UNASSIGNED: The large cell neuroendocrine carcinoma (LCNEC) of the urinary bladder is a rare malignancy. With its high aggressiveness and poor prognosis, the disease is often accompanied by metastasis or recurrence. The lack of specific clinical manifestations and imaging features causes considerable challenges for clinical diagnosis and treatment.
UNASSIGNED: We report a case of LCNEC of the urinary bladder. The patient was a 79-year-old male admitted to our hospital with recurrent episodes of asymptomatic gross hematuria. Based on the computed tomography (CT) scan findings, our patient presented with a bladder mass displaying invasion into the serosal layer, suggestive of muscle involvement and indicative of malignancy. The patient received a radical cystectomy, and the postoperative pathology confirmed primary, pure LCNEC of the urinary bladder. We gave him 16 cycles of toripalimab immunotherapy. As of follow-up, the patient was alive, and periodic CT reexamination showed no evidence of recurrence.
UNASSIGNED: We reviewed domestic and foreign literature and found no explicit treatment protocols exist for the disease. Surgical resection combined with chemotherapy were the most common treatments. Herein, we reported the first case of primary, pure LCNEC of the urinary bladder treated by radical cystectomy combined with pure immunotherapy, achieving sustained remission, which provides a new idea for the immunotherapy and integrative treatment of the disease.

Background: Large cell neuroendocrine carcinoma (LCNEC) of the liver, gallbladder, pancreas, and ampulla is rare and usually arises in case reports, and thus to date, no studies have well described the treatment options and outcomes of those patients. Methods: The data of 108 patients diagnosed as hepatopancreatobiliary and ampulla LCNEC between 2004 and 2015 were retrieved from the surveillance, epidemiology, and final results. Results: In the entire cohort, the median overall survival (OS) was 10 months. For nonmetastatic patients, the median OS was 32 months for surgery of the primary tumor alone (n = 17), 19 months for surgery of the primary tumor and adjuvant therapy (n = 19), and 1 month for nonsurgical treatment (n = 8). For metastatic patients, the median OS was 14 months for patients who received surgery of the primary tumor with and without adjuvant therapy (n = 16), 9 months for patients undergoing adjuvant treatment alone (n = 30), and 1 month for patients who had no treatment (n = 16). Multivariate analysis revealed that surgery of the primary tumor was an independent factor for improved survival. Conclusions: This disease offers a very poor prognosis despite aggressive treatment. Radical resection is the first choice for resectable tumors, whereas surgical resection of the primary tumor plus adjuvant therapy might represent a valid option for metastatic disease. However, further studies are needed to confirm this.

BACKGROUND: Large cell neuroendocrine carcinomas (LCNEC) are rare pulmonary malignancies. Reported survival rates are heterogeneous and the optimal therapeutic strategy is still debated. The prognosis of LCNEC is generally inferior compared to other non-small lung cancers. In early stages, surgery is recommended but might not be sufficient alone.
METHODS: We retrospectively analyzed all consecutive LCNEC patients operated at three institutions with curative intent between May 2005 and January 2017. Data retrieved from individual clinical databases were analyzed with the aim to identify prognostic parameters.
RESULTS: A total of 251 patients with LCNEC underwent curative intent surgery during the observation period. The median age was 64 years, 156 patients (62.2%) were male and 88.4% were smokers. The pathologic AJCC stage was I in 136 patients, II in 77, III in 33, and IV in 5 patients. Median follow-up was 26 months. Lymphatic vessel invasion (P=0.031) was identified as significant prognostic factor by multivariable analysis. There was a trend towards decreased survival in patients with blood vessel invasion (P=0.067). Even in earlier tumor stages, adjuvant chemotherapy had a positive effect on survival. The overall 1-, 3- and 5-year survival rates were 79.2%, 48.6% and 38.8% respectively.
CONCLUSIONS: Lymphatic invasion (L1) is an independent prognostic factor. Surgery in LCNEC is beneficial in early tumor stages and platinum-based adjuvant chemotherapy may help in achieving better long-term outcomes resulting in most obvious survival differences in stage Ib.

Primary neuroendocrine carcinomas of the gallbladder and biliary tract are rare, with pure large cell neuroendocrine carcinomas (LCNEC) being exceedingly rare and with a particularly poor prognosis.
We performed a review of published data on biliary tract large cell neuroendocrine carcinomas in PubMed.
Preliminary search revealed over 2000 results but we found only 12 cases of pure large cell neuroendocrine carcinomas of biliary tract noted in literature to date. Because it commonly presents with non-specific symptoms of abdominal pain and jaundice, diagnosis is made after resection with histo-pathological and immunohistochemical analysis. These cancers are particularly aggressive with high recurrence rates, most often presenting with metastasis to regional lymph nodes and/or the liver resulting in a poor prognosis. Overall, complete surgical excision with systemic chemotherapy is the treatment mainstay. If the cancer is unresectable due to multiple metastases, medical management with systemic chemotherapy is the primary treatment modality.
The prognosis of hepatobiliary LCNEC remains poor with median survival of only 11 months from initial diagnosis. Studies focusing on high grade neuroendocrine carcinoma are needed to enhance our understanding of biology and therapeutics in this rare but aggressive cancer.