Mechanism of Cu entry into the brain:many unanswered questions

Brain tissue requires high amounts of copper(Cu)for its key physiological processes,such as energy production,neurotransmitter synthesis,maturation of neuropeptides,myelination,synaptic plasticity,and radical scavenging.The requirements for Cu in the brain vary depending on specific brain regions,cell types,organism age,and nutritional status.Cu imbalances cause or contribute to several life-threatening neurologic disorders including Menkes disease,Wilson disease,Alzheimer’s disease,Parkinson’s disease,and others.Despite the well-established role of Cu homeostasis in brain development and function,the mechanisms that govern Cu delivery to the brain are not well defined.This review summarizes available information on Cu transfer through the brain barriers and discusses issues that require further research.

Effects of obstructive sleep apnea on retinal microvasculature

AIM:To detect retinal microvascular variations in obstructive sleep apnea syndrome patients.METHODS:This prospective,observational case-control study included healthy controls and patients with mild,moderate,and severe obstructive sleep apnea syndrome.Vascular parameters,foveal avascular area,and flow areas in macula-centered,6.00×6.00 mm2 scan size optical coherence tomography angiography images were compared.RESULTS:The control group had the highest whole image,parafoveal,and perifoveal vessel density among the groups in both superficial and the deep capillary plexus(all P<0.05).Rapid eye movement sleep apnoea-hypopnoea index was reversely correlated with whole(Rho=-0.195,P=0.034),parafoveal(Rho=-0.242,P=0.008),perifoveal(Rho=-0.187,P=0.045)vessel density in the superficial capillary plexus,and whole(Rho=-0.186,P=0.046),parafoveal(Rho=-0.260,P=0.004),perifoveal(Rho=-0.189,P=0.043)vessel density in the deep capillary plexus,though the mean and non-rapid eye movement sleep apnoeahypopnoea index related with only parafoveal vessel density in the superficial capillary plexus(Rho=-0.213,P=0.020;Rho=-0.191,P=0.038)and the deep capillary plexus(Rho=-0.254,P=0.005;Rho=-0.194,P=0.035).CONCLUSION:This study shows decreased vessel density and its reverse correlation with the apnoea-hypopnoea index in patients with obstructive sleep apnea syndrome.

Color Doppler ultrasound imaging in varicoceles: Is the difference in venous diameter encountered during Valsalva predictive of palpable varicocele grade?

Objective:The clinical grading system for varicoceles is subjective and dependent on clinician experience.Color Doppler ultrasound(US)has not been standardized in the diagnosis of varicoceles.We aimed to determine if US measurement of varicocele could be predictive of World Health Organization(WHO)varicocele grade.Methods:Men who presented for either scrotal pain or infertility to a tertiary men’s health clinic underwent physical examination,and varicoceles were graded following WHO criteria(0Zsubclinical,1,2,3).US was used to measure largest venous diameter in the pampiniform plexus bilaterally at rest and during Valsalva maneuver.Receiver operator characteristic curve analysis was used to determine if resting diameter,diameter during Valsalva,or change in diameter between at rest and during Valsalva provided the highest sensitivity and specificity for determining clinical grade.Threshold values for diameter were determined from these receiver operator characteristic curves.Results:A total of 102 men(50 with clinical varicocele and 52 with subclinical varicocele)were included.Diameter at rest was the best ultrasonographic discriminator between subclinical and clinical varicoceles(area under the curve[AUC]Z0.67)with a diameter threshold of 3.0 mm(sensitivity 79%,specificity 42%).Diameter during Valsalva had the greatest AUC for determining clinical Grades 1 versus 2(AUCZ0.57)with diameter threshold of 5.7 mm(sensitivity 71%,specificity 33%).For differentiating between Grades 2 and 3,diameter at rest had the greatest AUC of 0.65 with a threshold of 3.6 mm(sensitivity 71%,specificity 58%).Conclusion:Our results corroborate other studies that have shown a weak correlation between US and clinical grading.The use of diameter during Valsalva was less predictive than diameter at rest and was only clinically significant in differentiating between Grade 1 and 2 varicocele.A standardized method for determining clinically relevant varicoceles on US would allow for improved patient counseling and clinical decision-making.

Choroid plexus imaging to track neuroinflammation—a translational model for mouse and human studies

The choroid plexus(ChP)is a highly vascularized and secretory tissue in each of the brain ventricles that represents the key structure between the blood and the cerebrospinal fluid(CSF).Besides its essential role in CSF production and brain waste clearance pathways,the ChP also contributes to the regulation of central nervous system(CNS)immunosurveillance(Ghersi-Egea et al.,2018).Indeed,the ChP forming the blood-CSF barrier(BCSFB)regulates the entry of immune cells and solute molecules into the brain and vice versa.When antigen-specific,autoreactive immune activation occurs in the periphery,inflammatory cells migrate through the brain barriers towards the CNS(Strominger et al.,2018),initiating neuroinflammatory diseases such as multiple sclerosis(MS).

Motor neuron-specific RhoA knockout delays degeneration and promotes regeneration of dendrites in spinal ventral horn after brachial plexus injury

Dendrites play irreplaceable roles in the nerve conduction pathway and are vulnerable to various insults.Peripheral axotomy of motor neurons results in the retraction of dendritic arbors,and the dendritic arbor can be re-expanded when reinnervation is allowed.RhoA is a target that regulates the cytoskeleton and promotes neuronal survival and axon regeneration.However,the role of RhoA in dendrite degeneration and regeneration is unknown.In this study,we explored the potential role of RhoA in dendrites.A line of motor neuronal conditional knockout mice was developed by crossbreeding HB9~(Cre+)mice with RhoA~(flox/flox)mice.We established two models for assaying dendrite degeneration and regeneration,in which the brachial plexus was transection or crush injured,respectively.We found that at 28 days after brachial plexus transection,the density,complexity,and structural integrity of dendrites in the ventral horn of the spinal cord of RhoA conditional knockout mice were slightly decreased compared with that in Cre mice.Dendrites underwent degeneration at 7 and 14 days after brachial plexus transection and recovered at 28–56 days.The density,complexity,and structural integrity of dendrites in the ventral horn of the spinal cord of RhoA conditional knockout mice recovered compared with results in Cre mice.These findings suggest that RhoA knockout in motor neurons attenuates dendrite degeneration and promotes dendrite regeneration after peripheral nerve injury.

Changes of retinal vessel density in low to moderate myopic eyes with orthokeratology evaluated by optical coherence tomography angiography

AIM:To explore the effect of orthokeratology(OK)fitting on retinal vessel density in low to moderate myopia adolescents by using optical coherence tomography angiography.METHODS:Children aged 10 to 14y with a cycloplegic spherical equivalent refraction of−0.50 diopter(D)to−5.00 D and astigmatism with more than−1.50 D were recruited.The enrolled adolescents were divided into OK group and spectacle group.During regular followup,adolescents were measured respectively at pre-wear,1,3,and 6mo after treatment.The follow-up included uncorrected distance visual acuity(UDVA),axial length(AL),superficial capillary plexus density(SCPD),deep capillary plexus density(DCPD),central retinal thickness(CRT),foveal avascular zone area(FAZ-A),foveal avascular zone perimeter(FAZ-P)and foveal vessel density in a 300-μmwide region around foveal avascular zone(FD-300).The collected data were analyzed using statistical methods.RESULTS:By one month,SCPD significantly increased in the fovea and superior retina,and DCPD significantly increased inferiorly in OK group compared to spectacle group(P<0.05).By three months,there were significant increases in SCPD in the fovea and inferior retina,and DCPD in the parafovea,superior,and inferior retina in OK group(P<0.05),while the increase in SCPD and DCPD in the fovea were observed by six months(P<0.05).The FD-300 significantly increased at every follow-up in OK group compared to spectacle group(P<0.05).No significant differences in the CRT,FAZ-A and FAZ-P and FD-300 were observed between two groups(P>0.05).OK group showed a significant improvement in UDVA after wearing OK,compared to spectacle group(P<0.01),while the AL did not show a significant difference between two groups(P>0.05).CONCLUSION:Short-term OK worn can increase local retinal vessel density in adolescents with low-to-moderate myopia.

Hemodynamic instability following intravenous dexmedetomidine infusion for sedation under brachial plexus block: Two case reports

BACKGROUND Dexmedetomidine(DMED)is frequently used as a sedative in several medical fields.The benefits of DMED include enhanced quality of regional anesthesia,prolonged analgesia,and postoperative opioid-sparing when administered intravenously or perineurally in combination with regional anesthesia.Severe hemodynamic complications,such as profound bradycardia and hypotension,can occur after DMED administration in critically ill patients or overdosage;however,there are few reports of complications with DMED administration following brachial plexus block(BPB).CASE SUMMARY We present two cases of hemodynamic instability that occurred following the initial loading of DMED under supraclavicular BPB.A healthy 29-year-old man without any medical history showed profound bradycardia after receiving a loading dose of DMED 0.9μg/kg for 9 min.DMED administration was promptly stopped,and after receiving a second dose of atropine,the heart rate recovered.A 62-year-old woman with a history of cardiomyopathy became hypotensive abruptly,requiring the administration of inotrope and vasopressors after receiving a reduced loading dose of 0.5μg/kg for 10 min.Half of the recommended loading dose of DMED was administered due to the underlying heart dysfunction.Decrea-sed blood pressure was maintained despite the intravenous administration of ephedrine.With continuous infusion of dopamine and norepinephrine,the vital signs were maintained within normal ranges.Inotropic and vasopressor support was required for over 6 h after the initial loading dose of DMED.CONCLUSION DMED administration following BPB could trigger hemodynamic instability in patients with decreased cardiac function as well as in healthy individuals.

Late brachial plexopathy after a mid-shaft clavicle fracture:A case report

BACKGROUND Clavicle fractures can rarely be associated with brachial plexus injury.These are commonly caused by tractional injury at the time of trauma,but unfrequently can be caused by compression of the brachial plexus from excessive callus or granulation tissue formation.CASE SUMMARY We report a rare case of an adult male who sustained a mid-shaft clavicle fracture and had a late presentation of brachial plexus palsy due to compression from excessive callus formation.CONCLUSION We reported a case of a rare occurrence of delayed brachial plexus palsy due to compression from excessive callus formation in a midshaft clavicle fracture.Early diagnosis and surgical decompression of the brachial plexus is critical,as when managed efficiently,a full recovery of the brachial plexus palsy can be expected in these patients.

Long-Term Postoperative Perfusion Indices in Surgically Resolved Myopic Traction Maculopathy

Background: Pathological myopia can be complicated by the presence of posterior staphyloma, macular atrophy, ruptures in Bruch’s membrane, pathologic choroidal neovascularization, and different degrees of myopic traction maculopathy. Purpose: To report the structural, functional and perfusional outcomes in patients underwent surgery for different stages of myopic traction maculopathy (MTM). Methods: A retrospective, consecutive, comparative, interventional, one-surgeon, case-control study was conducted in 46 eyes of 34 individuals between April 2015 and May 2021. Participants included normal emmetropic eyes (Control emmetropia, n = 25), healthy myopic eyes (Control high myopia, n = 20), and operated and structurally fully resolved myopic eyes with different stages of MTM (Surgically treated group, n = 46). Long-term postoperative functional and perfusional follow-up evaluations were performed with spectral domain-optical coherence tomography (SD-OCT) and OCT angiography. The primary outcome measure included long-term functional, structural and perfusion macular status across groups. Results: Forty-six eyes in 34 patients were included in the study group, with both eyes affected in 12 (26.3%) patients. The mean axial length was 29.89 ± 1.67 mm. The preoperative logMAR was 1.29 ± 0.54 and the postoperative logMAR was 0.60 ± 0.52 (P Conclusion: Compared to emmetropic and healthy myopic eyes, surgically-resolved MTM eyes generally have larger superficial foveal avascular zone area, lower vessel density, smaller choriocapillaris flow area, thinner central subfoveal thickness, and more macular defects. Eyes with stage III or IV MTM had larger deviation compared to eyes at earlier stages. Visual function change after surgery was associated with superficial foveal avascular zone area. Better functional, structural and perfusion index outcomes were observed when highly myopic eyes underwent early surgery.

Axillary Vessels and Brachial Plexus Traumas in Abidjan: Lesional Aspects and Surgical Difficulties

Introduction-Objectives: Through the presentation of epidemiological, anatomo-clinical and surgical aspects, we report our experience in the management of traumatic axillary lesions. Materials and Methods: A descriptive retrospective study was based on the medical records of patients who suffered vascular axillary and/or brachial plexus trauma and who underwent surgical repair at the Abidjan Cardiology Institute from January 2008 to June 2022. Epidemiological, anatomo-clinical and surgical data were studied. Results: Thirty-four medical files belonging to 33 men and one woman, aged 32 on average, were collected. The circumstances of occurrence were dominated by the stab wound (n = 22). The combinations of injuries were as follows: associated involvement of the axillary artery and vein (n = 4);isolated involvement of axillary artery (n = 3);isolated involvement of the axillary vein (n = 2);associated involvement of the axillary artery and brachial plexus (n = 17);associated involvement of the axillary artery and vein and brachial plexus (n = 08). Anatomic lesions included acute arterial lesions (n = 29) and arteriovenous fistula (n = 1) and false aneurysms (n = 4). All patients were operated on under general anesthesia;vascular repair included direct suturing (n = 16), arterial and venous bypass using a long saphenous graft (n = 9), prosthetic arterial bypass (n = 5) and prosthetic flattening-graft (n = 4). Brachial plexus surgery consisted of an end-to-end anastomosis of each transected bundle in all cases (n = 25). The medium-term postoperative course was marked by success without functional sequelae in 88.24% of cases (n = 30) and by the persistence of distal paralysis of the thoracic limb after 6 months in 05.88% (n = 2) of all patients, i.e., 8% of patients who presented with brachial plexus injury. Conclusion: The concomitant surgical treatment of these axillary vascular and nerve lesions has given good results. However, if paralysis of the thoracic limb persists after 6 to 12 months, the patient should be referred to a specialist in brachial plexus surgery.

ARRHYTHMIA INDUCED BY NICOTINE ACTIVATING CARDIAC INTRINSIC NEURONS IN CANINE ATRIAL AND VENTRICULAR GANGLIAL PLEXUS

Objective To study the arrhythmia induced by stimulation of nicotine-sensitive neurons in cardiac ganglial plexuses. Methods When nicotine (100 μg ) was injected into canine right atrial ganglial plexus (RAGP) and ganglial plexus between aorta and pulmonary artery (A-PGP) in 33 anesthetized open-chest dog, electrocardiogram, atrial force and ventricular intramyocardial pressures (IMP) were recorded. The responses were also recorded following administration of atropine or propranolol and after heart acute decentralization. Results Ventricular arrhythmia (VA) was induced by injections of nicotine into A-PGP, but not by injections of nicotine into RAGP in 13 dogs. Atrioventricilar (A-V) block was induced by nicotine activating RAGP in 10 dogs, but not by nicotine activating A-PGP. Propranolol could reduce the frequency of VA elicited by stimulating A-PGP, atropine could reduce the frequency of A-V block elicited by stimulating RAGP. After acute decentralization, VA was still induced by activation of A-PGP in 9 dogs, but A-V block elicited by stimulating RAGP was decreased. Conclusion VA is induced by stimulating N receptor in cardiac nicotine-sensitive efferent sympathetic neurons of ventricular ganglial plexus (A-PGP), and then modifying β receptor of ventricles. A-V block is elicited by stimulating N receptor in atrial ganglial plexus (RAGP), then modifying M receptor of A-V node not only via efferent parasympathetic neurons, but also via afferent pathway.

Electroacupuncture attenuates neuropathic pain after brachial plexus injury

Electroacupuncture has traditionally been used to treat pain, but its effect on pain following brachial plexus injury is still unknown. In this study, rat models of an avulsion injury to the left brachial plexus root （associated with upper-limb chronic neuropathic pain） were given electroacupuncture stimulation at bilateral Quchi （LIll）, Hegu （LI04）, Zusanli （ST36） and Yanglingquan （GB34）. After electroacupuncture therapy, chronic neuropathic pain in the rats＇ upper limbs was significantly attenuated. Immunofluorescence staining showed that the expression of β-endorphins in the arcuate nucleus was significantly increased after therapy. Thus, experimental findings indi- cate that electroacupuncture can attenuate neuropathic pain after brachial plexus injury through upregulating β-endorphin expression.

CT and MR imaging patterns for pancreatic carcinoma invading the extrapancreatic neural plexus (Part Ⅱ):Imaging of pancreatic carcinoma nerve invasion

Computed tomography (CT) and magnetic resonance imaging (MRI) are excellent modalities which have the ability to detect,depict and stage the nerve invasion associated with pancreatic carcinoma.The aim of this article is to review the CT and MR patterns of pancreatic carcinoma invading the extrapancreatic neural plexus and thus provide useful information which could help the choice of treatment methods.Pancreatic carcinoma is a common malignant neoplasm with a high mortality rate.There are many factors influencing the prognosis and treatment options for those patients suffering from pancreatic carcinoma,such as lymphatic metastasis,adjacent organs or tissue invasion,etc.Among these factors,extrapancreatic neural plexus invasion is recognized as an important factor when considering the management of the patients.

Human amniotic epithelial cell transplantation for the repair of injured brachial plexus nerve: evaluation of nerve viscoelastic properties

The transplantation of embryonic stem cells can effectively improve the creeping strength of nerves near an injury site in animals. Amniotic epithelial cells have similar biological properties as em-bryonic stem cells; therefore, we hypothesized that transplantation of amniotic epithelial cells can repair peripheral nerve injury and recover the creeping strength of the brachial plexus nerve. In the present study, a brachial plexus injury model was established in rabbits using the C6root avulsion method. A suspension of human amniotic epithelial cells was repeatedly injected over an area 4.0 mm lateral to the cephal and caudal ends of the C6 brachial plexus injury site （1 × 106 cells/mL, 3μL/injection, 25 injections） immediately after the injury. The results showed that the decrease in stress and increase in strain at 7,200 seconds in the injured rabbit C6 brachial plexus nerve were mitigated by the cell transplantation, restoring the viscoelastic stress relaxation and creep properties of the brachial plexus nerve. The forepaw functions were also signiifcantly improved at 26 weeks after injury. These data indicate that transplantation of human amniotic epithelial cells can effec-tively restore the mechanical properties of the brachial plexus nerve after injury in rabbits and that viscoelasticity may be an important index for the evaluation of brachial plexus injury in animals.

Role of endoscopic ultrasound in the diagnosis of pancreatic cancer

Endoscopic ultrasonography(EUS) with or without fine needle aspiration has become the main technique for evaluating pancreatobiliary disorders and has proved to have a higher diagnostic yield than positron emission tomography,computed tomography(CT) and transabdominal ultrasound for recognising early pancreatic tumors.As a diagnostic modality for pancreatic cancer,EUS has proved rates higher than 90%,especially for lesions less than 2-3 cm in size in which it reaches a sensitivity rate of 99% vs 55% for CT.Besides,EUS has a very high negative predictive value and thus EUS can reliably exclude pancreatic cancer.The complication rate of EUS is as low as 1.1%-3.0%.New technical developments such as elastography and the use of contrast agents have recently been applied to EUS,improving its diagnostic capability.EUS has been found to be superior to the recent multidetector CT for T stagingwith less risk of overstaying in comparison to both CT and magnetic resonance imaging,so that patients are not being ruled out of a potentially beneficial resection.The accuracy for N staging with EUS is 64%-82%.In unresectable cancers,EUS also plays a therapeutic role by means of treating oncological pain through celiac plexus block,biliary drainage in obstructive jaundice in patients where endoscopic retrograde cholangiopancreatography is not affordable and aiding radiotherapy and chemotherapy.

Magnetic resonance imaging with three-dimensional fast imaging employing steady-state acquisition with phase-cycled and short T1 inversion recovery pulse sequence for evaluating brachial plexus injury

There is a large amount of fat in the postganglionic segment of the brachial plexus nerve.The use of short T1 inversion recovery pulse sequence may improve signal strength of the brachial plexus postganglionic segment.The present study revealed that the combination of three-dimensional fast imaging employing steady-state acquisition with phase-cycled and short T1 inversion recovery pulse sequence clearly displayed the anatomical morphology and structure of the brachial plexus nerve,together with maximum intensity projection,volume rendering and other three-dimensional reconstruction techniques.Our results suggested that this method is also suitable for providing accurate assessment and diagnosis of the site,severity and scope of brachial plexus injury.

Perineural invasion of hilar cholangiocarcinoma in Chinese population: One center’s experience

BACKGROUND Hilar cholangiocarcinoma(HCCA)often produces perineural invasion(PNI)extending to extra-biliary sites,while significant confusion in the incidence of PNI in HCCA has occurred in the literature,and the mechanism of that procedure remains unclear.AIM To summarize the incidence of PNI in HCCA and to provide the distribution of nerve plexuses around hepatic portal to clinical surgeons.METHODS Reported series with PNI in HCCA since 1996 were reviewed.A clinicopathological study was conducted on sections from 75 patients with HCCA to summarize the incidence and modes of PNI.Immunohistochemical stains for CD34 and D2-40 in the cancer tissue were performed to clarify the association of PNI with microvessel and lymph duct.Sections of the hepatoduodenal ligament from autopsy cases were scanned and handled by computer to display the distribution of nerve plexuses around the hepatic portal.RESULTS The overall incidence of PNI in this study was 92%(69 of 75 patients),while the rate of PNI in HCCA in the literature ranging from 38%to 100%.The incidence of PNI did not show any remarkable differences among various differentiated groups and Bismuth-Corlette classification groups.Logistic regression analysis identified the depth of tumor invasion was the only factor that correlated significantly with PNI(P<0.01).In spite of finding tumor cells that could invade microvessels and lymph ducts in HCCA,we did not find tumor cells invaded nerves via microvessels or lymph ducts.Three nerve plexuses in the hepatoduodenal ligament and Glisson’s sheath were classified,and they all surrounded the great vessels very closely.CONCLUSION The incidence of PNI of HCCA in Chinese population is around 92%and correlated significantly with a depth of tumor invasion.It also should be considered when stratifying HCCA patients for further treatment.

CT and MR imaging patterns for pancreatic carcinoma invading the extrapancreatic neural plexus (Part Ⅰ): Anatomy, imaging of the extrapancreatic nerve

Pancreatic carcinoma is an extremely high-grade malignant tumor with fast development and high mortality. The incidence of pancreatic carcinoma continues to increase. Peripancreatic invasion and metastasis are the main characteristics and important prognostic factors in pancreatic carcinoma, especially invasion into the nervous system; pancreatic nerve innervation includes the intrapancreatic and extrapancreatic nerves. A strong grasp of pancreatic nerve innervation may contribute to our understanding of pancreatic pain modalities and the metastatic routes for pancreatic carcinomas. Computed tomography (CT) and magnetic resonance imaging (MRI) are helpful techniques for depicting the anatomy of extrapancreatic nerve innervation. The purpose of the present work is to show and describe the anatomy of the extrapancreatic neural plexus and to elucidate its characteristics using CT and MRI, drawing on our own previous work and the research findings of others.

Cell transplantation for the treatment of spinal cord injury–bone marrow stromal cells and choroid plexus epithelial cells

Transplantation of bone marrow stromal cells （BMSCs） enhanced the outgrowth of regenerating axons and promoted locomotor improvements of rats with spinal cord injury （SCI）. BMSCs did not survive long-term, disappearing from the spinal cord within 2-3 weeks after transplantation. Astrocyte-devoid areas, in which no astrocytes or oligodendrocytes were found, formed at the epicenter of the lesion. It was remarkable that numerous regenerating axons extended through such astrocyte-devoid areas. Regenerating axons were associated with Schwann cells embedded in extracellular matrices. Transplantation of choroid plexus epithelial cells （CPECs） also enhanced axonal regeneration and locomotor improvements in rats with SCI. Although CPECs disappeared from the spinal cord shortly after transplantation, an extensive outgrowth of regenerating axons occurred through astrocyte-devoid areas, as in the case of BMSC transplantation. These findings suggest that BMSCs and CPECs secret neurotrophic factors that promote tissue repair of the spinal cord, including axonal regeneration and reduced cavity formation. This means that transplantation of BMSCs and CPECs promotes ＂intrinsic＂ ability of the spinal cord to regenerate. The treatment to stimu- late the intrinsic regeneration ability of the spinal cord is the safest method of clinical application for SCI. It should be emphasized that the generally anticipated long-term survival, proliferation and differentiation of transplanted cells are not necessarily desirable from the clinical point of view of safety.

Celiac plexus neurolysis in the management of unresectable pancreatic cancer:When and how?

Pancreatic cancer is the second most common abdominal cancer in North America with an estimated 20%resectability at diagnosis,and overall 5-year survival of 5%.Pain is common in pancreatic cancer patients with 70%-80%suffering substantial pain.Celiac plexus neurolysis(CPN)is a technique that can potentially improve pain control in pancreatic cancer while preventing further escalation of opioid consumption.CPN is performed by injecting absolute alcohol into the celiac plexus neural network of ganglia.This review sets out to explore the current status of CPN in non-resectable pancreatic cancer.We will examine:(1)the efficacy and safety of percutaneous-CPN and endoscopic ultrasound guided-CPN;(2)specific technique modifications including bilateral(vs central)injections and celiac ganglia neurolysis;and(3)the issue of CPN timing,early at pancreatic cancer diagnosis vs traditional late use as salvage therapy.