Targeted therapy for small cell carcinoma of prostate: a case report / 中华泌尿外科杂志

A patient aged 68 years old presented urinary frequency, urgency, and gross hematuria for 1 month, with initial PSA of 72.72 ng/ml and alkaline phosphatase (ALP)of 114 U/L. Prostate biopsy pathology showed small cell neuroendocrine carcinoma of prostate. The patient was immediately administered 6 cycle of chemotherapy including etoposide and cisplatin combined with medical castration. The CDK4 gene was detected 1.99 times amplification by peripheral blood free DNA (cfDNA)gene analysis. The chemotherapy was followed by parbosini therapy. The number and density of bone metastases continued to decrease significantly by bone scan at 3 and 6 months after treatment, with a continuous decline of ALP and PSA. After 1 year of follow-up, pelvic MRI and bone systemic imaging indicated stable lesions, with PSA of 0.05 ng/ml and ALP of 59 U/L.

Clinicopathological features and survival analysis of gastric cancer patients with neuroendocrine differentiation after radical resection / 中华胃肠外科杂志

Objective: To compare the clinicopathological characteristics and the prognosis of gastric adenocarcinoma patients with and without neuroendocrine differentiation (NED) after radical gastrectomy plus D2 lymph node dissection. Methods: A retrospective cohort study was performed. The inclusion criteria were as follows: (1) patients who underwent radical resection of gastric cancer plus D2 lymph node dissection and were confirmed as gastric adenocarcinoma by postoperative pathology and received immunohistochemical examination of neuroendocrine markers Syn and/or CgA; (2) patients aged 20 to 75 years with normal organ function; (3) patients who did not receive neoadjuvant chemotherapy or radiotherapy before operation; (4) patients with postoperative pathological stage I to III according to the 8th edition of tumor staging system of American Joint Committee on Cancer (AJCC); and (5) patients who completed adjuvant chemotherapy according to the postoperative pathological stage. Those who had other malignant tumors in the past 5 years and who could not be followed up according to the required rules were excluded. According to the above criteria, the clinicopathological characteristics of gastric cancer patients who underwent radical resection plus D2 lymph node dissection in Zhongshan Hospital of Fudan University from January 2010 to June 2017 were collected and compared. All patients were followed up till June 2020. The disease-free survival (DFS) and overall survival (OS) between the patients with and without NED were compared, and the effect of NED on the prognosis was corrected by Cox proportional hazards model. The propensity score matching method was used for sensitivity analysis. Results: A total of 539 patients were enrolled in this study, including 35 with NED and 504 without NED. Compared with the patients without NED, the patients with NED were older [(65.0±7.5) years vs. (54.5±11.3) years, t=-7.681, P<0.001], had higher proportion of undergoing proximal gastrectomy [22.9% (8/35) vs. 7.6% (36/504), χ(2)=10.335, P=0.006], higher proportion of intestinal-type based on Lauren classification [77.1% (27/35) vs. 42.5% (214/504), χ(2)=14.553, P<0.001], and higher proportion of pathologic stage III [65.7% (23/35) vs. 27.6% (139/504), χ(2)=25.653, P<0.001]. The 3-year DFS of patients with NED and those without NED was 48.9% (95% CI: 33.8%-70.8%) and 37.4% (95% CI: 32.9%-42.5%) respectively, and no significant difference was found (P=0.44). The 3-year OS was 56.1% (95% CI: 39.9%-79.1%) and 64.3% (95% CI: 59.3%-69.7%) respectively, and no significant difference was found as well (P=0.32). Univariate and multivariate analyses showed that NED was not an independent risk factor for DFS and OS (all P>0.05). Sensitivity analysis showed that there was no significant difference in DFS and OS between the two groups after propensity score matching. Conclusion: Compared with patients without NED, patients with NED were older at onset, had a higher proportion of proximal gastrectomy, intestinal-type, and later diagnostic stage, but the survival prognosis had no significant difference with that of patients without NED.

Clinical Characteristics, Treatment and Prognosis of 47 Non-small Cell Lung Cancer with Neuroendocrine Differentiation Patients / 中国肺癌杂志

BACKGROUND@#Non-small cell lung cancer (NSCLC) with neuroendocrine differentiation (NED) was a new pathologic type and uncommon in clinics. The aim of this study is to observe the relationship between clinical pathologic characteristics, imagination, biological behavior and prognosis in NSCLC-NED.@*METHODS@#The clinical data of 47 patients with NSCLC-NED admitted from January 2009 to November 2017 in the Fifth Medical Center of General Hospital of People's Liberation Army were collected. The demographic data and imaging characteristics were summarized. Pathological features, treatment and prognosis, analysis of the correlation between different factors and prognosis.@*RESULTS@#Of the 47 patients with NSCLC-NED, the median age was 61 years (45 years-78 years), 38 males and 9 females; 37 were poorly differentiated cancer with NED, and 10 were middle differentiated cancer with NED; 2 cases of driving gene positive (1 case of EGFR sensitive mutation, 1 case of ALK fusion), objective response rate (ORR) of first-line chemotherapy was 34.5%, and median progression-free survival (PFS) was 4 months; the median overall survival (OS) was 11 months, and only 2 cases (4.2%, 2/47) of OS were over 2 years.@*CONCLUSIONS@#NSCLC-NED is different from simple NSCLC or pulmonary neuroendocrine tumors. Males, ≤70 years old, severely smoking, and patients with lower tumor differentiation often have NED, and most of them are stage IV. This type of patient-driven gene positive proportion is lower than the general adenocarcinoma population, less sensitive to chemotherapy, and the overall survival is shorter, indicating a poor prognosis.

A Case of Middle Ear Neuroendocrine Adenoma in a Patient with Hearing Loss and Facial Palsy / 대한이비인후과학회지

Middle ear adenoma is a very rare disease which is benign and originates from the middle ear mucosa. Patients of middle ear adenoma usually come to the clinic for unilateral hearing loss or tinnitus, but rarely for accompanied facial palsy. It is non-gender specific and occurs over a wide range of ages. The recurrence rate is known to be very low, but few authors argue that neuroendocrine adenoma should be considered as a low grade carcinoma due to some cases of recurrence. A 18 years-old male who had a left side facial palsy about 3 years ago but has currently improved as compared with the initial onset, visited our clinic for the left side hearing loss. Pure tone audiogram showed about 30 dB of conductive hearing loss and a pinkish polypoid mass involving the left tympanic membrane. We removed a tumor via transmastoid approach. The final diagnosis was middle ear adenoma with neuroendocrine differentiation. Neither signs of complication nor recurrence were observed after six months of the surgery.

The regulatory pathways leading to stem-like cells underlie prostate cancer progression / 亚洲男科学杂志(英文版)

Prostate cancer (PCa) is the most common cause of malignancy in males and the third leading cause of cancer mortality in the United States. The standard care for primary PCa with local invasive disease mainly is surgery and radiation. For patients with distant metastases, androgen deprivation therapy (ADT) is a gold standard. Regardless of a favorable outcome of ADT, patients inevitably relapse to an end-stage castration-resistant prostate cancer (CRPC) leading to mortality. Therefore, revealing the mechanism and identifying cellular components driving aggressive PCa is critical for prognosis and therapeutic intervention. Cancer stem cell (CSC) phenotypes characterized as poor differentiation, cancer initiation with self-renewal capabilities, and therapeutic resistance are proposed to contribute to the onset of CRPC. In this review, we discuss the role of CSC in CRPC with the evidence of CSC phenotypes and the possible underlying mechanisms.

Beta-adrenergic signaling on neuroendocrine differentiation, angiogenesis, and metastasis in prostate cancer progression / 亚洲男科学杂志(英文版)

Prostate cancer is a complex, heterogeneous disease that mainly affects the older male population with a high-mortality rate. The mechanisms underlying prostate cancer progression are still incompletely understood. Beta-adrenergic signaling has been shown to regulate multiple cellular processes as a mediator of chronic stress. Recently, beta-adrenergic signaling has been reported to affect the development of aggressive prostate cancer by regulating neuroendocrine differentiation, angiogenesis, and metastasis. Here, we briefly summarize and discuss recent advances in these areas and their implications in prostate cancer therapeutics. We aim to provide a better understanding of the contribution of beta-adrenergic signaling to the progression of aggressive prostate cancer.

Beta-adrenergic signaling on neuroendocrine differentiation, angiogenesis, and metastasis in prostate cancer progression / 亚洲男科学杂志(英文版)

Prostate cancer is a complex, heterogeneous disease that mainly affects the older male population with a high-mortality rate. The mechanisms underlying prostate cancer progression are still incompletely understood. Beta-adrenergic signaling has been shown to regulate multiple cellular processes as a mediator of chronic stress. Recently, beta-adrenergic signaling has been reported to affect the development of aggressive prostate cancer by regulating neuroendocrine differentiation, angiogenesis, and metastasis. Here, we briefly summarize and discuss recent advances in these areas and their implications in prostate cancer therapeutics. We aim to provide a better understanding of the contribution of beta-adrenergic signaling to the progression of aggressive prostate cancer.

The regulatory pathways leading to stem-like cells underlie prostate cancer progression / 亚洲男科学杂志(英文版)

Prostate cancer (PCa) is the most common cause of malignancy in males and the third leading cause of cancer mortality in the United States. The standard care for primary PCa with local invasive disease mainly is surgery and radiation. For patients with distant metastases, androgen deprivation therapy (ADT) is a gold standard. Regardless of a favorable outcome of ADT, patients inevitably relapse to an end-stage castration-resistant prostate cancer (CRPC) leading to mortality. Therefore, revealing the mechanism and identifying cellular components driving aggressive PCa is critical for prognosis and therapeutic intervention. Cancer stem cell (CSC) phenotypes characterized as poor differentiation, cancer initiation with self-renewal capabilities, and therapeutic resistance are proposed to contribute to the onset of CRPC. In this review, we discuss the role of CSC in CRPC with the evidence of CSC phenotypes and the possible underlying mechanisms.

Serum levels of neuroendocrine differentiation markers predict the prognosis of patients with metastatic castration resistant prostate cancer treated with abiraterone acetate / 中华泌尿外科杂志

Objective To determine the influence of abiraterone acetate (AA) on neuroendocrine differentiation (NED) in metastatic castration-resistant prostate cancer (mCRPC) and the prognostic predicting value of the serum NED markers in mCRPC patients treated with AA.Methods We conducted an analysis in 115 chemotherapy-naive mCRPC patients who were treated with chemotherapy in Renji hospital from 2013 to 2017.The median age was 70,ranged from 65 to 76 years old.The median CgA,NSE and PSA levels were 101.1 ng/ml (78.5-150.0 ng/ml),13.4 ng/ml (10.5-17.6 ng/ml) and 38.8 ng/ml (11.2-123.2 ng/ml),respectively.Among them,48 cases were classified as the group without AA treatment.The other 67 cases were classified as group after AA failure.In group without AA treatment,the median CgA,NSE and PSA levels were 109.1 ng/ml(80-151.5 ng/ml);13.8 ng/ml(10.8-18.2 ng/ml) and 39.2 ng/ml (8.6-200 ng/ml),respectively.In group after AA failure,the median CgA,NSE and PSA levels were 105.4 ng/ml(78.8-175.5 ng/ml),13.8 ng/ml(10.8-17.6 ng/ml) and 39.0 ng/ml(8.4-219.8 ng/ml),respectively.In the group with serial evaluation of NED markers during AA treatment,the median serum CgA,NSE levels at baseline were 115.9 ng/ml(90.1-201.5 ng/ml),13.3 ng/ml (10.4-18.1 ng/ml),respectively.The endpoints were PSA PFS(progression-free survival) and radiographic PFS (rPFS).Results In 34 patients with serial evaluation,serum NED markers level in 19 patients increased after the failure of AA treatment.Median serum CgA and NSE levels were 115.9 ng/ml(90.1-201.5 ng/ml)and 13.25 ng/ml (10.37-18.14 ng/ml) at baseline.Median serum CgA and NSE levels were 129.6ng/ml (75.5-230.5 ng/ml) and 14.7 ng/ml (11.8-19.1 ng/ml) after 6 months treatment,respectively.The median serum CgA and NSE levels were 130.4 ng/ml (95.7-205.7 ng/ml) and 15.2 ng/ml(12.4-18.7 ng/ml) at the time of failure of AA treatment,respectively.There was no significant difference of NED markers between baseline and failure of AA treatment (P =0.243).In logistic univariate analysis,AA treatment and its duration were not independent factors influencing NED(P =0.30;P =0.52).Compared with the NED markers elevation group in the first 6 months of AA treatment and baseline supranormal NED markers group,the NED markers decline group(PSA PFS(17.1 vs.10.4 months,P ＜ 0.001) and rPFS (17.0 vs.10.4 months,P =0.003)) and baseline normal NED markers group(PSA PFS(14.1 vs.9.5 months,P =0.001) and rPFS(16.4 vs.10.5 months,P ＜ 0.001)) has a longer median PSA PFS and rPFS respectively.In multivariate Cox analysis,baseline NED markers level and NED markers variation during the first 6 months of AA treatment remained significant predictors of rPFS(P ＜ 0.05),and PSA-PFS (P ＜ 0.05).Conclusions We found there was heterogeneity in changes of NED markers in different mCRPC patients during AA treatment,and AA might not significantly lead to progression of NED of mCRPC in general.Serial CgA and NSE evaluation might help clinicians guide clinical treatment of mCRPC patients.Serum NED markers elevation during the first 6 months of AA treatment and elevated baseline NED markers levels indicated poor prognosis in mCRPC treated with AA.

Clinicopathological study of gastrointestinal pancreatic carcinoma with neuroendocrine differentiation and mixed adenocarcinoma of the pancreas and pancreas / 中国生化药物杂志

Objective To investigate the clinicopathological features of gastrointestinal carcinoma with neuroendocrine differentiation (NED) and mixed adenocarcinoma of the pancreas and pancreas (MANEC). Methods Clinical and pathological data of 29 cases in Zhejiang Chinese medicine hospital with gastrointestinal pancreatic cancer with neuroendocrine branch and 7 cases with gastrointestinal pancreatic MANEC patients were analyzed retrospectively. Hematoxylin eosin staining of the tissue (HE) and immunohistochemistry (IHC) were observed, the relationship between IHC index and tumor distant metastasis and clinical pathological indicators between. Results Gastrointestinal pancreatic cancer with NED and MANEC in patients with various clinicopathological parameters and IHC expression rate difference was not statistically significant;neuroendocrine index expression difference between the positive rate and clinical pathological factors were not statistically significant; there was no significant difference between distant metastasis and clinical pathological factors. Conclusion Combined with morphological HE staining and immunohistochemical IHC staining, gastrointestinal carcinoma with NED and MANEC has high heterogeneity. Clinical staging and grading are the major prognostic factors. Early diagnosis and treatment can improve the prognosis of patients.

Research progress on neuroendocrine prostate cancer induced by androgen depriva-tion therapy / 中国肿瘤临床

Patients with metastatic prostate cancer are typically managed with androgen deprivation therapy. Most patients initially respond to treatment, but many eventually develop castration-resistant prostate cancer. Neuroendocrine prostate cancer (NEPC) is a highly aggressive subtype of castration-resistant prostate cancer, which often results from neuroendocrine differentiation of prostate cancer cells. NEPC has a dismal outcome with an average survival of less than 1 year and exhibits less response to radiochemotherapy. At least 25%of patients with lethal castration-resistant prostate cancer are predicted to eventually develop this type of highly-aggres-sive NEPC. However, research on the molecular mechanism of NEPC is limited;thus, further studies are needed to explore the develop-ment and application of anticancer drugs for NEPC.

Mucinous carcinoma of breast with neuroendocrine differentiation: a rare case report with review of literature.

Mucinous carcinoma of the breast is a relatively rare malignancy accounting for 2% of all breast cancers. Mucinous carcinoma of the breast has a favourable prognosis and is usually seen in postmenopausal women. Here, we report a 60 year old female patient presented with right breast lump was diagnosed on cytology as ductal carcinoma of the breast, on histopathology diagnosed as mucinous carcinoma with neuroendocrine differentiation, which was subsequently confirmed on IHC marker synaptophysin and chromogranin A positive.

Clinical study of thermotherapy with chemotherapy in advanced non-small cell lung cancer with neuroendocrine differentiation / 中国基层医药

Objective To study the clinical efficacy of thermotherapy combined chemotherapy in the treatment of the advanced non-small cell lung carcinoma with neuroendocrine differentiation (NSCLC-NED).Methods The clinical data of 16 patients with NSCLC-NED were retrospectively reviewed.To analyzed the efficacy and survival of these patients.All patients were treated by thermotherapy with the combined chemotherapy regiment of platinum agents.Results There were 7 partial responses and 4 stable disease,The overall response rate (RR) was 43.8％.The one year survival rate was 37.5％ (6/16).The improvement rate of quality of life was 62.5％ (10/16).Conclusion Neuroendocrine differentiation is an important indicator of biological behavior of NSCLC.Thermochemotherapy is an active regimen in the advanced NSCLC-NED with an acceptabe toxicity.

A Rare Case of Gastric Carcinosarcoma with Neuroendocrine Differentiation

Carcinosarcoma of the stomach is a rare biphasic tumor that consists of both carcinomatous and sarcomatous components. In the gastrointestinal tract, carcinosarcoma is most frequently seen in the esophagus and rarely in the stomach. Tubular or papillary adenocarcinomas are common carcinomatous components, whereas mesenchymal sarcomatous components may vary. Neuroendocrine carcinomatous differentiation in carcinomatous components is extremely rare. We report a 62-year-old female patient with a history of dyspepsia for one-month-history. Endoscopic findings showed a ulcerofungating lesion, which infiltrated from the posterior wall of the antrum to the posterior wall of the gastric angle. Radical subtotal gastrectomy was performed. In the resected specimen, immunohistochemical studies showed two positive reactions for epithelial and mesenchymal markers. Based on the above findings, the patient was diagnosed with a gastric carcinosarcoma with neuroendocrine differentiation.

A Rare Case of Gastric Carcinosarcoma with Neuroendocrine Differentiation

Carcinosarcoma of the stomach is a rare biphasic tumor that consists of both carcinomatous and sarcomatous components. In the gastrointestinal tract, carcinosarcoma is most frequently seen in the esophagus and rarely in the stomach. Tubular or papillary adenocarcinomas are common carcinomatous components, whereas mesenchymal sarcomatous components may vary. Neuroendocrine carcinomatous differentiation in carcinomatous components is extremely rare. We report a 62-year-old female patient with a history of dyspepsia for one-month-history. Endoscopic findings showed a ulcerofungating lesion, which infiltrated from the posterior wall of the antrum to the posterior wall of the gastric angle. Radical subtotal gastrectomy was performed. In the resected specimen, immunohistochemical studies showed two positive reactions for epithelial and mesenchymal markers. Based on the above findings, the patient was diagnosed with a gastric carcinosarcoma with neuroendocrine differentiation.

Analysis of Clinicopathological Features and Prognosis of Gastric Carcinoma with Neuroendocrine Differentiation and Mixed Gonadal Neuroendocrine Carcinoma of the Stomach / 天津医药

Objective To investigate the clinical pathological features and prognosis of gastric carcinoma with neu-roendocrine differentiation (NED) and mixed gonadal neuroendocrine carcinoma of the stomach (MANECs). Methods A retrospective analysis of 61 cases of gastric carcinoma with NED and 34 cases of MANECs and their histochemistry and im-munohistochemistry were also observed. Prognosis of the 2 groups were compared by the Kaplan-Meiers survival analysis. Prognostic factors associated with patients with gastric cancer were analyzed by COX proportional hazards model. Results Tumor location, distant metastasis and lymph node metastasis were statistically different between these 2 groups (P<0.05). Syn positive expression rate is higher than CgA and CD56 in the gastric carcinoma with NED group;Postoperative survive pe-riod of the gastric carcinoma with NED is shorter than that of MANECs (P<0.05). Lymph node metastasis and distant region-al transfer is obviously correlated with prognosis (P<0.05). Conclusion Immunohistochemistry is important for the diag-nosis of these two tumor. The number of neuroendocrine cells can help to assess prognosis and guide treatment.

Carcinoma en tejido mamario ectópico axilar con diferenciación neuroendocrina: reporte de un caso / Carcinoma in ectopic axillary breast tissue with neuroendocrine differentiation: case report

Presentar un caso de carcinoma en tejido mamario ectópico axilar. Paciente femenina de 38 años de edad, quien consultó por aumento de volumen y nódulo en región axilar de un año de evolución y punción aspiración por aguja fina previa no diagnóstica. En la evaluación se observó mamas axilares bilaterales, palpando en la derecha tumor duro de superficie irregular, se realizó mamografía, C y biopsia por aguja gruesa. Por el diagnóstico de la biopsia por aguja gruesa, se practicaron estudios de extensión y se trató con neoadyuvancia y cirugía. El estudio histopatológico de la pieza quirúrgica concluyó carcinoma ductal infiltrante con patrón neuroendocrino y metástasis en 2 de 18 ganglios, recibió adyuvancia y se mantiene libre de enfermedad

A case of female patient 38 years of age, who consulted for increased volume and axillary node in a year of evolution and prior non-diagnostic FNA. The evaluation noted bilateral axillary breasts, feeling hard lump on the right an irregular surface, we performed mammography, PAAF and core needle biopsy. For the diagnosis of the biopsy needle, extension studies were performed and treated with neoadjuvant therapy and surgery. Histopathological examination of the surgical specimen concluded infiltrating ductal carcinoma neuroendocrine pattern and metastatic in 2 of 18 nodes, received adjuvant therapy and remains free of disease

Research status on gastric carcinoma with neuroendocrine differentiation / 国际外科学杂志

Gastric cancer is the leading cause of death of patients with malignancy and the most common malignancy in China.Stomach is also a secretory organ,thus the carcinogenesis of human stomach always accompanied neuroendocrine differentiation.There is not a explicit definition of neuroendocrine differentiation so far,and the influence of which in gastric patients prognosis is in dispute.With the deep intensive research of gastric adenocarcinoma,diagnosis and treatment in gastric adenocarcinoma with neuroendocrine differentiation becomes increasingly concerned.

A Case of Primary Cutaneous Mucinous Carcinoma with Neuroendocrine Differentiation

Primary cutaneous mucinous carcinoma is a rare malignant tumor that originates from the deepest portion of the eccrine sweat duct. Common sites of involvement are the face and scalp. Biopsy shows dermal epithelial cell islands embedded in mucin pools separated by fibrous septae. It is difficult to differentiate this tumor histologically from metastatic adenocarcinoma. Recurrence after excision is common but metastases are rare. We report a primary cutaneous mucinous carcinoma with neuroendocrine differentiation on the right cheek of a 63-year-old man.

Significance of Neuroendocrine Cell Differentiation in Specimens from Patients with Prostate Cancer / 대한비뇨기과학회지

PURPOSE: The neuroendocrine cell(NEC) is one of the constitutional cells found in the prostate gland; these cells secret neurotransmitters. These neuroendocrine products have been associated with prostate cancer progression. We evaluated the significance of neuroendocrine differentiation(NED) in radical prostatectomy specimens. MATERIALS AND METHODS: We studied 45 patients who underwent bilateral pelvic lymphadenectomy and radical prostatectomy. The patients were classified into three groups according to their pathological stage. Group A included cases with organ confined tumors, Group B local advanced tumors and Group C cases had any T stage and lymph node metastasis. The cellular expression of chromogranin A in matched samples from the same patients was evaluated by immunohistochemical staining using commercially available monoclonal antibodies. RESULTS: Sixteen(35.6%) tumors had chromogranin A stained cells. Chromogranin A immunoreactivity was greatest in cases with lymph node involvement(75.0%) compared to those with primary prostate cancer(5.9% in group A and 37.5% in group B). Pathologically advanced tumors or tumors with the highest histological grades were associated with increased NED. The median staining score was 0 in Group A, 0 in Group B and 1 in Group C. The logistic regression analysis the odds ratio for group C cases showed a relative risk of 32.07(95% CI: 2.783-369.416) for NED compared to Group A. An increased prostate-specific antigen(PSA) and Gleason score were also associated with the NED. CONCLUSIONS: The degree of NEC immunohistochemical staining using the chromogranin A monoclonal antibody was marginally useful for predicting the outcome in prostate cancer patients after radical prostatectomy, especially in node positive patients. However, it is important to determine a therapeutic plan for patients with low PSA and internal organ metastasis.