Surgical resection of mixed neuroendocrine-non-neuroendocrine neoplasm in the biliary system: a report of two cases

Background Mixed neuroendocrine-non-neuroendocrine neoplasm (MINEN) is a rare disease and there is scarce literature on its diagnosis, treatment, and prognosis. We encountered two unusual cases of MINEN in the biliary tract, one in the ampulla of Vater and the other in the distal bile duct. In this report, we describe the clinical course of these two cases in detail. Case presentation Case 1: A 69-year-old woman presented with a chief complaint of epigastric pain. When endoscopic sphincterotomy and retrograde biliary drainage were performed for gallstone pancreatitis, an ulcerated lesion was found in the ampulla of the Vater. Based on the biopsy results, the lesion was diagnosed as the ampulla of Vater carcinoma and subtotal stomach-preserving pancreatoduodenectomy (SSPPD) was performed. Postoperative histopathological examination revealed the coexistence of adenocarcinoma and neuroendocrine carcinoma components, consistent with the diagnosis of MINEN. In addition, lymph node metastasis was found on the dorsal side of the pancreas and the metastatic component was adenocarcinoma. Adjuvant chemotherapy with etoposide and cisplatin was administered for 6 months, and presently the patient is alive without recurrence 64 months after surgery. Case 2: A 79-year-old man presented with a chief complaint of anorexia. Cholangiography showed severe stenosis of the distal bile duct. A biopsy was conducted from the stenotic lesion and it revealed the lesion to be adenocarcinoma. A diagnosis of distal bile duct carcinoma was made, and SSPPD was performed. Histopathological examination revealed the coexistence of adenocarcinoma and neuroendocrine carcinoma components, and the tumor was confirmed as MINEN of the distal bile duct. No adjuvant chemotherapy was administered due to the poor performance status. 7 months later, the patient was found to have a liver metastasis. Conclusion We experienced two valuable cases of biliary MINEN. To identify better treatments, it is important to consider the diversity of individual cases and to continue sharing a variety of cases with different presentations

Digital Transcriptome Analysis of Putative Sex-Determination Genes in Papaya (<em>Carica papaya</em>)

<div><p>Papaya (<em>Carica papaya</em>) is a trioecious plant species that has male, female and hermaphrodite flowers on different plants. The primitive sex chromosomes genetically determine the sex of the papaya. Although draft sequences of the papaya genome are already available, the genes for sex determination have not been identified, likely due to the complicated structure of its sex-chromosome sequences. To identify the candidate genes for sex determination, we conducted a transcriptome analysis of flower samples from male, female and hermaphrodite plants using high-throughput SuperSAGE for digital gene expression analysis. Among the short sequence tags obtained from the transcripts, 312 unique tags were specifically mapped to the primitive sex chromosome (X or Y^h) sequences. An annotation analysis revealed that retroelements are the most abundant sequences observed in the genes corresponding to these tags. The majority of tags on the sex chromosomes were located on the X chromosome, and only 30 tags were commonly mapped to both the X and Y^h chromosome, implying a loss of many genes on the Y^h chromosome. Nevertheless, candidate Y^h chromosome-specific female determination genes, including a MADS-box gene, were identified. Information on these sex chromosome-specific expressed genes will help elucidating sex determination in the papaya.</p> </div

Confirmation of sex-dependent gene expression for Cp2671, which encodes a putative MADS-box protein.

<p>Confirmation of sex-dependent gene expression for Cp2671, which encodes a putative MADS-box protein.</p

Flower samples for the Ht-SuperSAGE analysis.

<p>The papaya flowers used for the RNA extraction and Ht-SuperSAGE analysis (P1: male 7-mm flower; P2: male 20-mm flower; P3: female 7-mm flower; P4: female 20-mm flower; P5: hermaphrodite 7-mm flower; and P6: 20-mm hermaphrodite flower).</p

Structure and expression analysis of the genes corresponding to the Cp3177 tag, which encodes a putative monodehydroascorbate reductase (MDAR).

<p>A) RT-PCR analysis of the MDAR gene corresponding to the Cp3177 tag. P1 to P6 correspond to the flower samples indicated in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0040904#pone-0040904-g001" target="_blank">Figure 1</a>. An actin gene was used as a constitutively expressed control gene <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0040904#pone.0040904-Porter1" target="_blank">[32]</a>. B) A list of the polymorphic tags and their counts for the MDAR genes in the Ht-SuperSAGE data. The polymorphic sequences among the tags are underlined. C) The regions flanking the Cp3177 tag on the BAC clones 46O19 (X chromosome) and 90D06 (Y^h chromosome). The arrows indicate the locations of the PCR primers used for amplification. The black regions represent the predicted exons. An insertion of the retroelement sequence was observed in the 90D06 sequence (Y^h chromosome). D) Genomic PCR amplification of the MDAR gene in each sex type. The smaller band was equally amplified in all of the sex types. The larger bands, indicating the insertion of retroelements, were only observed in males and hermaphrodites.</p

Surgical resection of mixed neuroendocrine-non-neuroendocrine neoplasm in the biliary system: a report of two cases

Background Mixed neuroendocrine-non-neuroendocrine neoplasm (MINEN) is a rare disease and there is scarce literature on its diagnosis, treatment, and prognosis. We encountered two unusual cases of MINEN in the biliary tract, one in the ampulla of Vater and the other in the distal bile duct. In this report, we describe the clinical course of these two cases in detail. Case presentation Case 1: A 69-year-old woman presented with a chief complaint of epigastric pain. When endoscopic sphincterotomy and retrograde biliary drainage were performed for gallstone pancreatitis, an ulcerated lesion was found in the ampulla of the Vater. Based on the biopsy results, the lesion was diagnosed as the ampulla of Vater carcinoma and subtotal stomach-preserving pancreatoduodenectomy (SSPPD) was performed. Postoperative histopathological examination revealed the coexistence of adenocarcinoma and neuroendocrine carcinoma components, consistent with the diagnosis of MINEN. In addition, lymph node metastasis was found on the dorsal side of the pancreas and the metastatic component was adenocarcinoma. Adjuvant chemotherapy with etoposide and cisplatin was administered for 6 months, and presently the patient is alive without recurrence 64 months after surgery. Case 2: A 79-year-old man presented with a chief complaint of anorexia. Cholangiography showed severe stenosis of the distal bile duct. A biopsy was conducted from the stenotic lesion and it revealed the lesion to be adenocarcinoma. A diagnosis of distal bile duct carcinoma was made, and SSPPD was performed. Histopathological examination revealed the coexistence of adenocarcinoma and neuroendocrine carcinoma components, and the tumor was confirmed as MINEN of the distal bile duct. No adjuvant chemotherapy was administered due to the poor performance status. 7 months later, the patient was found to have a liver metastasis. Conclusion We experienced two valuable cases of biliary MINEN. To identify better treatments, it is important to consider the diversity of individual cases and to continue sharing a variety of cases with different presentations