The adenocarcinoma of the ampulla of Vater is less frequent than pancreatic ductal adenocarcinoma (PDAC) [
Persistent jaundice has been implicated as an important risk factor for dismal results after PD [
Recently, the albumin-bilirubin (ALBI) grade has been used as an objective parameter to estimate liver function and predict morbidity and mortality after hepatectomy [
Timely identification of risk factors might help the clinician in patient selection and potentially decrease morbidity and mortality after PD in patients with ampullary adenocarcinoma. We conducted a cohort study to specifically assess the preoperative factors related to 90-day mortality and severe morbidity after PD in patients with adenocarcinoma of the ampulla of Vater at our centre.
We conducted a retrospective cohort study in patients with a diagnosis of ampullary adenocarcinoma who underwent an open PD between January 2010 and December 2019 at our tertiary centre. Demographic, clinical, and surgical variables were prospectively collected in our clinical database. Patients with other ampullary neoplasms were not included in the analysis. We specifically analysed the ALBI grade and the eGFR. Blood samples were obtained during the week before the index procedure as part of the routine testing. The ALBI grade and the eGFR were obtained retrospectively by one investigator (RF). Postoperative data were collected until postoperative day (POD) 90, and the last follow-up was recorded in May 2020. The Institutional Review Board approved the study in accordance with the Declaration of Helsinki [
All procedures were performed by an expert group of hepatopancreatobiliary surgeons from our centre. Determined on a case-by-case decision during multidisciplinary team (MDT) meetings, patients were considered generally unsuitable for surgery when any of the following items were found: poor performance status (ECOG ≥2), M1 disease (according to TNM staging), and bilirubin levels ≥300 mmol/L. In rare and selected cases, the latter threshold could have been crossed after MDT consensus. When bilirubin levels were above this upper limit or the patient had cholangitis, preoperative biliary stenting was indicated and PD was carried out after 4–6 weeks based on previous reassessment.
In brief, the operative technique entailed putting the patient in a supine position and beginning with a midline incision and inspection for metastases to other organs. Then a Kocher manoeuvre was performed to expose the posterior aspect of the duodenum and pancreatic head. Thereafter, the procedure was continued by mobilization of the proximal jejunum and the angle of Treitz, followed by the ligation and division of corresponding jejunal vessels. For ampullary adenocarcinomas, we performed a level 2 mesopancreatic resection [
The primary endpoint was to determine predictors of 90-day mortality after PD for ampullary adenocarcinoma. The secondary endpoint was to identify predictors of severe morbidity (>IIIb) according to the Dindo-Clavien classification [
Clinically relevant postoperative pancreatic fistula (CR-POPF), postpancreatectomy haemorrhage (PPH), biliary fistula, and delayed gastric emptying (DGE) were defined according to the International Study Group in Pancreatic Surgery (ISGPS) [
The ALBI grading is an ordinal measurement derived from a regression model that utilises the serum values of albumin and bilirubin and transforms them into a score, in order to assess liver function and estimate the survival of patients with hepatocellular carcinoma [
To further assess the renal function, we used the eGFR [
Postoperative follow-up was recorded until POD90 as this is a more consistent measure in hepatopancreatobiliary surgeries [
The continuous variables were reported as median (IQR) and categorical variables as counts (percentages). For the univariate analysis, the Mann–Whitney
101 patients were eligible for analysis (Figure
Patient selection flow chart.
Clinical, laboratory, and operative patient characteristics.
Age (y), median (IQR) | 60 (52–67) |
Sex, male : female (count, %) | 47 (46.5):54 (53.5) |
Body mass index (kg/m²), median (IQR) | 24.6 (21.7–27.5) |
MELD score, median (IQR) | 9 (7–14) |
eGFR <90 mL/min/1.73 m², count (%) | 18 (17.8) |
ALBI 1 score | 30 (29.7) |
ALBI 2 score | 46 (45.5) |
ALBI 3 score | 22 (21.8) |
Unknown | 3 (3) |
ASA I | 2 (2) |
ASA II | 74 (73.3) |
ASA III | 25 (24.8) |
Preoperative biliary drainage, count (%) | 29 (28.7) |
Endoscopic | 18 |
Percutaneous | 6 |
Surgical | 5 |
Previous history of cholangitis, count (%) | 8 (7.9) |
Number of RBC packs transfused†, median (IQR) | 0 (0-1) |
Haemoglobin (g/L), median (IQR) | 115 (107–126) |
Platelet count (109/L), median (IQR) | 285 (242–381) |
International Normalized Ratio, median (IQR) | 1.07 (1.02–1.16) |
Prothrombin time (sec), median (IQR) | 12.9 (11.8–14.5) |
Serum total bilirubin ( | 22.1 (12–101.4) |
Serum glucose ( | 5.1 (4.7–5.6) |
Serum creatinine ( | 55 (47–66) |
Serum albumin (g/L), median (IQR) | 37 (32–41) |
Serum CA 19-9 (IU/mL), median (IQR) | 22.2 (9.7–91.4) |
Continuous data are expressed as median (IQR). Categorical data are expressed as count (%). †Preoperative transfusion.
None of the patients were suspected for cirrhosis and neither had abnormalities reported on the liver surface. The median diameter of the pancreatic duct was 5 mm (3–7). In 27 cases, the pancreatic characteristics could not be retrieved. The median (IQR) fistula risk score (5) was 3 (2–5) (Table
Operative and pathologic patient characteristics.
| |
Soft pancreas | 48 (47.5) |
Hard pancreas | 26 (25.7) |
| |
Modified dunking | 50 (49.5) |
Blumgart | 37 (36.6) |
Classic duct-to-mucosa | 14 (13.9) |
Operative time in min, median (IQR) | 370 (305–435) |
Estimated blood loss in cc, median (IQR) | 300 (200–450) |
| |
Intestinal | 79 (78.2) |
Pancreatobiliary | 14 (13.9) |
Others | 8 (7.9) |
Maximum diameter in cm, median (IQR) | 27.5 (18–40) |
Lymph node invasion, count (%) | 41 (40.6) |
Number of lymph nodes retrieved, median (IQR) | 17 (12–23) |
| |
R0 | 100 (99) |
R1 | 1 (1) |
Hospitalization length of stay (days), median (IQR) | 12 (9–16) |
Severe morbidity (≥IIIb), count (%) | 21 (20.8) |
| |
Type B | 33 (33) |
Type C | 7 (7) |
| |
Type A | 5 (5) |
Type B | 18 (17.8) |
Type C | 10 (9.9) |
Delayed gastric emptying (ISGPS A, B, and C), count (%) | 2 (2) |
Postoperative death (90 days), count (%) | 11 (10.5) |
Continuous data are expressed as median (range). Categorical data are expressed as count (%).
The median tumour size was 27.5 mm and the majority of patients (79%) presented the intestinal type. Perineural invasion was 33% and microscopic vascular invasion was 38%.
After surgical resection, 40 patients had a clinically relevant POPF and 28 patients had a PPH [A: (
Postoperative mortality occurred in 11 patients. Causes of death were related to CR-POPF (type C: 5 patients) and PPH (type C: 6 patients).
After univariate analysis, age
Univariate and multivariable analysis for prediction of 90-day mortality after pancreaticoduodenectomy for ampullary adenocarcinoma.
Mortality | Univariate | Multivariable | |||||
---|---|---|---|---|---|---|---|
No ( | Yes ( | OR | CI 95 | ||||
Age (years), mean (SD) | 58.7 (11.3) | 68.8 (6) | 0.077 | 1.1 | 0.99 | 1.2 | |
Male sex, count (%) | 41 (45.1) | 6 (6) | 0.508 | ||||
Body mass index (kg/m2), mean (SD) | 24.9 (4.4) | 25.3 (3.1) | 0.737 | ||||
MELD score, mean (SD) | 10.5 (3.9) | 12.7 (5.9) | 0.225 | ||||
ALBI grade, count (%) | |||||||
ALBI 1 | 29 (31.9) | 1 (10) | 0.037 | ||||
ALBI 2 | 43 (47.3) | 3 (30) | 0.383 | 3.05 | 0.25 | 37.5 | |
ALBI 3 | 16 (17.6) | 6 (60) | |||||
Undetermined | 3 (3.2) | 0 | |||||
ASA score, count (%) | 0.385 | ||||||
ASA I | 2 (2.2) | 0 | |||||
ASA II | 70 (76.9) | 4 (40) | |||||
ASA III | 19 (20.9) | 6 (60) | |||||
eGFR <90 mL/min/1.73 m2, count (%) | 13 (14.3) | 5 (50) | |||||
Preoperative RBC transfusion, count (%) | 23 (25.3) | 6 (60) | 0.322 | ||||
Preoperative biliary drainage, count (%) | 27 (29.7) | 0 | 0.720 | ||||
Haemoglobin in g/L, mean (SD)† | 116.2 (14.2) | 119.6 (19.1) | 0.878 | ||||
Platelet count in 109/L, mean (SD)† | 336.4 (156) | 282 (89.3) | 0.403 | ||||
International Normalized Ratio, mean (SD)† | 1.09 (0.1) | 1.21 (0.3) | 0.202 | ||||
Prothrombin time, mean (SD)† | 13 (1.7) | 14.4 (2.8) | 0.114 | ||||
Serum total bilirubin in | 61.8 (79.7) | 98 (107.7) | 0.437 | ||||
Serum creatinine in | 57 (14.7) | 70.4 (20.9) | 0.028 | 0.223 | |||
Serum glucose in | 5.5 (1.8) | 4.97 (0.4) | 0.322 | ||||
Serum albumin in g/L, mean (SD)† | 36.6 (5.8) | 30.6 (10.4) | 0.291 |
Postoperative death rate according to the number of risk factors.
In the univariate analysis, eGFR <90 mL/min/1.73 m2
Severe morbidity (Clavien–Dindo ≥IIIb) rate after PD grouped by having an eGFR<90 mL/min/1.73 m2.
Univariate and multivariable analysis for prediction of 90-day severe morbidity (Clavien–Dindo ≥IIIb) after pancreaticoduodenectomy for ampullary adenocarcinoma.
Severe morbidity | Univariate | Multivariable | |||||
---|---|---|---|---|---|---|---|
No ( | Yes ( | OR | CI 95 | ||||
Age, mean ± SD | 59 (10.8) | 62.5 (12.9) | |||||
Male sex, count (%) | 35 (43.8) | 12 (57.1) | 0.273 | ||||
Body mass index (kg/m2), mean ± SD | 24.6 (4.2) | 26.1 (4.7) | 0.322 | ||||
MELD score, mean ± SD | 10.4 (3.9) | 11.8 (4.8) | 0.584 | ||||
ALBI grade, count (%) | 0.653 | ||||||
ALBI 1 | 25 (31.3) | 5 (23.8) | |||||
ALBI 2 | 36 (45) | 10 (47.6) | |||||
ALBI 3 | 16 (20) | 6 (28.6) | |||||
Undetermined | 3 (3.7) | 0 | |||||
ASA score, count (%) | 0.479 | ||||||
ASA I | 2 (2.5) | 0 | |||||
ASA II | 60 (75) | 14 (66.7) | |||||
ASA III | 18 (22.5) | 7 (33.3) | |||||
eGFR <90 mL/min/1.73 m2, count (%) | 10 (12.5) | 8 (38.1) | |||||
Preoperative RBC transfusion, count (%) | 22 (27.5) | 7 (33.3) | 0.599 | ||||
Preoperative biliary drainage, count (%) | 23 (28.7) | 6 (28.6) | 0.987 | ||||
Haemoglobin in g/L, mean ± SD† | 116.6 (14) | 116.5 (17.5) | 0.487 | ||||
Platelet count in 109/L, mean ± SD† | 339.1 (162) | 300 (90) | 0.682 | ||||
International Normalized Ratio, mean ± SD† | 1.08 (0.1) | 1.17 (0.2) | 0.800 | ||||
Prothrombin time, mean ± SD† | 12.9 (1.7) | 14.2 (2.2) | |||||
Serum total bilirubin in | 61.7 (78.2) | 80.1 (100.7) | 0.741 | ||||
Serum creatinine in | 56.3 (14.6) | 66.6 (17.9) | 0.417 | ||||
Serum glucose in | 5.5 (1.9) | 4.9 (0.5) | 0.245 | 0.6 | 0.3 | 1.4 | |
Serum albumin in g/L, mean ± SD† | 36.3 (6.2) | 34.7 (7.6) | 0.361 |
According to the present results, an ALBI 3 grade and an eGFR <90 mL/min/1.73 m2 are important preoperative predictors of mortality and morbidity after PD in ampullary adenocarcinoma. It is noteworthy that patients who had neither of these risk factors had a 2% chance of postoperative mortality.
This study shows data of a selected and prospectively followed up group of patients with adenocarcinoma of the ampulla of Vater who were treated in a comprehensive tertiary centre with a high volume of PD.
Despite a careful patient selection and the use of preoperative biliary stenting in selected cases with serum bilirubin levels ≥300 mmol/L as a cut-off, we had a higher mortality rate compared to PDAC (4.8%, unpublished data). This justified the search for other preoperative predictors of mortality.
Inherent limitations from a retrospective single-centre study were noticed, the first being related to the small sample and the number of events of interest from this population. Another drawback is that the ALBI grades could not be retrieved in three patients.
Several high-quality studies demonstrate no differences in morbidity and mortality for PJ reconstruction types [
The ALBI grade has been widely used in hepatocellular carcinoma and liver surgery. In case of patients who underwent PD, Sandini et al. [
Renal function impairment has been associated with complications after pancreatic surgery [
Perioperative red blood cell (RBC) transfusions have been identified as prognostic factors for overall survival [
These findings suggest that baseline renal function measured by the eGFR and liver function categorized with the ALBI grading are predictors of severe morbidity and mortality. We hypothesize that these conditions make the patient prone to severe morbidity or mortality if CR-POPF, PPH, or both occur. Standard bilirubin thresholds should be complemented with the ALBI grade in order to indicate preoperative biliary stenting and thus improve the clinical condition. The eGFR should be used as a screening method to assess the severity and chronicity of kidney disease and thus provide adequate perioperative care. If the clinical condition of these patients does not improve after preconditioning measures, PD should exhaust all the available strategies to mitigate the pancreatic fistula and minimize postpancreatectomy haemorrhage occurrence and severity provided the patient has been informed and accepted the higher risk associated. Otherwise, the use of less aggressive procedures (i.e., ampullectomy) could offer a probability of cure in this high-risk population with early ampullary adenocarcinomas.
The use of neoadjuvant treatments (i.e., chemoradiotherapy or chemotherapy) could mean a bridge to surgery while improving the clinical condition. Cloyd et al. [
To the best of our knowledge, this is the first study to have presented the ALBI grade as a predictor of mortality after PD. Further studies are warranted, especially in centres where ampullary adenocarcinomas are more frequent than pancreatic adenocarcinoma, as in the case of our institution.
The data used to support the findings of this study have not been made available because of institutional policies.
The authors declare that they have no conflicts of interest.
Table: comparison of intraoperative factors associated with severe morbidity and mortality.