3.1. Descriptive Analysis of All Pancreatic Resections and Histopathology
From January 2007 to April 2019, a total number of 1231 pancreatic resections were performed in our institution for primary pancreato-duodenal and distal bile duct disease entities, including pancreatic metastasis and rare cases of emergency pancreatic procedures. By far the most frequent procedure applied was pancreatoduodenectomy, usually with a preservation of the pylorus and in more than one quarter of cases in a laparoscopically assisted fashion. In frequency, distal pancreatectomy followed, with half of the procedures having been minimally invasive, demonstrating the change in the standard of care in the last decade. Extended distal resections involving the celiac trunk (Appleby’s procedure [
20]) were rare and were not performed in older individuals. Infrequently, total pancreatectomy and rarely, segmental resections or enucleations, were carried out, but were restricted to patients younger than 80 years of age. Only a small number of lateral longitudinal pancreaticojejunostomies according to Partington-Rochelle or Frey [
18,
19] were performed, most of them in younger patients (
Table 1).
With regard to definitive postoperative histopathological diagnosis, pancreatic adenocarcinoma was the by far most common entity, with location in the pancreatic head in about 78% of cases. Other malignancies, in descending order of their frequencies, were neuroendocrine tumor, ampullary carcinoma, distal bile duct carcinoma, pancreatic metastasis and duodenal carcinoma. A substantial number of pancreatic resections were performed in a preventive fashion for lesions with radiographically premalignant potential, yielding the final diagnosis of IPMN or (cyst-) adenoma and other benign entities in, together, 12.7% of all cases. For 15% of all resections performed, histopathological evaluation revealed chronic pancreatitis (CP) (
Table 1).
Septuagenarians and octogenarians comprised 31.3% and 6.9% of all patients in the full cohort, respectively. However, when looking into the subgroups of patients having undergone pancreatic resection for carcinoma in general or pancreatic adenocarcinoma in particular, their shares rose to 37.8% and 10.1% or 37.4% and 9.3%, respectively, thereby together representing almost half of the patients (
Table 1).
3.2. Postoperative Outcome after Pancreatoduodenectomy (PD) and Distal Pancreatectomy (DP)
For a comparative analysis of preoperative risk factors and postoperative complications, morbidity and mortality between the age groups, we excluded procedures other than pancreatoduodenectomy (PD) and distal pancreatectomy (DP), since they were infrequently or virtually never performed in septuagenarians or octogenarians, respectively (
Table 1). The remaining number of procedures was N = 1096.
In this subgroup, the relative frequency of older patients per year did not change substantially over the course of time (
Figure 1). Patients were distributed equally gender- (
p = 0.403) and BMI-wise (
p = 0.124). However, septuagenarians and octogenarians preoperatively more frequently displayed higher ASA-scores III and IV (
p < 0.001) and presented with more overall comorbidities (
p < 0.001), especially with cardiovascular (coronary artery disease and arterial hypertension, both
p < 0.001), chronic renal insufficiency (
p < 0.001), diabetes mellitus (
p = 0.048) and preoperative anemia (hemoglobin <10 g/dL) diagnoses, while pulmonary and hepatic comorbidities were not different in frequency between the age groups (
p = 0.782 and
p = 0.852, respectively). Positive history for alcohol abuse (
p = 0.001) and nicotine consumption (
p < 0.001) was less likely in older persons undergoing pancreatic resection (
Table 2).
The distribution between PD and DP was similar in all age groups (
p = 0.092). Yet, a final histopathological diagnosis of carcinoma was more frequent and one of neuroendocrine tumor or benign lesion less frequent in older patients (
p < 0.001). Compared with younger patients, portal vein resection was significantly more often performed in septuagenarians and octogenarians (
p = 0.008), but frequency of multivisceral resection was not different (+stomach:
p = 0.881; +colon:
p = 0.600; +liver:
p = 0.191). Overall operative time (0.792), amount of blood loss (
p = 0.582) and transfusion of packed red blood cells (
p = 0.264) were similar (
Table 2).
Regarding postoperative complications, only delayed gastric emptying (grades B+C, according to the ISGPS-definition) occurred significantly more frequently in older patients (
p < 0.001). All other measures, including biliary leak (
p = 0.627), clinically relevant postoperative pancreatic fistula (grades B+C, according to ISGPS-definition;
p = 0.303), post-pancreatectomy hemorrhage (grades B+C, according to ISGPS-definition;
p = 0.980), surgical site infection (
p = 0.838), necessity for reoperation (
p = 0.709) or intervention (
p = 0.111), postoperative sepsis (
p = 0.609), renal failure (
p = 0.501), pneumonia (
p = 0.761), thromboembolism (
p = 0.458) and the need for reintubation (
p = 0.232) were not different between the age groups. Length of intensive care/intermediate care unit (ICU) stay was not different accordingly (
p = 0.192), but overall hospital stay appeared to have been slightly longer for septuagenarians and octogenarians (
p = 0.031) (
Table 2). In univariate binary logistic regression, analyses for exploration of age group as a risk factor for postoperative morbidity (biliary leak, DGE, POPF, PPH, postoperative sepsis, renal failure, pneumonia, thromboembolism and length of hospital stay) after DP and PD, only the analysis for DGE yielded results suggestive for significant difference (octogenarians vs. <70: OR 1.75,
p = 0.079; septuagenarians vs. <70: OR 2.15,
p < 0.001; septuagenarians vs. octogenarians: OR 1.23,
p = 0.533).
Importantly, there was no statistical difference between age groups regarding postoperative in-hospital mortality (
p = 0.187), although the numbers (<70: 2.3%; septuagenarians: 3.1%; octogenarians: 6%) suggested a trend (
Table 2). Interestingly, the final determining etiologic factor for in-hospital mortality of older individuals compared with patients <70 years of age was rather related to surgical complications and less frequently of a mere medical nature (
Table 3). In addition, we performed binary logistic regression analyses for the identification of independent risk factors for postoperative mortality after PD and DP. Univariate analyses revealed a
p < 0.05 not for age groups, but for biliary leak, POPF (grades B+C), PPH (grades B+C), surgical site infection (SSI), reoperation and intervention, postoperative sepsis, renal failure, pneumonia, thromboembolism, reintubation, ICU- and overall hospital-stay. When including all variables with
p < 0.05 in univariate analyses (except for ICU-stay, due to a relevant N = 300 of missing data), as defined a priori as inclusion threshold, into a multivariable regression model, only postoperative sepsis (OR 7.84,
p = 0.033) and reintubation (OR 8.53,
p = 0.020) remained statistically relevant and independent risk factors for postoperative in-hospital mortality (
Table 4).
3.3. Oncological Outcome for Pancreatic Adenocarcinoma Patients after PD and DP
We further aimed at evaluating oncological outcomes for the subgroup of patients having undergone PD and DP for pancreatic adenocarcinoma. Specimens from the eligible 463 patients did not display differences in histopathological findings between the age groups, including tumor grade (
p = 0.193), tumor size (
p = 0.523), Union for International Cancer Control (UICC) stage (all parameters:
p ≥ 0.390), and resection margin status (
p = 0.934). However, neoadjuvant/induction chemotherapy was administered significantly less frequently for older patients (
p = 0.013), and adjuvant chemotherapy was more likely to be omitted in the postoperative care for septuagenarians and octogenarians (
p < 0.001) (
Table 5). Nevertheless, with regard to overall survival (OS), older patients virtually equally benefitted from surgical resection. Mean OS was 28 months, 21 months and 15 months for patients <70 years of age, septuagenarians and octogenarians, respectively (all Log-rank Mantel–Cox comparisons: not significant). However, the differences in the steepness of the Kaplan–Meier curves in the first 24–48 months postoperatively suggest a trend for worse OS with increasing age. Yet, the curves align after 60 months, resulting in an equal frequency of long-term survivors (
Figure 2) across the different age groups.
Cox proportional hazards regression modeling was used for identification of independent risk factors for shortened OS after PD and DP for pancreatic adenocarcinoma. In univariate analysis, only portal vein resection, operative time and histopathological variables (tumor grade, UICC pT/pN/pV/pL/pPn, lymph nodes ratio (LNR) and R-status), but not age group or BMI, ASA, comorbidities, procedure performed (including multivisceral resection), blood transfusion, tumor size or, surprisingly, (neo-) adjuvant therapy yielded a
p-value of <0.05, defined a priori as inclusion criterion for multivariable analysis. When including all these variables with
p < 0.05 in univariate analyses into a multivariable regression model, only tumor grade (G1/2 vs. G3/4: HR 0.59,
p < 0.001) LNR (from 0 to 1: HR 3.93,
p = 0.001) and R-status (R0 vs. R1/2: HR 0.65,
p = 0.008) remained statistically relevant and independent risk factors for overall survival after resection of pancreatic adenocarcinoma (
Table 6).