Pancreatic Neuropathy and Neuropathic Pain-A Comprehensive Pathomorphological Study of 546 Cases
Pancreatic Neuropathy and Neuropathic Pain-A Comprehensive Pathomorphological Study of 546 Cases
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DOI：
10.1053/j.gastro.2008.09.029
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发表时间：
2009-01-01
期刊：
影响因子：
29.4
通讯作者：
Friess, Helmut
中科院分区：
文献类型：
--
作者：
Ceyhan, Gueralp O.;Bergmann, Frank;Friess, Helmut
背景与目的：慢性胰腺炎（CP）和胰腺腺癌（PCa）的特点是胰内神经改变和疼痛。我们的目的是：(a) 调查诸如胰腺神经炎、神经密度增加和肥大等神经性改变是否仅在 CP 中出现，或者它们是否在其他胰腺疾病中也很明显，(b) 研究恶性胰腺肿瘤中神经癌细胞侵袭的可能变化，以及 (c) 探索这些神经性改变是否会导致疼痛感。方法：研究了 PCa（n = 149）、CP（n = 141）、胰腺肿瘤（PTm）（包括浆液性/粘液性囊腺瘤、侵袭性/非侵袭性导管内肿瘤）的神经病理性变化。乳头状粘液性肿瘤、良性/恶性神经内分泌肿瘤、壶腹癌 (n = 196) 和正常胰腺 (n = 60)。结果与 GAP-43 表达、组织炎症、胰神经炎、神经侵袭、纤维化、结缔组织增生、疼痛和患者生存相关。结果：仅在 PCa 和 CP 中检测到神经密度增加和肥大，并且与 GAP-43 过度表达和腹痛密切相关。胰腺神经炎的严重程度在 PCa 中最为严重，并且与神经密度和肥大的变化密切相关。神经癌细胞侵袭的侵袭性在 PCa 中最为突出，并且与神经病变、结缔组织增生和疼痛有关。严重且持久的疼痛与 PCa 患者的不良预后密切相关。结论：神经密度增强和肥大只是所有研究的胰腺疾病中 CP 和 PCa 的典型特征。这种神经性变化，包括炎症和/或癌细胞对神经的损害，似乎会增强并产生胰腺神经性疼痛。
Background & Aims: Chronic pancreatitis (CP) and pancreatic adenocarcinoma (PCa) are characterized by intrapancreatic neural alterations and pain. Our aims were to: (a) Investigate whether neuropathic changes like pancreatic neuritis, increased neural density, and hypertrophy are phenomena only in CP or whether they are also evident in other pancreatic disorders as well, (b) study possible variations in neural cancer cell invasion among malignant pancreatic tumors, and (c) explore whether these neuropathic changes contribute to pain sensation. Methods: Neuropathic changes were studied in PCa (n = 149), in CP (n = 141), in pancreatic tumors (PTm) including serous/mucinous cystadenomas, invasive/noninvasive intraductal. papillary mucinous neoplasias, benign/malignant neuroendocrine tumors, ampullary cancers (n = 196), and in normal pancreas (n = 60). The results were correlated with GAP-43 expression, tissue inflammation, pancreatic neuritis, neural invasion, fibrosis, desmoplasia, pain, and patient survival. Results: Increased neural density and hypertrophy were only detected in PCa and CP and were strongly associated with GAP-43 over expression and abdominal pain. The severity of pancreatic neuritis was strongest in PCa and was closely linked to changes in neural density and hypertrophy. The aggressiveness of neural cancer cell invasion was most prominent in PCa and was related to neuropathic changes, desmoplasia, and pain. Severe and enduring pain were strongly associated with poor prognosis in PCa patients. Conclusions: Enhanced neural density and hypertrophy are only typical features of CP and PCa among all investigated pancreatic disorders. Such neuropathic changes, including damage to nerves by inflammatory and/or cancer cells, seem to enhance and generate pancreatic neuropathic pain.