Small Bowel Adenocarcinoma

See Small Bowel Neoplasms for the general small-bowel-tumor overview. Content below is from a textbook reference chapter (Sabiston Ch50 - Infectious Enteritis & Small Bowel Neoplasms), not primary literature.

Epidemiology and pathology

Adenocarcinomas constitute approximately 40% of malignant tumors of the small bowel. Median age at diagnosis is in the 6th decade, with a slight male predominance. Most tumors are located in the duodenum and proximal jejunum (Fig. 50.32). Those arising in association with Crohn disease tend to occur at a somewhat younger age and, more than 70% of the time, arise in the ileum. Small bowel adenocarcinoma may have important gene mutations (APC, β-CATENIN, EGFR, VEGF-A, KRAS, HER2, TP53). The most common familial associations are FAP, Lynch syndrome, and Peutz-Jeghers syndrome.

Tumors of the duodenum tend to manifest somewhat earlier than tumors of the jejunum/ileum because of earlier symptom presentation (usually jaundice and chronic bleeding). Adenocarcinomas of the jejunum and ileum usually produce more nonspecific symptoms — vague abdominal pain and weight loss. Intestinal obstruction and chronic bleeding may also occur. Perforation is uncommon.

As with adenocarcinomas in other organs, survival relates to stage at diagnosis. Unfortunately, diagnosis is often delayed and disease is advanced at the time of surgery, secondary to a variety of factors (vagueness of symptoms, absence of physical findings, lack of clinical suspicion because of the rarity of these lesions).

Diagnosis

A variety of radiologic and endoscopic techniques may be used, including CT of the abdomen/pelvis with enteroclysis, video capsule endoscopy, and double balloon enteroscopy (for biopsy and diagnosis) — see Small Bowel Neoplasms for general diagnostic modality detail.

Treatment

Determined by location and stage. An R0 resection of the primary tumor with locoregional lymph node resection is the only curative treatment. Neoadjuvant chemotherapy is appropriate to consider if there is tumor invasion into adjacent structures — patients are reevaluated for surgery after 2–3 months of treatment.

• Duodenal: resection can be performed for a noninfiltrating tumor if located in the first, third, or fourth portion of the duodenum, but this is not recommended if an expected R0 resection (no microscopic tumor at margin) is not possible. Residual microscopic tumor after resection (R1 status) or grossly visible tumor after resection (R2 status) are associated with poor prognosis. Resectable adenocarcinomas in the second portion of the duodenum are treated with pancreaticoduodenectomy, plus regional lymphadenectomy of the periduodenal, peripancreatic, and hepatic lymph nodes as well as involved vascular structures as necessary.
• Jejunal and ileal: require surgical resection with regional lymphadenectomy and jejunojejunal or ileoileal anastomosis (Fig. 50.33: resection with a wide margin of normal bowel and a wedge of mesentery to remove the immediate draining lymph nodes, end-to-end anastomosis and mesenteric repair). If the terminal ileum is involved, an ileocecectomy with right hemicolectomy should be performed with ligation of the ileocolic artery and subsequent regional lymphadenectomy.

There is currently no standard adjuvant protocol for small bowel adenocarcinoma. Despite this, most guidelines suggest patients with poorly differentiated cancers or those with incomplete lymph node resections (<10 nodes identified) should at least be considered for adjuvant chemotherapy. Adjuvant regimens are often dictated by location, although studies have suggested fluoropyrimidine and oxaliplatin may increase overall survival in patients with advanced disease. A prospective international phase 3 trial (BALLAD study), comparing observation vs. adjuvant chemotherapy in patients with an R0 resection, is currently accruing subjects — proposes that adjuvant chemotherapy will improve disease-free and overall survival vs. observation alone after potentially curative surgery for stage I, II, and III small bowel adenocarcinoma. In patients with metastatic disease, studies have determined that using FOLFOX (oxaliplatin, 5-FU, leucovorin) and FOLFIRI (irinotecan, 5-FU, leucovorin) as first-line therapy significantly improves performance status and progression-free survival. Unresectable metastatic disease may require surgical intervention for uncontrolled bleeding, bowel obstruction, or perforation.

Prognosis

Poor, probably because of delayed presentation and advanced disease at diagnosis. Five-year survival rates are typically 14–33%, although duodenal adenocarcinoma has a 5-year survival rate of 50%, probably because of earlier symptom presentation/diagnosis. Lymph node invasion is the main prognostic factor for local small bowel adenocarcinoma; the number of lymph nodes assessed and the number of positive lymph nodes are also of prognostic value. In stage III patients, having more than three positive lymph nodes was associated with a worse 5-year disease-free survival rate than having one or two positive nodes (37% vs. 57%, respectively). Multivariate analysis identified advanced age, advanced stage, ileal location, recovery of fewer than 10 lymph nodes, and number of positive nodes as significant predictors of poor overall survival. Notably, any attempts at curative resection should always include an extensive regional lymphadenectomy.

Open items / gaps

• No primary literature yet in the wiki independently appraising the BALLAD study, FOLFOX/FOLFIRI trial data, or the SEER/Medicare survival comparison with colorectal cancer cited on Small Bowel Neoplasms — currently only the textbook’s narrative summary.
• No standard adjuvant protocol exists per this source as of writing — worth revisiting once BALLAD or comparable trial data is available/ingested.