Neuroendocrine survival

The survival of all species depends on the integrity of its reproductive system. Reproductive toxicology may be defined as the study of the effects of physical and chemical agents on the reproductive and neuroendocrine systems of adult males and females, as well as those of the embryo, fetus, neonate, and prepubertal animal. This chapter focuses primarily on the potential sites of toxic insult in the reproductive systems of adult mammals, the biochemical mechanisms of such toxicants, and the manifestations that may result. The latter part of the above definition is a subspecialty of developmental toxicology (Chapter 34) and is discussed only in brief. 

Model. Blood digestion plays a key role in the survival of vector arthropods and in the transmission of many important diseases such as malaria, dengue and Lyme disease (21.22). Collating these observations, a model for the control of trypsin biosynthesis in the mosquito is proposed. After the blood meal the midgut epithelial cells start to S3mthesize trypsin in concert with the neuroendocrine system that synthesizes oostatic hormone, as was proposed for Rhodnius by Davey and Kunster (11), which accumulates in the developing ovary as a prohormone. The... 

Morbidity should not exceed 30%. Lethality is between 0-3%. The 5-year survival rate following RO resection in metastatic colorectal carcinoma is 20-40%, in neuroendocrine tumours 90-100%, in malignant melanoma 15-25%, and in breast cancer 10-30%. Prognosis is poor in metastasizing renal cell carcinoma and in gastric or pancreatic carcinoma. Both R1 and R2 resection worsen the prognosis to the same extent. 

Systemic chemotherapy is usually not indicated in non-colorectal liver metastases due to lack of response. The systemic administration of cytostatics (also in combination) possesses the status of palliative therapy. However, in metastatic neuroendocrine tumours, a combination of octreotide -i- IFN had a positive effect on the survival time. Systemic chemotherapy produced remission rates of up to 60%. (320) In metastatic breast cancer, systemic chemotherapy is indicated, usually in combination with hormonal and immune therapy. (316, 342) In metastatic gastric carcinoma, palliative chemotherapy can achieve a remission rate of up to 40%, with a slight extension of survival time. 

Bostwick DG, Qian J, Pacelli A, et al. Neuroendocrine expression in node positive prostate cancer correlation with systemic progression and patient survival. J Urol. 2002 168 1204. 

Jakobs et al. [35] reported results on 39 treated patients (17 women, 22 men) that included colorectal cancer, metastatic breast cancer, hepatocellular carcinoma, neuroendocrine tumors, and a mixed group composed of metastatic pancreatic cancer, carcinoma of unknown primary, cholangiocellular carcinoma, thymus carcinoma, malignant melanoma, and choroid melanoma. In this mixed tumor group, two patients were lost for follow-up immediately after treatment. Two patients died before first follow-up 3 months after SIRT (one patient with choroid melanoma and one with carcinoma of unknown primary). However, at the first followup 3-4 months after SIRT, five of six patients presented with stable disease or partial response. The same applied for two of three patients at the followup at 5-6 months. Stable disease was noted in two of three patients at 10-11 months after SIRT. The median time to progression was 8 months (range 3-11 months), although two patients were lost and two died before first follow-up and were therefore not included in this analysis. The median survival was 2.2 months. 

Another area worthy of future investigation is the treatment of non-colorectal, non-neuroendocrine cancers metastatic to the liver. Often referred to as mixed neoplasia, these refer to patients with liver-dominant metastatic disease to the liver from various primaries (breast, melanoma, pancreas, and lung). Although several reports have been described, controlled phase II studies using time-to-progression, tumor response, or progression-free-survival would be clinically relevant given the dearth of options for some of these patients [51-54]. 

DaSilva JO, Amorino GP, Casarez EV, Pemberton B, Parsons SJ. Neuroendocrine-derived peptides promote prostate cancer cell survival through activation of IGF-IR signaling. Prostate. 2013 73 801-12. doi 10.1002/pios.22624. 

Chemoembolization Moertel et al. (1994) have chronicled their 10 year experience in 111 patients with neuroendocrine hepatic metastases, usually hypervascular, receiving vascular occlusion therapy by a variety of methods. A total of 71 patients also received subsequent alternating chemotherapy regimens (dacarbazine + doxorubicin and streptozotocin + 5-fluorouracil). Objective regression rates of 60% with vascular occlusion alone and 80% with sequential therapy of vascular occlusion and chemotherapy were observed. A median survival time of 37 months was experienced in patients with islet cell carcinoma and 49 months with carcinoid hepatic metastases. Repeated embolizations were preferred. 

Hepatic artery embolotherapy (with or without chemotherapeutic agent) has been established as an effective method in long-term control of hormonal symptoms and pain, and in the reduction of tumor growth in patients who are not suitable for surgical excision and refractory to medical therapy [48, 61-65]. Recently, Roche and coworkers proposed the use of chemoembolization as the primary line of treatment in patients with unresectable neuroendocrine liver metastases [64]. The authors reported a 90% symptomatic and a 75% hormonal response in comparison to the 30%-75% response rate with somatostatin analogues, 43% objective tumor reduction in comparison to 5%-15% with somatostatin analogues, and a 5- and 10-year survival of 83% and 56%, respectively, which are considerably better than the previously reported survival rates of 0%-40% in patients who received only conventional medical treatment [2,3,9,10]. 

Chen H, Hardacre JM, Uzar A, et al. (1998) Isolated liver metastases from neuroendocrine tumors does resection prolong survival J Am Coll Surg 187 88-93... 

Sarmiento JM, Heywood G, Rubin J, et al. (2003) Surgical treatment of neuroendocrine metastases to the liver a plea for resection to increase survival. J Am Coll Surg 197 29-... 

Lifetable analysis of gastric carcinoids in the SEER (1973-1991) file. The overall observed 5-year survival rate is 48.6%. This grouping may, however, reflect the outcome of a variety of different types of gastric neuroendocrine tumors. Many of the tumors were probably of the sporadic type (type III), whose prognosis is very much worse than the lesions associated with hypergastrinemia (types I and II). 

RF ablation also appears to be a safe and effective technique for the treatment of patients with systemic symptoms from neuroendocrine metastases, although an effect on survival has not been established in this clinical setting (Henn et al. 2003). 

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