Fiorillo C, Alfieri S, Biffoni B, Langellotti L, Lucinato C, Massimiani G, Menghi R, De Sio D, Puzzangara MC, Rosa F, Gentili V, Gambaro E, Tondolo V, Quero G. Exocrine pancreatic insufficiency and quality of life after oncologic gastric surgery: Evaluation from a single tertiary center. World J Gastrointest Surg 2025; 17(9): 107789 [DOI: 10.4240/wjgs.v17.i9.107789]
Corresponding Author of This Article
Beatrice Biffoni, MD, Digestive Surgery Unit, Fondazione Policlinico Universitario “Agostino Gemelli” IRCCS, Largo Agostino Gemelli 8, Roma 00168, Italy. beatrice.biffoni@guest.policlinicogemelli.it
Research Domain of This Article
Surgery
Article-Type of This Article
Observational Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Claudio Fiorillo, Sergio Alfieri, Beatrice Biffoni, Lodovica Langellotti, Chiara Lucinato, Giuseppe Massimiani, Roberta Menghi, Davide De Sio, Elisabetta Gambaro, Giuseppe Quero, Digestive Surgery Unit, Fondazione Policlinico Universitario “Agostino Gemelli” IRCCS, Roma 00168, Italy
Sergio Alfieri, Roberta Menghi, Maria C Puzzangara, Fausto Rosa, Giuseppe Quero, Department of Surgery, Università Cattolica del Sacro Cuore di Roma, Roma 00168, Italy
Vanessa Gentili, U.O.C. Laboratorio Analisi, Ospedale San Giovanni Evangelista, Tivoli 00019, Lazio, Italy
Vincenzo Tondolo, Digestive Surgery Unit, Fatebenefratelli Isola Tiberina–Gemelli Isola, Roma 00186, Italy
Author contributions: Fiorillo C and Biffoni B conceptualized the study; Alfieri S and Tondolo V supervised the project; Langellotti L and Quero G wrote the original draft of the manuscript; Lucinato C, Massimiani G, and Gentili V performed the analysis and investigation; Menghi R, De Sio D, and Gambaro E were responsible for the methodology; Puzzangara MC and Rosa F reviewed and edited the manuscript; all of the authors read and approved the final version of the manuscript to be published.
Institutional review board statement: The study was approved by the Institutional Review Board and the Ethical Committee.
Informed consent statement: All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964 and later versions. Informed consent to be included in the study, or the equivalent, was obtained from all patients.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at beatrice.biffoni@guest.policlinicogemelli.it. Patients' consent for data sharing was not obtained but the presented data are anonymized and risk of identification is low.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Beatrice Biffoni, MD, Digestive Surgery Unit, Fondazione Policlinico Universitario “Agostino Gemelli” IRCCS, Largo Agostino Gemelli 8, Roma 00168, Italy. beatrice.biffoni@guest.policlinicogemelli.it
Received: March 30, 2025 Revised: April 14, 2025 Accepted: July 18, 2025 Published online: September 27, 2025 Processing time: 179 Days and 16.8 Hours
Abstract
BACKGROUND
Gastrectomy is recognized as a potential cause of exocrine pancreatic insufficiency (EPI). However, limited data are available regarding the incidence and impact of EPI on quality of life (QoL) following gastric surgery.
AIM
To evaluate incidence and severity of EPI after gastrectomy and its effect on QoL at least one year after surgery.
METHODS
EPI was assessed using fecal elastase measurement and classified into: (1) No-EPI (fecal elastase > 200 μg/g); (2) Moderate EPI (fecal elastase 100–200 μg/g); and (3) severe EPI (fecal elastase < 100 μg/g). QoL was measured using the Gastrointestinal Quality of Life Index (GIQLI) questionnaire.
RESULTS
Sixteen out of 44 (36.4%) patients developed EPI post-operatively: 9 (56.2%) patients had moderate EPI while 7 (43.8%) patients had severe EPI. Severe EPI was more frequently observed in younger patients (5/7: 71.4%; P = 0.05), in more advanced disease stages (7/7: 100%; P = 0.05), lymph nodes metastases (7/7: 100%; P = 0.04) and in the mixed histotypes (4/7: 66.7%; P = 0.02) compared to the no-EPI and moderate EPI groups. QoL analysis showed that severe EPI was associated with a significantly lower overall GIQLI score [65 (59–92)] compared to the no-EPI/moderate EPI groups [89 (84–100)] (P = 0.002). Lower scores were particularly evident in the core (P < 0.0001) and disease-specific symptoms domains (P = 0.002) in the severe EPI group compared to the no-EPI/moderate EPI groups.
CONCLUSION
Gastrectomy is a cause of EPI. Younger patients, aggressive disease and advanced stages are significant risk factors for more severe EPI. Severe EPI worsens QoL, being associated with a higher rate of gastrointestinal symptoms.
Core Tip: Gastrectomy is a recognized cause of exocrine pancreatic insufficiency (EPI), yet its impact on quality of life (QoL) remains under-investigated. This study confirms gastrectomy as a significant contributor to EPI and identifies younger age, advanced stage, and aggressive histology as risk factors for more severe forms. Severe EPI is associated with a higher burden of gastrointestinal symptoms and leads to a notable deterioration in postoperative QoL.
Citation: Fiorillo C, Alfieri S, Biffoni B, Langellotti L, Lucinato C, Massimiani G, Menghi R, De Sio D, Puzzangara MC, Rosa F, Gentili V, Gambaro E, Tondolo V, Quero G. Exocrine pancreatic insufficiency and quality of life after oncologic gastric surgery: Evaluation from a single tertiary center. World J Gastrointest Surg 2025; 17(9): 107789
Gastric cancer (GC) currently represents the fifth most common malignant tumor and the fourth leading cause of cancer-related mortality, with an estimated incidence of approximately 1.1 million new cases and 770000 associated deaths in 2020[1]. Recent advancements in multimodal treatment strategies have significantly improved oncological outcomes for patients with GC. This progress has led to a concomitant growing interest in enhancing the quality of life (QoL), particularly for those patients undergoing gastric surgery with curative intent[2].
According to recent reports, up to 90% of patients undergoing total gastrectomy (TG) or subtotal gastrectomy (STG) for GC develop postoperative maldigestion syndrome, which may lead to chronic malnutrition in the most severe cases. This condition inevitably affects QoL, with clinical manifestations ranging from nutritional deficiencies to acid and biliary refluxes, altered gastric emptying and dumping syndrome[3,4]. In this context, the development of exocrine pancreatic insufficiency (EPI) after TG or STG appears to play a key role. Several factors have been identified as potential causes of EPI following gastric resection: (1) Reduced acid secretion; (2) Bacterial proliferation/overgrowth that inhibits enzymes activation; (3) A decrease in cholecystokinin levels; (4) A faster bolus transit through the upper intestine; and (5) Vagal denervation which disrupts the neuroendocrine signals that normally stimulate the pancreas to secrete digestive enzymes[5,6]. These alterations result in a decline in the secretion of amylase, lipase and protease, leading to reduced absorption of essential macronutrients, micronutrients and vitamins, ultimately contributing to the development of maldigestion symptoms and an overall decline in QoL[7].
Although the connection between gastric resection and the development of EPI has been widely demonstrated, only few studies[8–11] have investigated the incidence of EPI after gastrectomy and its impact on QoL of patients undergoing surgery.
Based on these premises, the aim of this prospective study is to assess the incidence of EPI following gastrectomy for GC at a tertiary referral center for the surgical treatment of gastric tumors and to evaluate the impact of EPI on QoL of affected patients.
MATERIALS AND METHODS
After Institutional Review Board and Ethical Committee approvals, all patients aged 18 years or older who underwent surgery for GC between March 2016 and January 2023 at the Digestive Surgery Unit of Fondazione Policlinico Universitario “Agostino Gemelli” IRCCS of Rome were retrospectively enrolled from a prospectively maintained database. Exclusion criteria included a previous history of major abdominal surgery, preoperative malnutrition or malabsorption, and/or the development of postoperative pancreatitis.
Perioperative data collected encompassed demographic characteristics, patients’ comorbidities (diabetes, cardiovascular and pulmonary diseases), the American Society of Anesthesiologists score, tumor location categorized as proximal (cardia and gastric fundus), middle (gastric body) or distal (gastric antrum), neoadjuvant therapy (NAT), type of surgical procedure performed [TG, STG and superior polar gastrectomy (SPG)] and reconstruction technique after STG (Billroth II or Roux-en-Y reconstructions), histological type according to Lauren classification, and tumor staging according to the 8th edition of the American Joint Committee on Cancer. Postoperative courses and follow up data were additionally registered, including post-operative complications categorized according to the Clavien-Dindo classification[12], adjuvant therapy and tumor recurrence at the last follow-up.
A prospective evaluation of the incidence rate of EPI through the measurement of fecal elastase levels and QoL using the Gastrointestinal Quality of Life Index (GIQLI) questionnaire was conducted in patients with a follow up of at least one year.
EPI definition and grading
EPI was defined as fecal elastase levels ≤ 200 μg/g and graded as severe for levels < 100 μg/g and moderate for levels between 100 μg/g and 199 μg/g[13]. Stool specimens were collected from each enrolled patient for fecal elastase measurement. The measurements were performed using the Diasorin LIAISON® Elastase-1 test, an in vitro chemiluminescent diagnostic test for the quantitative determination of fecal pancreatic elastase in fecal samples. To objectively evaluate the incidence rate of EPI following gastric resection, fecal elastase levels observed in the study population were compared with those of a control population of healthy subjects.
QoL evaluation
For QoL evaluation, the GIQLI questionnaire was administered either personally or electronically via email to all enrolled patients.
The GIQLI questionnaire[14] comprises 36 items, grouped into 5 domains: (1) 19 questions on gastrointestinal symptoms (subdivided into core and disease-specific symptoms); (2) 7 questions on physical conditions; (3) 5 questions on emotional conditions; (4) 4 questions on social setting; and (5) 1 question on the effects of medical treatment. Each question is scored on a scale from 0 to 4, where 4 represents the best condition. The total score ranges from 0 to 144, with higher scores reflecting a better QoL. For the purpose of this study, the medical treatment domain was excluded from the analysis, as it included only a single question.
Surgical technique
The details of the surgical procedures were previously reported[15,16]. All gastric resections were performed by the same surgical team throughout the study period. In brief, an open approach was used in all cases. A Roux-en-Y esophagojejunostomy using a circular stapler was performed in case of TG, while a Billroth II or Roux-en-Y reconstruction was employed after STG according to the operating surgeon’s preference. The biliary limb length in the Roux-en-Y reconstruction after TG and STG ranged from 40 cm to 60 cm. For SPG, the procedure involved resection of the upper two-thirds of the stomach and the distal esophagus, followed by esophagogastrostomy. A D2 lymphadenectomy was performed and considered the standard of care in all the procedures.
Study outcomes
The primary endpoint of the study was to objectively determine the incidence rate and severity of EPI following gastrectomy, with a particular focus on the potential influence of clinico-demographic and surgery-related factors on its development. The secondary endpoint was to evaluate changes in QoL after surgery, with a sub-analysis assessing QoL variations according to EPI severity.
Statistical analysis
All continuous data were reported as median and quartile rank while numbers and percentages were used for all categorical data. Univariate analysis included Mann-Whitney U test, Student’s t-tests, χ2 test, and Fisher’s exact test. For all tests, a P value ≤ 0.05 was considered statistically significant. All data were analyzed using Statistical Package for the Social Sciences for Windows, version 25 (SPSS Inc., Chicago, IL, United States).
RESULTS
From March 2016 to January 2023, 255 patients underwent gastric resection for GC at the Digestive Surgery Unit of Fondazione Policlinico Universitario “Agostino Gemelli” IRCCS of Rome. Of them, 131 (51.4%) patients underwent STG, 89 (34.9%) patients underwent TG, 25 (9.8%) patients underwent SPG, and 9 (3.5%) patients underwent a degastro-gastrectomy. Two hundred and eleven (82.7%) patients were excluded from the study for the following reasons: (1) 6 (2.3%) patients developed postoperative pancreatitis; (2) 16 (7.6%) patients died within one year after surgery; (3) 53 (25.1%) patients had a history of major surgical procedures; and (4) 136 (64.4%) patients either declined participation in the prospective evaluation of EPI and QoL or were lost to follow-up. Thus, the final study cohort consisted of 44 (17.3%) patients.
The clinico-demographic characteristics of the study population are reported in Table 1. As a whole, 25 (56.8%) patients received NAT. Fourteen patients out of 44 (31.8%) patients underwent TG, 26 (59.1%) patients underwent STG and 4 (9.1%) patients underwent SPG. After STG, a Roux-en-Y reconstruction was the most frequently performed (19 out of 44 cases: 73.1%). Most patients presented an advanced disease with a T3-T4 stage in 26 (59.1%) cases and lymph nodes metastases in 25 (56.8%) patients. The intestinal type was the most frequently observed histological subtype, reported in 23 (52.3%) patients. Post-operatively, 24 (54.5%) patients underwent adjuvant therapy. The median follow up was 31 (18-42) months, with a disease recurrence rate of 25% (11 out of 44 patients).
Table 1 Clinico-demographic characteristics of the study population and comparative analysis between no-exocrine pancreatic insufficiency and exocrine pancreatic insufficiency cohorts, n (%).
EPI incidence rate and related risk factors analysis
Overall, 16 out of 44 (36.4%) patients developed EPI after gastrectomy, with a median fecal elastase value of 120.5 (52.75-194.5) μg/g as compared to 476 (345.75-631.75) μg/g in the no-EPI group (P < 0.0001). As shown in Table 1, no significant differences in clinico-demographic characteristics were observed between the two cohorts. Furthermore, no difference was documented in terms of surgical procedure performed (P = 0.18), although TG more frequently related to a higher rate of EPI (7 out 14 TGs: 50%) than SGT (9 out of 26: 34.6%) and SPG (0%). Of the EPI population, 9 (56.2%) patients presented a moderate EPI grade while 7 (43.8%) patients presented a severe EPI grade (Table 2). A higher risk of severe EPI was observed in younger patients (5 out of 7: 71.4%) as compared to patients older than 65 years (2 out of 7: 28.6%; P = 0.05). No difference was observed in terms of EPI severity among STG, TG and SPG. Additionally, no significant differences were found when comparing reconstruction techniques after STG (Roux-en-Y vs Billroth II, P = 0.91). An advanced disease stage and lymph nodes metastases were significantly associated with severe EPI. Specifically, all patients with severe EPI presented a T3- T4 stage as compared to 5 out of 9 (55.6%) in the moderate EPI group and 14 out 28 (50%) in the no-EPI cohort (P = 0.05). Similarly, lymph node metastases were documented in 100% of patients with severe EPI, compared to 4 out of 9 (44.4%) in the moderate EPI group and 14 out of 28 (50%) in the no-EPI cohort (P = 0.04). Patients with severe EPI also showed a significantly higher prevalence of mixed and diffuse histotypes (P = 0.02).
Table 2 Comparative analysis of clinico-demographic characteristics according to exocrine pancreatic insufficiency severity, n (%).
To assess the impact of gastrectomy on EPI development, fecal elastase levels were compared between the study cohort and a control group of healthy subjects. Patients who underwent gastrectomy had significantly lower median fecal elastase levels (343.5 μg/g, range: 157–513.75 μg/g) compared to healthy controls (800 μg/g, range: 610–800 μg/g, P = 0.001).
QoL evaluation
At the QoL evaluation, no difference was noted in terms of GIQLI score between the EPI and no-EPI cohort and no significant difference was documented based on the clinico-demographic characteristics of patients, surgical procedures and histopathological features. However, patients with severe EPI had a significantly lower median GIQLI score [65 (59-92)] compared to those with no-EPI and moderate EPI [89 (84-100) (P = 0.002)] (Table 3). In the analysis of GIQLI domains (Table 4), patients with severe EPI more frequently reported gastrointestinal symptoms than those in the no-EPI/moderate EPI group. Specifically, the core symptoms score was significantly lower in the severe EPI group [13 (12–18)] compared to the no-EPI/moderate EPI group [23 (22–26) (P < 0.0001)]. Similarly, the disease-specific symptoms score was significantly higher in patients with severe EPI [28 (23–36)] compared to those with no-EPI or moderate EPI [34 (33–36)].
Table 3 Gastrointestinal Quality of Life Index score according to the clinico-demographic characteristics and exocrine pancreatic insufficiency severity of the study population, n (%).
Variables
Study population (n = 44)
Gastrointestinal Quality of Life Index, median (QR)
The recent implementation of multimodal treatments and targeted therapies for GC has significantly improved long-term outcomes, particularly in terms of overall and disease-free survival, especially for patients undergoing gastric resection with curative intent[2]. This inevitably brought patients and health care providers to pay more attention to QoL, that is currently recognized as a key oncological outcome on par with treatment safety and efficacy[17]. Indeed, several authors extensively demonstrated the prognostic role of QoL on survival outcomes of oncological patients[18,19], further emphasizing the importance of combining effective treatment strategies with the maintenance of an adequate QoL.
This is particularly true for patients undergoing gastric resection, who frequently experience a range of functional and nutritional deficiencies that significantly impact their daily lives[5,7]. In this context, the development of EPI after gastric resection may play a critical role in both gastrointestinal symptoms and QoL[20,21]. Although the pathophysiological mechanisms of EPI development after gastrectomy remain unclear, postoperative bacterial overgrowth is likely to induce a reduced secretory response to endogenous stimuli, leading to decreased activation of pancreatic enzymes[7,8,22]. Additional hypotheses suggest that vagal denervation during surgery or faster bolus transit to the small intestine could act as triggering factors for EPI onset[5,6]. Importantly, this type of pancreatic insufficiency must be distinguished from primary EPI caused by pancreatic parenchyma loss, since post-gastrectomy direct pancreatic stimulation tests with secretagogues administration have demonstrated a normal pancreatic response[23,24]. Overlooking the literature, contrasting data are currently present on the effective incidence rate of EPI after gastrectomy[25,26] as well as few data are reported on the influence of EPI in QoL in this subset of patients[8,11]. This is primarily due to the lack of a standardized definition of EPI, which is often based on subjective symptomatology reported by patients. Furthermore, existing evidence is derived from small study cohorts with limited follow-up durations and no stratification based on the type of surgical procedure performed[27].
Given these premises, we conducted a prospective evaluation of the incidence rate of EPI and changes in QoL on a retrospective cohort of study after at least 1 year from gastric resection for GC, with particular focus on the variation of EPI rate and severity according to the clinico-demographic characteristics and surgery-related features. Furthermore, an additional analysis was performed to assess the potential impact of EPI on QoL within the same study population.
The choice of fecal elastase-1 as the primary marker for diagnosing EPI in our study is supported by recent evidence highlighting its clinical relevance[28–30]. Fecal elastase is a non-invasive, cost-effective, and widely available tool that provides an indirect but reliable measure of pancreatic exocrine function. It is highly stable in stool samples and has demonstrated strong correlation with direct pancreatic function tests[28]. Recent guidelines and studies have further validated its role in both the diagnosis and monitoring of EPI, particularly in non-pancreatic surgical populations such as patients undergoing gastrectomy[29,30]. Additionally, low fecal elastase values have been associated not only with maldigestion but also with deterioration in nutritional status and QoL, thus reinforcing the importance of its systematic evaluation in post-gastrectomy follow-up protocols[31].
According to our results, gastric surgery is confirmed as a predisposing procedure to EPI development with more severe manifestations in younger patients and advanced disease stage. More importantly, the development of a severe EPI has been shown to negatively impact patients’ QoL with a higher incidence of gastrointestinal symptoms compared to patients with no-EPI or moderate EPI.
In our study cohort, the incidence of EPI after gastric resection was observed in 16 out of 44 (36.4%) patients, with a median value of fecal elastase of 120.5 (52.75-194.5) μg/g. This finding aligns with most current reports in the literature. Heptner et al[26] reported an EPI incidence of 30% in patients undergoing gastric resection. Similarly, in the recent meta-analysis by Hall et al[27], the incidence of EPI exceeded 50% following esophagogastric surgery. However, the authors did not find any statistically significant difference in EPI rates between TG (66.2%) and STG (46.9%) (P = 0.6), while no comparative data are reported between the different types of reconstruction after STG. Overlooking our data, no statistically significant difference in EPI incidence was observed between the TG and STG cohorts (P = 0.18), although a higher rate was evidenced after TG (50%) compared to STG (34.6%). While these findings are consistent with Hall et al[27], the observed tendency towards a higher EPI rate after TG in our cohort should not be overlooked. The lack of statistical significance may be attributable to the small sample size of our study population. Indeed, Straatman et al[5] reported TG as a surgical procedure more prone to the development of EPI. Although the underlying pathophysiological mechanism remains unclear, it is hypothesized that vagotomy performed during TG may significantly reduce neuroendocrine signaling, leading to decreased pancreatic secretion[6].
Regarding EPI severity in relation to the clinico-demographic characteristics of the study population, younger age, more advanced disease stages and a more aggressive histotypes were identified as potential risk features for a more severe EPI grade. These findings may be explained by the need for more extensive surgical procedures in younger patients and in cases of advanced or aggressive disease. It is plausible that highly demolitive procedures contribute to more extensive pancreatic denervation, disrupting normal neural signaling pathways and consequently reducing the hormonal stimuli necessary for adequate exocrine secretion[22].
As an additional finding, the postoperative onset of EPI was associated with a negative impact on QoL in our cohort. For this analysis, the GIQLI questionnaire was administered to all patients. Although it was not specifically conceived to evaluate QoL after gastric surgery, several authors demonstrated its validity and reliability in QoL evaluation of patients with GC undergoing gastrectomy[32,33]. Furthermore, the choice of this specific scale was based on its suitability for the characteristics of our study population, and its ability to comprehensively capture the physical, emotional, social, and functional dimensions of QoL after a surgical procedure. Although other QoL assessment tools are available—such as the generic Short-Form 36[34], the symptom-focused Gastrointestinal Symptom Rating Scale[35], or condition-specific instruments like the Irritable Bowel Syndrome Quality of Life[36]—we selected the GIQLI due to its disease-specific focus and multidimensional structure, which align closely with the aims of our study. We also acknowledge the value of alternative approaches, including objective measures and qualitative methods such as interviews or focus groups, which can offer deeper insights into patient experiences. However, for the purposes of this study, the GIQLI provided a standardized, practical, and clinically relevant means of QoL assessment. In this context, the GIQLI questionnaire has demonstrated robust test-retest reliability, strong interclass correlation, internal consistency, and psychometric validity in assessing chronic gastrointestinal disorders[37].
According to our findings, the onset of severe EPI was associated with a significantly lower overall GIQLI score as compared to patients with no-EPI or moderate EPI. Furthermore, significantly lower values were specifically documented for the gastrointestinal symptoms domains in case of severe EPI onset.
To contextualize our findings within the existing literature, we systematically compared the results of this study with those of previous investigations on EPI following gastric resection. While some earlier studies, such as those by Heptner et al[26] and Hall et al[27] , reported variable incidence rates of EPI post-gastrectomy, our results align more closely with the intermediate prevalence reported by Heptner et al[26] (30% vs 36.4% in our cohort). Moreover, unlike prior analyses that lacked long-term follow-up or detailed stratification, our study uniquely focuses on patients at least one year after surgery and considers both surgical type and clinico-pathological characteristics.
Regarding outcome measures, we integrated both objective assessment of pancreatic function via fecal elastase-1 and patient-reported outcomes using the GIQLI questionnaire, which allowed us to explore the relationship between EPI severity and QoL deterioration—a connection that has been sparsely documented in previous literature[8,11]. Additionally, our results revealed that more severe EPI occurs in younger patients and those with advanced disease, possibly reflecting the impact of more extensive surgical procedures. This demographic-specific observation may offer new insights into risk stratification.
The innovative aspects of our study include the combination of objective biochemical markers and validated QoL tools, the stratification of EPI severity, and the prospective application of these parameters on a retrospectively identified cohort with extended follow-up. These elements distinguish our work from earlier reports and contribute to a more nuanced understanding of post-gastrectomy functional outcomes. By emphasizing the clinical relevance of EPI assessment beyond the immediate postoperative period, our study underscores the need for systematic follow-up protocols that integrate both nutritional and QoL dimensions.
These data path the way to the potentially contributing role of enzyme supplementation after gastrectomy. However, no unanimous consensus is currently present in the literature on this topic. Hillman[38] reported a significant reduction of fecal fats levels with enzyme supplementation after STG. Conversely, the first randomized clinical trial[39], failed to demonstrate any advantage for the enzyme supplementation after gastrectomy. Interestingly, the same authors, on a larger series of 52 patients, reported a positive impact of post-gastrectomy enzyme supplementation on QoL of patients[21]. A similar finding was reported by Catarci et al[8], who demonstrated both nutritional and QoL benefits of enzyme supplementation after gastrectomy, especially between the first and third month after surgery. These conflicting findings underscore the need for large-scale randomized controlled trials specifically designed to evaluate the potential benefits of post-gastrectomy enzyme supplementation with the ultimate goal of improving post-gastrectomy QoL.
While the present study focuses on functional and nutritional outcomes, it is important to consider broader clinical indicators of surgical quality in oncological gastric surgery, including curative resection rates, postoperative complication profiles, and long-term survival outcomes, which represent key components of comprehensive patient care[40,41]. Moreover, complementary and alternative medicine therapies, such as acupuncture, mind-body techniques, and herbal supplementation, have shown promising results in alleviating gastrointestinal symptoms, reducing anxiety, and enhancing recovery in oncological patients[42,43]. Although not assessed in this study, future investigations may benefit from integrating these dimensions to further improve postoperative QoL and long-term well-being.
Our study presents several limitations. Firstly, although our findings align with previous reports, the sample size of the study population is too small to draw solid conclusions and generalize the results. Secondly, the absence of a comparative group of patients undergoing enzyme supplementation after gastrectomy prevents us from clearly assessing the potential benefits of such treatment in this context. Thirdly, the complexity of gastric surgery and the multitude of functional consequences beyond EPI make it challenging to isolate and evaluate the specific impact of EPI on gastrectomy outcomes and QoL. On the other hand, we objectively demonstrated (by the fecal elastase measurement) the incidence rate of EPI after gastrectomy, reporting the correlation between EPI onset and QoL deterioration, with statistically significant data even in a small sample size of patients.
CONCLUSION
In conclusion, our study confirms gastric surgery as a procedure potentially leading to EPI onset, with a subset of patients, namely younger individuals and those with advanced disease stages, more prone to the development of pancreatic insufficiency. In addition, the onset of a more severe grade of EPI was demonstrated to negatively impact the QoL of patients at least one year after surgery with significant consequences in terms of gastrointestinal symptoms. However, further studies, possibly in a randomized controlled setting, are needed to validate our findings and define the potential benefits of enzyme supplementation after gastric surgery.
Footnotes
Provenance and peer review: Unsolicited article; Externally peer reviewed.
Peer-review model: Single blind
Specialty type: Gastroenterology and hepatology
Country of origin: Italy
Peer-review report’s classification
Scientific Quality: Grade A
Novelty: Grade B
Creativity or Innovation: Grade A
Scientific Significance: Grade A
P-Reviewer: Xu B S-Editor: Luo ML L-Editor: A P-Editor: Lei YY
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