Objective: To evaluate the effect of postoperative radiotherapy and high-risk pathological factors on the prognosis of early-stage neuroendocrine carcinoma of cervix (NECC). Methods: A single-center retrospective cohort study of early-stage NECC in Peking Union Medical College Hospital from January 2011 to April 2022 were enrolled. The patients were treated with radical hysterectomy±adjuvant treatment. They were divided into postoperative non-radiation group and postoperative radiation group. The possible postoperative recurrence risk factors identified by univariate analysis were assessed using multivariate logistic regression. The Kaplan-Meier method was used to analyze the progression free survival (PFS), overall survival (OS), recurrence rate, and mortality rate. Results: (1) Sixty-two cases were included in the study, including 33 cases in postoperative non-radiation group and 29 cases in postoperative radiation group. (2) The median follow-up time was 37 months (ranged 12-116 months), with 23 cases (37%) experienced recurrences. There were 7 cases (11%) pelvic recurrences and 20 cases (32%) distant recurrences, in which including 4 cases (6%) both pelvic and distant recurrences. Compared with postoperative non-radiation group, the postoperative radiation group had a lower pelvic recurrence rate (18% vs 3%; P=0.074) but without statistic difference, a slightly elevated distant recurrence rate (24% vs 41%; P=0.150) and overall recurrence rate (33% vs 41%; P=0.513) without statistically significances. Univariate analysis showed that lymph-vascular space invasion and the depth of cervical stromal invasion≥1/2 were risk factors for postoperative recurrence (all P<0.05). Multivariate analysis showed lymph-vascular space invasion was an independent predictor for postoperative recurrence (OR=23.03, 95%CI: 3.55-149.39, P=0.001). (3) During the follow-up period, 18 cases (29%, 18/62) died with tumor, with 10 cases (30%, 10/33) in postoperative non-radiation group and 8 cases (28%, 8/29) in postoperative radiation group, without significant difference (P=0.814). The postoperative 3-year and 5-year survival rate was 79.2%, 60.8%. The depth of cervical stromal invasion≥1/2 was more common in postoperative radiation group (27% vs 64%; P=0.011), and postoperative radiation in such patients showed an extended trend in PFS (32.3 vs 53.9 months) and OS (39.4 vs 73.4 months) but without statistic differences (P=0.704, P=0.371). Compared with postoperative non-radiation group, the postoperative radiation did not improve PFS (54.5 vs 37.3 months; P=0.860) and OS (56.2 vs 62.4 months; P=0.550) in patients with lymph-vascular space invasion. Conclusions: Postoperative radiation in early-stage NECC patients has a trend to reduce pelvic recurrence but not appear to decrease distant recurrence and overall recurrence, and has not improved mortality. For patients with the depth of cervical stromal invasion≥1/2, postoperative radiation has a trend of prolonging OS and PFS but without statistic difference. Lymph-vascular space invasion is an independent predictor for postoperative recurrence, but postoperative radiation in such patients does not seem to have any survival benefits.
Female ; Humans ; Cervix Uteri/surgery* ; Prognosis ; Retrospective Studies ; Uterine Cervical Neoplasms/surgery* ; Carcinoma, Neuroendocrine/surgery* ; Recurrence

Female ; Humans ; Cervix Uteri/surgery* ; Carcinoma, Neuroendocrine/surgery*

Female ; Humans ; Teratoma/pathology* ; Ovarian Neoplasms/pathology* ; Carcinoma, Small Cell/surgery* ; Carcinoma, Squamous Cell/pathology* ; Carcinoma, Neuroendocrine/surgery*

Carcinoma, Large Cell ; Carcinoma, Neuroendocrine/surgery* ; Female ; Humans ; Uterine Cervical Neoplasms

Carcinoma, Endometrioid/pathology* ; Carcinoma, Neuroendocrine/surgery* ; Carcinoma, Small Cell/surgery* ; Endometrial Neoplasms/pathology* ; Female ; Humans ; Ovarian Neoplasms/surgery* ; Uterus/pathology*

Objective: To investigate the correlation between CLOCK and BMAL1 genes and MEN2 medullary thyroid carcinoma (MTC). Methods: Thirteen cases with MEN2 MTC and thirteen cases with non-MEN2 MTC were selected who were treated in the Yantai Yuhuangding Hospital between January 2013 and September 2021. Clinical indicators such as blood calcitonin level, tumor diameter and metastatic lymph node of patients were collected. The expression differences of CLOCK and BMAL1 between MEN2 MTC and para-carcinoma tissue as well as between MEN2 MTC and non-MEN2 MTC were detected by immunohistochemistry and qPCR. The correlation between lymph node metastasis and CLOCK or BMAL1 expression was analyzed. Protein-protein interaction (PPI) network analysis combined with qPCR and correlation analysis was used to explore the expression regulation relationship between RET and circadian clock genes. The rhythm disorder of MEN2 cells was verified by lipopolysaccharide cell stimulation experiment after dexamethasone rhythm synchronization. Results: MEN2 MTC exhibited typical RET gene mutation. The mean blood calcitonin level, the tumor diameter and the number of metastatic lymph nodes of patients with MEN2 MTC were higher than those of patients with non-MEN2 MTC (t value was 2.76, 2.53, 2.26, all P<0.05). Immunohistochemical results showed that the expression levels of CLOCK and BMAL1 in MEN2 MTC were higher than those in non-MEN2 MTC, while negatively expressed in para-cancerous thyroid follicle. qPCR displayed that the expression of CLOCK gene in cancer tissues was higher than that in non-MEN2 MTC and para-cancerous tissues (t value was 2.68 and 2.86, all P<0.05); the expression of BMAL1 gene in MEN2 MTC was higher than that in non-MEN2 MTC and para-cancerous tissues (t value was 2.21 and 2.35, all P<0.05). Correlation analysis showed that the expression levels of CLOCK and BMAL1 genes were positively correlated with the number of lymph node metastases in patients with MEN2 MTC (r=0.65, P<0.001; r=0.52, P=0.005). PPI network analysis indicated that the expression of CLOCK gene was positively correlated with the abnormal expression of RET gene (r=0.96, P<0.001). With lipopolysaccharide to stimulate cultured cells in vitro after dexamethasone rhythm synchronization, the expressions of CLOCK and BMAL1 in MEN2 MTC cells (0.47±0.22 and 2.60±1.48) at 12 hours of synchronization were significantly lower than those in para-cancerous tissues (1.70±1.62 and 8.23±2.52), the difference was statistically significant(t=5.04, P=0.007; t=3.34, P=0.029). Conclusion: CLOCK and BMAL1 are correlated with the occurrence and development of MEN2 MTC, and may be potential targets for the development of new therapeutic strategies for MEN2 MTC.
ARNTL Transcription Factors/genetics* ; CLOCK Proteins/genetics* ; Calcitonin ; Carcinoma, Neuroendocrine/genetics* ; Dexamethasone ; Humans ; Lipopolysaccharides ; Lymphatic Metastasis ; Multiple Endocrine Neoplasia Type 2a/genetics* ; Thyroid Neoplasms/surgery*

Neuroendocrine neoplasms (NEN) are rare neoplasms originating from all major systems, in which gastric neuroendocrine neoplasms (G-NEN) is rarely malignant neoplasm originated in stomach. In 2019, the 5th WHO classification of digestive system tumors updated the classification of G-NEN and solved several naming problems. Since the classification of G-NEN has become more specific and more scientific, the surgical treatment of G-NEN is becoming more individual and more precise. Generally, endoscopic resection is often recommended for the treatment of type I gastric neuroendocrine tumors (NET). Type II gastric NET is mostly secondary to gastrinoma originating from the duodenum or pancreas, and thus surgical treatment of primary gastrinoma deserves enough attention. The decision of operation for type III gastric NET needs comprehensive consideration of tumor size, invasive depth and lymph node metastasis. For gastric neuroendocrine carcinomas without distant metastasis, aggressive surgery should be performed, and the resection range of primary site and lymph nodes can refer to the standard of gastric adenocarcinoma. For locally advanced gastric NEC, it has not been reported whether neoadjuvant chemotherapy or neoadjuvant chemoradiotherapy could reduce tumor stage and improve radical resection rate. In addition, for functional gastric NEN with distant metastasis, radical resection or palliative surgery can be performed to control hormone secretion and may improve the survival. In general, it is an important principle to thoroughly consider biological behavior, extent of primary and metastatic sites, resectability and function of tumor before surgery of gastric neuroendocrine neoplasm, and thus multi-disciplinary treatment (MDT) is recommended.
Carcinoma, Neuroendocrine ; Gastrointestinal Neoplasms ; Humans ; Lymphatic Metastasis ; Neuroendocrine Tumors/surgery* ; Stomach Neoplasms/surgery*

BACKGROUND: Medullary thyroid carcinoma (MTC) is a rare disease, but it exhibits more aggressive behaviors. The aim of this study was to improve the diagnostic accuracy of MTC before surgery by analyzing the clinical and ultrasonic data of patients with MTC. METHODS: The study included 71 patients (96 lesions) with histopathologically proven MTC between April 2011 and September 2016 in the Cancer Hospital of Chinese Academy of Medical Sciences and Peking Union Medical College. The clinical characteristics and sonographic findings were retrospectively reviewed and compared between the ultrasonic correct diagnosis group and the ultrasonic misdiagnosis group with the t test or Mann-Whitney U test for quantitative parameters and the χ test or Fisher exact test for qualitative parameters. RESULTS: Compared with the ultrasonic correct diagnosis group, the proportion of the cystic change in the ultrasonic misdiagnosed group was high (25.0% vs. 4.2%), the uncircumscribed margin and irregular shape proportions were low (20.8%, 58.3% vs. 74.7%, 87.3%), calcification was relatively rare (20.8% vs. 56.3%), and rich vascularity was relatively rare (25.0% vs. 78.9%). CONCLUSIONS In the case of atypical MTC, such as cystic change, circumscribed margin, regular shape, no calcification, no rich vascularity, and normal cervical lymph nodes, MTC is easily misdiagnosed as benign by ultrasound. Therefore, ultrasound, cytology and serum calcitonin should be comprehensively evaluated for a preoperative diagnosis of MTC.
Adult ; Carcinoma, Neuroendocrine ; diagnosis ; diagnostic imaging ; surgery ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Thyroid Neoplasms ; diagnosis ; diagnostic imaging ; surgery ; Ultrasonography

OBJECTIVETo investigate clinicopathological features and prognostic factors of appendiceal neuroendocrine neoplasms(a-NEN).

METHODSClinical data of 20 patients diagnosed with a-NEN at Zhongshan Hospital of Fudan University between January 2000 and December 2016 were retrospectively analyzed. Pathological diagnosis was based on the WHO classification criteria of digestive system tumors (2010 edition). Based on the mitotic count and Ki-67 index, a-NENs were divided into grade 1 neuroendocrine tumor (NET G1), grade 2(G2) NET G2) and grade 3 (neuroendocrine carcinoma, NEC). Some special types of a-NEN (e.g. goblet cell carcinoid) and mixed adenoneuroendocrine neoplasms were classified as mixed adenoneuroendocrine carcinoma (MANEC). Follow-up was conducted by telephone or return visits. Univariate analysis was carried out using the Kaplan-Meier method, and the log-rank test was used to draw survival curves.

RESULTSOf 20 patients, 14 were male and 6 were female with median age of 54 years. Seventeen cases presented acute right lower quadrant abdominal pain, 1 chronic right lower quadrant abdominal pain, 1 persistent abdominal discomfort with outburst whole abdominal pain and 1 was found during body check without symptoms. Twenty cases comprised 8 G1 patients, 4 G2 patients, 3 G3 patients, and 5 MANEC patients. When diagnosed, there was 1 patient with liver metastasis, 1 patient with abdominal and pelvic metastases, and 2 patients with postoperative pathological findings of lymph node metastasis. Six patients underwent appendectomy, 12 underwent right hemicolectomy, 1 underwent right hemicolectomy plus small intestine resection, and 1 underwent partial hepatectomy plus right hemicolectomy. The follow-up time was 7-187 months(average, 36 months). The total 1- and 3-year survival rates were 94.7% and 60.2%, respectively. Univariate analysis showed that age >50 years (χ=7.036, P=0.008), pathology grade as MANEC (χ=5.297, P=0.021), and metastasis (χ=6.558, P=0.010) indicated lower 5-year survival rate.

CONCLUSIONSMost a-NEN patients have no typical symptoms, and the main complaint at consultation is acute right lower quadrant abdominal pain. Prognosis is poor for patients with age >50 years, MANEC pathology grade and metastasis.

Appendiceal Neoplasms ; complications ; diagnosis ; surgery ; Carcinoma, Neuroendocrine ; complications ; diagnosis ; therapy ; Female ; Gastrointestinal Neoplasms ; Humans ; Male ; Middle Aged ; Neuroendocrine Tumors ; complications ; diagnosis ; surgery ; Prognosis ; Retrospective Studies

OBJECTIVETo explore the feasibility and efficacy of laparoscopic D2 radical gastrectomy in patients with gastric neuroendocrine carcinoma (GNEC).

METHODSClinical data of 84 patients with GNEC undergoing laparoscopic D2 radical gastrectomy in Union Hospital from January 2006 to December 2012 were analyzed respectively. Among these patients, 44 cases underwent laparoscopic D2 gastrectomy (LAG group) and 40 cases underwent open gastrectomy (OG group). The short- and long-term outcomes, 3-year survival and recurrence-free survival were compared between two groups.

RESULTSThe LAG group and OG group did not differ significantly in terms of clinicopathologic characteristics. All the patients completed operations successfully and no patients in the LAG group ware converted to laparotomy. The operative time was similar (P>0.05). As compared to OG group, LAG group had less intra-operative blood loss [(85±21) ml vs. (192±89) ml, P=0.003], lower ratio of transfusion [2.3%(1/44) vs. 15.0%(6/40), P=0.048], shorter time to ambulation after surgery [(2.5±1.1) days vs. (3.5±1.1) days, P=0.001], faster postoperative gastrointestinal function recovery [(2.9±1.1) days vs. (5.1±1.0) days, P=0.001], shorter time to resume soft diet [(4.1±1.2) days vs. (5.7±1.3) days, P=0.001] and shorter postoperative hospital stay [(12.0±3.4) days vs. (15.0±5.5) days, P=0.002]. No significant difference was observed in average dissected lymph node number between LAG and OG group (35.0±16.4 vs. 31.6±12.1, P=0.204). Morbidity of postoperative complication of LAG group and OG group was 11.4%(5/44) and 17.5%(7/40) respectively (P=0.422). The overall 3-year survival rate was 54.0% for all the patients, while 3-year survival rate was 56.3% in LAG group and 51.4 % in OG group (P=0.478). In addition, there was no significant difference in recurrence-free survival between the two group (33.0 months vs. 31.5 months, P=0.703).

CONCLUSIONCompared with open gastrectomy, laparoscopic D2 radical gastrectomy has the advantages of faster recovery and less blood loss, and similar short-term and long-term outcomes in treatment of patients with GNEC, thus it is a safe and feasible treatment for GNEC.

Blood Loss, Surgical ; Carcinoma, Neuroendocrine ; surgery ; Female ; Gastrectomy ; methods ; Humans ; Laparoscopy ; Laparotomy ; Length of Stay ; Lymph Node Excision ; Male ; Middle Aged ; Operative Time ; Postoperative Complications ; Postoperative Period ; Stomach Neoplasms ; surgery ; Survival Rate ; Treatment Outcome