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Mixed adenoneuroendocrine carcinoma (MANEC) is a rare tumor of the gastrointestinal tract that consists of a dual adenocarcinomatous and neuroendocrine differentiation. Frequently only one component is identified, leading to incomplete diagnosis and suboptimal treatment. This kind of tumors therefore constitutes a diagnostic challenge. They represent a minority of gastrointestinal neoplasms, being more frequent in the stomach, gallbladder and pancreas. Only a hundred cases have been described in the colon, and specifically only 6 cases in the transverse colon have been published in the English literature.

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the study. Patients with advanced pancreatic cancer (APC) often present with extrahepatic bile duct obstruction, which can result in elevated Tbil levels. Normalization of Tbil by biliary drainage can take weeks, so safety data to support treatment initiation in patients with elevated Tbil levels are desirable. Therefore, we attempted to evaluate the safety of GN, in terms of the risk of hematological toxicity in APC patients presenting with hyperbilirubinemia secondary to bile duct obstruction. Methods: Data of a total of 351 patients with APC who were treated with GN as firstline treatment at our department between Dec. 2014 and Dec. 2017 were reviewed retrospectively. Patients who underwent biliary drainage before the initiation of GN and received no initial dose reduction were included, while patients with irreversible hyperbilirubinemia due to liver metastasis were excluded. The patients were divided into two groups according to the Tbil levels at the initiation of GN: the normal bilirubin group (NB-G group; Tbil Ϲ1.5 mg/dL) and hyperbilirubinemia group (HB-G group; Tbil >1.5 mg/dL). The incidence of severe hematotoxicity during the first cycle of treatment was compared between the two groups. The p-values < 0.05 were considered statistically significant and all p-values were two sided. Results: A total of 78 patients, including 59 from the NB-G group and 19 from the HB-G group were included in this analysis. The patient characteristics (NB-G vs. HB-G groups) were as follows: median age, 66 vs. 69; ECOG-PS 0-1/2, 56/3 vs. 19/0; male/ female, 28/31 vs. 9/10; UICC-TNM stage III/IV, 22/37 vs. 8/11; primary site head/bodytail, 56/3 vs. 19/0; biliary intervention with plastic stent/metallic stent/surgical bypass, 12/45/2 vs. 3/16/0; median pretreatment Tbil, 0.72 mg/dL (0.22-1.49) vs. 1.8 mg/dL (1.51-2.76). During the first cycle of treatment, severe hematologic adverse events (grade 3/4 neutropenia and/or grade 3/4 thrombocytopenia) occurred in a total of 31 patients and febrile neutropenia in a total of 7 patients. There were no significant differences in the incidence of severe hematological adverse events between the two groups (22 in the NB-G group and 9 in the HB-G group; p ¼ 0.59). Conclusion:The safety of GN, in terms of the risk of hematological toxicity was similar between the NB-G and HB-G groups in this study. For APC patients presenting with hyperbilirubinemia secondary to bile duct obstruction, it might be safe to initiate GN without dose reduction if a suitable procedure for biliary drainage is undertaken prior to the initiation of the treatment.

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