Intestinal obstruction caused by early stage primary ileum adenocarcinoma: A case report and review of literature

Abstract

BACKGROUND

Ileum adenocarcinoma (IA), a type of small bowel adenocarcinoma, is a rather uncommon factor associated with obstruction in small bowel. Owing to its location and indefinite clinical symptoms, the diagnosis of IA is difficult, and survival is usually poor. With respect to the rarity of this disease, very few studies have reported such cases to provide a reference for treatment.

CASE SUMMARY

In this manuscript, a case of a 48-year-old man presented with chronic right lower abdominal pain and distention, queasiness and emesis. A computed tomography scan revealed intestinal wall thickening and an intestinal obstruction in the terminal ileum. He was diagnosed with inflammatory bowel disease. However, his symptoms were not relieved after conservative treatment. The patient subsequently underwent exploratory laparotomy, and a tumour in the ileum measuring approximately 2.0 cm × 2.0 cm that was located 20 cm from the ileocolic valve was discovered incidentally and was operatively resected along with the enlarged lymph nodes. Pathological examination revealed a stage IIA (T3N0M0) ulcerative IA. Along with imaging examinations, a diagnosis of primary IA with no lymph or distant metastases was considered. The patient was discharged and recovered well as of the writing of this manuscript.

CONCLUSION

IA should be considered as a differential diagnosis in cases of intestinal obstruction, and the recommended method for local disease treatment is surgery.

Key Words: Intestinal obstruction; Ileum adenocarcinoma; Exploratory laparotomy; Diagnosis; Therapy; Case report

Core Tip: Adenocarcinoma in the ileum is an extremely rare pathological type. Its clinical presentation is indefinite, and its diagnosis is challenging. Here, the case of a 48-year-old man who was diagnosed with primary ileum adenocarcinoma was presented. Proper diagnosis and early intervention are important for the prognosis of patients. For local disease, surgical excision along with the removal of regional lymph nodes en bloc is recommended.

INTRODUCTION

Compared with other gastrointestinal carcinomas, cancers in small bowel are rare, accounting for only 3% of the cancers that occur within this system[1]. The most frequent histological subtypes are neuroendocrine neoplasms, adenocarcinomas, lymphomas and gastrointestinal stromal neoplasms[2]. The proportion of small bowel adenocarcinomas (SBAs) is approximately 30%-40%. SBAs occur often in the duodenum but less in the jejunum or ileum[3]. Compared to those with jejunal tumours, patients with ileum adenocarcinoma (IA) are easier to develop gastrointestinal obstruction[4]. Among patients with small bowel cancers, jejunal tumours have a better overall survival (OS) than ileal and duodenal tumours do[5]. The rate of recurrence is higher among IA cases (77%) than among duodenal (54%) or jejunal adenocarcinoma cases (65%)[6]. Owing to its rarity and vague clinical manifestations, most patients with SBA have a poor prognosis because of advanced-stage presentations. It has been reported that 33% of patients have high-grade malignancies with lymph node involvement and that 56% of patients have distant metastasis at diagnosis[7]. The median OS and 5-year survival rates from cancer diagnosis data are 20 months and 26%, respectively[8]. Thus, early diagnosis and management are crucial, as this can significantly affect patient survival. In this manuscript, we present a case of the surgical treatment of a 48-year-old man with ileus of the small intestine resulting from early-stage primary adenocarcinoma in the ileum.

CASE PRESENTATION

Chief complaints

The patient was a 48-year-old man whose main symptoms were chronic right lower abdominal aches with distention, queasiness and emesis.

History of present illness

The patient came to our hospital after experiencing an abdominal ache and distention in the right lower abdomen for one month. He experienced nausea approximately one hour after eating and vomited stomach contents. These symptoms were alleviated by proton pump inhibitors. Five days prior to admission, the patient’s abdominal pain intensified with concomitant cessation of defecation and flatus. He reported weight loss of 5 kg over the last two months.

History of past illness

The patient presented with no history of previous abdominal surgery. He was diagnosed with hypertension two years prior, and this was effectively controlled with oral medication.

Personal and family history

The patient presented no previous experience with SBA, and there was no history of cancer in his family.

Physical examination

A physical examination was performed on the patient. The body temperature was 36.8 °C, the pulse was normal at 88 beats/minute, and the respiratory rate was 18 breaths/minute. Abdominal examination indicated the presence of abdomen tenderness and muscle tension. The abdomen appeared distended, accompanied by a weak rumbling sound. No lump was palpated, and digital rectal examination was insignificant.

Laboratory examinations

Routine blood tests revealed a white blood cell count of 6.0 × 10⁹/L, a red blood cell count of 4.730 × 10¹²/L, a platelet count of 279 × 10⁹/L, an alpha-fetoprotein level of 2.35 ng/mL (range: 0.00-9.00 ng/mL), a cancer antigen 199 (CA19-9) level of 4.8 U/mL (range: 0.0-35.0 U/mL), a carcinoembryonic antigen (CEA) level of 1.76 ng/mL (range: 0.00-5.00 ng/mL), and an abnormal triglyceride level of 8.84 mmol/L (range: 0.20-1.70 mmol/L).

Imaging examinations

Abdominal radiography revealed dilation of the small bowel and the presence of gas-fluid interfaces (Figure 1A). Computed tomography (CT) scans revealed localized thickening of the ileum wall and small bowel obstruction in the terminal ileum, with no evident mass observed (Figure 1B and C).

Figure 1 Digital radiology and computed tomography images of the abdomen. A: Gas and fluid accumulation in the abdomen; B: Computed tomography (CT) scan showing intestinal obstruction; C: Uneven thickening of the ileum wall; D-F: Abdominal CT images after surgery. Two months after surgery, no recurrence or metastasis was observed under CT.

FINAL DIAGNOSIS

An ulcerative adenocarcinoma of the ileum measuring approximately 2.0 cm × 1.8 cm × 0.7 cm, that had invaded the full thickness of the ileal wall was confirmed by histopathology. The tumour cells manifested as moderately differentiated carcinoma. Tumour thrombus was found in the blood vessel, but perineural invasion was not observed. Furthermore, 12 lymph nodes were resected, and metastases were not discovered in any of them (Figure 2A and B). The immunohistochemical results indicated significant positivity for cytokeratin (Figure 2C and D). The patient was finally diagnosed with Stage IIA ulcerative IA (T3N0M0).

Figure 2 Histopathological examination of the ileal mass. A and B: Microscopic view revealed that the ulcerative adenocarcinoma had invaded the entire thickness of the ileal wall; × 10 (A); × 20 (B); C and D: Immunohistochemical staining demonstrates strong positivity for cytokeratin; × 10 (C); × 20 (D).

TREATMENT

Owing to the lack of data regarding SBA, including in the patient’s history and in the physical examination, the normal CEA and CA19-9 values, vague results of abdominal CT, and limited digestive tract radiography, he was misdiagnosed with inflammatory bowel disease (IBD). A series of conservative treatments, including pharmacologic therapies and nasogastric tube decompression, were applied accordingly. However, the symptoms were not alleviated, so exploratory laparotomy was performed.

Laparotomy revealed constriction in the terminal ileum. Adhesions across the entire abdomen and approximately 100 mL of overt effusion were observed around the constriction. The small intestine was dilated on the proximal side of the constriction. A mass measuring 2.0 cm × 2.0 cm was located 20 cm from the ileocecal junction. No metastatic foci were found within the liver or peritoneal region (Figure 3). The constriction was resected en bloc, and end-to-end intestinal anastomosis was carried out. Approximately 1500 mL of physiological saline solution was injected to flush the abdominal cavity.

Figure 3 Exploratory laparotomy findings. A: Adhesion in the ileum is indicated by the arrow; B: Intestinal obstruction caused by cancer.

OUTCOME AND FOLLOW-UP

The operation was completed successfully, and the postoperative recovery of the patient was excellent. After two months of follow-up, a CT scan revealed that there was no reappearance of the disease (Figure 1D-F). Currently, his condition is stable and will be followed up further.

DISCUSSION

Although the small bowel accounts for 90% of the mucosal area in the gastrointestinal tract, small intestine cancers are relatively uncommon and comprise only approximately 3% of all cancers[9]. This rarity may be caused by the rapid turnover of small bowel cells or the brief transit period of the small bowel[10,11]. SBA comprises 30%-40% of all histological subtypes[3]. In most cases, the SBA is located in the duodenum (52%), much more than the jejunum (29%). IA is extremely rare and accounts for only 19% of cases[6]. There are no differences in altered genes between duodenal adenocarcinoma and IA[12]. The interactions of pancreaticobiliary secretions with carcinogens in the duodenum may explain these differences[13]. Risk factors for IA include smoking, alcohol consumption and IBD, especially Crohn’s disease, which has appeared to be the greatest risk factor in recent years[14]. Therefore, when a patient with chronic IBD has a change in clinical symptoms, a diagnosis of IA should be considered. However, these risk factors were not present in our patient. The clinical manifestations of IA are often nonspecific, and accurate differentiation from other diseases, such as appendicitis, pancreatitis or cholelithiasis, is a major challenge.

The incidence rate of SBA varies across geographic areas. It is more prevalent in Western Europe and North America but relatively less prevalent in Asian countries. On the basis of available reports, the incidence of SBA are more often among men. In one study, patients with a median age of 67 years were found to be more likely to be affected[1], whereas in another study, patients with a median age of 58 years were affected[6]. Our patient was 48 years old, which was younger than the previously reported trends. It is challenging to diagnose SBA accurately on the basis of only clinical presentations. In one study involving 241 patients with a diagnosis of SBA, that the presenting symptoms were shown to vary: 37.3% of patients presented with abdominal pain, 32.8% with weight reduction, 16.2% with jaundice, 14.6% with gastrointestinal bleeding, and 13.1% with no symptoms[15]. However, most patients with SBA occur with an urgent situation, commonly with cramping abdominal pain, ileus in the ileum or at the gastric outlet, and biliary obstruction in the duodenum[16]. Our patient had similar symptoms. With respect to this disease, both CEA and CA19-9 can assist in the diagnosis of SBA, with elevated levels of approximately 30% and 40%, respectively, in patients[17]. In our patient, the CEA and CA19-9 levels were both normal. Despite multiple efforts, there are no sensitive or specific tumour biomarkers for the identification of this disease. These biomarkers are usually employed for monitoring disease status.

Conventional CT or magnetic resonance (MR) imaging can be used to assess the degree of local tumour invasion or distant metastases at the initial workup. However, new imaging technologies, such as CT or MR enterography or MR enteroclysis (MRE), can improve the imaging effect of small intestine. An anticipatory investigation was conducted to identify the effect of CT and MR enterography in 150 patients suffering from small intestine disease. The results revealed that MR enterography had markedly higher sensitivity than CT enterography did, especially for neoplastic disease (P = 0.0412)[18]. In one study, two cases of Crohn’s disease-related IA were preoperatively diagnosed by MRE[19]. In a retrospective study involving 158 patients who received MRE and histological examination (HE) of surgical specimens, the consistency between MRE and HE was 100% for location and 62.2% for histological diagnosis[20]. On the basis of these data, MRE has an obvious impact on the localization of small bowel tumours and their staging, particularly if surgical planning is considered. Our patient underwent digestive tract radiography. The results revealed that there was a small bowel obstruction. Oesophago gastroduodenoscopy with endoscopic ultrasound is recommended for the detection and pathologic diagnosis of neoplasms in the proximal part of the duodenum and distal part of the ileum[21]. Other endoscopic methods, such as double-balloon endoscopy and capsule endoscopy, are recommended under certain conditions. The application of double-balloon endoscopy is especially beneficial for patients with small bowel constriction[22]. Even though capsule endoscopy is not recommended for initial workup, it is a preferred modality to detect the whole mucosa of the small intestine and reveal a primary lesion. However, it is contraindicated for situations involving small intestine obstruction or constriction, which may cause difficulty in capsule excretion[23].

SBA staging is based on American Joint Committee on Cancer Staging Manual, 8^th edition. T1 neoplasms invade the submucosa or lamina; T2 neoplasms penetrate the submucosa to the muscularis propria; T3 neoplasms infiltrate the subserosa or invade through nonperitonealized perimuscular tissue; and T4 neoplasms penetrate the splanchnic peritoneum or infiltrate other organs. Lack of spread to regional lymph nodes is defined as N0; spread to 1-2 lymph nodes is defined as N1, and spread to 3 or more lymph nodes are referred to as N2. With respect to metastasis, SBA is considered M1. Stage I is defined as T1, T2, N0, M0; stage II is defined as T3, T4, N0, M0; stage III is defined as any T, N1, N2, M0; and stage IV is defined as any T, any N, M1. The IA in our patient was classified as stage IIA (T3N0M0)[24].

Surgical excision accompanied by resection of regional lymph nodes represents a main therapy for local SBA. The OS times of the patients with resected and unresected tumours are 94.4 and 30.1 months, respectively[25]. For patients with nonmetastatic disease, oncologic surgery results in the best outcomes, and negative margins predict longer survival[26]. The type of resection is contingent on the position of the primary neoplasm. In general, segmental resection is the standard surgical therapy[27]. Pancreaticoduodenectomy or segmental duodenal removal is needed for tumour located in the duodenum[28]. In cases of neoplasms in the ileum or jejunum, segmental resection along with lymph node removal and ileoileal or jejunojejunal anastomosis is the preferred approach[29]. The recommendation in multiple studies is to retrieve more than 9 regional lymph nodes during the process of SBA excision[30,31].

For unresectable and distant metastatic SBA, there is no truly effective standard adjuvant therapy. On the basis of limited studies, 5-fluorouracil plus platinum is referred to the first-line therapy for SBA. Irinotecan plus 5-fluorouracil is the most common second-line therapy[32]. Recently, programmed death-ligand 1-positive cell-targeting antibody drugs have been studied for the treatment of gastrointestinal malignancies. Several studies have reported the effectiveness of pembrolizumab in treating colorectal cancer (CRC) adenocarcinoma[33,34]. In another study, nivolumab, along with ipilimumab, thus inhibition of programmed death-1 and cytotoxic T-lymphocyte-associated protein 4, was reported to have clinical significance in terms of improvements with respect to metastatic CRC[35]. According to these positive results, the National Comprehensive Cancer Network guidelines suggest nivolumab or pembrolizumab, along with or without ipilimumab, as second-line therapies of SBA[36].

SBA patients have a dismal prognosis, with the 5-year OS rate varying from 15% to 35%[37-39]. The results of the multivariate analysis suggested that age, tumour stage, tumour location and lymph node invasion were significant prognostic factors for SBA. The prognosis among males aged over 55 years was predicted to be poor[40]. Additionally, the 5-year OS rates ranged from 50%-60% in patients of stage I, 30%-55% in patients of stage II, 10%-40% in patients of stage III and 3%-5% in patients of stage IV[41-43]. Compared with primary duodenal and ileal tumours, a jejunal tumour has a better prognosis[44]. Patients with fewer involved lymph nodes have longer survival following resection[45].

For our patient, IA led to complete small bowel obstruction and typical gastrointestinal symptoms. Symptomatic treatment was not provided until exploratory laparotomy was performed. A case of adenocarcinoma of the ileum was subsequently discovered unexpectedly. Here, we emphasize the importance of timely detection of tumours, which may strongly affect early staging and prognosis. If the symptoms and CT images are indefinite, surgery should be considered. Here, our aim was to describe our experience of diagnosis and treatment of IA, and we look forward to developing precision therapy for SBA soon.

CONCLUSION

Adenocarcinoma of the ileum poses diagnostic challenges because of vague clinical presentations. Imaging can be used only for auxiliary diagnosis. Although IA is insidious, attention should be provided to patients experiencing symptoms of small bowel obstruction. Laparotomy is recommended for the diagnosis and treatment of SBA in the initial stage. Currently, an accurate diagnosis is still lacking, and the long-term survival rate remains low (see Video 1). Consequently, new investigative strategies and treatments are needed for further research to achieve better outcomes.