. All measurements were taken twice, independently, by two researchers to minimize error. The same digital Vernier caliper and protractor were utilized for all the measurements throughout the study. All measurements represent the mean of the two independent readings; in cases of discrepancy, the mean of the two values was recorded. The anatomical characteristics were presented as photomacrographs, and their frequency distribution was noted. We used the independent samples t-test to compare intramural, extramural, and total ampulla length measurements between sexes and a one-way analysis of variance (ANOVA) to compare these measurements across age groups.
Results
Study demographics
We identified 150 specimens for inclusion in the study and selected 140 specimens for the final analysis. Of the 10 excluded cases, 4 had duodenal ulceration, 3 had lodged gallstones, 2 had gastrointestinal malignancy, and 1 had a surgically altered anatomy. Specimens were obtained from 81 (57.86%) males and 59 (42.14%) females. The mean age of the participants was 39.7 (±14.1) years, ranging from 18 to 88 years, with a median of 37 years. The mean age was 38.9 (±10.4) years for males and 40.9 (±11.2) years for females. The independent samples t-test did not find any statistically significant differences in age or sex distribution (p = 0.444 and p = 0.501, respectively). Age was then classified into three groups (18–38 years, 39–58 years, and 59+ years) based on a tertile distribution of the available sample, which was deemed appropriate for enabling comparisons across young, middle-aged, and older adult subgroups in the context of the study’s aims.
Morphological features of the pancreaticobiliary junction
We characterized the junction types and assessed the distribution by age groups and sex. The three junction types observed were the proximal junction, the intramural junction, and the separate-type junction. The proximal junction was the most prevalent morphology, found in 83 cases (59.30%). Within this group, the B-P subtype was more common, occurring in 59 cases (42.14%)—38 (27.14%) males and 21 (15.00%) females—than the P-B subtype, which was observed in 24 cases (17.14%)—14 (10.00%) males and 10 (7.14%) females. The intramural junction was found in 48 cases (34.30%), comprising 23 (16.43%) in males and 25 (17.90%) in females. The separate (V-type) pattern was the least frequent, occurring in nine cases (6.43%)—six (4.30%) males and three (2.14%) females. The separate type of papilla was more common among the youngest age group (18–38 years). The distribution of junction types by age group is presented in Table 1. The B-P type was the most common across all age groups except in the 18-38 age group, while the separate type was the least frequent in every age group. Fisher’s exact test showed no significant relationship in the type of PBJ between age groups (χ2=7.991, p = 0.211, df=6) (Table 1) and by sex (χ2=3.272, p = 0.355, df=3). Figure 1 shows the types of PBJ observed. Figure 2 shows a diagrammatic depiction of the junction types.
The union of the common bile duct and the pancreatic duct by age groups
No statistically significant association was observed between the type of PBJ and age group (p > 0.05). However, the B-P type was the most common across all age groups, while the separate junction was the least frequent.
B-P, biliopancreatic; P-B, pancreaticobiliary; PBJ, pancreaticobiliary junction.
Photomacrographs displaying the different junction patterns observed: pancreaticobiliary (P-B) junction, biliopancreatic (B-P) junction, accessory pancreatic ducts (APD), ampulla (AD), common bile duct (CBD), common channel (CC), cystic duct (CD), common hepatic duct (CHD), duodenal wall (DW), pancreatic duct (PD), gallbladder (GB), junction (J), septum (S). In the P-B junction (A), the MPD appears to join the CBD. In the B-P junction (B), the CBD appears to join the MPD. Additionally, an illustration (broken lines) shows how the angle between the CBD and MPD was measured. In the intramural junction (C), the CBD and the MPD join as they traverse the duodenal wall. In the separate exit (D), the CBD and the MPD exit separately.
Illustration of the pancreaticobiliary junction types. A: Separate-type junction. B: Intramural junction. C: P-B type junction. D: B-P type junction. B-P, biliopancreatic; CBD, common bile duct; P-B, pancreaticobiliary; PD, pancreatic duct.
Morphometry of the pancreaticobiliary junction
The morphometric analysis included measures of intramural CC length, extramural CC length, and the junction angle between the CBD and MPD, stratified by age group and sex. The intramural CC measured 0.33–6.00 mm in length with a mean of 2.86±1.46 mm. The extramural CC, formed outside the duodenal wall in the proximal junction subtypes, had a mean length of 8.91±4.07 mm. The hepatopancreatic ampulla length was 8.58±5.52 mm. The extramural CC and ampulla were on average longer in males than in females, but these differences did not reach statistical significance (p = 0.077, F=3.212; p = 0.072, F=3.300) (Table 2). Of all participants, 4.29% (n=6) had an extramural CC ≥15 mm. Males had more cases of extramural CC exceeding 15 mm (n=5; mean 16.64±1.04 mm) than females (n=1; 16.40 mm).
One-way ANOVA demonstrated a statistically significant age-related difference in extramural CC length (p = 0.019, F=4.158) (Table 3). Tukey’s post hoc test confirms that the difference lies between the 39–58 and 59+ age groups: the oldest group (≥59 years) had a substantially longer mean extramural CC (11.28±3.39 mm) compared to the middle-aged group (7.60±3.39 mm). No statistically significant difference was found between the youngest (≤38 years; 9.28±4.43 mm) and either of the other age groups.
Comparison of common duct and ampulla lengths by sex
Comparison between male and female participants was performed using the independent samples t-test. Statistical significance was considered at p < 0.05. F=F-statistic. (—) Not applicable due to limited sample size in the ≥15-mm category.
Comparison of common duct and ampulla lengths by age groups
One-way ANOVA was used to compare mean lengths among the three age groups. Statistical significance was set at p < 0.05. F=F-statistic. (—) No applicable comparison due to a null data value in this group data.
ANOVA, analysis of variance; SD, standard deviation.
*Statistically significant difference at p < 0.05.
The angle of the common bile and pancreatic duct junction by sex
Independent samples t-test was used to compare the mean junctional angles between sexes. Statistical significance was set at p < 0.05. F=F-statistic.
The angle between the CBD and MPD ranged from 15° to 95°, averaging at 49.40° (standard deviation ±23.24°). The mean angle size was higher in males (52.37°±22.89°) than in females (45.34°±23.29°); however, the independent samples t-test did not show statistically significant differences in the mean angle between the sexes (p = 0.862, F=0.034) (Table 4). The mean angle was highest among middle-aged individuals (39–58 years). However, the one-way ANOVA test did not show statistically significant differences in mean angle size among the three age groups (p = 0.688, F=0.376) (Figure 3).
Comparison of the mean angle between the common bile duct (CBD) and main pancreatic duct (MPD) across age groups. The bars represent the mean angle (in degrees) for each age group, with error bars indicating standard deviation. One-way analysis of variance (ANOVA) revealed no statistically significant differences in the mean angle among the age groups (p = 0.688).
Discussion
The most prevalent junction type in this study was the B-P type, observed in 42.14% of specimens, followed by the intramural type (34.30%), P-B type (17.14%), and separate type (6.43%). This predominance of an extramural, proximal union is consistent with published literature: Misra and Dwivedi reported an extramural CC in approximately 63% of subjects assessed by endoscopic retrograde cholangiopancreatography (ERCP), while postmortem studies have found extramural CC configurations in up to 83% of specimens, with separate openings in approximately 17% (3, 20). Sherifi et al. (2), in their magnetic resonance cholangiopancreatography (MRCP)-based cohort, similarly found the B-P type to be the most prevalent extramural variant, constituting 31.7% of cases, although their study recorded a higher proportion of separate (V)-type junctions at 28.6%, a discrepancy that may reflect methodological differences between postmortem dissection and in vivo imaging, as well as population-specific anatomical variation. The clinical significance of the predominant B-P configuration observed in this study warrants emphasis. In the B-P type, the CBD appears to drain into the MPD; because the junction lies proximal to the sphincter of Oddi, the sphincteric mechanism can no longer independently regulate flow between the two ductal systems. This results in a reversed pressure gradient that facilitates the reflux of pancreatic juice into the biliary tree, promoting chronic mucosal inflammation and epithelial metaplasia. In addition, through the actions of lysolecithin and phospholipase A2 generated when pancreatic juice mixes with bile, a biochemical environment conducive to malignant transformation is created (3). Accordingly, the B-P subtype has been specifically associated with congenital cystic dilatation of the CBD and gallbladder carcinoma (3). Conversely, the P-B type, present in 17.1% of specimens in this study, has been implicated in the pathogenesis of acute pancreatitis, as bile reflux into the MPD is thought to activate pancreatic enzymes prematurely within the ductal system (9, 11).
The separate junction type, though least prevalent at 6.43%, has been associated with an elevated risk of gallstone disease and alcohol-induced chronic pancreatitis; Misra and Dwivedi found separate openings in 70% of patients with gallstone disease compared to only 37% of controls (p < 0.001), proposing that the absence of a CC alters sphincteric dynamics at the distal CBD, promoting bile stasis and stone formation (3). Although no statistically significant association was found between junction type and age group or sex in this study (Fisher’s exact test: p = 0.211 and p = 0.355, respectively), a finding similarly reported by Sherifi et al. (2), who found no significant sex-based difference in junction type distribution, the clinical implications of the predominant B-P configuration merit attention. A substantial proportion of this population may carry an anatomical predisposition toward biliary pathology, underscoring the importance of pre-procedural evaluation of junctional morphology in patients presenting for ERCP or biliary surgery.
The PBJ’s location relative to the duodenal wall appeared to determine the length of the CC. The intramural CC in the current study measured 0.33–6.00 mm in length with a mean of 2.86±1.46 mm. This is similar to the study by Mchonde and Gesase (20), who reported values ranging between 1 and 3 mm. In cases with a proximal junction outside the duodenal wall (59.28%) in the current study, the MPD joined the CBD obliquely to form an extramural CC, which ranged from 2 to 18 mm in length, with a mean length of 8.91±4.07 mm from the duodenal wall. The resulting total ampulla length ranged from 0.33 to 20 mm, with a mean of 8.58±5.52 mm. These values are similar to those reported by Mchonde and Gesase (20), who found the length of the extramural channel and ampulla to range from 0.2 to 10 mm and 7 to 15 mm (mean 10.1 mm), respectively. Sherifi et al. reported a mean ampulla length of about 5 mm (2). The present study found that older individuals had a significantly longer CC compared to middle-aged individuals, which indicates potential age-related changes in the CC length. This is in keeping with Bachar et al.’s findings, who noted increased metrics of the extrahepatic ducts with age (23). This is due to progressive fibroelastic remodeling and smooth muscle atrophy documented in aging biliary ducts, which may contribute to duct elongation and altered compliance over time (23). Although no normative age-referenced growth curve for CC length has been formally established in the literature, the 15-mm threshold for a long CC is understood to represent a clinically meaningful cut-off associated with pathological pancreaticobiliary reflux, irrespective of patient age (14).
A long CC is one longer than 15 mm (14). It was found in 4.29% of subjects in the current study. The scientific basis for the clinical significance of a long CC lies in the compromised function of the sphincter of Oddi: when the PBJ is situated proximal to the sphincteric mechanism, the sphincter can no longer independently regulate flow between the bile duct and pancreatic duct, facilitating bidirectional reflux. This reflux of activated pancreatic secretions into the biliary tree and vice versa underlies the association of long CC with choledochal cysts, cholangiocarcinoma, acute and chronic pancreatitis, and hyperamylasemia (5, 12, 14-17). The prevalence found in the current study is similar to that reported in other regions, including Japan (1.5–3.2%), Taiwan (8.7%), India (5.0%), and Europe (1%) (3, 5, 24). Hence, this suggests that about 4% of the study population is likely to be at higher risk for these maladies.
In our study, the angle of the junction between the CBD and the MPD ranged from 5º to 95º, averaging at about 49°. The wide range observed is consistent with the considerable inter-individual variation reported globally and reflects the complex embryological basis of the PBJ. The PBJ forms during the fifth to seventh weeks of embryogenesis, when the ventral pancreatic bud rotates to fuse with the dorsal bud; the final angle of the junction is determined by the degree and timing of this rotation, as well as differential growth of the surrounding duodenal wall (7). Genetic and environmental differences, as influenced by ethnicity and region, may further explain the diversity of reported values across populations, although specific genomic sequences conferring susceptibility to particular junction geometries have not yet been identified (5). The observed values in the current study are roughly similar to those noted in the Argentinian population (38.9°, 10º–70°) and to those reported by Sherifi et al. (35.6º±21.1°, 4°–90°) (2, 25). Since there were no statistically significant differences between the age groups or sex and the angle size between CBD and MDP, it suggests that the junctional angle may represent a stable anatomical parameter unaffected by age or sex.
The study population revealed larger acute angles than other populations. This may partially be explained by population-specific anatomical characteristics, though the precise biological determinants remain unclear and warrant further investigation. With respect to the relationship between angle size and reflux pancreatitis, Liu et al. (9) demonstrated in an MRCP-based study that a wider PBJ angle was independently associated with acute pancreatitis, suggesting that larger angles may impair adequate CC emptying and promote stasis, thereby facilitating reflux. While no universally accepted cut-off angle for clinical risk stratification has been established, the consistent trend in the literature suggests that angles exceeding approximately 50°–60° may confer increased susceptibility to reflux-related pathology (9). Given the mean angle of 49° in the current study and a distribution extending to 95°, a subset of this population may be at elevated risk for pancreatic reflux disease.
This study has some limitations: The population was specifically from Kenya, offering valuable population-specific anatomical data for this demographic; however, this may limit the external validity of the results as the anatomy of the PBJ may differ across ethnic and geographic populations. Therefore, our findings may not be directly generalizable to non-Kenyan populations. Future multicenter studies incorporating participants from different counties and regions would improve population representativeness and reduce potential bias. Second, as much as a key strength of our study is the use of postmortem specimens instead of cadaveric specimens, which avoids the inaccuracies associated with tissue fixation and foreshortening, postmortem changes may still introduce a degree of measurement imprecision; however, these changes are likely to result in minor underestimation of morphometric measurements rather than systematic overestimation. The magnitude of this bias is expected to be small but should be acknowledged. Third, the absence of imaging correlation (e.g., ERCP or MRCP) or clinical outcome data means that the functional significance of the observed anatomical variants could not be directly assessed. Future studies should consider using imaging techniques such as ERCP on live patients, which would yield more real-time accurate results, corroborate our findings, and provide valuable insights into the practical implications of variant PBJ anatomy in a clinical setting.
Conclusion
The PBJ exhibits considerable inter-individual variation in this population, with the B-P type being the most prevalent configuration. This pattern is broadly consistent with the international literature, affirming that PBJ anatomical heterogeneity is universal while contributing novel population-specific normative data for Kenya. A long CC was identified in 4.29% of subjects, placing a meaningful subset at anatomical risk for pancreaticobiliary reflux-related pathology. Older individuals demonstrated significantly longer extramural CC, suggesting age-related morphometric changes with potential disease implications.
Recommendations
Pre-procedural imaging evaluation of the PBJ using MRCP or endoscopic ultrasound prior to ERCP or biliary surgery is recommended, where feasible, to guide cannulation and reduce the risk of iatrogenic injury. This study provides a population-specific anatomical evidence base to support this practice for Kenya.
Author contributions
O.M.K., P.O.O., P.M.I., J.K.K., M.A.F., I.N.K., H.S.W, and B.N. contributed to the study concept and design, data analysis and interpretation, and drafting of the manuscript. O.M.K., J.K.K., M.A.F., I.N.K., and H.S.R. were responsible for the acquisition of data. P.O.O., P.M.I., and B.N. contributed to the critical revision of the manuscript and approval of the article.
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