ObjectiveTo explore the mechanisms of perineural invasion (PNI) in pancreatic cancer so as to find a new treatment for pancreatic cancer. MethodsThe literatures on PNI, neurotropism, nerve-tumor microenvironment and nerve growth factor in pancreatic cancer were reviewed and the mechanisms of PNI were summarized. ResultsThe rich innervation of pancreatic tissue itself and the minute slits within perineural structure were the anatomic basis of PNI. Tumor cells expressed neural antigens were the pathological basis of PNI. Tumor-nerve microenvironment and nerve growth factor family and themselves receptors might play an important molecular role in PNI. However, tumor cells expressed neural antigens were not only closely related to the PNI, but also the interaction between tumor cells and nerves played an important role in PNI. ConclusionsThe detailed mechanisms of PNI are extremely complex and controversial up to today. However, it is possible to search a new therapeutic target in pancreatic cancer according to the mechanisms of PNI.
Objective To further comprehend the definition， molecular mechanism， and clinical significance of perineural invasion （PNI） so as to explore new therapy for the tumors. Methods The literatures about the definition， molecular mechanism， and clinical study of PNI were reviewed and analyzed. Results At present， widely accepted definition of PNI was that at least 33% of the circumference of the nerve should be surrounded by tumor cells or tumor cells within any of three layers of the nerve sheath. The newest theory on molecular mechanism of PNI was that PNI was more like infiltration， invasion， not just diffusion. “Path of low-resistance” and “Reciprocal signaling interactions” were the main theories. More recently， the studies had demonstrated that “Reciprocal signaling interactions” could more clearly explain the mechanism of PNI. Stromal elements， including fibroblasts， seemed to play a key role in the complex signaling interactions driving PNI. Neurotrophins and axonal guidance molecules had been implicated in promoting the progress of PNI. PNI was a prognosis index in the cancers of the head and neck， stomach， pancreas， colon and rectum， and prostate， which was positive indicated that the patients would have a poor prognosis and a low 5-year survival rate. Conclusions The mechanism of PNI is very complex， and its clear mechanism is still undefined. Keeping on researching the mechanism of PNI could provide theoretical foundation to disclose the mechanism and the therapy of PNI.
Objective To establish perineural invasion xenograft model of hilar cholangiocarcinoma. Methods The cultured cells of cholangiocarcinoma cell line QBC939 were inoculated subcutaneously in the nude mice so as toestablish primary subcutaneous model of cholangiocarcinoma. The primary tumor tissues were inoculated intraperitoneallyaround the liver in the nude mice so as to establish the second generation intraperitoneal xenograft model. The successful xenografted tumor tissues were obtained for anatomical and pathological examinations. Results The tumor formation rate of primary subcutaneous xenograft of hilar cholangiocarcinoma was 100% （5/5）， and no nerve infiltration was observed. The tumor formation rate of the second generation intraperitoneal xenograft was 45% （9/20）， and two mice （2/9， 22%） manifested nerve infiltration. The rate of nerve infiltration was 10% （2/20）， and the tumor cells had different size and diversity， irregular shape， low differentiation， decreased cytoplasm and nucleus karyomegaly， visible atypical and fission phase， and no obvious gland tube structure by pathological examination. Conclusions Hilar cholangiocarcinoma cell has the particular features of perineural invasion， it is a good experiment platform for researching the mode and biological characteristics of perineural invasion of hilar cholangiocarcinoma by applicated QBC939 cell lines to establish the perineural invasion xenograft model of cholangiocarcinoma.
ObjectiveTo summarize the incidence, patterns and laws of perineural invasion, and explore the path and the influencing factors of perineural invasion in hilar cholangiocarcinoma. MethodsA clinicopathologic study was conducted on sections from 52 patients with hilar cholangiocarcinoma to summarize the incidence and patterns of perineural invasion. The relationship of perineural invasion to lymph node metastasis, serum CA19-9, CEA, total bilirubin (TBIL) level, Bismuth-Corllet classification, or tumor penetration depth of bile duct walls was analyzed by association analysis. ResultsThe overall incidence of perineural invasion was 90.38% (47/52). However, the incidences of perineural invasion had no significant differences among various differentiated adenocarcinoma groups (P > 0.05). The incidences of perineural invasion were not correlated with the lymph node metastasis, serum CA19-9, CEA, TBIL level, and Bismuth-Corlette classification (P > 0.05), which was correlated with the tumor penetration depth of bile duct walls (P < 0.01). There were four patterns of perineural invasion, sequenced them according their incidences from high to low as follows: typeⅡ> typeⅢ> typeⅣ> typeⅠ. The pattern of perineural invasion was correlated with the degree of tumor differentiation (χ2=31.04, P < 0.01). ConclusionsThe incidence of perineural invasion is very high in hilar cholangiocarcinoma. The patterns of perineural invasion are similar in the same patient, and a variety of invasion patterns might coexist. While the pattern of perineural invasion is correlated with the degree of tumor differentiation. The incidence of perineural invasion is correlated with the tumor penetration depth of bile duct walls.
Objective To systematically review the prognostic value of perineural invasion (PNI) for patients with early-stage cervical cancer. Methods We searched PubMed, EMbase, The Cochrane Library (Issue 10, 2016), CNKI, WanFang Data, CBM and VIP databases to collect case-control studies about prognostic value of PNI in cervical cancer from inception to October, 2016. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then meta-analysis was performed by using RevMan 5.3 software. Results Seven case-control studies from eight articles involving 1 218 patients were included. The results of meta-analysis showed that: (1) On Cox's model multivariate analysis, PNI was not identified as an independent risk factor for disease free survival (DFS) (HR=0.73, 95%CI 0.33 to 1.58,P=0.42) or overall survival (OS) (HR=0.89, 95%CI 0.41 to 1.94,P=0.77) with no significant difference; (2) On Kaplan-Meier-curves, DFS (HR=1.86, 95%CI 1.20 to 2.88,P=0.006) and OS (HR=2.43, 95%CI 1.63 to 3.62,P<0.000 1) were both significantly decreased in patients with PNI positive group. Conclusion PNI represents a decreasing disease-free survival and overall survival in patients with early-stage cervical cancer, and is one of the poor prognosis factors which be informed management decisions regarding adjuvant therapy. However, there is no evidence that PNI is an independent factor affecting the prognosis. In view of the limitation of the studies, a large sample prospective controlled trial is warranted to verify the above conclusion.