Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive lethal malignancy, characterized by late diagnosis, aggressive growth, and therapy resistance, leading to a poor overall prognosis. Emerging evidence shows that the peripheral nerve is an important non-tumor component in the tumor microenvironment that regulates tumor growth and immune escape. The crosstalk between the neuronal system and PDAC has become a hot research topic that may provide novel mechanisms underlying tumor progression and further uncover promising therapeutic targets. In this review, we highlight the mechanisms of perineural invasion and the role of various types of tumor innervation in the progression of PDAC, summarize the potential signaling pathways modulating the neuronal-cancer interaction, and discuss the current and future therapeutic possibilities for this condition.
Humans ; Carcinoma, Pancreatic Ductal/pathology* ; Pancreatic Neoplasms/therapy* ; Signal Transduction ; Peripheral Nerves/metabolism* ; Tumor Microenvironment

Electrodiagnostic tests (EDX) is essential for the diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP). EDX could provide information about demyelinating pathology in the peripheral nerves. According to phenotypes, CIDP could be classified several phenotypes, which has different clinical manifestations, EDX could present a different distribution pattern of demyelinating lesions. In addition, EDX could be useful markers for predicting treatment response of prognosis of CIDP.
Classification ; Diagnosis ; Electrodiagnosis ; Neural Conduction ; Pathology ; Peripheral Nerves ; Phenotype ; Polyneuropathies ; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating ; Prognosis

OBJECTIVE: Because the anatomical structure of the brachial plexus is very complex, surgical treatment of tumors in this region is challenging. Therefore, a lot of clinical and surgical experience is required for successful treatment; however, many neurosurgeons have difficulty accumulating this experience owing to the rarity of brachial plexus tumors. The purpose of this report is to share our surgical experience with brachial plexus tumor with other neurosurgeons.METHODS: The records of 18 consecutive patients with brachial plexus tumors who underwent surgical treatment between January 2010 and December 2017 in a single institution were retrospectively reviewed. The surgical approach was determined according to the tumor location and size, and intraoperative neurophysiological monitoring (IONM) was used in most of cases to prevent iatrogenic nerve injury during surgery. In addition, to evaluate the differences in tumor characteristics according to pathologic diagnosis, the tumors were divided twice into two groups, based on two separate classifications, and statistical analysis was performed.RESULTS: The 18 brachial plexus tumors comprised 15 (83.3%) benign peripheral nerve sheath tumors including schwannoma and neurofibroma, one (5.6%) malignant peripheral nerve sheath tumor, one (5.6%) benign tumor of non-neural sheath origin (neurogenic cyst), and one (5.6%) metastatic tumor (papillary carcinoma). The authors analyzed relationship between tumor size/location and tumor characteristic parameters such as age, size, right-left, and pathology. There were no statistically significant differences except a tendency of bigger tumor size in young age.CONCLUSION: For a successful surgical outcome, an appropriate surgical approach is essential, and the appropriate surgical approach is determined by the location and size of the tumor. Furthermore, applying IONM may prevent postoperative complications and it is favorable option for brachial plexus tumors surgery.
Brachial Plexus Neuropathies ; Brachial Plexus ; Classification ; Diagnosis ; Humans ; Intraoperative Neurophysiological Monitoring ; Monitoring, Intraoperative ; Nerve Sheath Neoplasms ; Neurilemmoma ; Neurofibroma ; Neurosurgeons ; Pathology ; Peripheral Nerves ; Postoperative Complications ; Retrospective Studies

OBJECTIVETo study the ability of aqueous extract of Hericium erinaceus mushroom in the treatment of nerve injury following peroneal nerve crush in Sprague-Dawley rats.

METHODSAqueous extract of Hericium erinaceus was given by daily oral administration following peroneal nerve crush injury in Sprague-Dawley rats. The expression of protein kinase B (Akt) and mitogen-activated protein kinase (MAPK) signaling pathways; and c-Jun and c-Fos genes were studied in dorsal root ganglia (DRG) whereas the activity of protein synthesis was assessed in peroneal nerves by immunohistochemical method.

RESULTSPeripheral nerve injury leads to changes at the axonal site of injury and remotely located DRG containing cell bodies of sensory afferent neurons. Immunofluorescence studies showed that DRG neurons ipsilateral to the crush injury in rats of treated groups expressed higher immunoreactivities for Akt, MAPK, c-Jun and c-Fos as compared with negative control group (P <0.05). The intensity of nuclear ribonucleoprotein in the distal segments of crushed nerves of treated groups was significantly higher than in the negative control group (P <0.05).

CONCLUSIONH. erinaceus is capable of promoting peripheral nerve regeneration after injury. Potential signaling pathways include Akt, MAPK, c-Jun, and c-Fos, and protein synthesis have been shown to be involved in its action.

Agaricales ; chemistry ; Animals ; Axons ; pathology ; Female ; Ganglia, Spinal ; metabolism ; Glucans ; analysis ; MAP Kinase Signaling System ; Nerve Crush ; Nerve Regeneration ; physiology ; Peripheral Nerves ; enzymology ; physiology ; Peroneal Nerve ; physiology ; Protein Biosynthesis ; Proto-Oncogene Proteins c-akt ; metabolism ; Proto-Oncogene Proteins c-fos ; genetics ; metabolism ; Proto-Oncogene Proteins c-jun ; genetics ; metabolism ; Rats, Sprague-Dawley

PURPOSE: To evaluate the clinical features and biochemical recurrence (BCR) in prostate cancer (PCa) with high-grade prostatic intraepithelial neoplasia (HGPIN). MATERIALS AND METHODS: We retrospectively analyzed the medical records of 893 patients who underwent a radical prostatectomy for PCa between 2011 and 2012 at Asan Medical Center; 752 of these patients who did not receive neoadjuvant or adjuvant therapy and were followed up for more than 1 year were included. The cohort was divided into two groups-patients with and without HGPIN-and their characteristics were compared. The Cox proportional hazards model was used to analyze factors affecting BCR. RESULTS: In total, 652 study patients (86.7%) had HGPIN. There were no significant differences in preoperative factors between the two groups, including age (p=0.369) and preoperative prostate-specific antigen concentration (p=0.234). Patients with HGPIN had a higher Gleason score (p=0.012), more frequent multiple tumor (p=0.013), and more perineural invasion (p=0.012), but no other postoperative pathologic characteristics were significantly different between the two groups. There were no significant differences in BCR (13.0% vs. 11.5%, p=0.665) and HGPIN was not associated with BCR (p=0.745). In multivariate analysis, only the T stage (p<0.001) was associated with BCR. CONCLUSIONS: PCa patients with HGPIN have a higher Gleason score, more frequent multiple tumors, and more perineural invasion than those without HGPIN. The presence of HGPIN is not an independent predictor of BCR.
Aged ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Peripheral Nerves/pathology ; Prognosis ; Prostatectomy ; Prostatic Intraepithelial Neoplasia/*pathology/surgery ; Prostatic Neoplasms/*pathology/surgery ; Recurrence ; Retrospective Studies

Small round cell tumors (SRCTs) are a heterogeneous group of neoplasms composed of small, primitive, and undifferentiated cells sharing similar histology under light microscopy. SRCTs include Ewing sarcoma/peripheral neuroectodermal tumor family tumors, neuroblastoma, desmoplastic SRCT, rhabdomyosarcoma, poorly differentiated round cell synovial sarcoma, mesenchymal chondrosarcoma, small cell osteosarcoma, small cell malignant peripheral nerve sheath tumor, and small cell schwannoma. Non-Hodgkin\'s malignant lymphoma, myeloid sarcoma, malignant melanoma, and gastrointestinal stromal tumor may also present as SRCT. The current shift towards immunohistochemistry and cytogenetic molecular techniques for SRCT may be inappropriate because of antigenic overlapping or inconclusive molecular results due to the lack of differentiation of primitive cells and unavailable genetic service or limited moleculocytogenetic experience. Although usage has declined, electron microscopy (EM) remains very useful and shows salient features for the diagnosis of SRCTs. Although EM is not always required, it provides reliability and validity in the diagnosis of SRCT. Here, the ultrastructural characteristics of SRCTs are reviewed and we suggest that EM would be utilized as one of the reliable modalities for the diagnosis of undifferentiated and poorly differentiated SRCTs.
Chondrosarcoma, Mesenchymal ; Cytogenetics ; Diagnosis ; Gastrointestinal Stromal Tumors ; Genetic Services ; Humans ; Immunohistochemistry ; Lymphoma ; Melanoma ; Microscopy ; Microscopy, Electron ; Microscopy, Electron, Transmission* ; Neurilemmoma ; Neuroblastoma ; Neuroectodermal Tumors ; Osteosarcoma ; Pathology ; Peripheral Nerves ; Reproducibility of Results ; Rhabdomyosarcoma ; Sarcoma, Myeloid ; Sarcoma, Synovial

BACKGROUND/AIMS: Vitis vinifera grape seed extract (VVE) contains oligomeric proanthocyanidins that show antioxidant and free radical-scavenging activities. We evaluated VVE for its neuroprotective effect in prediabetic mice induce by a high-fat diet (HD). METHODS: Mice were divided into four groups according to VVE dose: those fed a normal diet (ND; n = 10), HD (n = 10), HD with 100 mg/kg VVE (n = 10), and HD with 250 mg/kg VVE (n = 10). After 12 weeks, immunohistochemical analyses were carried out using a polyclonal antibody against antiprotein gene product 9.5 (protein-gene-product, 9.5), and intraepidermal innervation was subsequently quantified as nerve fiber abundance per unit length of epidermis (intraepidermal nerve fiber, IENF/mm). RESULTS: Daily administration of VVE at doses of 100 or 250 mg/kg for 12 weeks protected HD mice from nerve fiber loss compared to untreated mice, as follows (IENF/mm): controls (40.95 +/- 5.40), HD (28.70 +/- 6.37), HD with 100 mg/kg (41.14 +/- 1.12), and HD with 250 mg/kg (48.98 +/- 7.01; p < 0.05, HD with VVE vs. HD). CONCLUSIONS: This study provides scientific support for the therapeutic potential of VVE in peripheral neuropathy in an HD mouse model. Our results suggest that VVE could play a role in the management of peripheral neuropathy, similar to other antioxidants known to be beneficial for diabetic peripheral neuropathy.
Animals ; Antioxidants/*pharmacology ; Biological Markers/blood ; Blood Glucose/drug effects/metabolism ; Body Weight/drug effects ; Diabetic Neuropathies/blood/etiology/pathology/*prevention & control ; *Diet, High-Fat ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Epidermis/*innervation ; Grape Seed Extract/*pharmacology ; Lipids/blood ; Male ; Mice ; Mice, Inbred C57BL ; Neuroprotective Agents/*pharmacology ; Peripheral Nerves/*drug effects/pathology ; Phytotherapy ; Plants, Medicinal ; Prediabetic State/blood/*drug therapy/etiology ; Time Factors ; *Vitis

OBJECTIVETo investigate the clinical significance of perineural invasion(PNI) in rectal cancer.

METHODSClinical data of 204 patients undergoing resection of low rectal cancer from January 2003 to January 2005 at the First People's Hospital of Chenzhou were analyzed retrospectively. Paraffin sections of surgical specimens from all the patients who underwent resection of low rectal cancer were stained with HE. PNI-positive was defined as infiltration of carcinoma cell into the perineurium or neural fascia. The association of PNI with clinicopathologic features and prognosis of rectal cancer was analyzed.

RESULTSPNI was positive in 31.9%(65/204) of the patients. The tumor size, depth of invasion, lymph node metastasis, TNM stage, tumor growth pattern, histologic grade, tumor resection were significantly associated with PNI. The overall survival time of the PNI-positive patients was shorter than that of the PNI-negative patients[(43.8±1.5) months vs.(57.2±1.5) months, P<0.01]. Furthermore, the overall survival time of the PNI-positive stage II( patients was shorter than that of the stage III( patients [(46.5±3.2) months vs. (55.7±1.2) months, P<0.05].

CONCLUSIONPNI can be used as one of the indicators to predict the prognosis of patients with rectal cancer.

Female ; Humans ; Male ; Neoplasm Invasiveness ; Peripheral Nerves ; pathology ; Prognosis ; Rectal Neoplasms ; diagnosis ; pathology ; Retrospective Studies

OBJECTIVETo study the role of CYP2E1 in the protective effects and mechanism of garlic oil (GO) on the peripheral nerve injuries induced by n-hexane.

METHODSFifty male Wistar rats were randomly divided into five groups (n = 10): the control, the GO (80 mg/kg) control, the n-hexane (2000 mg/kg) model, the low dose GO (40 mg/kg) plus n-hexane, and the high dose GO (80 mg/kg) plus n-hexane groups. All rats were treated by intragastric administration 6 times a week for 10 weeks. The gait scores were determined every two weeks for monitoring the peripheral neurotrosis. All rats were sacrificed in 10 weeks, the activities and expression levels of hepatic CYP2E1 and 2, 5-HD in serum were examined.

RESULTSAs compared with control group, the content and activity of hepatic CYP2E1 in GO control group reduced by 83.1% and 48.3% respectively (P < 0.01), the content and activity of hepatic CYP2E1 in model group increased by 112.5% and 72.2% respectively (P < 0.01). As compared with model group, the contents of hepatic CYP2E1 in low dose and high dose GO groups reduced by 32.9% and 39.1% respectively, the activities of hepatic CYP2E1 in low dose and high dose GO groups reduced by 27.4% and 44.5% respectively (P < 0.01); the contents of serum 2,5-HD in low dose and high dose GO groups reduced by 47.7% and 78.7% respectively (P < 0.01). The gait scores in model, low dose and high dose GO groups were significantly lower than that in control group, but the gait scores in low dose and high dose GO groups were significantly lower than that in model group (P < 0.05).

CONCLUSIONGarlic oil can effectively reduce the peripheral neurotrosis induced by n-hexane due to the decreased content and activity of hepatic CYP2E1, resulting in the reduced formation of 2, 5-HD from n-hexane.

Animals ; Cytochrome P-450 CYP2E1 ; metabolism ; Garlic ; Hexanes ; toxicity ; Liver ; drug effects ; enzymology ; Male ; Peripheral Nerves ; drug effects ; pathology ; Plant Oils ; pharmacology ; Rats ; Rats, Wistar

OBJECTIVETo investigate the association between perineural invasion(PNI) and clinicopathological factors and the effect of PNI on overall survival in patients with gastric carcinoma.

METHODSA total of 178 patients with gastric carcinoma from January 2004 to May 2008 were analyzed retrospectively. Paraffin sections of surgical specimens from all the patients who underwent gastric resection were stained with laminin. PNI-positive was defined as infiltration of carcinoma cells into the perineurium or neural fascicles. The association of PNI with clinicopathologic features and prognosis of gastric carcinoma was studied.

RESULTSPNI was positive in 78 of 178 patients(43.8%). The proportions of T stage, lymph node metastasis and TNM stage were significantly higher in PNI-positive group than those in PNI-negative group(all P<0.01). The PNI positive rate was correlated with the depth of gastric mural invasion and clinical stage. The overall survival in PNI-positive group was significantly lower than that in PNI-negative group by univariate analysis(P<0.01). The mean survival of PNI-positive patients(28.6 months) was significantly shorter than that of PNI-negative patients (44.3 months, P<0.01), which was also influenced by pN stage, pT stage, and clinical stage(P<0.01). By multivariable Cox proportional hazards model of overall survival, the positivity of PNI appeared to be an independent prognostic factor (hazards ratio=2.257, 95% CI:1.268-4.019, P=0.006).

CONCLUSIONSPNI is associated with the degree of malignancy in gastric cancer. PNI can be a candidate of new prognostic factor.

Aged ; Carcinoma ; pathology ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Peripheral Nerves ; pathology ; Prognosis ; Retrospective Studies ; Stomach ; pathology ; Stomach Neoplasms ; pathology