Anxiety and depression in patients with hepatobiliary and pancreatic malignancies: Influence of disease stage and psychosocial factors

Abstract

BACKGROUND

Hepatobiliary and pancreatic malignancies, with their aggressiveness and poor prognosis, often trigger anxiety and depression in patients, but the roles of disease stage and psychosocial factors in this remain unclear.

AIM

To explore the clinical characteristics and factors influencing comorbid anxiety and depression in patients with malignant liver, gallbladder, and pancreatic tumors.

METHODS

This study enrolled 150 participants, including 48 patients with early stage (IA-IB) hepatobiliary and pancreatic malignancies (Control Group 1), 52 patients with middle-stage (IIA-IIIA) tumors (Observation Group), and 50 healthy individuals undergoing physical examination (Control Group 2). Anxiety and depression detection rates, and scores on the Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS), and Life Event Scale were compared across groups. The factors influencing emotion of each patient were collected and analyzed by group.

RESULTS

Anxiety and depression detection rates were significantly higher in the Observation Group (82.69% and 92.31%, respectively; P < 0.05) than those in Control Groups 1 (62.50% and 66.67%, respectively) and 2 (10.00% and 8.00%, respectively). SAS and SDS scores showed similar trends. Life event stress scores and the presence of influencing factors, such as treatment side effects, pain, and economic burden, were also significantly elevated in the Observation Group. These findings suggest that psychological distress worsens as the disease progresses.

CONCLUSION

Patients with hepatobiliary and pancreatic malignancies are prone to comorbid anxiety and depression, with increasing severity in the later disease stages. Despite the relatively small sample size, our findings suggest the need for psychological assessments and interventions in comprehensive cancer care. Future studies should consider expanding the sample size to enhance generalizability. Strengthening psychosocial support may improve patient outcomes and quality of life.

Key Words: Hepatobiliary and pancreatic malignancies; Anxiety; Depression; Comorbidity; Psychological factors; Clinical characteristics

Core Tip: Patients with hepatobiliary and pancreatic malignancies often experience comorbid anxiety and depression; however, the association between disease stage and psychological status remains unclear. This study uniquely compared early-stage (IA-IB) and intermediate-stage (IIA-IIIA) patients with healthy controls. Significantly higher anxiety detection rates and life event scores were observed in intermediate-stage patients, highlighting disease progression as a key burden. We propose integrating psychological interventions into comprehensive cancer care to enhance treatment efficacy and quality of life.

INTRODUCTION

Attributable to aging, environmental pollution, and lifestyle changes, among other factors, tumors have become a common physical and mental disease threatening the health of individuals in China[1]. Among the various tumor types, malignant tumors of the liver, gallbladder, and pancreas are particularly aggressive and associated with poor prognosis and significant psychological burden. These cancers often progress rapidly and are usually diagnosed at a late stage, leaving patients with limited treatment options and a high mortality risk.

Anxiety and depression are common psychological issues among patients with tumours of the liver, gallbladder or pancreas. Studies have shown that there is a complex, two-way interaction between tumours and psychological factors in patients. On the one hand, receiving a diagnosis of a malignant tumour can have an adverse impact on patients' mental state, leading to negative emotions such as anxiety and depression[2,3].

However, anxiety and depression can also negatively impact treatment and rehabilitation and may exacerbate certain physical symptoms, such as pain and fatigue[4]. Patients with tumours, especially malignant tumours, experience varying degrees of psychological distress. Some studies have shown that approximately 30%-50% of patients with tumours experience clinically significant anxiety or depression[5,6]. In order to implement a patient-centred approach rather than a disease-centred one, clinicians have paid extensive attention to the comorbidity of anxiety and depression in patients with malignant tumours. However, relatively few studies have examined the comorbidity of anxiety and depression in patients with malignant tumours of the liver, gallbladder or pancreas in China. This study aimed to collect and analyse relevant questionnaire data from patients with these tumours to explore their clinical indicators and influencing factors, and to provide a basis of reference for the clinical treatment and intervention of comorbid anxiety and depression.

MATERIALS AND METHODS

Clinical data

The data of 100 patients with malignant tumors of the liver, gallbladder, and pancreas who were treated at Jingzhou Hospital Affiliated to Yangtze University from August 2021 to August 2024 were retrospectively analyzed. According to the different disease stages, patients were divided into Control Group 1 (48 patients with early stage IA and IB, n = 48) and the Observation Group (52 patients with middle-stage IIA to IIIA, n = 52). In addition, 50 healthy patients who visited Jingzhou Hospital Affiliated to Yangtze University for physical examination during the same period were selected as the Control Group 2. In Control Group 1, there were 25 males and 23 females. The age range was from 30 to 80 years old, with an average age of 50.26 ± 15.81 years. Of these patients, 40 were married and eight were unmarried. In terms of educational attainment, 18 had completed middle school or less, 15 had completed high school, and 15 had completed college or more. Control Group 2 comprised 24 males and 26 females, with ages ranging from 31 to 80 years old and an average age of 50.11 ± 15.46 years. Of these patients, 41 were married and 11 were unmarried. In terms of educational attainment, 19 had completed middle school or less, 17 had completed high school, and 16 had completed college or more. In the Observation Group, there were 27 males and 25 females. The age range was from 30 to 80 years old, with an average of 50.47 ± 15.72 years. In this group, 41 patients were married and nine were unmarried. In terms of educational attainment, 18 patients had a middle school education or below, 16 patients had a high school education and 16 patients had a college education or above. There were no statistically significant differences in general clinical data such as age, sex, marital status and educational attainment among the three groups of subjects, which were comparable (P > 0.05, Table 1). However, unmeasured confounding factors such as prior mental health history, individual coping mechanisms and family psychiatric history may still influence emotional outcomes and should be considered in future research.

Table 1 Baseline characteristics of the three groups, n (%).

Variable	Control Group 1 (n = 48)	Control Group 2 (n = 50)	Observation Group (n = 52)
Male	25 (52.1)	24 (48.0)	27 (51.9)
Female	23 (47.9)	26 (52.0)	25 (48.1)
Age (mean ± SD)	50.26 ± 15.81	50.11 ± 15.46	50.47 ± 15.72
Married	40 (83.3)	41 (82.0)	41 (78.8)
Education level
Middle school or less	18 (37.5)	19 (38.0)	18 (34.6)
High school	15 (31.3)	17 (34.0)	16 (30.8)
College or above	15 (31.3)	16 (32.0)	16 (30.8)

Written informed consent was obtained from all patients and their family members after providing detailed information about the study. Ethical approval was granted by the Medical Ethics Committee of Jingzhou Hospital, Yangtze University.

Inclusion and exclusion criteria

Inclusion criteria included: (1) Subjects in Control Group 1 and the Observation Group were all patients with malignant tumors of the liver, gallbladder, and pancreas that were clearly diagnosed using pathological or imaging methods; (2) An Eastern Cooperative Oncology Group score of 0/1, and a survival period no less than 3 months; (3) The patient showed good compliance with treatment; and (4) Patients were included if they had no mental or cognitive disorders and had not recently received interventions with psychotropic drugs.

Exclusion criteria included: (1) Patients who were unwilling to participate in this survey; and (2) Patients with combined mental and cognitive disorders.

Methods

The subjective feelings of patients in the three groups were evaluated using the Self-Rating Depression Scale (SDS) and Self-Rating Anxiety Scale (SAS). The Life Event Scale (LES) and a self-made collection of factors influencing negative emotions were used to compare Control Group 1 and the Observation Group.

Clinical data collection form

The self-made clinical data collection form included multiple dimensions such as sex, age, marital status, and educational attainment.

SDS

The scale comprised 20 items, each rated on a 7-point Likert scale. It assessed four dimensions: Psychoemotional symptoms, somatic complaints, psychomotor disturbances, and psychological depressive features. A total score between 53 and 62 indicated mild depression, 63 to 72 indicated moderate depression, and scores above 73 reflected severe depression. Higher total scores corresponded to greater severity of depressive symptoms[7].

SAS

The SAS consists of 20 items in total. Higher scores reflect greater severity of anxiety symptoms. Specifically, scores ranging from 50 to 59 represent mild anxiety, 60 to 69 indicate moderate anxiety, and scores above 70 suggest severe anxiety.

LES

The LES includes multiple dimensions, such as the frequency of negative events, malignant events, neutral events, and life events. This scale has been widely used in psychosomatic and behavioral medicine to assess the cumulative impact of life stressors on physical and emotional health. It quantifies the intensity of life events that may contribute to emotional instability, particularly in patients with chronic or life-threatening diseases[8].

Collection form of influencing factors of negative emotions

A self-made collection form of influencing factors of negative emotions, including multiple dimensions, such as disease stage, treatment side effects, economic burden, insufficient social support, understanding of the condition, physical pain, insufficient self-care ability, impact on work, loss of self-esteem due to the disease, and threats to life. The scale has two options: Yes or no. If "yes" is selected, it is recorded as 1 point, and if "no" is selected, it is recorded as 0 point.

Data processing

Data were initially recorded using Excel and subsequently analyzed with SPSS version 24.0. Scores from the anxiety scale, depression scale, and LES were presented as mean ± SD, and intergroup comparisons were conducted using independent sample t-tests. The detection rates of anxiety and depression, along with associated influencing factors, were expressed as frequencies (n). A P value of less than 0.05 was considered statistically significant.

RESULTS

Comparison of the incidence rates of depression and anxiety among the three groups

The anxiety detection rate in the Observation Group was 82.69%, significantly higher than that observed in Control Group 1 (62.50%) and Control Group 2 (10.00%) (P < 0.05). Similarly, the depression detection rate in the Observation Group reached 92.31%, which was also markedly higher than the rates in Control Group 1 (66.67%) and Control Group 2 (8.00%) (P < 0.05). Detailed data are provided in Table 2.

Table 2 Comparison of depression and anxiety incidence in three groups, n (%).

Group	Case	Anxious	Non-anxious	Depression	Non-depression
Control 1	48	30 (62.50)	18 (37.50)	32 (66.67)	16 (33.33)
Control 2	50	5 (10.00)	45 (90.00)	4 (8.00)	46 (92.00)
Observation	52	43 (82.69)	9 (17.31)	48 (92.31)	4 (7.69)
χ2					6.148
P value					< 0.05

Comparison of the scores of the SDS and the SAS among the three groups

The SAS score in the Observation Group was significantly higher than those in Control Group 1 and Control Group 2 (P < 0.05). Similarly, the SDS score in the Observation Group was also significantly elevated compared to both control groups (P < 0.05). Detailed results are shown in Table 3.

Table 3 Comparison of self-assessment scales of depression and anxiety in three group (mean ± SD).

Group	Control Group 1	Control Group 2	Observation	F value	P value
SAS	27.48 ± 5.01	34.74 ± 4.73	56.82 ± 2.18a	649.5	< 0.05
SDS	27.73 ± 4.95	38.06 ± 9.61	60.05 ± 4.83a	751.8	< 0.05

^aP < 0.05 vs Control Group 1 and Control Group 2.

SAS: Self-Rating Anxiety Scale; SDS: Self-Rating Depression Scale.

Comparison of the LES scores between the two groups

The LES score in the Observation Group was higher than that in the Control Group 1. Specific data are presented in Table 4.

Table 4 Comparison of the scores of two groups of life event scales (mean ± SD).

Group	Case	Negative events	Nasty incident	Neutral event	Life events
Control 1	48	4.13 ± 0.48	1.15 ± 0.07	1.28 ± 0.36	1.47 ± 0.16
Observation	52	5.86 ± 0.54a	2.09 ± 0.14a	1.84 ± 0.21a	1.95 ± 0.37a
χ2					8.036
P value					< 0.05

^aP < 0.05 vs Control Group 1.

Analysis of influencing factors

With the progression of malignant tumors, the cancer phobia of the patients in the Observation Group increased, and the scores of various influencing factors were significantly higher than those in Control Group 1 (P < 0.05). Specific data are presented in Table 5.

Table 5 Comparison of influencing factors between the two groups, n (%).

Factor	Control Group 1 (n = 48)	Observation (n = 52)
Staging	24 (50.00)	35 (67.31)a
Side effects of treatment	30 (62.50)	41 (78.85)a
Lack of social support	21 (43.75)	27(51.92)a
Financial burden	30 (62.50)	38 (73.08)a
Insufficient knowledge of the disease	10 (20.83)	18 (34.62)a
Pain	20 (41.67)	39 (75.00)a
Lack of self-care ability	15 (31.25)	33 (63.46)a
Work was affected	26 (54.17)	34 (65.38)a
The disease robs them of their self-esteem	20 (41.67)	40 (68.97)a
Lives are at risk	36 (75.00)	45 (86.54)a

^aP < 0.05 vs Control Group 1.

DISCUSSION

Malignant tumors of the liver, gallbladder, and pancreas are common in clinical practice. Malignant tumor incidence rates continue to increase globally, and are characterized by rapid disease progression, treatment difficulty, and a relatively poor prognosis[9-11]. Therefore, these individuals often face complex psychological challenges. Anxiety and depression are also common psychological problems for patients with malignant tumors and are independent risk factors for an increase in the mortality rate of tumors[12]. This study confirmed that patients with intermediate stage (IIA-IIIA) hepatobiliary and pancreatic cancers had significantly higher levels of anxiety and depression than those in the early stages or healthy individuals. These findings highlight the psychological burden of disease progression, suggesting that tumor burden, worsening prognosis, and cumulative treatment toxicity may contribute to escalating emotional distress.

From a pathophysiological perspective, advanced tumors are often accompanied by inflammatory cytokine release (e.g., interleukin 6, tumor necrosis factor-alpha), which has been associated with depression-like symptoms through neuroimmune pathways. In parallel, existential fear and diminished self-efficacy in managing illnesses may further exacerbate the psychological burden.

Compared to previous studies, our inclusion of healthy controls and cross-stage comparisons provides unique insights into the psychological trajectories of these patients. However, the results also underscore the urgent need for integrated psychological services in oncology departments, especially during the mid-to-late treatment phases.

Furthermore, higher LES scores and psychosocial burden scores in the observation group suggest that addressing stress-inducing life events, such as economic pressure and social isolation, could mitigate negative emotions and potentially improve treatment compliance. Some studies have shown that emotional and psychological factors such as anxiety and depression form a two-way vicious cycle with malignant tumors of the liver, gallbladder, and pancreas at the physiological, behavioral, and social levels. During the process of disease diagnosis, treatment and rehabilitation, patients with malignant tumors will have adverse emotions such as fear, melancholy, tension and frustration, and the clinical term "comorbidity" is thus applied[13].

Many studies have pointed out that patients with malignant tumors who have comorbid anxiety and depression have a higher disease recurrence rate and reduced treatment compliance; in severe cases, suicidal behavior may occur[14]. The mental state of a patient may significantly affect the quality of life and treatment effects. The occurrence and development of tumors in the liver, gallbladder, and pancreas are closely related to the mental and psychological factors of patients. At present, there are few studies on the direction of tumor-comorbid emotional disorders, and most existing studies are limited to small samples or specific populations. There is a lack of large-scale multicenter clinical studies, resulting in limited universality and applicability of the results. At the same time, most existing studies focused on short-term observation and evaluation of the curative effect, and there is a lack of long-term follow-up evaluations of patients' emotions and quality of life, making it difficult to comprehensively measure the long-term psychological state of patients. In addition, there are few studies on the influencing factors, and the incidence rate of tumor-comorbid emotional disorders in clinical practice is high, but the recognition rate is low[15]. Therefore, this study retrospectively analyzed the clinical characteristics of comorbid anxiety and depression in patients with malignant tumors of the liver, gallbladder, and pancreas to improve the clinical diagnosis rate of tumor comorbid emotional disorders and provide timely and effective treatment for tumor patients.

The SDS and SAS are widely utilized in clinical settings to assess emotional disorders. In this study, the detection rates of both anxiety and depression in the Observation Group were significantly higher than those in Control Groups 1 and 2 (P < 0.05). Correspondingly, SAS and SDS scores in the Observation Group were markedly elevated compared to the control groups (P < 0.05), suggesting that patients with malignant tumors are more susceptible to experiencing negative emotions such as anxiety and depression throughout the course of diagnosis and treatment. Furthermore, the prevalence of these emotional disturbances appeared to increase with disease progression. This trend may be influenced by multiple factors, including the psychological burden of the illness, the stress of medical interventions, and social or environmental pressures. From a physiological standpoint, tumor progression may trigger the release of specific hormones or inflammatory mediators, disrupting neurotransmitter balance and contributing to the development of anxiety and depressive symptoms[16,17].

The LES is a widely used tool for assessing the physical and mental health of participants[18]. The findings of this study demonstrate that the LES score in the Observation Group was significantly higher than that in Control Group 1 (P < 0.05), aligning with the results reported by Vitale et al[19]. This suggests that as the disease progresses, patients with malignant tumors experience greater disruptions to both physical and psychological well-being. In terms of contributing factors, this study identified economic burden, treatment-related toxicity and side effects, physical pain, and the perceived threat to life as the primary sources of psychological stress among these patients, with statistically significant differences observed (P < 0.05). These findings are consistent with the results reported by Li et al[20], further underscoring the complex interplay between physical illness and emotional distress in oncology populations. This may be because the clinical treatment regimens for patients with malignant tumors are mostly chemotherapy, radiotherapy, and targeted therapy, which are accompanied by high treatment costs, increasing the economic burden on patients and their families[21]. At the same time, treatment-related side effects, such as fatigue, nausea, hair loss, and decreased immunity, as well as pain caused by the primary disease and treatment, also cause great pain to patients[22-24]. At the same time, some people do not respond to treatment during the treatment process; they feel the threat of death and feel painful, helpless, and fearful, which may be accompanied by physical symptoms. Therefore, most patients with malignant tumors have comorbid anxiety and depression[25].

This study had several limitations. Firstly, the sample size was relatively small and was drawn from a single-centre retrospective cohort, which may limit its generalisability. Second, we did not assess the patients' prior psychiatric history or coping styles, which may have acted as confounding variables. Third, emotional assessments relied solely on self-reported scales, potentially introducing subjective bias. To reduce response bias, future studies should incorporate interviewer-administered scales or triangulate them with clinician-rated tools (e.g., the Hamilton Depression Scale). In addition, blinding investigators to group assignments during scale scoring and including follow-up assessments may enhance the reliability. Stratifying future samples according to socioeconomic status, comorbid conditions, and mental health history could further clarify the sources of psychological vulnerability.

CONCLUSION

In conclusion, patients with malignant tumors of the liver, gallbladder, or pancreas face relatively serious comorbid anxiety and depression. As the disease progresses, negative emotions become increasingly severe. Therefore, in the treatment of malignant tumors, in addition to paying attention to the physical condition of the patients, it is also necessary to pay attention to their comorbid emotional disorders. The treatment of anxiety and depression should be integrated into the treatment of cancer as part of comprehensive treatment and intervention. By intervening in depressive emotions, the treatment effects and quality of life of patients can be improved.