Cancer-related fatigue and functional gastrointestinal disorders after total gastrectomy: A case report

Abstract

BACKGROUND

Improved survival after gastric cancer (GC) surgery has shifted clinical attention toward persistent non-organic symptoms, including cancer-related fatigue (CRF) and functional gastrointestinal disorders (FGIDs). These conditions frequently emerge during routine follow-up yet remain underrecognized and undertreated. This study reports a case of concurrent CRF and FGID after total gastrectomy and reviews relevant literature to clarify diagnostic considerations, underlying pathophysiological mechanisms, and multidisciplinary management strategies.

CASE SUMMARY

Clinical records, laboratory data, imaging findings, endoscopic results, and follow-up information were retrospectively analyzed. Fatigue severity was assessed using a numeric rating scale, and differential diagnoses excluded organic etiologies, including tumor recurrence and mechanical obstruction. A 55-year-old woman developed persistent postprandial abdominal pain and fatigue after total gastrectomy and perioperative chemotherapy. Her highest fatigue score reached 6/10, significantly impairing daily activities. Although multidimensional fatigue instruments were not used, clinical manifestations met the diagnostic criteria for CRF after exclusion of secondary causes. Gastrointestinal symptoms were consistent with FGID associated with post-gastrectomy syndrome. Literature review supported overlapping mechanisms involving nutritional deficiencies, altered motility, microbiota imbalance, and brain-gut axis dysregulation. Multidisciplinary management, including prokinetics, probiotics, nutritional supplementation, and traditional Chinese medicine, resulted in symptom improvement.

CONCLUSION

Recognizing CRF and postoperative FGID after GC surgery requires systematic assessment and integrated multidisciplinary strategies to improve long-term postoperative outcomes.

Key Words: Gastric cancer; Cancer-related fatigue; Functional gastrointestinal disorders; Post-gastrectomy syndrome; Case report

Core Tip: Cancer-related fatigue and functional gastrointestinal disorders (FGID) frequently coexist in patients after gastric cancer (GC) surgery, particularly following total gastrectomy. Their clinical manifestations are insidious, heterogeneous, and often overlooked once tumor recurrence has been excluded. This case underscores the importance of comprehensive differential diagnosis, multidisciplinary management, and holistic symptom assessment that extends beyond oncological surveillance. Early recognition and individualized intervention for cancer-related fatigue and FGIDs are crucial for improving long-term outcomes and enhancing the quality of life in post- GC surgery patients.

INTRODUCTION

As one of the most common malignant tumors of the digestive tract, gastric cancer (GC) treatment has evolved from surgery alone to a multidisciplinary and comprehensive approach centered on surgical intervention[1,2]. For locally advanced GC, perioperative chemotherapy (including neoadjuvant and adjuvant chemotherapy) combined with radical surgery with D2 lymph node dissection has become the standard treatment, significantly improving both disease-free and overall survival[3,4]. However, with improved survival rates, long-term treatment-related complications and their adverse effects on quality of life have become increasingly prominent and are now a major focus of clinical attention[5,6].

Among numerous postoperative complications, cancer-related fatigue (CRF) and gastrointestinal dysfunction represent two core symptom clusters[7]. The National Comprehensive Cancer Network defines CRF as “a subjective, persistent sense of tiredness related to cancer or its treatment that is disproportionate to recent activity, cannot be effectively relieved by routine rest, and results in significant impairment of cognitive, emotional, and physical functioning”[8,9]. Furthermore, radical total gastrectomy, as a destructive anatomical reconstruction procedure, inevitably disrupts the storage, grinding, emptying, and endocrine functions of the stomach, leading to altered food transit kinetics, nutritional malabsorption, and intestinal microecological imbalance. These physiological disturbances, in turn, precipitate a series of functional gastrointestinal disorders (FGIDs) primarily characterized by abdominal pain, bloating, early satiety, diarrhea, or constipation[10,11].

It is noteworthy that CRF and FGIDs do not occur independently in patients after GC surgery[12]. Common accompanying symptoms of FGIDs-such as chronic pain, sleep disturbances, anxiety, and depression-serve as important precipitating and aggravating factors for CRF. Conversely, the reduced overall functioning and weakened coping capacity associated with CRF lower patients’ tolerance to gastrointestinal discomfort, thereby creating a vicious cycle[13,14]. At present, systematic research on this comorbid phenomenon remains limited.

By carefully analyzing the complete diagnostic and therapeutic course of a representative patient with poorly differentiated gastric adenocarcinoma, this study aims to elucidate the clinical manifestations, internal associations, and epidemiological background of CRF and postoperative FGIDs. The goal is to provide clinicians with a practical framework for the comprehensive evaluation and management of patients after GC surgery, thereby advancing the patient-centered concept of precision rehabilitation.

CASE PRESENTATION

Chief complaints

A 55-year-old female freelancer residing in Yongzhou City, Hunan Province, was admitted to the Department of Oncology, Xiangya Changde Hospital, on September 3, 2020, with complaints of acid reflux and heartburn for more than 9 months, comprehensive treatment for GC 2 months prior, and abdominal pain for 2 days.

History of present illness

The patient initially developed unexplained acid reflux and heartburn in early December 2019, which worsened after meals. On December 17, 2019, she underwent gastroscopy and biopsy at Xiangya Changde Hospital. The pathological report dated December 19, 2019, revealed poorly differentiated adenocarcinoma of the gastric body.

Subsequently, she received two cycles of neoadjuvant chemotherapy with docetaxel plus tegafur-gimeracil-oteracil potassium at Xiangya Hospital, Central South University, and underwent total gastrectomy with esophagojejunal Roux-en-Y anastomosis on March 20, 2020. The postoperative pathological stage was ypT3N0M0, stage II.

The patient recovered well after surgery and completed five cycles of adjuvant chemotherapy using the same regimen between April and July 2020. Two days before this admission, she experienced paroxysmal upper abdominal colic after meals without identifiable precipitating factors.

During home recuperation after the last chemotherapy session (July 27, 2020), her mental state and sleep were acceptable, although her appetite was poor. Her bowel and bladder functions were normal, and her body weight had not changed significantly over the previous two months.

History of past illness

The patient denied a history of hypertension, diabetes mellitus, coronary heart disease, and other chronic non-communicable diseases. She had no history of hepatitis, tuberculosis, or other infectious diseases. No history of asthma, allergies, or blood transfusion was reported. She denied any history of abdominal surgery or trauma before the GC treatment. Her past general health condition was fair.

Personal and family history

The patient denied any family history of malignant tumours.

Physical examination

Physical examination on admission: Temperature: 36.3 °C; pulse: 78 beats/min; Respiratory rate: 20 breaths/min; blood pressure: 102/64 mmHg. The patient was of normal build, in good nutritional condition, fully conscious, and exhibited a chronic illness appearance. Her gait was normal, and she was able to ambulate independently. A postoperative scar approximately 15 cm in length was observed along the midline of the abdomen, showing good healing. The abdomen was soft, with mild tenderness in the upper region, no rebound tenderness, and no palpable masses. Bowel sounds were present at a rate of approximately three per minute with a regular rhythm. The Eastern Cooperative Oncology Group performance status score was 1.

Laboratory examinations

The patient underwent routine hematologic and biochemical testing during both the initial admission and postoperative follow-up periods. A fully automated hematology analyzer was used to measure white blood cell count, red blood cell count, hemoglobin concentration, and platelet count. Biochemical analyses included liver function indicators-alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase and total bilirubin (as well as renal function indicators-serum creatinine (Scr) and blood urea nitrogen (together with blood glucose, electrolytes, and lactate dehydrogenase levels. Tumor marker monitoring included carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9). According to clinical indications, thyroid function, iron metabolism, vitamin B₁₂, and folate assays were performed at selected time points to exclude the potential influence of anemia and endocrine abnormalities on fatigue symptoms.

Imaging examinations

Multidetector computed tomography (CT) served as the primary imaging modality for assessment. Plain and contrast-enhanced CT scans of the upper abdomen or the thorax, abdomen, and pelvis were performed both preoperatively and during postoperative follow-up. The main objective was to evaluate the primary lesion, anastomotic site, liver, and retroperitoneal lymph nodes for evidence of recurrence or metastasis. In addition, intestinal dilation and pneumatosis were assessed to exclude mechanical intestinal obstruction.

Endoscopic examinations included gastroscopy conducted preoperatively and during postoperative follow-up to evaluate the primary tumor and the condition of the postoperative esophagojejunal anastomosis. When the patient exhibited changes in stool characteristics or bowel habits, colonoscopy was performed to assess mucosal inflammation, polyps, and other abnormalities in the colon and rectum. Biopsy was carried out when necessary to exclude intestinal malignancy.

Assessment of CRF

Fatigue severity was evaluated using an 11-point numeric rating scale (0-10). The patient reported the worst fatigue score of 6/10 over the preceding 24 hours, indicating moderate fatigue with evident interference in daily activities and appetite.

Further evaluation excluded reversible causes, including anemia, thyroid dysfunction, infection, electrolyte imbalance, and major depressive disorder. Although standardized multidimensional instruments, such as the Brief Fatigue Inventory or EORTC QLQ-FA12, were not administered at initial assessment, the clinical presentation satisfied established diagnostic criteria for CRF after secondary etiologies were ruled out.

The absence of validated multidimensional fatigue scales represents a methodological limitation of this study and is discussed accordingly.

MULTIDISCIPLINARY EXPERT CONSULTATION

Based on the results of a comprehensive assessment, an individualized treatment plan was jointly developed by the Departments of Oncology, Gastroenterology, and Integrated Traditional Chinese and Western Medicine Rehabilitation. The plan included pharmacotherapy, dietary modification, exercise counseling, and traditional Chinese medicine intervention. Throughout the treatment course, changes in the patient’s symptoms and physical findings were evaluated during ward rounds and outpatient follow-up visits. Dynamic changes in body weight, complete blood count, and biochemical parameters were also documented.

FINAL DIAGNOSIS

Laboratory examination results

Routine blood test on admission: The white blood cell count was 11.56 × 10⁹/L (reference range: 3.5-9.5 × 10⁹/L), with a neutrophil percentage of 73.0%. The red blood cell count was 3.75 × 10¹²/L, and the hemoglobin concentration was 122 g/L (reference range: 115-150 g/L), indicating mild anemia. The platelet count was 232 × 10⁹/L.

Blood biochemical test results: ALT was 23 U/L, AST was 24 U/L, and lactate dehydrogenase was not measured. The blood urea concentration was 2.65 mmol/L, Scr was 48.4 μmol/L, and amylase was 25 U/L (reference range: 25-125 U/L). Overall, the findings indicated that liver and renal functions were within normal limits, with no evidence of acute organ injury.

Imaging and endoscopic examination results

Initial endoscopic and pathological findings (December 17, 2019): The patient underwent esophagogastroduodenoscopy at our hospital. Endoscopic findings were as follows: The esophageal mucosa was smooth; the cardia opened and closed well; the gastric fundus mucosa was congested and edematous, with thickened rugae and surface erosion; the gastric body mucosa was congested and edematous, with thickened rugae, partial rugal disappearance, a rough and eroded surface, and restricted gastric cavity distension; a 0.4 cm × 0.3 cm polyp was observed in the gastric angle; and the gastric antrum mucosa appeared congested and edematous. Because of the extensive and severe mucosal lesions described above, the endoscopist obtained eight deep biopsy specimens from the gastric body. The pathological report (December 19, 2019) confirmed poorly differentiated adenocarcinoma of the gastric body. Immunohistochemical staining results were as follows: CKpan (+), Villin (+), Her-2(0), and Ki-67 (approximately 20% positive) (Figure 1).

Figure 1 Electronic gastroscopic and routine biopsy pathology findings of the gastric mucosa. A: Duodenal bulb; B: Antrum; C: Gastric angle; D: Fundus; E: Body; F: Esophagus; G and H: Hematoxylin and eosin staining of gastric body mucosal tissue; I: Immunohistochemical staining of biopsy specimen.

To clarify the cause of abdominal pain, the patient underwent contrast-enhanced CT of the thorax, abdomen, and pelvis on September 4, 2020. The imaging demonstrated postoperative changes consistent with total gastrectomy and esophagojejunostomy. The anastomotic wall appeared slightly thickened, without any space-occupying lesions or abnormally enhanced foci, effectively ruling out local recurrence. Mild dilation and pneumatosis were observed in a segment of the small intestine, with visible fluid levels within the intestinal lumen. This finding had persisted since June 2020, suggesting a high likelihood of functional intestinal motility disorder. A mesenteric lymph node was enlarged compared with previous scans, measuring approximately 12 mm × 8 mm. Although this required clinical vigilance, there was no supportive evidence of tumor metastasis when combined with other examination results. In addition, the CT revealed several nonspecific findings, including a cyst in the posterior segment of the right hepatic lobe, small calculi in the left kidney, a small amount of pelvic effusion, and uniform wall thickening at the hepatic flexure of the colon (maximum thickness, approximately 11 mm) (Figure 2).

Figure 2 Contrast-enhanced computed tomography scans of the upper abdomen. A and B: Axial; C: Coronal; D: Sagittal.

Considering the CT finding of wall thickening at the colonic hepatic flexure and the patient’s persistent abdominal pain, further gastrointestinal endoscopic evaluation was performed. Esophagogastroduodenoscopy (September 4, 2020): The endoscope was inserted smoothly and advanced to the jejunum. The esophageal mucosa appeared normal. An esophagojejunal anastomosis, approximately 4 cm in diameter, was observed about 38 cm from the incisor teeth, with mild local mucosal edema and visible staples surrounding the anastomosis; no ulceration was noted. The mucosa of the saddle area appeared normal. The afferent loop had a relatively short lumen with edematous mucosa, whereas the efferent loop was unobstructed with nearly normal mucosal morphology. Based on the overall endoscopic findings, the diagnosis was consistent with post-Billroth II gastrectomy changes complicated by anastomotic inflammation (Figure 3).

Figure 3 Electronic gastroscopy findings. A: Lower esophagus; B: Anastomosis; C: Efferent loop; D: Saddle region.

Colonoscopy (September 8, 2020): The endoscope was advanced along the intestinal lumen to the terminal ileum, which appeared patent and free of significant abnormalities. The ileocecal valve was labial in shape and demonstrated good contractility. A pedunculated polypoid lesion, approximately 0.5 cm × 1.0 cm in size, was identified in the ascending colon near the hepatic flexure; its surface mucosa was congested and eroded, and the lesion was soft in texture. One biopsy specimen was obtained from this site. The rectal mucosa exhibited diffuse congestion and edema with locally disordered vascular patterns. The endoscopic impression was ascending colon polyp and proctitis. Follow-up histopathological results (September 11, 2020) confirmed that the ascending colon polyp was inflammatory in nature (Figure 4).

Figure 4 Electronic colonoscopy and pathological biopsy findings. A: Terminal ileum; B: Ascending colon; C: Rectum; D: Immunohistochemical staining of biopsy specimen; E: Hematoxylin and eosin staining of biopsy tissue.

The patient was initially diagnosed with a gastric malignant tumor (poorly differentiated adenocarcinoma, ypT3N0M0, stage II, post–neoadjuvant chemotherapy and surgery) and abdominal pain of unknown origin upon admission. For the evaluation of abdominal pain, organic causes such as acute cholecystitis, tumor-related intestinal obstruction, and anastomotic recurrence were first considered and systematically excluded. The patient had a negative Murphy’s sign, and imaging revealed no gallbladder abnormalities, indicating a low likelihood of acute cholecystitis. Contrast-enhanced CT of the thorax, abdomen, and pelvis, as well as gastroendoscopy, demonstrated no space-occupying lesions, abnormal enhancement, or newly suspicious lymph nodes at the anastomotic site. Serum levels of CEA and CA19-9 were within normal limits, and biopsy results were negative, effectively ruling out tumor recurrence or metastasis. CT findings showed only mild small intestinal dilation with a small amount of intraluminal fluid levels, without significant proximal dilation or a “step-ladder” pattern. Normal bowel movements and passage of flatus further argued against mechanical high-grade or complete intestinal obstruction. Gastroscopy revealed only mild mucosal edema at the anastomosis, without ulceration, erosion, or stenosis, suggesting a low probability of anastomotic ulcer or stricture. As chemotherapy had been completed two months earlier and no signs of mucosal toxicity were observed, the possibility of drug-induced gastrointestinal injury was considered low.

On the basis of excluding organic lesions-and considering the anatomical and motility alterations after total gastrectomy, the recurrent CT findings of small intestinal pneumatosis and fluid levels, and the chronic inflammation observed on endoscopy-the diagnosis was inclined toward FGIDs associated with post-gastrectomy syndrome. The patient exhibited persistent fatigue that was disproportionate to the level of physical activity and unrelieved by rest, accompanied by decreased energy and appetite. Other potential causes, such as overt anemia, thyroid dysfunction, electrolyte imbalance, and active infection, had been excluded, findings consistent with the characteristics of CRF. No typical manifestations of anxiety or depression were noted; thus, psychological factors were not considered primary contributors. Given that total gastrectomy commonly leads to deficiencies in vitamin B₁₂, iron, calcium, and other nutrients, the mild anemia and fatigue in this case were also likely related to malnutrition, for which nutritional assessment was recommended. Based on the patient’s persistent fatigue complaints, NRS fatigue score, and laboratory results, there was no evidence of tumor recurrence, and the likelihood of mechanical obstruction was low. The final diagnosis was revised to: Gastric malignant tumor (poorly differentiated adenocarcinoma, ypT3N0M0, stage II, post-operation), abdominal pain of unknown origin (likely FGIDs), and CRF (highly suspected).

TREATMENT

On September 6, a consultation was conducted by the Department of Gastroenterology. The patient was prescribed oral mosapride (5 mg, three times daily) and a bifidobacterium preparation (420 mg, twice daily) to promote gastrointestinal motility and regulate the intestinal flora. A colonoscopy was also arranged to evaluate the lower gastrointestinal tract. On September 9, a consultation was performed by the Department of Integrated Traditional Chinese and Western Medicine Rehabilitation. The diagnosis of “abdominal pain” was established, and syndrome differentiation indicated a “gastrointestinal damp-heat pattern complicated by yang deficiency”. Coix seed, Aconite, and Patrinia Decoction (Yiyifuzi Baijiang San) was administered to clear heat, resolve dampness, warm yang, and relieve pain. On the same day, the patient was transferred to the Department of Integrated Traditional Chinese and Western Medicine Rehabilitation for comprehensive management.

OUTCOME AND FOLLOW-UP

After treatment with prokinetic agents, probiotics, and traditional Chinese medicine, the patient’s postprandial abdominal pain and distension were alleviated. She was discharged from the hospital on September 16 with clinical improvement.

DISCUSSION

GC survival has improved with perioperative chemotherapy and standardized surgical procedures. Clinical priorities have therefore expanded from short-term survival to long-term quality of life. Persistent symptoms, including CRF and FGID, are increasingly recognized but remain insufficiently assessed during routine follow-up.

This case report incorporates a focused literature review rather than an epidemiological analysis, aiming to illustrate diagnostic complexity and clinical blind spots in postoperative management[15].

CRF is defined as persistent, distressing fatigue related to cancer or its treatment, disproportionate to recent activity, and not relieved by rest. In this patient, abdominal pain was the primary complaint, whereas fatigue developed insidiously, presenting as decreased appetite, reduced vitality, and functional decline[16]. A fatigue score of 6/10 indicated moderate fatigue. Although multidimensional instruments were not used, alternative medical causes were systematically excluded. We did not use validated fatigue scales, which remains a methodological limitation[17].

From a pathophysiological perspective, chronic inflammation and neuroimmune activation are central mechanisms in CRF. Chemotherapy exposure, surgical stress, and postoperative nutritional deficiencies may potentiate inflammatory cytokine signaling and central fatigue processing[18-20].

Total gastrectomy markedly alters gastrointestinal anatomy and physiology. Loss of reservoir capacity, rapid intestinal transit, partial vagal denervation, and hormonal disruption collectively disturb motility and cause visceral hypersensitivity[21]. Although the patient did not fulfill criteria for a discrete Rome IV subtype, her presentation aligned with FGID secondary to postgastrectomy syndrome rather than primary idiopathic FGID. This distinction prevents imprecise diagnostic labeling[22].

Emerging evidence indicates shared mechanisms between CRF and FGID within the brain-gut axis framework. Disruption of vagal signaling after gastrectomy may impair central autonomic regulation[23-25]. Concurrent intestinal dysbiosis and mucosal immune activation may sustain low-grade systemic inflammation, influencing hypothalamic-pituitary-adrenal axis activity and central fatigue pathways. Thus, CRF and FGID may therefore represent parallel manifestations of neuroimmune dysregulation rather than independent sequelae.

Clinically, this case illustrates a common phenomenon: Once tumor recurrence is excluded, persistent symptoms can be attributed to normal postoperative recovery. Standardized screening for CRF is not routinely implemented in many oncology settings, and gastrointestinal complaints may be underestimated. Such underrecognition delays targeted rehabilitation[26].

This study has some limitations. First, multi-dimensional fatigue assessment tools were not used. Second, structured Rome IV diagnostic interviews were not conducted. Third, the objective biomarkers of inflammation, autonomic function, and microbiota composition were not evaluated. Therefore, the mechanistic interpretations are hypothesis-generating[27].

Despite these constraints, this case underscores the need for systematic symptom assessment beyond oncological surveillance. Integrating validated fatigue scales, structured functional gastrointestinal evaluations, and multidisciplinary rehabilitation may improve long-term outcomes after total gastrectomy.

CONCLUSION

Currently, systematic research on the comorbidity of CRF and FGIDs after GC surgery remains limited. Clinical follow-up generally focuses on tumor recurrence while overlooking the “soft” symptoms that profoundly affect long-term quality of life. The key aspect of this case is that the medical team did not confine their evaluation to the single diagnosis of anastomotic inflammation but instead implemented comprehensive and systematic symptom management based on the biopsychosocial model through multidisciplinary collaboration involving the Departments of Gastroenterology and Integrated Traditional Chinese and Western Medicine Rehabilitation. This case highlights the need to establish an integrated assessment framework for postoperative management of GC. In addition to imaging examinations and tumor marker monitoring, greater attention should be directed toward patient-reported outcomes-such as screening for CRF using the Brief Fatigue Inventory and conducting systematic evaluations of digestive function-to truly realize a patient-centered approach to precision rehabilitation and improve the long-term quality of postoperative care.