Primary duodenal adenocarcinoma

Primary adenocarcinoma of the duodenum is a rare condition accounting between 0.3% and 0.5 % of all gastrointestinal malignancies; and account for 10% of periampullary neoplasms. It appears to be more frequent in the periampullary area, but has also been shown to arise in the third and fourth duodenal portions. The neoplasm begins in duodenal mucosa or arises in the background of other pre-existing benign duodenal neoplasms such as polyps, familial adenomatous polyposis, lymphatic hyperplasia, gastric and pancreatic heterotopia, Peutz-Jeghers syndrome. Other conditions associated with primary adenocarcinoma of the duodenum include Crohn’s disease and von Recklinghausen’s disease, and celiac disease.

Here are outlined the principal symptoms of primary duodenal adenocarcinoma:

  • Weight loss
  • Weakness
  • Abdominal pain
  • Dyspepsia
  • Bleeding and anemia
  • Duodenal obstruction 
  • Jaundice (in periampullary lesions)

Upper endoscopy and endoscopic ultrasound are widely employed to investigate duodenal neoplasms, that most of the times are exophytic. It is possible to perform biopsies for diagnostic confirmation. CT-scan is employed for tumor staging. The current staging is based on the TNM system (tumor/node/metastasis), according to the American Joint Commitee on Cancer (AJCC, Tumor stage is expressed in Roman numerals I through IV. Here are the AJCC stage groups of for small bowel neoplasms (seventh edition, 2010):

  • Stage 0: The neoplasm is confined within the duodenal mucosa (carcinoma in situ).
  • Stage I: The neoplasm is confined within the muscularis propria. It has not spread to nearby lymph nodes or distant sites. 
  • Stage IIA: The neoplasm is confined within the serosa (peritoneum). It has not spread to nearby lymph nodes or distant sites. 
  • Stage IIB: The neoplasm has grown outside the serosa and has spread to adjacent organs. It has not spread to nearby lymph nodes or distant sites. 
  • Stage IIIA:  The neoplasm has spread to nearby lymph nodes (<=3) but not to distant sites.
  • Stage IIIB: The neoplasm has spread to nearby lymph nodes (>3) but not to distant sites.
  • Stadio IV: The neoplasm has spread to distant sites.

Radiologic staging divides primary duodenal adenocarcinoma into groups based on whether or not it is likely it can be removed surgically. 

The therapeutic approach to resectable primary duodenal adenocarcinoma (stage 0-IIB) is similar to that of pancreatic head ductal adenocarcinoma. The operation of choice is a potentially curative pancreaticoduodenectomy with regional lymphadenectomy. Resection with synchronous portal vein resection can be performed when needed.

Locally advanced primary duodenal adenocarcinoma is a stage IIB-IIIA/B tumor that results to be technically unresectable (e.g. because of diffuse infiltration of superior mesenteric artery). If the neoplasm has caused symptoms, a palliative treatment may be necessary to relieve them:

  • If jaundice is present, a plastic or metal stent can be placed endoscopically to relieve the blocked common bile duct. Alternatively, a percutaneous biliary drainage may be placed.
  • If necessary, surgery can reroute the stomach connection to the duodenum to relieve or prevent duodenal obstruction. The flow of bile from the common bile duct can be rerouted at this time directly into the small intestine, bypassing the obstructed area (bypass operation). Furthermore, intraoperative biopsies may be performed. 
The first-line treatment of locally advanced unresectable primary duodenal adenocarcinoma is medical therapy. Chemotherapy involves the use of medications to kill cancer cells, and may be given intravenously or by mouth. These drugs are usually given in cycles, with alternating periods of treatment and recovery, and may be given alone or in conjunction with radiation therapy (chemo-radiotherapy). The Oncology team chooses the best treatment plan for any given patient. Once the treatment schedule has been completed, re-staging is performed. This involves a detailed clinical examination, the measurement of serum tumor markers, and cross-sectional imaging (CT-scan or PET-CT). The results are discussed within our multidisciplinary team. If the disease has been downstaged, surgical exploration and – if possible – radical resection can be attempted.
Metastatic cancer is cancer that has spread, through the bloodstream or lymphatic system, from the place where it first started to another place in the body. Distal cholangiocarcinoma most frequently metastasizes to the liver and distant lymph nodes (stage IV).
Standard medical treatment for metastatic primary duodenal adenocarcinoma typically involves chemotherapy. There appear to be interesting and potentially promising combinations of several two or more conventional medical treatment drug agents which are in practice and under study for the treatment of metastatic gastrointestinal neoplasms. Additionally, there is a wide range of single-mode medical treatment approaches currently in clinical trials. These include some of the newer experimental therapies which are aimed more at molecular targets and at interrupting genetic signaling pathways. Individualized medical treatment regimens as tailored by expert oncologists involving single agents or combination therapy may prolong survival and quality of life. And finally, clinical trials remain an option.


Duodenal GIST

Gastrointestinal stromal tumor (GIST) is a rare cancer affecting the digestive tract or nearby structures within the abdomen. GIST account for 1-3% of gastrointestinal neoplasms. The most frequent site for GIST is the stomach (about 55%), followed by the duodenum and small intestine (about 30%), esophagus (about 5%), rectum (about 5%), colon (about 2%), and rare other locations. Most GISTs show mutations of the CD117 protein (c-kit). 

Duodenal GIST present with abdominal pain, bleeding and duodenal obstruction. They are mostly located in the second portion of the duodenum, and do not tend to invade nearby organs, lymph nodes or distant organs. Surgery is the mainstay of the GIST therapy. If a GIST is small and is attached to a section of the duodenum far enough away from the ampulla of Vater, then it may be possible to perform a segmental resection. For duodenal GISTs that involve the bile ducts or are very close to the ampulla of Vater, and for GISTs that are adherent to adjacent organs, pancreaticoduodenectomy is needed.

The risk of recurrence or metastasis of a surgically resected primary GIST seems to be independent from the type of operation performed, and can be predicted on the basis of tumor size and mitotic count (NIH risk table). For further information click here.   

Imatinib mesylate is the first effective drug treatment for GIST, and was the first marketed molecular targeted therapy for cancer. This means that the drug affects only those cells that express highly specific targets, in contrast to conventional cancer chemotherapies that affect all fast-growing cells in the body. The targets of imatinib in GIST patients are two growth-factor receptors that block c-kit protein and other protein kinases that regulate cell proliferation. Imanitib was initially approved for metastatic GIST. Afterwards, it has been used in adjuvant setting (after radical resection), and it is currently under evaluation in neoadjuvant therapy (to shrink a resectable tumor and allow a segmental resection, or to downstage locally advanced neoplasms). Other molecular targeted therapies have been recently approved for the treatment of GIST (sunitinib).