Mixed adenoneuroendocrine carcinoma (MANEC) of the lower gastrointestinal tract: A systematic review with Bayesian hierarchical survival analysis

Grossi, Ugo; Bonis, Alessandro; Carrington, Emma V.; Mazzobel, Enrico; Santoro, Giulio Aniello; Cattaneo, Laura; Centonze, Giovanni; Gallo, Gaetano; Nava, Andrea; Romano, Maurizio; Tanna, Gian Luca Di; Zanus, Giacomo

doi:10.1016/j.ejso.2021.05.021

Cited by 11 publications

(9 citation statements)

References 59 publications

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“…The third leading cause of cancer death is colorectal cancer, with a high level of burden [ 1 ]. Surveillance, Epidemiology, and End Results (SEER) 18 registry showed an incidence rate of up to 3.56 per 100,000 in gastrointestinal sites [ 2 ]] [[ 3 ]. The prevalence of colorectal cancer is higher in men than women [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

A bayesian approach to model the underlying predictors of early recurrence and postoperative death in patients with colorectal Cancer

Mahmoudi

Fallah

Roshanaei

et al. 2022

BMC Med Res Methodol

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Objective This study aimed at utilizing a Bayesian approach semi-competing risks technique to model the underlying predictors of early recurrence and postoperative Death in patients with colorectal cancer (CRC). Methods In this prospective cohort study, 284 patients with colorectal cancer, who underwent surgery, referred to Imam Khomeini clinic in Hamadan from 2001 to 2017. The primary outcomes were the probability of recurrence, the probability of Mortality without recurrence, and the probability of Mortality after recurrence. The patients ‘recurrence status was determined from patients’ records. The Bayesian survival modeling was carried out by semi-competing risks illness-death models, with accelerated failure time (AFT) approach, in R 4.1 software. The best model was chosen according to the lowest deviance information criterion (DIC) and highest logarithm of the pseudo marginal likelihood (LPML). Results The log-normal model (DIC = 1633, LPML = -811), was the optimal model. The results showed that gender(Time Ratio = 0.764: 95% Confidence Interval = 0.456–0.855), age at diagnosis (0.764: 0.538–0.935 ), T3 stage (0601: 0.530–0.713), N2 stage (0.714: 0.577–0.935 ), tumor size (0.709: 0.610–0.929), grade of differentiation at poor (0.856: 0.733–0.988), and moderate (0.648: 0.503–0.955) levels, and the number of chemotherapies (1.583: 1.367–1.863) were significantly related to recurrence. Also, age at diagnosis (0.396: 0.313–0.532), metastasis to other sites (0.566: 0.490–0.835), T3 stage (0.363: 0.592 − 0.301), T4 stage (0.434: 0.347–0.545), grade of differentiation at moderate level (0.527: 0.387–0.674), tumor size (0.595: 0.500–0.679), and the number of chemotherapies (1.541: 1.332–2.243) were the significantly predicted the death. Also, age at diagnosis (0.659: 0.559–0.803), and the number of chemotherapies (2.029: 1.792–2.191) were significantly related to mortality after recurrence. Conclusion According to specific results obtained from the optimal Bayesian log-normal model for terminal and non-terminal events, appropriate screening strategies and the earlier detection of CRC leads to substantial improvements in the survival of patients.

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Section: Introductionmentioning

confidence: 99%

A bayesian approach to model the underlying predictors of early recurrence and postoperative death in patients with colorectal Cancer

Mahmoudi

Fallah

Roshanaei

et al. 2022

BMC Med Res Methodol

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“…Although MiNENs can occur throughout the human body, much more reports of MiNENs with larger number of patients in distal digestive tract were published than other organs, indicating its anatomical site preferences (7,18,19). In a systematic review of lower digestive tract MiNENs, Grossi et al (20) reported that 60.3% of them were in the appendix, 29.3% were in the colon, and 10.4% were in the anorectum. In this study, we found the majority of the cases in midgut and hindgut organs, and only 13.1% of them were located in organs derived from the foregut, including the respiratory system, esophagus, stomach, and hepato-biliary-pancreatic system.…”

Section: Discussionmentioning

confidence: 99%

“…In a systematic review of lower digestive tract MiNENs, Grossi et al. ( 20 ) reported that 60.3% of them were in the appendix, 29.3% were in the colon, and 10.4% were in the anorectum. In this study, we found the majority of the cases in midgut and hindgut organs, and only 13.1% of them were located in organs derived from the foregut, including the respiratory system, esophagus, stomach, and hepato-biliary-pancreatic system.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs): A SEER database analysis of 767 cases

et al. 2023

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BackgroundMixed neuroendocrine non-neuroendocrine neoplasm (MiNEN) is an extremely rare entity, consisting of neuroendocrine and non-neuroendocrine components. It can occur in various organs throughout the body, with a rising incidence. Its clinical management is a rapidly growing field of interest; however, large-scale patient cohorts are still missing to guide clinical practice.Patients and methodsThe demographic, clinicopathological, and survival information of all patients diagnosed with MiNEN in the national Surveillance, Epidemiology, and End Results (SEER) program database (2000–2017) were extracted and further analyzed. The information of the patients before and after 2010 was compared to understand the epidemiological changes of MiNEN. The characteristics of MiNEN originating in different organs were compared. The clinical significance of surgical resection for metastatic MiNENs was also analyzed.ResultsA total of 1081 patients were screened, and after applying the exclusion criteria, 767 patients were finally analyzed. There was no obvious sex preference (49.2% vs 50.8%, p>0.05) and the majority of the patients were Caucasians (n=627, 81.7%). A total of 88.3% of the patients were older than 50 years old, and the median age was 60 years. 79.3% of the tumors are located in the distal digestive tract, and 67.7% were grade 3/4. Distant metastasis was presented in 33.9% of the patients at diagnosis. A total of 88% of the patients underwent surgical treatments. The number of patients increased 10-fold between 2000 and 2017. There was no significant difference in sex, race, stage, or surgical treatments among the patients diagnosed before and after 2010. More patients older than 60 years were diagnosed after 2010 (p=0.009). The median survival was 61.0 ± 9.8 months for the whole cohort. After multivariate analysis, older age (>60 years, p<0.01), more advanced stage (p<0.01), grade 3/4 (p<0.01), and non-surgical treatment (p<0.01) were independent risk factors for poorer survival. The appendiceal MiNENs showed the best prognosis. A total of 260 metastatic MiNENs were further analyzed. Only patients with metastatic MiNENs originating from the appendix had a potential benefit from surgical resection, compared to other sites (p=0.05).ConclusionThis study provides the epidemiological, clinicopathological, and survival information of the largest number of MiNEN patients. Although MiNEN is an extremely rare malignant neoplasm, its incidence increases rapidly. The majority of the patients suffered from advanced-stage disease, which highlights the need for improvement of early detection in the future. The appendix is the most common primary site of MiNEN, and surgical resection for selected metastatic MiNEN originating in the appendix has favorable survival outcomes.

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“…A few studies conducted in the recent past indicate that MiNENs constitute 10% of malignancies at this location. On the other hand, a systematic review showed that among the lower gastrointestinal tract organs, these tumors were most frequently (60.3%) localized in the appendix[ 82 ]. An interesting finding is that the age-adjusted incidence for MiNENs increased from 0.01/100000 person-years to 0.07/100000 person-years (range 2004-2016), with an annual percentage change (APC) of 13.8%[ 83 ].…”

Section: Organ-specific Clinicopathological Findingsmentioning

confidence: 99%

“…A recent systematic review also demonstrated that in MiNENs of the lower gastrointestinal tract, the site of origin in those with metastatic disease at diagnosis appeared to inﬂuence prognosis. The median survival time was 12.3 mo for those with primary colonic tumors vs 11.7 mo for those with primary anorectal tumors, with hazard ratios of 1.13 vs 0.80, respectively[ 82 ].…”

Section: Organ-specific Clinicopathological Findingsmentioning

confidence: 99%

Mixed neuroendocrine–nonneuroendocrine neoplasms of the gastrointestinal system: An update

Elpek¹

2022

WJG

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Mixed neuroendocrine-nonneuroendocrine neoplasms (MiNENs) of the digestive tract are a rare heterogeneous group of tumors that present many challenges in terms of diagnosis and treatment. Over the years, the diagnostic criteria, classification, and clinical behavior of these tumors have been the subjects of ongoing debate, and the various changes in their nomenclature have strengthened the challenges associated with MiNENs. This review is performed to provide an understanding of the key factors involved in the evolution of the designation of these tumors as MiNEN, highlight the current diagnostic criteria, summarize the latest data on pathogenesis and provide information on available treatments. Moreover, this work seeks to increase the awareness about these rare neoplasms by presenting the clinicopathological features and prognostic factors that play important roles in their behavior and discussing their different regions of origin in the gastrointestinal system (GIS). Currently, the MiNEN category also includes tumors in the GIS with a nonneuroendocrine component and epithelial tumors other than adenocarcinoma, depending on the organ of origin. Diagnosis is based on the presence of both morphological components in more than 30% of the tumor. However, this value needs to be reconfirmed with further studies and may be a limiting factor in the diagnosis of MiNEN by biopsy. Furthermore, available clinicopathological data suggest that the inclusion of amphicrine tumors in the definition of MiNEN is not supportive and warrants further investigation. The diagnosis of these tumors is not solely based on immunohistochemical findings. They are not hybrid tumors and both components can act independently; thus, careful grading of each component separately is required. In addition to parameters such as the metastatic state of the tumor at the time of diagnosis and the feasibility of surgical resection, the aggressive potential of both components has paramount importance in the choice of treatment. Regardless of the organ of origin within the GIS, almost MiNENs are tumors with poor prognosis and are frequently encountered in the elderly and men. They are most frequently reported in the colorectum, where data from molecular studies indicate a monoclonal origin; however, further studies are required to provide additional support for this origin.

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Mixed adenoneuroendocrine carcinoma (MANEC) of the lower gastrointestinal tract: A systematic review with Bayesian hierarchical survival analysis

Cited by 11 publications

References 59 publications

A bayesian approach to model the underlying predictors of early recurrence and postoperative death in patients with colorectal Cancer

A bayesian approach to model the underlying predictors of early recurrence and postoperative death in patients with colorectal Cancer

Comprehensive analysis of mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs): A SEER database analysis of 767 cases

Mixed neuroendocrine–nonneuroendocrine neoplasms of the gastrointestinal system: An update

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