Gastrointestinal neuroendocrine tumor (NET) associated with a metachronous intestinal adenocarcinoma is rare. We report the case of a 71-year-old man with an ileal NET. Patient has previously undergone a left colectomy for sigmoid cancer. We report a complete review both of the metachronous and synchronous NET. A comprehensive systematic literature search in PubMed, EMBASE, and MEDLINE identified a total of 35 relevant studies. This study includes an analysis of review articles, case reports, case series, retrospective studies and population-based studies. In the English literature to date, there are 21 case reports (19 synchronous cases and 2 metachronous cases), 3 case series and 3 review articles, and less than 10 retrospective studies or population-based studies. A total of 31 patients in 24 articles were included in the study: 28 patients with a synchronous gastrointestinal NET and colorectal adenocarcinoma and 3 patients with metachronous gastrointestinal NET and colorectal adenocarcinoma. The incidence of synchronous cancer (particularly for colorectal and gastric cancer) with a gastrointestinal NET ranges from 10 to 50%, while for the metachronous ones it is still unclear. This is the third metachronous case report and the first descriptive case of gastrointestinal NET diagnosed 2 years after a colorectal adenocarcinoma. An endoscopic follow-up program for gastrointestinal NET patients and/or for first-degree relatives of NET patients appears recommendable.

The diagnosis of neuroendocrine differentiation (NED) is made primarily on the basis of ultrastructure and/or immunohistochemistry (IHC). Synaptophysin (Syn) and chromogranin A (CgA) are two important frequently used NED markers in colorectal cancer (CRC). The association between NED and the prognosis of stage II CRC remains controversial. Administration of adjuvant chemotherapy remains challenging for stage II CRC. Identification of reliable factors that improve the selection of patients with stage II CRC at high risk following surgery is of great importance. A total of 151 cases of patients with stage II CRC who received radical surgery in The Second Affiliated Hospital of Zhejiang University (Hangzhou, China) between January 2002 and March 2011 were assayed for Syn and CgA using IHC, following which patients were classified as NED(+) or NED(-). Survival curves were constructed using the Kaplan-Meier estimator, and the prognostic value was determined using a log-rank test and Cox's regression test. In the 151 cases of stage II CRC examined, the incidence of NED was 34.44%. The overall survival of the NED(+) group was significantly less favorable than that of the NED(-) group (P=0.001). The 5-year survival rate was 68% for NED(+) (n=51) and 90% for NED(-) (n=97). The independent prognostic factors of survival of patients with stage II CRC following multivariate analysis were age ≥65 years (P=0.007) and NED-positivity (P=0.014). NED was revealed to be an independent factor of poor prognosis for patients with stage II CRC, which may offer potential for improved therapy stratification.

Malignant neoplasms of the appendix are rare and represent less than 1% of gastrointestinal cancers. Goblet cell carcinoids (GCC) tumors are a distinctive group of heterogeneous appendiceal neoplasm that exhibit unique clinical and pathologic features. This review focuses on the current diagnostic procedures, pathogenesis, possible signaling mechanisms and treatment options for GCC. Perspectives for future research are discussed. The tumor likely arises from pluripotent intestinal epithelial crypt base stem cells. Previous findings of Notch signaling as a tumor suppressor in Neuroendocrine tumors may have a similar role in this tumor too. Loss of Notch signaling may be the driver mutation with other successive downstream mutations likely favors them into progressing and behavior similar to poorly differentiated adenocarcinoma with minimal neuroendocrine differentiation. A multidisciplinary approach is suggested for optimal outcomes. Surgery remains the main treatment modality. Simple appendectomy may be sufficient in early stages while right hemicolectomy is recommended for advanced tumors. Cytoreductive surgery with heated intraperitoneal chemotherapy may improve survival in a select few with metastatic peritoneal disease. These tumors have an unpredictable behavior even in early stages and local recurrence and delayed metastases may be seen. Lifelong surveillance is warranted.

Primary small-bowel malignancies (SBM) are rare tumors but their incidence is rising. An estimated 9160 new cases and 1210 deaths due to SBM may occur in the USA in 2014. We review advances made in tumor biology, immunohistochemistry, and discuss treatment strategies for these malignancies.

Relevant articles from PubMed/Medline and Embase searches were collected using the phrases "small-bowel adenocarcinoma, gastrointestinal carcinoids, gastrointestinal stromal tumors, small-bowel leiomyosarcoma, and small-bowel lymphoma".

Advances in imaging techniques such as wireless capsule endoscopy, CT and MRI enterography, and endoscopy (balloon enteroscopy) along with discovery of molecular markers such as c-kit and PDGFRA for GIST tumors have improved our ability to diagnose, localize, and treat these patients. Early detection and surgical resection offers the best chance for long-term survival in all tumors except bowel lymphoma where chemotherapy plays the main role. Adjuvant therapy with imatinib has improved overall survival for GIST tumors, somatostatin analogs have improved symptoms and also inhibited tumor growth and stabilized metastatic disease in carcinoid disease, but chemotherapy has not improved survival for adenocarcinoma.

Recent advances in molecular characterization holds promise in novel targeted therapies. Currently ongoing trials are exploring efficacy of targeted therapies and role of adjuvant therapy for adenocarcinoma and results are awaited. Early detection and aggressive surgical therapy for all localized tumors and lymph node sampling particularly for adenocarcinoma remains the main treatment modality.