A prospective survey was conducted for patients who visited the outpatient clinic following surgery at a single tertiary hospital from October 2017 to March 2018. Patient aged between 20 and 65 years who underwent surgery for HBP cancer and borderline malignancy diagnosis were recruited for this retrospective study. Most patients underwent a complete pancreatectomy or hepatectomy. Patients with a periampullary cancer underwent a pancreaticoduodenectomy and patients with a left-sided pancreatic cancer underwent a distal pancreatectomy. Patients with a hilar cholangiocarcinoma underwent bile duct resection with or without major hepatectomy. This study was approved by the Institutional Review Board of the Samsung Medical Center (approval no. 2019-02-041). This study was conducted after obtaining IRB approval and informed consent from patients prior to the start of the survey.

CS was assessed using the questionnaire described by Cho et al. [20], which consisted of 12 questions in three domains: (1) impossibility of recovery; (2) stereotypes; and (3) experience of discrimination. In terms of impossibility of recovery, four questions were used to assess the impossibility of recovery, likelihood of cure, impossibility of social activities, and impaired task ability at work. The stereotypes about cancer patients were evaluated with the following 4 questions. The questionnaire consisted of questions about perception of cancer patients (identifying a person with cancer by their appearance), cancer patients' sexual intimacy, cancer patients' vulnerability, and social contribution of cancer patients. These questions were assessed using a 4-point Likert scale ranging from 1 point (strongly disagree) to 4 points (strongly agree). We calculated average score of 12 items. We then divided patients into a no stigma group and a stigma group according to the median score (> 1.375).

To assess social discrimination, we used dichotomous questions to ask whether patients’ friends tended to avoid interactions with them, whether neighbors avoided interactions with them, whether they had problems within their family or marriage, and whether employers or coworkers discriminated against them because of their cancer diagnosis.

QoL was measured using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30), which was translated into Korean and validated [21]. QoL functional and symptom scores ranged from 0 to 100, with a higher score on the EORTC representing a better QoL or a better level of functioning. A higher score on the EORTC also represented a more severe level of symptom. We scored EORTC QLQ-C30 answers according to a scoring manual [22]. Data were linearly transformed to yield scores ranging from 0 to 100. We analyzed incomplete questionnaires according to developers’ recommendations. A higher score indicated a better status of the functioning domain but a worse status for the symptom domain. QoL mean and the proportion of ‘problematic groups’ in each QoL scale were also determined. Problematic groups were defined as scores that were lower than 66 in global health status/QoL and better functioning and those higher than 33 on the symptom score. To interpret QoL scores, we defined ‘clinically significant’ difference in QoL as a 10-point difference in mean score [22].

Patients’ sociodemographic characteristics including gender, age, marital status, education, current employment status, and current monthly family income were obtained for this study. Clinical data such as primary cancer subtype, stage, type of surgery, adjuvant treatment, and treatment-related complications were obtained from each patient’s electronic medical records.

To assess stigma, the mean and standard deviation were calculated for each item in each domain for impossibility of recovery and stereotypes of cancer patients. Descriptive statistics were used to report social discrimination and prevalence of unemployment.

We used univariable and multivariable linear regression models to identify the association between CS and QoL, including functions and symptoms. All statistical analyses were performed using the Stata 14 software (StataCorp LP). We used two-sided p-values. p < 0.05 was considered statistically significant.

Among 75 recruited patients, two participants who did not undergo surgery were excluded. Thus, we performed analysis for the remaining 73 patients. The median score of CS was 1.375. Compared to the no stigma group, patients with stigma were more likely to be females (p = 0.05). The number of working patients throughout the data collection period was significantly higher in the no stigma group (p = 0.014). Among the total patients, 62 (84.9%) were diagnosed with cancer, including 22 (35.5%) who had pancreatic ductal adenocarcinoma. A total of 40 (64.6%) patients had advanced stage II or higher. There were no significant differences in rates of postoperative complications or survival between the no stigma group and the stigma group (Table 1).

Among the four items related to impossibility of recovery, more than 85% of patients were positive for at least three items. However, for questions related to job performance at the workplace, 14 (19.2%) patients believed that their ability to work efficiently decreased even after successful cancer treatment (Table 2). According to the type of discrimination endured, 15 (20.5%) patients reported that they experienced discrimination from both employers and coworkers. Forty-two (57.5%) patients disclosed cancer diagnosis to a colleague and 25 (34.2%) patients disclosed cancer diagnosis to customers (Table 3). Results of subgroup analysis for cancer patients also showed a similar trend to that for all patients (Supplementary Table 1, 2).

Using an unadjusted model of linear regression, we found that the stigma group was more likely to report a lower score in overall QoL (78.51 vs. 62.62, p < 0.01) and in all functional scales, particularly the cognitive scale (92.11 vs. 69.52, p < 0.001). In addition, patients in the stigma group were significantly more likely to exhibit higher levels of all symptoms, particularly fatigue (23.10 vs. 46.98, p = 0.005). After adjusting for age, sex, and disease stage, this association remained statistically and clinically significant (Table 4, Fig. 1). In subgroup analysis, QoL was lower in the stigma group of cancer patients (77.94 vs. 60.12, p < 0.01). In the advanced stage, the stigma group showed significantly lower QoL (82.14 vs. 58.33, p < 0.01). Furthermore, the QoL of the stigma group was significantly lower in patients who received adjuvant chemotherapy (80.70 vs. 61.67, p < 0.01). There were also significant differences in adjusted models. Moreover, according to coefficient of the adjusted models 1 and 2, the association between CS and overall QoL was stronger in cancer patients (–19.23, –13.25) and advanced stage (–22.58, –16.20) than in patients with borderline disease and early stage, respectively (Table 5).

CS is typically linked to a negative stereotype and hopeless feeling for oneself. It has been recently found to influence outcomes of cancer patients [14]. This study clarified the relationship between QoL and CS in a group of HBP cancer patients. The stigma group had a significantly lower QoL than the no stigma group (Table 4, Fig. 1). In order to find out whether CS and QoL showed a correlation while minimizing the influence of surgical complications, subgroup analysis was performed by equalizing surgical groups by type of surgery. In patients who underwent pancreaticoduodenectomy, QoL was lower in the stigma group than in the no-stigma group. Furthermore, after adjusting for pain, diarrhea, nausea, and constipation, the stigma group had a significantly lower QoL than the no stigma group (Table 5). Several studies have reported an association between CS and QoL among patients with other cancer types and found that reducing stigmatization can decrease the risk of both psychological and physiological issues [10,13,16,19,26,40]. This is a rare study that presents the relation between CS and QoL in HBP cancer patients. It shows results consistent with several previous studies on other cancers and new clinical outcomes.

This study had some limitations. First, our study group was composed of a small and heterogeneous group of patients. Second, this study was conducted with a cross-sectional design, which was limited in accurately asserting a causal relationship between CS and QoL because neither questionnaire administered to patients before surgery nor information on preoperative clinical symptoms of patients were investigated. Therefore, further large cohort and longitudinal studies are needed. A prospective study on HBP cancer that determines the difference in QoL according to the treatment plan of patients will give more insight regarding the relationship between CS and long-term survival.

In summary, CS is an important factor that can negatively affect overall QoL and clinical symptoms of HBP cancer patients despite its lack of effect on cancer survival. Appropriate treatment selection and patient management, especially if intensive psychological support therapy is performed for cancer patients diagnosed in an advanced stage who have received chemotherapy, it will be helpful to improve their overall QoL and long-term prognosis after surgery.