Adenocarcinoma of the Duodenojejunal Flexure in a Patient With Intestinal Nonrotation

ABSTRACT

Small bowel adenocarcinoma involving the duodenojejunal (DJ) flexure is rare, and its coexistence with intestinal nonrotation is exceptionally uncommon. A 53-year-old man presented with postprandial fullness, recurrent vomiting, and weight loss. Imaging revealed intestinal nonrotation and a malignant lesion involving the fourth part of the duodenum and DJ flexure. Histopathology confirmed moderately differentiated adenocarcinoma. The patient underwent segmental resection with R0 margins and had an uneventful recovery.

INTRODUCTION

Small bowel adenocarcinoma (SBA) is an uncommon gastrointestinal malignancy, accounting for less than 5% of all gastrointestinal cancers despite the small intestine constituting the majority of the gastrointestinal mucosal surface area. SBA most commonly arises in the duodenum, followed by the jejunum and ileum.¹ Tumors involving the duodenojejunal (DJ) flexure are particularly rare and often present significant diagnostic and therapeutic challenges due to their deep anatomical location and nonspecific clinical presentation.

The incidence of SBA has been steadily increasing globally over the past few decades, likely due to improved imaging modalities, increased utilization of endoscopy, and enhanced pathological characterization.^2,3 However, delayed diagnosis remains common and many patients present with locally advanced or metastatic disease at diagnosis.

Intestinal nonrotation is a congenital anomaly resulting from failure of normal embryological midgut rotation and is often identified incidentally in adults. The coexistence of SBA and intestinal nonrotation is exceedingly uncommon, with only a few cases reported in the literature.

We report a rare case of moderately differentiated adenocarcinoma arising at the D4–DJ flexure in a patient with intestinal nonrotation who presented with upper gastrointestinal obstructive symptoms and weight loss. This case highlights the diagnostic and therapeutic challenges posed by this unusual association. Informed consent was obtained from the patient.

CASE REPORT

A 53-year-old man presented with a 4-month history of progressive postprandial fullness, abdominal bloating, recurrent nonbilious vomiting, anorexia, and unintentional weight loss of approximately 6 kg. He had a history of chronic tobacco and alcohol use. There was no history of inflammatory bowel disease, celiac disease, hereditary polyposis syndromes, or other familial gastrointestinal malignancies. Laboratory evaluation revealed mild normocytic anemia (hemoglobin 11 g/dL), while liver and renal function tests and other hematological parameters were within normal limits.

Contrast-enhanced computed tomography (CECT) revealed intestinal nonrotation along with irregular circumferential wall thickening involving the fourth part of the duodenum (D4) and extending into the DJ flexure, with adjacent enlarged lymph nodes (Figure 1). Upper gastrointestinal endoscopy demonstrated irregular mucosal thickening with luminal narrowing at the DJ flexure (Figure 2). Histopathological examination of endoscopic biopsies showed moderately differentiated adenocarcinoma. Immunohistochemistry demonstrated positivity for caudal-type homeobox 2 (CDX2), cytokeratin 20 (CK20), and Mucin 1, with negative cytokeratin 7 (CK7) expression, supporting a primary intestinal-type adenocarcinoma (Figure 3). Positron emission tomography–computed tomography (PET-CT) demonstrated fluorodeoxyglucose-avid asymmetric mural thickening involving the D4–DJ flexure region with significant luminal narrowing and no evidence of distant metastases. Following multidisciplinary discussion, the patient underwent exploratory laparotomy with segmental resection of the D4–DJ flexure segment and primary end-to-end anastomosis. Gross examination revealed an ulceroinfiltrative circumferential lesion causing marked luminal narrowing. Histopathology confirmed moderately differentiated adenocarcinoma infiltrating through the muscularis propria into the subserosa. Lymphovascular invasion was present, whereas perineural invasion was absent. Surgical margins were free of tumor (R0 resection), and all examined lymph nodes were negative for metastasis.

Figure 1.

Endoscopic appearance of the DJ flexure lesion. Upper gastrointestinal endoscopy demonstrating an irregular circumferential lesion with mucosal thickening and luminal narrowing at the DJ flexure, causing partial gastric outlet/proximal small bowel obstruction. DJ, duodenojejunal.

Figure 2.

CECT demonstrating intestinal nonrotation and DJ adenocarcinoma. (A) Coronal-oblique image showing irregular circumferential mural thickening involving the fourth part of the duodenum and DJ flexure. (B) Axial image demonstrating asymmetric wall thickening with luminal narrowing and adjacent enlarged lymph nodes. (C) Parasagittal image depicting the extent of the lesion across the D4–DJ flexure region. (D) Multiplanar reconstructed image highlighting the tumor and associated intestinal nonrotation. CECT, contrast-enhanced computed tomography; D4, fourth part of the duodenum; DJ, duodenojejunal.

Figure 3.

Histopathological and immunohistochemical features of the tumor. (A, B) H&E-stained sections showing distorted villoglandular architecture with atypical gland-forming epithelial cells exhibiting nuclear stratification, pleomorphism, hyperchromasia, and increased mitotic activity, consistent with moderately differentiated adenocarcinoma (H&E, ×40 and ×100, respectively). (C) Strong nuclear positivity for CDX2 (IHC, ×100). (D) Diffuse cytoplasmic positivity for CK20 (IHC, ×100). (E) Cytoplasmic and luminal positivity for MUC1 (IHC, ×100). (F) Negative staining for CK7 (IHC, ×100). CDX2, caudal-type homeobox 2; CK20, cytokeratin 20; CK7, cytokeratin 7; IHC, immunohistochemistry; H&E, hematoxylin and eosin; MUC1, Mucin 1.

The postoperative course was uneventful, with resolution of obstructive symptoms and improved oral intake. At 3-month follow-up, the patient remained asymptomatic with no clinical or radiological evidence of disease recurrence and continues under regular oncological surveillance.

DISCUSSION

Primary adenocarcinoma of the small intestine remains a rare entity, with tumors involving the DJ flexure representing an especially uncommon subset. The present case is noteworthy for 2 reasons: the uncommon location of the tumor at the D4–DJ flexure and its occurrence in the setting of intestinal nonrotation. Although approximately 50%–60% of small bowel adenocarcinomas arise in the duodenum, the majority occur in the periampullary region or second part of the duodenum, whereas involvement of the fourth part of the duodenum and DJ flexure is distinctly uncommon.⁴ Furthermore, the coexistence of SBA with intestinal malrotation or nonrotation is exceedingly rare. A review of the available literature identified only a few published cases of adenocarcinoma arising in the duodenum, DJ flexure, or proximal jejunum in association with rotational anomalies of the intestine (Table 1).^5–7 The relationship between intestinal malrotation and gastrointestinal malignancy remains poorly understood. Several mechanisms have been proposed, including chronic intestinal stasis, bacterial overgrowth, altered exposure of the mucosa to bile acids and luminal carcinogens, and recurrent low-grade inflammation resulting from abnormal intestinal anatomy.^8–11 Genetic factors implicated in the development of intestinal malrotation include mutations in the Forkhead box F1 (FOXF1) gene and genes involved in left-right embryonic patterning.¹² However, no specific molecular pathway linking these developmental abnormalities to carcinogenesis has been established. SBA is known to harbor genetic alterations involving oncogenes and tumor suppressor genes such as Kirsten rat sarcoma viral oncogene homolog, Tumor protein p53, adenomatous polyposis coli, SMAD family member 4, and mismatch repair pathway genes, but whether congenital rotational anomalies predispose to the acquisition of these mutations remains unknown. Future studies incorporating molecular profiling of tumors arising in patients with intestinal malrotation may help clarify the natural history of this association and determine whether a shared developmental or genetic basis exists. Nevertheless, the concurrence of these 2 rare conditions may still be coincidental.

Table 1.

Reported cases of DJ flexure/fourth-part duodenal adenocarcinoma associated with intestinal malrotation or nonrotation

Author/Year	Age/Sex	Presenting symptoms	Tumor location	Associated anomaly/Condition	Surgery performed	Histopathology	Outcome
Ines et al,6 2015	40/M	Gastric pain, vomiting, and constipation	DJ flexure, jejunum	Incomplete intestinal malrotation	Resection of the small bowel carrying tumor was done with an end- to-end anastomosis. (R0 resection)	Well-differentiated adenocarcinoma of the jejunum with 30% of mucinous component	Postoperative course was uneventful. The patient was well on follow-up at 6 months after surgery
Li et al,7 2018	76/M	Melanotic stools and anemia	Duodenum	Partial malrotation at the third and fourth portions of the duodenum	Pancreatico-duodenectomy (the Whipple procedure)	Invasive moderately differentiated adenocarcinoma	Postoperatively, the patient experienced transient delirium and developed an International study Group for Pancreatic Fistula (ISGPF) grade B pancreatic leak that was drained percutaneously. He was discharged to a rehabilitation facility on postoperative day 13
Current case report	53/M	Postprandial fullness, bloating, nonbilious vomiting, anorexia, and weight loss	Fourth part of the duodenum and DJ flexure	Intestinal nonrotation	Segmental resection followed by end-to-end anastomosis	Moderately differentiated adenocarcinoma Distorted villo-glandular architecture composed of atypical gland-forming epithelial cells exhibiting nuclear stratification, pleomorphism, hyperchromasia, and increased mitotic activity	Postoperative course was uneventful, with gradual resolution of obstructive symptoms and improvement in oral intake. At the 3-month follow-up, the patient remained clinically stable and asymptomatic, with significant improvement in appetite and nutritional status

DJ, duodenojejunal; R0, complete surgical resection with microscopically negative margins.

Diagnosis of SBA is frequently delayed because presenting symptoms are often vague and nonspecific. In the present case, progressive postprandial fullness, recurrent vomiting, and weight loss reflected developing luminal obstruction at the DJ flexure. The lesions at the distal duodenum and DJ flexure may not always be accessible with conventional upper gastrointestinal endoscopy. In such situations, push enteroscopy, balloon-assisted enteroscopy, endoscopic ultrasound-guided sampling, image-guided biopsy of accessible lesions, or surgical exploration may be necessary to establish a definitive diagnosis. In addition, cross-sectional imaging plays a pivotal role in diagnosis. In our patient, CECT not only demonstrated asymmetric mural thickening involving D4 and the DJ flexure but also identified the underlying intestinal nonrotation, thereby facilitating both diagnosis and surgical planning. Histopathological examination remains the gold standard for diagnosis. The tumor demonstrated features of moderately differentiated adenocarcinoma with expression of CDX2 and CK20 and absence of CK7 expression, supporting intestinal differentiation.¹³ Immunohistochemistry is particularly useful in excluding metastatic lesions and distinguishing primary intestinal adenocarcinoma from pancreatobiliary or other gastrointestinal malignancies when tumors arise in the proximal small bowel.^14,15

Complete surgical resection remains the cornerstone of treatment for localized SBA. The optimal surgical approach depends on tumor location and extent of involvement. Lesions involving the periampullary region often require pancreaticoduodenectomy, whereas tumors confined to the D4 segment and DJ flexure may be managed by segmental resection with adequate margins and regional lymphadenectomy.

The prognosis of SBA is largely determined by stage at diagnosis, lymph node involvement, tumor differentiation, and completeness of surgical resection. Unfortunately, outcomes are generally inferior to those of colorectal cancer because many patients present with advanced disease. In the present case, the absence of distant metastases and successful complete resection were favorable prognostic factors. Nevertheless, the relatively short duration of follow-up represents a limitation, and continued oncological surveillance is warranted to assess long-term disease-free survival. Reported 5-year survival rates vary widely depending on stage, nodal involvement, and completeness of resection. Lymph node metastasis, poor differentiation, positive surgical margins, and metastatic disease are associated with adverse outcomes. Early-stage diagnosis remains the most important determinant of survival.^16–18

In conclusion, this case highlights a rare presentation of moderately differentiated adenocarcinoma arising at the D4–DJ flexure in association with intestinal nonrotation. The report emphasizes the importance of considering distal duodenal and proximal jejunal malignancies in patients presenting with persistent upper gastrointestinal obstructive symptoms and weight loss. Early use of cross-sectional imaging and careful evaluation of congenital intestinal anomalies may facilitate timely diagnosis and appropriate surgical management.

DISCLOSURES

Author contributions: A. Singla: Contributed to case identification, collection and interpretation of clinical data, literature review, preparation of the initial manuscript draft, and incorporation of revisions. A. Bhardwaj: Participated in clinical evaluation and patient management, acquisition of clinical and follow-up data, literature review, manuscript drafting, and critical revision of the manuscript. A. Singh: Conceived the report, supervised manuscript development, contributed to data interpretation and scientific content, and critically revised the manuscript for important intellectual content. K. Gupta: Interpreted radiological findings, selected and annotated radiological images, contributed to diagnostic assessment, and critically reviewed the manuscript. A. Jindal: Performed histopathological and immunohistochemical evaluation, interpreted pathological findings, prepared pathology figures, and critically reviewed the manuscript. P. Bhutani: Interpreted PET-CT findings, contributed to staging and diagnostic evaluation, and critically reviewed the manuscript. S. Singh Virk: Managed the surgical aspects of patient care, contributed operative findings and surgical interpretation, and critically reviewed the manuscript. V. Midha: Contributed to clinical interpretation, contextualization of findings within the existing literature, manuscript refinement, and critical intellectual review. A. Sood: Provided overall supervision and mentorship, contributed to study conception, interpretation of findings, critical revision of the manuscript, and final approval of the submitted version. All authors contributed substantially to the work, critically revised the manuscript, approved the final version for publication, and agree to be accountable for all aspects of the work. A. Singh is the article guarantor.

Financial disclosure: A. Sood received honorarium for speaker events from Pfizer India and Takeda India. The remaining authors disclose no conflicts.

Informed consent was obtained for this case report.

ABBREVIATIONS:

CDX2

caudal-type homeobox 2

CECT

contrast-enhanced computed tomography

CK20

cytokeratin 20

CK7

cytokeratin 7

D4

fourth part of the duodenum

DJ

duodenojejunal

FOXF1

Forkhead box F1

IHC

immunohistochemistry

MUC1

Mucin 1

PET-CT

positron emission tomography–computed tomography

R0

complete surgical resection with microscopically negative margins

SBA

small bowel adenocarcinoma