NADPH-diaphorase histochemistry was combined with demonstration of acetylcholinesterase and immunocytochemistry for calcitonin gene-related peptide to study esophageal innervation in the rat. Most of the myenteric neurons stained positively for NADPH-diaphorase, as did numerous varicose nerve fibers in the myenteric plexus, among striated muscle fibers, around arterial blood vessels, and in the muscularis mucosae. A majority of motor endplates (as demonstrated by acetylcholinesterase histochemistry or calcitonin gene-related peptide immunocytochemistry) were associated with fine varicose NADPH-diaphorase-positive nerve fibers. Analysis of brainstem nuclei, sensory vagal, spinal, and sympathetic ganglia in normal and neonatally capsaicin-treated rats, and comparison with anterogradely labeled vagal branchiomotor, preganglionic and sensory fibers led to the conclusion that NADPH-diaphorase-positive fibers on motor endplates originate in esophageal myenteric neurons. No association of NADPH-diaphorase-positive nerve fibers with motor endplates was found in other organs containing striated muscle. These results suggest extensive, presumably nitrergic, co-innervation of esophageal striated muscle fibers by enteric neurons. Thus, control of peristalsis in the esophagus of the rat may be more complex than hitherto assumed.

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Background Colorectal high-grade neuroendocrine carcinomas (HGNEC) are a rare but aggressive group of malignancies without standard management recommendations. Methods We retrospectively reviewed the records of 100 consecutive patients with histologically confirmed colorectal HGNEC diagnosed at MD Anderson Cancer Center between 1991 and 2013. Results In our cohort, most tumors (89 %) were small cell carcinoma, and most (60 %) involved the sigmoid or the anorectal regions. Sixty-four patients (64 %) presented with metastatic disease at diagnosis. Striking epidemiological and clinical differences between those established in small cell lung cancer (SCLC) and our cohort were noted, including significantly lower rates of smoking and lower risk of bone, brain metastases. Over 30% of the tumors were found associated with an adenoma. Median overall survival (OS) of the cohort was 14.7 months, with 2-year and 5-year OS rates of 23 % and 8 %, respectively. In patients with localized disease, multimodality therapy was associated with a trend toward improved median OS (20.4 versus 15.4 months, p = 0.08). Metastases at presentation (OS 20.63 vs 8.7 months; localized vs metastatic disease at presentation, p < 0.001) and elevated LDH were strongly associated with a worse outcome. Conclusion In comparison to SCLC, less than half patients with colorectal HGNEC have history of smoking; metastatic patterns are also different between the two cancers. Nevertheless, HGNEC also has a aggressive biology with the rectum being the most common site of origin. For localized disease, multimodality approach seems to be associated with better outcomes, while systemic chemotherapy is the mainstay of treatment for advanced disease.

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