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Flaminia Coluzzi,1,2 Francesca Felicia Caputi,3 Domenico Billeci,4 Antonio Luigi Pastore,1,5 Sanzio Candeletti,3 Monica Rocco,2,6 Patrizia Romualdi3 1Department of Medical and Surgical Sciences and Biotechnologies, Sapienza University of Rome, Polo Pontino, Latina, Italy; 2Unit of Anesthesia, Intensive Care and Pain Medicine, Sant’Andrea University Hospital, Rome, Italy; 3Department of Pharmacy and Biotechnology, Alma Mater Studiorum University, Bologna, Italy; 4Division of Neurosurgery, Ca’Foncello Hospital, ASL Marca Trevigiana, University of Padova, Treviso, Italy; 5Unit of Urology, Sapienza c/o I.C.O.T, Polo Pontino, Latina, Italy; 6Department of Clinical and Surgical Translational Medicine, Sapienza University of Rome, Rome, ItalyCorrespondence: Flaminia ColuzziDepartment of Medical and Surgical Sciences and Biotechnologies, Sapienza University of Rome, Corso della Repubblica 79, Polo Pontino 04100, Latina, ItalyTel +39 06 33775673Email flaminia.coluzzi@uniroma1.itAbstract: In patients suffering from moderate-to-severe chronic kidney disease (CKD) or end-stage renal disease (ESRD), subjected to hemodialysis (HD), pain is very common, but often underestimated. Opioids are still the mainstay of severe chronic pain management; however, their prescription in CKD and HD patients is still significantly low and pain is often under-treated. Altered pharmacokinetics and the lack of clinical trials on the use of opioids in patients with renal impairment increase physicians’ concerns in this specific population. This narrative review focused on the correct and safe use of opioids in patients with CKD and HD. Morphine and codeine are not recommended, because the accumulation of their metabolites may cause neurotoxic symptoms. Oxycodone and hydromorphone can be safely used, but adequate dosage adjustments are required in CKD. In dialyzed patients, these opioids should be considered as second-line agents and patients should be carefully monitored. According to different studies, buprenorphine and fentanyl could be considered first-line opioids in the management of pain in CKD; however, fentanyl is not appropriate in patients undergoing HD. Tapentadol does not need dosage adjustment in mild-to-moderate renal impairment conditions; however, no data are available on its use in ESRD. Opioid-related side effects may be exacerbated by common comorbidities in CKD patients. Opioid-induced constipation can be managed with peripherally-acting-μ-opioid-receptor-antagonists (PAMORA). Unlike the other PAMORA, naldemedine does not require any dose adjustment in CKD and HD patients. Accurate pain diagnosis, opioid titration and tailoring are mandatory to minimize the risks and to improve the outcome of the analgesic therapy.Keywords: opioids, chronic kidney disease, pain, hemodialysis, neuropathic pain, PAMORA

Domenico Billeci,1 Flaminia Coluzzi2 1Division of Neurosurgery, Ca’Foncello Hospital, University of Padova, Treviso, 2Department of Medical and Surgical Sciences and Biotechnologies, Unit of Anaesthesiology, Intensive Care Medicine, and Pain Therapy, Faculty of Pharmacy and Medicine, Sapienza University of Rome, Latina, Italy Background: The role of opioids in the management of chronic neck pain is still poorly investigated. No data are available on tapentadol extended release (ER). In this article, we present 54 patients with moderate-to-severe chronic neck pain treated with tapentadol ER. Patients and methods: Patients received tapentadol ER 100 mg/day; dosage was then adjusted according to clinical needs. The following parameters were recorded: pain; Douleur Neuropathique 4 score; Neck Disability Index score; range of motion; pain-associated sleep interference; quality of life (Short Form [36] Health Survey); Patient Global Impression of Change (PGIC); Clinician GIC; opioid-related adverse effects; and need for other analgesics. Results: A total of 44 of 54 patients completed the 12-week observation. Tapentadol ER daily doses increased from 100 mg/day to a mean (standard deviation) dosage of 204.5 (102.8) mg/day at the final evaluation. Mean pain intensity at movement significantly decreased from baseline (8.1 [1.1]) to all time points (P

Background: This paper reports the results of the treatment of our first 200 cases of lumbar disc herniation and foraminal stenosis using full-endoscopic transforaminal lumbar discectomy (FETLD). We analyzed outcomes and radiological parameters to overcome failure and inappropriate indications and also highlighted the red flags for surgeons coming to this field as well as the pathways to success., Methods: Data on endoscopic procedures were retrospectively analyzed between October 2018 and March 2023. We abstracted sex, age, leg pain by NPRS, postoperative satisfaction according to the MacNaab score, postoperative surgical complications/adverse events (≤30 days), and history of any previous surgery. Furthermore, we measured different radiological parameters to determine the grade of stenosis or discopathy., Results: Once the learning curve was completed, patients' satisfaction increased to 94%, with only a small percentage (6%) of patients unsatisfied 30 days after the operation. Perioperatively, 33.5% of the patients experienced mild to moderate transitory paresthesia. Univariate analysis showed a tendency toward a higher risk of failure in those patients with degenerative listhesis (odds ratio [OR] 4.8, 95% CI 0.97-23.9, P=0.055) as well as those with severely degenerated discs (OR 8.7, 95% CI 0.96-79.4, P=0.054). Conversely, the chances of failure seemed to be lower in patients with severe foraminal stenosis., Conclusions: FETLD proved its efficacy in treating several degenerative spine conditions or was useful for avoiding previous scarring in patients already operated on to the same extent. Therefore, FETLD can be safely used in patients with comorbidities, the elderly, and when the invasiveness of an open technique is not suitable.

Opioids are widely used in chronic pain management, despite major concerns about their risk of adverse events, particularly abuse, misuse, and respiratory depression from overdose. Multi-mechanistic opioids, such as tapentadol and buprenorphine, have been widely studied as a valid alternative to traditional opioids for their safer profile. Special interest was focused on the role of the nociceptin opioid peptide (NOP) receptor in terms of analgesia and improved tolerability. Nociceptin opioid peptide receptor agonists were shown to reinforce the antinociceptive effect of mu opioid receptor (MOR) agonists and modulate some of their adverse effects. Therefore, multi-mechanistic opioids involving both MOR and NOP receptor activation became a major field of pharmaceutical and clinical investigations. Buprenorphine was re-discovered in a new perspective, as an atypical analgesic and as a substitution therapy for opioid use disorders; and buprenorphine derivatives have been tested in animal models of nociceptive and neuropathic pain. Similarly, cebranopadol, a full MOR/NOP receptor agonist, has been clinically evaluated for its potent analgesic efficacy and better tolerability profile, compared with traditional opioids. This review overviews pharmacological mechanisms of the NOP receptor system, including its role in pain management and in the development of opioid tolerance. Clinical data on buprenorphine suggest its role as a safer alternative to traditional opioids, particularly in patients with non-cancer pain; while data on cebranopadol still require phase III study results to approve its introduction on the market. Other bifunctional MOR/NOP receptor ligands, such as BU08028, BU10038, and AT-121, are currently under pharmacological investigations and could represent promising analgesic agents for the future., (© 2022. The Author(s).)

Introduction: Spinal endoscopic techniques have recently been applied to complex degenerative conditions or failed back surgery syndrome. We performed a systematic review and meta-analysis to assess transforaminal endoscopic lumbar foraminotomy (TELF) outcomes and adverse event rates. We also analyzed the effectiveness of the technique for chronic pain after arthrodesis or previous spinal surgery., Methods: Multiple databases were searched for studies published in the English language, involving patients > 18 years old who underwent endoscopic foraminotomy. Outcomes included the rate of patients who showed "excellent" and "good" postoperative improvement, decreased leg pain, and improved Oswestry Disability Index (ODI) scores. Adverse events considered in the analysis included nerve root damage and intraoperative dural tear, the proportion of patients requiring revision surgery or recurrences, and infections., Results: A total of 14 studies, encompassing 600 patients, were identified. Approximately 85% of patients improved significantly after TELF, without significant differences among different groups (85% vs. 78%, respectively). Mean leg pain decreased an average of 5.2 points, and ODI scores improved by 41.2%. Patients with previous spine surgery or failed back surgery syndrome had higher postoperative leg dysesthesia rates after TELF (14% vs. 1%, respectively)., Conclusion: TELF is a useful and safe method to achieve decompression in foraminal stenosis. This technique is indicated in the elderly or patients with comorbidities. Preoperative planning is paramount in determining the foraminal size and endoscope trajectory. A diamond burr is recommended because it has an advantage over the regular endoscopic shaver in bleeding control and complication avoidance., (© 2021. The Author(s).)

Background: Despite the high prevalence of neck pain, few studies have addressed the pharmacological treatment of this condition. Purpose: We evaluated the effectiveness of tapentadol prolonged-release (PR) in patients with or without a neuropathic pain component, with a focus on functional movements, disability and Quality of Life (QoL). Study design/setting: Observational, retrospective study. Patient sample: Ninety-four adult patients with severe neck pain not responsive to opioid step III treatment. Outcome measures: The primary endpoint was a  ≥ 30% improvement of pain intensity at 4 weeks (W4). Several secondary outcomes were evaluated, including neck disability index (NDI), range of motion (ROM), and QoL. Methods: Patients received tapentadol PR at the starting dose of 100 mg/day. Dose titration was allowed in 50 mg increments, up to 500 mg daily. Results: At W4, the primary endpoint of ≥30% improvement of pain was reported in 70% ( n  = 35; 95% confidence interval [CI]: 55-82%) of patients with a neuropathic pain component and in 69% ( n  = 20; 95% CI: 49-85%) of those without a neuropathic component. The percentage of patients reporting a neuropathic pain component significantly decreased from baseline (64.2%) to W4 (27.8%). NDI significantly improved in both groups at W12. ROM significantly improved in all three planes of motion ( p  < .01), with no difference between the two groups. Interference of pain with sleep and QoL also improved. Conclusions: The reduction in pain provided by tapentadol is associated with functional recovery, which may in turn be linked to an improvement in QoL.

Introduction: One of the most challenging occurrences in full-endoscopic surgery for lumbar disc protrusions are up-migrated or down-migrated herniations. Those occurrences are difficult to retrieve with transforaminal or interlaminar approaches., Presentation of Case: We describe our experience in dealing with a right paramedian down-migrated L3-L4 disc herniation. The patient underwent full endoscopic transpedicular endoscopic discectomy (FETD), by reaming the right L4 peduncle for intracanal access and fragment retrieval. We also reviewed the recent literature to summarize the advantages of transpedicular approaches, along with current indications and contraindications for this procedure., Discussion: We highlighted how FETD is safe and feasible for down-migrated and up-migrated disc herniation showing excellent results in our patient and in the small cohorts of patients already published in the literature., Conclusion: FETD was effective in treating up-migrated and down-migrated disc herniation, as well as discal cysts, showing the feasibility and safety of the technique from any level from L1 to S1., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Spindle cell oncocytoma (SCO) is a rare pituitary tumor, classified as a WHO grade I neoplasm. Due to its rarity, SCO is often preoperatively misdiagnosed as a pituitary macroadenoma. In the present study we report two recent cases of SCO, a 61-year-old male and a 65-year-old female presenting at Treviso General Hospital between March 2014 and April 2015. Tumor resection was achieved by endoscopic transsphenoidal approach but massive hemorrhagic events hampered surgery, endangering the patient's life in both cases. Both tumors featured fascicles of spindle cells with eosiniphilic cytoplasm expressing vimentin, S-100 and thyroid transcription factor-1 (TTF-1). The diagnosis of SCO was confirmed by second opinion in both cases. Extensive review of available literature, about 30 cases from 2002 to 2015, provided valuable clinical data for preoperative diagnosis and surgical removal of SCO tumors., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objectives Cerebrospinal fluid (CSF) leakage is an undesirable complication of transsphenoidal skull base surgery. The issue of the most appropriate sellar dura repair remains unresolved, although a multilayer technique using autologous fascia lata is widely used. We describe the novel application of a homologous banked fascia lata graft as an alternative to an autologous one in the reconstruction of sellar dura defects in endoscopic transsphenoidal surgery. Design The clinical records of patients who underwent endoscopic transsphenoidal surgery at our department from June 2012, when we started using homologous fascia lata, up to July 2014 were reviewed retrospectively. The data concerning diagnosis, reconstruction technique, and surgical outcome were analyzed. Results We treated 16 patients successfully with banked fascia lata. Twelve patients presented intraoperative CSF leakage, and four patients were treated for postoperative rhinoliquorrhea. Banked fascia lata was used in a single-to-multilayer technique, depending on the anatomical features of the defect and of the sellar floor. No complications or failures in sella reconstruction occurred. Conclusion A banked fascia lata graft proved reliable and safe in providing an effective sellar dura reconstruction. Used in a multilayer strategy, it should be considered a viable alternative to an autologous fascia lata graft.

Merkel cell carcinoma (MCC) is a malignant neuroendocrine tumor of the skin that demonstrates a remarkable tendency to metastasize. However, only a few cases of MCC brain metastases have been reported in the literature. We here present a unique case of a pituitary metastasis of MCC in a 65-year-old patient with a history of pituitary adenoma. This case is particularly novel due to the fact that the primary site of the MCC is unknown.

Transaqueductal navigation of the fourth ventricle has long been considered dangerous and of no clinical relevance. After the refinement of the endoscopic technique and supported by the extensive experience gained at the authors' institution since 1994, endoscopic exploration of the fourth ventricle has been performed by the same surgeon in 54 patients. In all cases reviewed, endoscopic navigation of the fourth ventricle was successfully performed with no related neurological deficit. This preliminary experience shows the feasibility of transaqueductal navigation of the fourth ventricle, which is made possible by the use of small, flexible endoscopes in expert hands.

Case Report: We report on the successful conservative treatment of a child harbouring a right-temporal arachnoid cyst associated with bilateral hygroma., Treatment: Medical treatment was by corticosteroids for several days and acetazolamide (15 mg/kg/die) for 10 months., Outcome: Clinical symptoms and signs disappeared completely with partial resolution of the bilateral hygroma at MRI follow-up.

Introduction: Transnasal endoscopic repair of cerebrospinal fluid (CSF) fistulas is recommended for patients with CSF leaks who do not respond to conservative treatment. It is a safer and more successful alternative to transcranial surgery., Patients and Methods: We present our experience on using transnasal endoscopy for the repair of anterior skull base cerebrospinal fluid fistulas. Between 1999 and 2003 we observed 20 patients with CSF rhinorrhea. The etiology was heterogeneous: post-traumatic in 6 cases, iatrogenic in 6 cases (one interesting case of meningioma of the sphenoethmoid plate), dysembryogenetic - due to encephaloceles - in 4 patients (one with Cruzon syndrome and one with Down syndrome) and idiopathic in the other 4 patients. Use of a rigid transnasal endoscope allowed the localization and repair of all fistulas, with the use of fluorescein in 6 cases. Different grafts were used, in particular fat, bone or chondral septum with mucoperiosteum or perichondral mucosa. Generally the graft was inserted with the underlay or the sandwich technique. Lumbar drainage was used in the postoperative period only in 6 cases. No antibiotic prophylactic therapy was used., Results: Endoscopy was successful in 90 % of patients at the first attempt, and in 95 % of patients at the second approach. We had two late complications such as infections. In one child with a post-traumatic fistula and shunt for hydrocephalus, we observed meningitis 2 years after the first endoscopic surgery and he underwent both transnasal endoscopic surgery and transcranial surgery. The second patient was a woman with a spontaneous fistula, who had rhinoliquorrhea three years after the first surgical treatment. During surgery a strange similar purulent material filling the submucous space of the ethmoid roof was found, suggestive for an intranasal abscess that was removed. We did not see any complications such as hematomas or seizures. The follow-up (range: 6 months to 3 years) made both with MRI and rhinoscopy has not shown any relapse until now in 19 of 20 patients treated only with endoscopy., Conclusions: The endoscopic approach is highly effective and safe in the treatment of CSF fistulas, with great visualization and minimal invasiveness, for which it is associated to a very low morbidity. The fluorescein technique is extremely helpful for the diagnosis and surgery of CSF leaks.

Rathke's cleft cyst is a non neoplastic lesion remnant of the Rathke's poutch. Symptomatic cysts must be surgically treated. There are no specific neuroradiological features for this lesion. We present a series of 14 symptomatic Rathke's cleft cysts treated with transphenoidal endoscopic technique, and we correlate the MRI intensity images with the intraoperative findings, the pathological analysis, the growth pattern and the recurrence tendency, to understand wether there is a better way to recognize these lesions, especially the asyntomatic ones, that, despite other neoplastic cysts, colud only be observed with a MRI follow up.

Background: The particular biomechanics of the upper cervical spine require, when trauma occurs, careful evaluation of the stability of the lesions, in order to guarantee the best possible therapeutic and prognostic approach. To date, there has been no uniformity of opinion in merit, especially with reference to treatment of odontoid fractures. It is necessary for this reason as much as for the opportune standardisation of the patients' classification parameters to establish what is meant by stability and which lesions are to be held as being unstable in the upper cervical spine., Methods: All the cases of upper cervical spine instability treated in our Unit from '94 to date have been reviewed. Four fractures to the first cervical vertebra, 29 to the odontoid process, 9 isolated fractures in the C2 body, 12 hangman fractures, 7 fractures of the articular processes, 2 to the occipital condyles and 4 C1-C2 dislocations without fractures were localised. Using precise prognostic indexes as our classification criteria, 56 of the 58 patients observed were addressed towards either conservative treatment or directly towards surgical treatment. In particular, 29 patients were conservatively treated with a collar or Halo-Vest. Twenty-seven surgical operations were carried out: 14 screw fixations, 6 anterior fixations using plates and screws, 4 rear ones using metal wire or wire with bone graft, 3 odontectomy operations associated with posterior fixation., Results: In the follow-up, using a range of between three months to six years, good fusion with spine stabilisation was achieved in all the patients treated. In particular, surgery was carried out as the first therapeutic indication in 25 cases, obtaining excellent results. Surgery was necessary in only 2 cases after the failure of external stabilisation., Conclusions: The judgement passed on instability in traumatic lesions in the upper cervical spine represents the decisive factor in the choice of the therapeutic option. Instead of always opting for conservative treatment, in the case of C1-C2 fractures-luxations, and going ahead with surgery only when there is instability or non-fusion of the segments resulting after successive monitoring, we believe that the definition and standardisation of the prognostic factors is opportune, in order to provide patients with a specific solution, in such a way as to reduce the failure percentage of the first treatment and optimise the healing time.