Prospective Observational Study on Perioperative Dysgeusia and Trace Metal Elements in Patients Undergoing Pancreatoduodenectomy

Abstract

Objective:

This study aimed to evaluate the nature of perioperative dysgeusia and its associated factors in patients undergoing pancreatoduodenectomy (PD).

Background:

Perioperative dysgeusia is an unfavorable symptom associated with malnutrition.

Methods:

The Taste Alteration Survey and Trace Elements in patients undergoing PD (TASTE-PD) study was a single-center prospective observational study performed between April 2021 and September 2022. Dysgeusia was evaluated using a questionnaire administered to 100 patients undergoing PD during hospitalization. A blood examination was also performed for the detection of trace metal elements. Statistical analyses were performed between patients with and without preoperative dysgeusia and between those with and without postoperative dysgeusia.

Results:

Thirty-three (33%) patients experienced dysgeusia during hospitalization (11 with preoperative dysgeusia and 22 with postoperative dysgeusia). Preoperative albumin (3.7 vs 3.9 g/dL, P = 0.040) and hemoglobin levels (11.6 vs 12.4 g/dL, P = 0.029) were significantly lower in the patients with preoperative dysgeusia than in those without. Comparing patients with and without postoperative dysgeusia, those with dysgeusia were significantly older (73 vs 68 years, P = 0.007), and their serum iron levels referenced to the preoperative levels were significantly decreased on postoperative day 1 (20.5% vs 24.4%, P = 0.039), with insufficient recovery by postoperative day 14 (27.4% vs 44.0%, P = 0.020).

Conclusions:

One-third of the patients experienced dysgeusia. Hypoalbuminemia and anemia were associated with preoperative dysgeusia, and advanced age and insufficient iron recovery were associated with postoperative dysgeusia. Further studies will be conducted to evaluate the impact of iron supplementation for improving dysgeusia and postoperative nutritional status.

INTRODUCTION

Pancreatoduodenectomy (PD) is essential for the complete resection of hepato-biliary-pancreatic malignancies.^1,2 However, patients undergoing PD frequently present with malnutrition due to tumor progression, preoperative intervention, and multiple organ resections, which impair the absorption of various nutrients.^3–5 Particularly, trace elements are mainly absorbed in the duodenum and proximal jejunum,^6,7 and PD frequently induces deficiency in trace elements.^8–10

Dysgeusia, an unfavorable symptom that exacerbates malnutrition, is frequently induced by a deficiency in trace metal elements due to dysfunction of the digestive system.^11,12 Therefore, patients undergoing PD are particularly prone to experiencing dysgeusia, and the associated malnutrition may impact not only the patients’ quality of life but also contributes to extended hospital stays and poor survival.^13–17

Despite the patients undergoing PD are under the conditions conducive to dysgeusia, limited studies have been performed in this area, probably because it is a highly subjective sensation and is difficult to be measured quantitatively.¹² Therefore, this study aimed to explore the nature of perioperative dysgeusia during hospitalization for PD and investigate the association between dysgeusia and significant clinical factors, including trace metal elements.

METHODS

Study Design and Ethical Statement

The Taste Alteration Survey and Trace Elements in patients undergoing Pancreatoduodenectomy (TASTE-PD) study was a single-center, prospective, and observational study of 100 patients who underwent PD at the Shizuoka Cancer Center, Shizuoka, Japan. The registration, patient follow-up, and data collection began in April 2021 and was completed in September 2022.

This study was approved by our Institutional Review Board (T2020–55) and registered in the UMIN Clinical Trials Registry (UMIN000055160). The study protocol conformed to the ethical guidelines of the 1964 Helsinki Declaration and its later amendments, and written informed consent was obtained from all patients before their participation in the study.

Patients

Figure 1 shows the inclusion and exclusion criteria, and categorization of patients in this study. This study included patients who were able to provide written informed consent and were aged 20 to 79 years. Patients with psychiatric diseases or dementia were initially excluded, and all study patients were considered reliable in expressing their symptoms using a questionnaire. The study included patients scheduled to undergo PD. Patients who had received preoperative chemotherapy or had a history of gastrectomy were also included. Patients scheduled to undergo hepato-PD were initially excluded. To eliminate dysgeusia related to severe comorbidities, patients who presented with liver cirrhosis, renal failure (serum creatinine levels of ≥2 mg/dL), and anemia (serum hemoglobin [Hb] levels of <9.0 g/dL) were excluded. Patients who already had dysgeusia before surgery were primarily categorized into the preoperative dysgeusia group. Patients without preoperative dysgeusia were categorized based on whether they developed dysgeusia postoperatively (postoperative dysgeusia group) or not (non-dysgeusia group).

FIGURE 1.

Inclusion and exclusion criteria and categorization of patients in this study. The 100 patients fulfilled the inclusion criteria and participated in the study protocol. The patients who had dysgeusia before surgery were primarily classified into the preoperative dysgeusia group, and those who developed dysgeusia after surgery were classified into the postoperative dysgeusia group.

Primary and Secondary Outcomes

The primary outcomes were the frequency and characteristics of perioperative dysgeusia during hospitalization for PD. The secondary outcome was the association between dysgeusia and serum levels of trace metal elements by comparing preoperative dysgeusia, postoperative dysgeusia, and non-dysgeusia groups.

Assessment of Dysgeusia

A questionnaire was developed in collaboration with the Division of Nutrition at our institution to assess dysgeusia subjectively as a patient-reported outcome (Fig. 2). The first question was to confirm dysgeusia, and the following questions were designed to evaluate appetite loss and taste alterations in salty, sweet, bitter, and metallic tastes, which have been reported as typical taste alterations in cancer patients.¹⁸

FIGURE 2.

The questionnaire for assessing dysgeusia, which was designed in collaboration with the Division of Nutrition. The first question is to confirm if the patients have dysgeusia, and additional questions were listed for patients with dysgeusia to evaluate appetite loss and details of taste alterations.

Study Protocol

The questionnaire was distributed to all patients. Patients were asked to complete the questionnaires the day before surgery and on postoperative days 3, 7, 14, and 21 and then place the sheets into an opaque file to blind them from all medical workers. Blood samples were collected on the day before surgery and on postoperative days 1, 3, 7, 14, and 21. General biochemical variables and trace metal elements, including iron, zinc, magnesium, copper, inorganic phosphate, and calcium, were measured. These trace metal elements were selected based on their general measurability and coverage under the National Health Insurance. If patients were discharged before the survey date, the questionnaires and blood examinations were discontinued.

Perioperative Variables and Data Collection

Our surgical procedure has been previously reported.^19,20 Briefly, all patients underwent open PD, in which the stomach was resected at the angular lesion, and the jejunum was resected approximately 20 cm anal side from the Treitz ligament. A modified Child’s method was used for reconstruction, and an enteral nutritional tube was placed percutaneously into the jejunum. Postoperative dietary intake began on postoperative day 3 according to the patient’s condition, and supportive enteral nutrition was administered to patients with low dietary intake. Data on surgical variables, postoperative complications according to the Clavien-Dindo classification system,²¹ postoperative dietary intake, administration of enteral nutrition, and body weight were recorded during hospitalization for PD.

Sample Size

The sample size was calculated to examine the significant differences in trace metal elements between the groups with and without dysgeusia as the secondary outcome. Based on our previous experience, the prevalence of perioperative dysgeusia was estimated to be approximately 20%. Postoperative serum levels of trace metal elements, such as iron and zinc, are expected to decrease to approximately 30% of their preoperative levels. The difference in median values and standard deviations for trace metal elements between groups with and without dysgeusia was set at 10%. A valid response rate for the questionnaire was estimated to be about 60%, and the required sample size was set to 100 cases using an independent 2-sample t test, aiming for a power of 0.8 and a significance level (α) of 0.05.

Statistical Analyses

Statistical analyses were performed between patients with and without preoperative dysgeusia, as well as those with and without postoperative dysgeusia. Continuous data were expressed as medians and ranges and were compared using the Mann–Whitney U test. Statistical analyses of categorical variables were performed using Fisher’s exact probability test. Statistical significance was set at P <0.05. Statistical analyses were performed using the Statistics Package for Social Science version 26.0 (IBM Corp., Armonk, NY, USA). Graphs were generated using GraphPad Prism version 9.5.1 for Windows (GraphPad Software, Boston, MA, USA, www.graphpad.com).

RESULTS

Study Patients

Between April 2021 and September 2022, 172 patients underwent PD at our institution. Among them, 100 fulfilled the inclusion criteria and participated in the study. The clinical characteristics of all patients are included in Table 1. Among the 100 patients, 90 had cancer, including 60 with pancreatic cancer and 12 with biliary tract cancer. Preoperative chemotherapy was administered to 46 patients, and all of them had pancreatic cancer. Postoperative morbidity of Clavien-Dindo classification system ≥IIIa was observed in 13 patients, and mortality was null.

TABLE 1.

Comparison of Clinical Factors Between Patients With and Without Preoperative Dysgeusia

Variables	All Patients	Preoperative Dysgeusia		P
	n = 100, (%)	Present n = 11, (%)	Absent n = 89, (%)
Age (years)*	70 (41–79)	71 (52–79)	70 (41–79)	0.856
Sex (male/female)	73 (73)/27 (27)	8 (73)/3 (27)	65 (73)/24 (27)	0.616
BMI (kg/m2)*	22 (15–31)	20 (17–25)	22 (15–31)	0.118
Current smoker	16 (16)	4 (36)	12 (14)	0.073
Regular alcohol intake	66 (66)	7 (64)	59 (66)	1.000
Diseases (cancer/non-cancer)
Cancer	90 (90)	11 (100)	79 (89)	0.596
Non-cancer	10 (10)	0	10 (11)
Details of diseases
Pancreatic cancer	60 (60)	8 (73)	52 (58)	0.639
Bile duct cancer	12 (12)	1 (9)	11 (12)
IPMN	11 (11)	0	11 (12)
Ampullary cancer	7 (7)	1 (9)	6 (7)
Duodenal cancer	4 (4)	1 (9)	3 (3)
Others	6 (6)	0	6 (7)
Jaundice	42 (42)	6 (55)	36 (40)	0.519
Preoperative biliary drainage
Internal biliary drainage	33 (33)	5 (46)	28 (32)	0.632
External biliary drainage	9 (9)	1 (9)	8 (9)
Preoperative chemotherapy	46 (46)	7 (64)	39 (44)	0.337
Preoperative radiation therapy	3 (3)	1 (9)	2 (2)	0.298
Preoperative blood examination
Hemoglobin (g/dL)*	12.4 (9.3–16.2)	11.6 (10.5–12.8)	12.4 (9.3–16.2)	0.029
Hematocrit (%)*	38 (29–49)	37 (32–41)	39 (29–49)	0.048
Total protein (g/dL)*	6.6 (5.6–7.8)	6.4 (5.8–7.6)	6.7 (5.6–7.8)	0.049
Albumin (g/dL)*	3.9 (2.5–4.8)	3.7 (2.6–4.3)	3.9 (2.5–4.8)	0.040
Surgical variables
Operation time (min)*	456 (282–690)	459 (392–659)	455 (282–690)	0.343
Blood loss (g)*	587 (102–3927)	1127 (251–3927)	573 (102–1969)	0.123
Blood transfusion	1 (1)	1 (9)	0	0.110
Lymph nodes dissection	100 (100)	11 (100)	89 (100)	1.000
Combined organs resection	3 (3)	0	3 (3)	1.000
Portal vein resection	34 (34)	5 (46)	29 (33)	0.297
Hepatic artery resection	5 (5)	0	5 (6)	0.551
Morbidity (CD ≥ IIIa)	13 (13)	0	13 (15)	0.198
Duration of hospital stay (days)*	20 (10–80)	17 (12–80)	21 (10–59)	0.260
Mortality	0	–	–	–

^*Median (range).

BMI indicates body mass index; CD, Clavien-Dindo classification; IPMN, intraductal papillary mucinous neoplasm.

Frequency and Characteristics of Dysgeusia

Figure 3A shows the number of patients with dysgeusia at each observation point. The response rates to the questionnaire on the day before surgery and on postoperative days 3 and 7 were maintained at 100%, 99%, and 100%, respectively. The response rates for the questionnaire on postoperative days 14 and 21 decreased by 90% and 51%, respectively, owing to the cancelation of the surveys among discharged patients. Dysgeusia was observed in 33 patients (33%) during the study period. Among them, 11 already had dysgeusia before surgery (preoperative dysgeusia), and 22 had newly developed dysgeusia after surgery (postoperative dysgeusia). Figure 3B shows the incidence of dysgeusia at each observation point in the preoperative dysgeusia group. The number of patients with preoperative dysgeusia decreased over time and none of the patients hospitalized on postoperative day 21 complained of dysgeusia. Figure 3C shows the incidence of dysgeusia at each observation point in the postoperative dysgeusia group. The number of patients with postoperative dysgeusia gradually increased, peaking on postoperative day 7, and over half of the hospitalized patients still experienced dysgeusia on postoperative day 21. Figures 4A, B show the percentages of each taste alteration experienced by the preoperative and postoperative dysgeusia groups, respectively. In the preoperative dysgeusia group, 81.8% of the patients experienced appetite loss and loss of deliciousness, followed by bitterness and a weak sensation of salty taste. In the postoperative dysgeusia group, 81.8% of the patients experienced appetite loss and loss of deliciousness, similar to those in the preoperative dysgeusia group. Notably, they experienced a strong sweetness instead of bitterness.

FIGURE 3.

The number of patients suffering from dysgeusia at each observation point. A, All patients (n = 100). Dysgeusia was observed in 33 patients (33%) throughout the study period. Among them, 11 patients already had dysgeusia before surgery (preoperative dysgeusia), and 22 patients developed dysgeusia after surgery (postoperative dysgeusia). B, The preoperative dysgeusia group (n = 11). The population suffering from dysgeusia decreased over time. C, The postoperative dysgeusia group (n = 22). The population suffering from dysgeusia gradually increases, peaking on postoperative day 7.

FIGURE 4.

The percentage of each taste alteration was calculated based on the responses to the questionnaire. A, The preoperative dysgeusia group (n = 11). Preoperative dysgeusia was characterized by a loss of deliciousness, bitterness, and a weak sensation of taste. B, The postoperative dysgeusia group (n = 22). Postoperative dysgeusia was characterized by a loss of deliciousness, weak sensation of taste, and strong sweetness.

Clinical Factors Associated With Preoperative and Postoperative Dysgeusia

Table 1 shows a comparison of the clinical characteristics between patients with and without preoperative dysgeusia. Preoperative dysgeusia was more common in smokers and exclusively detected in patients with cancer; however, no significant differences were observed. A preoperative general blood examination revealed that Hb and albumin levels were significantly lower in patients with preoperative dysgeusia than in those without. Table 2 shows a comparison of the clinical characteristics between patients with and without postoperative dysgeusia. The patients with postoperative dysgeusia were significantly older than those without; however, clinical factors, including cancer status, were not significantly associated with the incidence of postoperative dysgeusia. Supplementary Tables 1 https://links.lww.com/AOSO/A497 and 2 https://links.lww.com/AOSO/A498 show comparisons of other blood examinations between the patients with and without preoperative dysgeusia and between those with and without postoperative dysgeusia, respectively. Barely any significant differences were found between the 2 groups.

TABLE 2.

Comparison of Clinical Factors Between Patients With and Without Postoperative Dysgeusia

Variables	Postoperative Dysgeusia		P
	Present n = 22, (%)	Absent n = 67, (%)
Age (years)	73 (62–79)	68 (41–79)	0.007
Sex (male/female)	15 (68)/ 7 (32)	50 (75)/ 17 (25)	0.586
BMI (kg/m2)*	23 (18–28)	22 (15–31)	0.981
Current smoker	5 (23)	7 (10)	0.161
Regular alcohol intake	16 (73)	43 (64)	0.605
Diseases (cancer/non-cancer)
Cancer	19 (86)	60 (90)	0.704
Non-cancer	3 (14)	7 (10)
Details of diseases
Pancreatic cancer	13 (59)	39 (58)	0.249
Bile duct cancer	3 (14)	8 (12)
IPMN	5 (23)	6 (9)
Ampullary cancer	0	6 (9)
Duodenal cancer	1 (5)	2 (3)
Others	0	6 (9)
Jaundice	10 (46)	26 (39)	0.623
Preoperative biliary drainage
Internal biliary drainage	6 (27)	22 (33)	0.219
External biliary drainage	4 (18)	4 (6)
Preoperative chemotherapy	11 (50)	28 (42)	0.622
Preoperative radiation therapy	1 (5)	1 (2)	0.435
Preoperative blood examination
Hemoglobin (g/dL)*	12.6 (9.3–15.0)	12.4 (9.4–16.2)	0.732
Hematocrit (%)*	39 (30–45)	39 (29–49)	0.816
Total protein (g/dL)*	6.7 (6.2–7.5)	6.7 (5.6–7.8)	0.519
Albumin (g/dL)*	4.0 (3.1–4.8)	3.9 (2.5–4.7)	0.756
Surgical variables
Operation time (min)*	457 (353–690)	460 (282–685)	0.783
Blood loss (g)*	594 (102–1969)	578 (168–1839)	0.559
Lymph nodes dissection	22 (100)	67 (100)	1.000
Combined organs resection	1 (5)	2 (3)	1.000
Portal vein resection	10 (46)	19 (28)	0.190
Hepatic artery resection	2 (9)	3 (5)	0.594
Morbidity (CD ≥ IIIa)	4 (18)	9 (13)	0.728
Duration of hospital stay (days)*	24 (10–44)	21 (11–59)	0.376

^*Median (range).

BMI indicates body mass index; IPMN, intraductal papillary mucinous neoplasm; CD, Clavien-Dindo classification.

Trace Metal Elements Associated With Preoperative and Postoperative Dysgeusia

Supplementary Figure 1a, see https://links.lww.com/AOSO/A494, shows a comparison of the serum levels of preoperative trace metal elements between patients with and without preoperative dysgeusia. Although no significant differences were observed, serum iron levels were lower in patients with preoperative dysgeusia. Supplementary Figure 1b, see https://links.lww.com/AOSO/A495, shows a comparison of the serum levels of postoperative trace metal elements at each observation point between patients with and without preoperative dysgeusia. Percentages referenced to preoperative values are presented. No significant differences were observed between the 2 groups, except that inorganic phosphate on postoperative day 14 were higher in patients with preoperative dysgeusia than those without.

Figure 5A shows a comparison of the serum levels of preoperative trace metal elements between the postoperative dysgeusia and non-dysgeusia groups. No significant differences were observed between the 2 groups, except that preoperative serum magnesium level was higher in patients with postoperative dysgeusia than those without. Figure 5B shows a comparison of the serum levels of postoperative trace metal elements at each observation point between the postoperative dysgeusia and non-dysgeusia groups. Percentages referenced to preoperative values are presented. In the postoperative dysgeusia group, serum iron levels significantly decreased on postoperative day 1 (20.5% vs 24.4%, P = 0.039) and less recoveries were recorded by postoperative day 14 (27.4% vs 44.0%, P = 0.020) than in the non-dysgeusia group. Serum magnesium levels temporarily decreased on postoperative day 3 in the postoperative dysgeusia group; however, they recovered during hospitalization.

FIGURE 5.

A, Comparison of serum levels of preoperative trace metal elements between the postoperative dysgeusia (Present) and the non-dysgeusia groups (Absent). No significant differences were observed between the 2 groups except for the preoperative serum magnesium level. B, Comparison of the serum level of postoperative trace metal elements at each observation point between the postoperative dysgeusia (present) and the non-dysgeusia group (absent). A percentage based on the preoperative value is presented. In the postoperative dysgeusia group, serum iron levels significantly decreased on postoperative day 1 (20.5% vs 24.4%, P = 0.039) and were less recovered by postoperative day 14 (27.4% vs 44.0%, P = 0.020) than in the non-dysgeusia group. n.s. indicates not significant.

Postoperative Nutritional Status of the Study Patients

Supplementary Figure 2, see https://links.lww.com/AOSO/A496, shows the changes in postoperative dietary intake, the proportion of patients who received supportive enteral nutrition, body weight, and serum albumin levels in each group. Dietary intake is presented as a mean percentage of whole meals provided, and body weight and serum albumin levels are presented as mean percentages referenced to the preoperative values. The P value indicates the difference between the postoperative dysgeusia and non-dysgeusia groups. The postoperative dysgeusia group showed a relatively lower dietary intake and albumin recovery rate, as well as a higher rate of supportive enteral nutrition than the non-dysgeusia group.

DISCUSSION

This study established original questionnaires for assessing dysgeusia as a patient-reported outcome and investigated the association between dysgeusia and trace metal elements during hospitalization for PD. All patients participated in the study protocol, and the response rate to the survey was maintained at over 90% until postoperative day 14. Results revealed that one-third of the patients experienced dysgeusia at some point during hospitalization including 11 with preoperative dysgeusia and 22 with postoperative dysgeusia. Furthermore, 81.8% of patients in both the preoperative and postoperative dysgeusia groups reported an unfavorable impact of dysgeusia on appetite loss. Particularly, the postoperative dysgeusia group exhibited a lower dietary intake than the other groups, leading to a higher frequency of enteral nutrition and a longer hospital stay. In the statistical analysis, preoperative hypoalbuminemia and anemia were significantly associated with preoperative dysgeusia, and advanced age and postoperative insufficient iron recovery were significantly associated with postoperative dysgeusia. The results suggested that perioperative dysgeusia is affected by multiple contributing factors, with a potential association with iron status.

Taste alteration is a highly subjective sensation, and methods for assessing dysgeusia have not been standardized. Previous studies assessing dysgeusia adopted either objective methods, such as filter paper discs, or subjective methods, such as questionnaires and interview.^22–24 Objective methods are suitable for assessing physiological taste alterations and temporal changes in the same individual patient; however, when comparing multiple patients, they cannot eliminate age-related variations and measurement errors between examiners.^25–27 Conversely, subjective methods cannot be used to assess physiological taste alterations. However, they faithfully describe patients’ experiences, and several recent studies have emphasized the significance of patient-reported outcomes for better surgical outcomes.^26,28–30 In our study, all patients completed the questionnaire within the hospitalization period, except one on postoperative day 3, thereby demonstrating its validity.

The questionnaire for taste perception revealed that both the preoperative and postoperative dysgeusia groups commonly exhibited a lack of deliciousness and a weak taste sensation, especially for salty flavor, suggesting that perioperative dysgeusia is characterized more by a decrease in taste sensation (hypogeusia) rather than pronounced taste alteration. In addition to hypogeusia, the preoperative dysgeusia group experienced a heightened sense of bitterness (72.7%), which is a representative taste alteration that frequently occurs in cancer patients.¹⁸ In contrast to the preoperative group, 63.6% of patients with postoperative dysgeusia experienced a strong sense of sweetness. In surgical procedures that exclude the duodenum and proximal small intestine from the dietary pathway, the secretion of glucagon-like peptide-1 from L cells of the small intestine is enhanced, which suppresses appetite and stimulates sweet taste buds.^31,32 Therefore, this phenomenon has been frequently reported in Roux-en-Y gastric bypass surgery. Based on the same principle, PD, which involves resection of the duodenum and proximal jejunum, can also induce a sweet taste sensation.^33,34

Preoperative dysgeusia was observed only in patients with cancer and was significantly associated with hypoalbuminemia and anemia. Notably, dysgeusia gradually improved following surgery, along with the recovery of serum albumin and iron levels. These findings suggest a strong association between dysgeusia and cancer-related malnutrition and anemia, which potentially improved through surgical tumor resection. In contrast, postoperative dysgeusia was observed in both cancer and non-cancer patients, peaking on postoperative day 7. Given that gustatory receptor cells have a short lifespan and rapid turnover of 10 days, postoperative dysgeusia was most likely triggered by surgical invasion rather than by the underlying disease.²⁶ Furthermore, the postoperative dysgeusia was significantly associated with insufficient iron recovery and advanced age, suggesting that postoperative dysgeusia may result from deterioration of the oral environment due to insufficient iron recovery, as well as by the delayed regeneration of gustatory receptor cells due to advanced age.^35,36 An investigation into the nature and associated factors of dysgeusia suggested that preoperative and postoperative dysgeusia resulted from different triggers and multiple contributing factors. However, as decreased serum iron levels and anemia were observed in the preoperative dysgeusia group, and insufficient iron recovery was noted in the postoperative dysgeusia group, a potential association between inadequate iron status and dysgeusia was suggested. Therefore, careful follow-up with iron supplementation may be considered for patients undergoing PD to prevent perioperative dysgeusia and mitigate iron deficiency and anemia.^8,9

Recent study evaluating oral supplementation of trace elements in patients undergoing PD revealed that iron and zinc deficiencies were prevalent despite supplementation.¹⁰ As the duodenum and proximal jejunum, where iron and zinc are mainly absorbed, are resected during PD, oral supplementation may be ineffective in patients undergoing PD. In contrast, intravenous iron supplementation has recently been demonstrated to improve postoperative Hb levels.³⁷ Therefore, it may be a viable option to improve postoperative serum iron levels, and further studies are required to evaluate the impact of iron supplementation for improving dysgeusia and perioperative nutritional status.

Perioperative dysgeusia can induce appetite loss, posing a risk of malnutrition and a long hospital stay.^13,14 In this study, 81.8% of patients in both the preoperative and postoperative dysgeusia groups reported an unfavorable impact of dysgeusia on appetite loss. Particularly, the postoperative dysgeusia group exhibited a lower dietary intake than the other groups, leading to a higher frequency of enteral nutrition and a longer hospital stay. Therefore, supportive nutritional care may be required for high-risk patients, such as older patients and those with prolonged postoperative iron deficiency. Furthermore, monitoring perioperative serum iron levels may be beneficial in patients where malnutrition after PD is a concern.

This study has some limitations. The primary disease, tumor classification, and additional surgical procedures were diverse, which may have affected the incidence of dysgeusia. Particularly, pancreatic cancer constitutes over half of all cases, and selection bias may have occurred. The questionnaires were not administered to patients who were discharged before each observational point; therefore, the rate of dysgeusia on postoperative days 14 and 21 may have been underestimated. In addition, this study did not evaluate physiological mechanisms directly affecting gustatory receptor cells, and subjective findings may not always correspond to data derived from objective measurements, which may overestimate the degree of dysgeusia.³⁸ This study was conducted under the National Health Insurance system, and general trace metal elements were investigated. Therefore, other possible factors associated with dysgeusia and iron dynamics, such as ferritin and selenium levels, were not investigated.

In conclusion, this study found that 33% of patients experienced dysgeusia during hospitalization for PD, including 11 patients with preoperative dysgeusia and 22 with postoperative dysgeusia. Hypoalbuminemia and anemia were significantly associated with preoperative dysgeusia, and advanced age and insufficient iron recovery were significantly associated with postoperative dysgeusia.

ACKNOWLEDGMENTS

The authors thank all the patients who participated in this study, as well as their families and caregivers. The authors also express their gratitude to all the healthcare professionals involved in this study, with special thanks to Ms. Masayo Kaneko, Mr. Yuichi Hashimoto, and Ms. Izumi Hirata for their support in clinical management and data compilation.

Supplementary Material

as9-6-e575-s001.pdf ^{(294.9KB, pdf)}

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