• Gastric neuroendocrine neoplasm
• Irinotecan plus cisplatin
• Liver metastasis
• Long-term survival
• Mixed neuroendocrine non-neuroendocrine neoplasm

• Digestive
• Gastroenteropancreatic
• Mixed neuroendocrine non-neuroendocrine neoplasms
• Mixed tumors
• Neuroendocrine carcinoma
• Neuroendocrine neoplasm

• Cell reprograming
• Mixed adeno-neuroendocrine cancer
• Mixed adenocarcinoma and neuroendocrine carcinoma
• Mixed neuroendocrine and non-neuroendocrine neoplasm
• Tumor plasticity

• Diagnosis
• Etiology
• Gastroenteropancreatic
• Mixed adeno-neuroendocrine carcinomas
• Mixed neuroendocrine non-neuroendocrine neoplasms
• Mixed tumours
• Treatment

• Classification
• Digestive tract
• Neuroendocrine neoplasm
• Terminology
• World Health Organization

• Humans
• Neuroendocrine Tumors/pathology
• Carcinoma, Neuroendocrine/pathology
• World Health Organization
• Gastrointestinal Tract/pathology
• Pancreatic Neoplasms/pathology

• Classification
• MANEC
• MiNENs
• Mixed neuroendocrine-non-neuroendocrine neoplasms
• Molecular characterization
• Neuroendocrine neoplasms

• Humans
• Neuroendocrine Tumors/diagnosis
• Neuroendocrine Tumors/genetics
• Neuroendocrine Tumors/therapy
• Carcinoma
• Biomarkers, Tumor/genetics
• Prognosis

Mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) are rare mixed tumors containing both neuroendocrine (NE) and non-NE components. Each component must occupy at least 30% of the tumor volume by definition. Recent molecular evidence suggests MiNENs are clonal neoplasms and potentially harbor targetable mutations similar to conventional carcinomas. There have been multiple changes in the nomenclature and classification of MiNENs which has created some confusion among pathologists on how to integrate the contributions of each component in a MiNEN, an issue which in turn has resulted in confusion in communication with front-line treating oncologists. This mini review summarizes our current understanding of MiNENs and outline diagnosis, prognosis, and management of these neoplasms. The authors emphasize the importance of treating the most aggressive component of the tumor regardless of its percentage volume.

• Mixed neuroendocrine non-neuroendocrine neoplasms
• Mixed adenoneuorendocrine carcinoma
• Mixed neuroendocrine neoplasms
• Neuroendocrine
• Non-neuroendocrine

• Carcinoma
• Digestive System/pathology
• Humans
• Mutation
• Neuroendocrine Tumors/genetics
• Neuroendocrine Tumors/therapy
• Prognosis

• Gallbladder
• Gastrointestinal system
• Liver
• Mixed adeno neuroendocrine carcinoma
• Mixed neuroendocrine–nonneuroendocrine neoplasms
• Pancreas

• Adenocarcinoma
• Aged
• Biopsy
• Gastrointestinal Tract/pathology
• Humans
• Male
• Neuroendocrine Tumors/diagnosis

• activated and silenced cancer stem cell niche
• cancer cell fusion
• cancer stem cells
• epithelial-mesenchymal transition
• mesenchymal stroma/stem-like cells
• post-hybrid selection process
• retrodifferentiation
• tumor plasticity

• MANEC
• MiNEN
• classification
• mixed neuroendocrine and non-neuroendocrine neoplasm
• prognosis

Salinity, alkalinity, and drought stress are the main abiotic stress factors affecting plant growth and development. Sophora alopecuroides L., a perennial leguminous herb in the genus Sophora, is a highly salt-tolerant sand-fixing pioneer species distributed mostly in Western Asia and northwestern China. Few studies have assessed responses to abiotic stress in S. alopecuroides. The transcriptome of the genes that confer stress-tolerance in this species has not previously been sequenced. Our objective was to sequence and analyze this transcriptome.

Twelve cDNA libraries were constructed in triplicate from mRNA obtained from Sophora alopecuroides for the control and salt, alkali, and drought treatments. Using de novo assembly, 902,812 assembled unigenes were generated, with an average length of 294 bp. Based on similarity searches, 545,615 (60.43%) had at least one significant match in the Nr, Nt, Pfam, KOG/COG, Swiss-Prot, and GO databases. In addition, 1673 differentially expressed genes (DEGs) were obtained from the salt treatment, 8142 from the alkali treatment, and 17,479 from the drought treatment. A total of 11,936 transcription factor genes from 82 transcription factor families were functionally annotated under salt, alkali, and drought stress, these include MYB, bZIP, NAC and WRKY family members. DEGs were involved in the hormone signal transduction pathway, biosynthesis of secondary metabolites and antioxidant enzymes; this suggests that these pathways or processes may be involved in tolerance towards salt, alkali, and drought stress in S. alopecuroides.

Our study first reported transcriptome reference sequence data in Sophora alopecuroides, a non-model plant without a reference genome. We determined digital expression profile and discovered a broad survey of unigenes associated with salt, alkali, and drought stress which provide genomic resources available for Sophora alopecuroides.

• Alkali
• Differentially expressed genes
• Drought
• Illumina sequencing
• Salt
• Sophora alopecuroides
• Transcriptome

Mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs) represent a rare diagnosis of the gastro-entero-pancreatic tract. Evidence from the current literature regarding their epidemiology, biology, and management is of variable quality and conflicting. Based on available data, the MiNEN has an aggressive biological behaviour, mostly driven by its (often high-grade) neuroendocrine component, and a dismal prognosis. In most cases, the non-neuroendocrine component is of adenocarcinoma histology. Due to limitations in diagnostic methods and poor awareness within the scientific community, the incidence of MiNENs may be underestimated. In the absence of data from clinical trials, MiNENs are commonly treated according to the standard of care for pure neuroendocrine carcinomas or adenocarcinomas from the same sites of origin, based on the assumption of a biological similarity to their pure counterparts. However, little is known about the molecular aberrations of MiNENs, and their pathogenesis remains controversial; molecular/genetic studies conducted so far point towards a common monoclonal origin of the two components. In addition, mutations in tumour-associated genes, including TP53, BRAF, and KRAS, and microsatellite instability have emerged as potential drivers of MiNENs. This systematic review (91 full manuscripts or abstracts in English language) summarises the current reported literature on clinical, pathological, survival, and molecular/genetic data on MiNENs.

• 2017 WHO classification
• 2019 WHO classification
• MANEC
• MiNENs
• mixed adeno-neuroendocrine carcinoma
• mixed non-neuroendocrine neuroendocrine neoplasms

We recently described metabolic nodal stage (mN) and response (mNR) of cancer of the esophagus and gastro-esophageal junction (GEJ) to neoadjuvant chemotherapy (NAC) using ¹⁸F-FDG PET-CT as new markers of disease progression, recurrence, and death. We aimed to validate our findings.

Our validation cohort comprised all patients consecutive to our discovery cohort, staged before and after NAC using PET-CT from 2014 to 2017. Multivariate binary logistic and Cox regression were performed.

Fifty-one of the 200 patients had FDG-avid nodes after NAC (25.5%; i.e., lack of complete mNR), and were more likely to progress during NAC to incurable disease on PET-CT or at surgery: odds ratio 3.84 (1.46–10.1; p = 0.006). In 176 patients undergoing successful resection, patients without complete mNR had a worse prognosis: disease-free survival hazard ratio 2.46 (1.34–4.50); p = 0.004. These associations were independent of primary tumor metabolic, pathological response, and stage. In a hybrid pathological/metabolic nodal stage, avid nodal metastases conferred a worse prognosis than non-avid metastases. Lack of complete mNR predicted recurrence or death at 1 and 2 years: positive predictive values 44.4% (31.7–57.8) and 74.1% (56.6–86.3) respectively.

This study provides temporal validation for mNR as a new and independent predictive and prognostic marker of esophageal and GEJ cancer treated with NAC and surgery, although external validation is required to assess generalizability. mNR may provide surrogate information regarding the phenotype of metastatic cancer clones beyond the mere presence of nodal metastases, and might be used to better inform patients, risk stratify, and personalize management, including adjuvant therapy.

• We previously described metabolic nodal response (mNR) of esophageal cancer to neoadjuvant chemotherapy using¹⁸F-FDG PET-CT as a predictor of unresectable disease, early recurrence, and death.

• We report the first validation of these findings. In an immediately consecutive cohort, we found consistent proportions of patients with and without mNR, and associations with abandoned resection, early recurrence, and death.

• This supports mNR as a new and actionable biomarker in esophageal cancer. Although external validation is required, mNR may provide surrogate information about the chemosensitivity of metastatic subclones, and the means to predict treatment success, guide personalized therapy, and follow-up.

The online version of this article (10.1007/s00330-019-06310-9) contains supplementary material, which is available to authorized users.

• Esophagectomy
• Metastases
• PET-CT
• Prognosis
• Recurrence

Mixed adenoneuroendocrine carcinoma (MANEC) is defined as a neoplasm composed of both exocrine and endocrine carcinomas, each comprising at least 30% of the tumor. MANEC can occur in various organs of the gastrointestinal tract, including the esophagus, stomach, and colon. We herein provide the first case report of surgically resected MANEC arising in Barrett’s esophagus (BE).

A 70-year-old man presenting with abdominal pain was referred to our hospital. Upper endoscopy showed a type 0-IIa + IIc elevated lesion adjacent to BE. According to a biopsy specimen, the elevated lesion was diagnosed as adenocarcinoma with neuroendocrine differentiation. No lymphatic or distant metastasis was detected in the preoperative examination. Laparoscopic distal esophagectomy and proximal gastrectomy were performed, and a diagnosis of MANEC in BE was determined according to the surgically resected specimen.

A very rare case of MANEC in BE was detected. BE can be the origin of esophageal MANEC as well as adenocarcinoma. Due to the small number of esophageal or esophagogastric MANEC cases reported, further accumulation of such cases is necessary to recommend an optimal management strategy for esophageal or esophagogastric MANEC.

• Barrett’s esophagus
• Mixed adenoneuroendocrine carcinoma (MANEC)
• Neuroendocrine tumor

• Mixed adenoneuroendocrine carcinomas
• diagnosis
• gastric
• grading
• neuroendocrine tumors
• prognosis