A single infusion of intravenous lidocaine for primary headaches and trigeminal neuralgia: a retrospective analysis.

Introduction: Intravenous (IV) lidocaine has been used as a transitional treatment in headache and facial pain conditions, typically as an inpatient infusion over several days, which is costly and may increase the risk of adverse effects. Here we report on our experience using a single one-hour IV lidocaine infusion in an outpatient day-case setting for the management of refractory primary headache disorders with facial pain and trigeminal neuralgia. Methods: This is a retrospective, single-center analysis on patients with medically refractory headache with facial pain and trigeminal neuralgia who were treated with IV lidocaine between March 2018 and July 2022. Lidocaine 5 mg.kg-1 in 60 mL saline was administered over 1 h, followed by an observation period of 30 min. Patients were considered responders if they reported reduction in pain intensity and/or headache frequency of 50% or greater. Duration of response was defined as short-term (< 2 weeks), medium-term (2-4 weeks) and long-term (> 4 weeks). Results: Forty infusions were administered to 15 patients with trigeminal autonomic cephalalgias (n = 9), chronic migraine (n = 3) and trigeminal neuralgia (n = 3). Twelve patients were considered responders (80%), eight of whom were complete responders (100% pain freedom). The average duration of the treatment effect for each participant was 9.5 weeks (range 1-22 weeks). Six out of 15 patients reported mild and self-limiting side effects (40%). Conclusion: A single infusion of IV lidocaine might be an effective and safe transitional treatment in refractory headache conditions with facial pain and trigeminal neuralgia. The sustained effect of repeated treatment cycles in some patients may suggest a role as long-term preventive therapy in some patients.

OnabotulinumtoxinA in elderly patients with chronic migraine: insights from a real-life European multicenter study.

INTRODUCTION: Although migraine prevalence decreases with aging, some older patients still suffer from chronic migraine (CM). This study aimed to investigate the outcome of OnabotulinumtoxinA (OBT-A) as preventative therapy in elderly CM patients. METHODS: This is a post hoc analysis of real-life prospectively collected data at 16 European headache centers on CM patients treated with OBT-A over the first three treatment cycles (i.e., Cy1-3). We defined: OLD patients aged ≥ 65 years and nonOLD those < 65-year-old. The primary endpoint was the changes in monthly headache days (MHDs) from baseline to Cy 1-3 in OLD compared with nonOLD participants. The secondary endpoints were the responder rate (RR) ≥ 50%, conversion to episodic migraine (EM) and the changes in days with acute medication use (DAMs). RESULTS: In a cohort of 2831 CM patients, 235 were OLD (8.3%, 73.2% females, 69.6 years SD 4.7). MHDs decreased from baseline (24.8 SD 6.2) to Cy-1 (17.5 SD 9.1, p < 0.000001), from Cy-1 to Cy-2 (14.8 SD 9.2, p < 0.0001), and from Cy-2 to Cy-3 (11.9 SD 7.9, p = 0.001). DAMs progressively reduced from baseline (19.2 SD 9.8) to Cy-1 (11.9 SD 8.8, p < 0.00001), to Cy-2 (10.9 SD 8.6, p = 0.012), to Cy-3 (9.6 SD 7.4, p = 0.049). The 50%RR increased from 30.7% (Cy-1) to 34.5% (Cy-2), to 38.7% (Cy-3). The above outcome measures did not differ in OLD compared with nonOLD patients. CONCLUSION: In a population of elderly CM patients with a long history of migraine OBT-A provided a significant benefit, over the first three treatment cycles, as good as in non-old patients.

Single-Pulse Transcranial Magnetic Stimulation for the preventive treatment of difficult-to-treat migraine: a 12-month prospective analysis.

BACKGROUND: Initial evidence have shown the short-term efficacy of sTMS in the acute and preventive treatment of migraine. It is unknown whether this treatment approach in the long-term is effective and well tolerated in difficult-to-treat migraine. METHODS: This is a prospective, single centre, open-label, real-world analysis conducted in difficult-to-treat patients with high-frequency episodic migraine (HFEM) and chronic migraine (CM) with and without medication overuse headache (MOH), who were exposed to sTMS therapy. Patients responding to a three-month sTMS treatment, continued the treatment and were assessed again at month 12. The cut-off outcome for treatment continuation was reduction in the monthly moderate to severe headache days (MHD) of at least 30% (headache frequency responders) and/or a ≥ 4-point reduction in headache disability using the Headache Impact test-6 (HIT-6) (headache disability responders). RESULTS: One hundred fifty-three patients were included in the analysis (F:M = 126:27, median age 43, IQR 32.3-56.8). At month 3, 93 out of 153 patients (60%) were responders to treatment. Compared to baseline, the median reduction in monthly headache days (MHD) for all patients at month 3 was 5.0 days, from 18.0 (IQR: 12.0-26.0) to 13.0 days (IQR: 5.75-24.0) (P = 0.002, r = - 0.29) and the median reduction in monthly migraine days (MMD) was 4.0 days, from 13.0 (IQR: 8.75-22.0) to 9.0 (IQR: 4.0-15.25) (P = 0.002, r = - 0.29). Sixty-nine out of 153 patients (45%) reported a sustained response to sTMS treatment at month 12. The percentage of patients with MOH was reduced from 52% (N = 79/153) at baseline to 19% (N = 29/153) at month 3, to 8% (N = 7/87) at month 12. There was an overall median 4-point reduction in HIT-6 score, from 66 (IQR: 64-69) at baseline to 62 at month 3 (IQR: 56-65) (P < 0.001, r = - 0.51). A total of 35 mild/moderate adverse events were reported by 23 patients (15%). One patient stopped sTMS treatment due to scalp sensitivity. CONCLUSIONS: This open label analysis suggests that sTMS may be an effective, well-tolerated treatment option for the long-term prevention of difficult-to-treat CM and HFEM.

Radiological assessment of response and adverse events associated with novel systemic oncological therapies.

The last decade has seen a paradigm shift in medical oncology treatment with the rise of novel systemic agents, principally molecular targeted therapy and immunotherapy. These new groups of anti-cancer treatment have revolutionised the prognostic landscape for certain patient cohorts with advanced disease, and it is hoped that through ongoing extensive clinical research, significant survival benefits may be demonstrated in the majority of tumour types. However, radiological response assessment of these new agents has become more nuanced for radiologists, as the behaviour of both responding and progressing tumour burden can be more diverse than with conventional chemotherapy. Additionally, radiologists need to be aware of adverse events associated with these treatments as some side effects carry a high morbidity/mortality and may manifest radiologically before they become clinically apparent. This review discusses radiological response assessment and adverse events associated with these novel agents, which have become fundamental aspects of systemic oncological therapy.

De-novo Upper Gastrointestinal Tract Cancer after Liver Transplantation: A Demographic Report.

BACKGROUND: Immunosuppression is essential after liver transplantation (LT). It, however, increases the risk for cancer. OBJECTIVE: To evaluate the prevalence and outcome of upper gastrointestinal (GI) tract cancer in LT patients and assess the perioperative risk of surgery for the upper GI malignancies post-LT. METHODS: 2855 patients underwent LT at our clinic from 1988 to 2018. 20 patients developed upper GI cancer. Data were retrospectively extracted from our database. Analysis included patients' specific data, tumor histopathology and stage, the treatment given and survival. RESULTS: 23 patients developed upper GI malignancies (2 gastric and 18 esophageal cancers; 3 excluded), translating to a incidence of 26.4 per 100,000 population per year. All patients were male. 80% showed alcohol-induced cirrhosis before LT. Most of the tumors were diagnosed at a stage ≥III. 70% underwent surgery and 78.6% developed postoperative complications. One-year-survival was 50%. Total survival rate was 28.6% with a median follow-up of 10 months (range: 0-184). CONCLUSION: Upper GI malignancies are more common after LT compared to the general population. Men after LT, due to alcohol-induced liver cirrhosis, are at a higher risk. Upper GI surgery after LT can be safe, but the severe risk for complications and a poor survival require strict indications.

The fifth cranial nerve in headaches.

The fifth cranial nerve is the common denominator for many headaches and facial pain pathologies currently known. Projecting from the trigeminal ganglion, in a bipolar manner, it connects to the brainstem and supplies various parts of the head and face with sensory innervation. In this review, we describe the neuroanatomical structures and pathways implicated in the sensation of the trigeminal system. Furthermore, we present the current understanding of several primary headaches, painful neuropathies and their pharmacological treatments. We hope that this overview can elucidate the complex field of headache pathologies, and their link to the trigeminal nerve, to a broader field of young scientists.

[Laparoscopic versus open gastrectomy for advanced gastric cancer : Operative and postoperative results]. / Laparoskopische vs. offene Gastrektomie bei fortgeschrittenem Magenkarzinom : Operative und postoperative Ergebnisse.

BACKGROUND: Minimally invasive gastrectomy is increasingly becoming established worldwide as an alternative to open gastrectomy (OG); however, the majority of available articles in the literature refer to Asian populations and early stages of gastric cancer. This makes an international comparison difficult due to a discrepancy in patient populations and tumor biology as well as Asian and western treatment approaches. Little is known, therefore, whether laparoscopic gastrectomy (LG) can be performed in advanced cancer, in particular with respect to laparoscopic D2 lymphadenectomy, with sufficient radicality and safety in this country. MATERIAL AND METHODS: All gastrectomies performed for the treatment of advanced gastric cancer with clinical UICC stages 2 and 3 between 2005 and 2017 were analyzed. A case match by age, gender and UICC stage was performed to compare the operative and early postoperative results of LG and OG. RESULTS: A total of 243 patients with advanced gastric cancer were analyzed. Of these 81 patients (33.3%) underwent LG. The operative time for LG was around 74 min longer (279.2 min vs. 353.4 min, OG vs. LG; p < 0.001), the hospital stay after LG was around 4 days shorter (22.9 days vs. 18.4 days, OG vs. LG; p < 0.001). Significantly more lymph nodes were resected by LG (24.1 lymph nodes vs. 28.8 lymph nodes, OG vs. LG; p < 0.001). In terms of morbidity and mortality there were no differences between the groups. CONCLUSION: The present study showed that minimally invasive gastrectomy can be performed safely and with comparable histopathological results to open surgery, even in advanced gastric cancer in western populations; however, larger case series and evidence from high-quality studies are urgently needed especially to compare short-term and long-term survival.

A multicentre assessment of prostate MRI quality and compliance with UK and international standards.

AIM: To assess prostate magnetic resonance imaging (MRI) image quality and compliance with technical standards between centres in the South West region of the UK. MATERIALS AND METHODS: Fifteen imaging sites in the region submitted seven consecutive anonymised MRI studies. These were assessed by two experienced radiologists in consensus. Overall, subjective image quality for T2-weighted imaging (T2W), diffusion weighted imaging (DWI), and dynamic contrast enhancement (DCE) was scored on a five-point Likert scale. Five additional quality parameters were also assessed visually, including image noise, motion, artefact, and distortion. The degree of compliance by each site with 21 published technical standards was also assessed. RESULTS: Ninety-four MRI examinations were reviewed from across all sites (mean 6.3 scans per site, range 5-7). Mean compliance with technical standards was 63% (range 38-86%). Forty-seven percent of sites did not perform DCE. One site used a 3 T scanner. The percentage of patients with overall quality scores of ≥3 (diagnostically acceptable) were 68% for T2W, 81% for DWI, and 60% for both T2W and DWI. Ninety-three percent of the 45 patients who underwent DCE had diagnostically acceptable studies. By scanner age, the percentage of patients with diagnostically acceptable T2W scores was 53% for scanners ≥7 years and 80% when <7 years (p=0.006). Comparing individual sites, the mean overall quality scores were 2.9 (range 2.2-4.2) for T2W, 3.2 (1.8-4.7) for DWI, and 3.4 (2.5-4.7) for DCE. CONCLUSION: There is wide variation in compliance with recognised technical standards and image quality across sites. If MRI is to replace biopsy in selected low-risk patients, improvements in image quality may be required.

Prospective real-world analysis of OnabotulinumtoxinA in chronic migraine post-National Institute for Health and Care Excellence UK technology appraisal.

BACKGROUND AND PURPOSE: The National Institute for Health and Care Excellence (NICE) in the UK recommends the use of OnabotulinumtoxinA (BoNTA, Botox® ) in the management of chronic migraine (CM) following specific guidelines within the National Health Service. In view of the lack of data on the efficacy of this therapy following implementation of these guidelines in clinical practice and on the evaluation of guidance compliance, we aimed to evaluate the effectiveness and safety of BoNTA in patients with CM following the NICE guidelines. METHODS: This was a prospective real-life audit study. RESULTS: After two treatments, 127 of 200 patients (63.5%) obtained at least a 30% reduction in headache days. Those who continued the treatment up to 3 years reported a stable beneficial effect compared with baseline. Amongst responders, 68 patients (53.5%) were reclassified as episodic migraineurs. A total of 57 of these patients (83.8%) converted to an episodic migraine pattern at 6-month follow-up. The majority of those whose migraine became episodic after BoNTA extended the treatment intervals beyond 3 months (range 4-8 months) before noticing any worsening of headache. We observed no significant differences in the efficacy measures in patients treated with 155 U BoNTA compared with those treated with >155 U BoNTA. CONCLUSIONS: When administered according to the NICE guidance, BoNTA produced a clinically meaningful effect in the long-term management of CM with and without medication overuse headache. Treatment discontinuation when CM becomes episodic may be useful in clinical practice to identify those who may benefit from extended treatment intervals. Our clinical experience indicates a lack of additional benefit from using the 'follow-the-pain' paradigm.

Hepatotoxicity following systemic therapy for colorectal liver metastases and the impact of chemotherapy-associated liver injury on outcomes after curative liver resection.

Patients with colorectal liver metastases (CLM) have remarkably benefited from the advances in medical multimodal treatment and surgical techniques over the last two decades leading to significant improvements in long-term survival. More patients are currently undergoing liver resection following neoadjuvant chemotherapy, which has been increasingly established within the framework of curative-indented treatment strategies. However, the use of several cytotoxic agents has been linked to specific liver injuries that not only impair the ability of liver tissue to regenerate but also decrease long-term survival. One of the most common agents included in modern chemotherapy regimens is oxaliplatin, which is considered to induce a parenchymal damage of the liver primarily involving the sinusoids defined as sinusoidal obstruction syndrome (SOS). Administration of bevacizumab, an inhibitor of vascular endothelial growth factor (VEGF), has been reported to improve response of CLM to chemotherapy in clinical studies, concomitantly protecting the liver from the development of SOS. In this review, we aim to summarize current data on multimodal treatment concepts for CLM, give an in-depth overview of liver damage caused by cytostatic agents focusing on oxaliplatin-induced SOS, and evaluate the role of bevacizumab to improve clinical outcomes of patients with CLM and to protect the liver from the development of SOS.

Engineering an endocrine Neo-Pancreas by repopulation of a decellularized rat pancreas with islets of Langerhans.

Decellularization of pancreata and repopulation of these non-immunogenic matrices with islets and endothelial cells could provide transplantable, endocrine Neo- Pancreata. In this study, rat pancreata were perfusion decellularized and repopulated with intact islets, comparing three perfusion routes (Artery, Portal Vein, Pancreatic Duct). Decellularization effectively removed all cellular components but conserved the pancreas specific extracellular matrix. Digital subtraction angiography of the matrices showed a conserved integrity of the decellularized vascular system but a contrast emersion into the parenchyma via the decellularized pancreatic duct. Islets infused via the pancreatic duct leaked from the ductular system into the peri-ductular decellularized space despite their magnitude. TUNEL staining and Glucose stimulated insulin secretion revealed that islets were viable and functional after the process. We present the first available protocol for perfusion decellularization of rat pancreata via three different perfusion routes. Furthermore, we provide first proof-of-concept for the repopulation of the decellularized rat pancreata with functional islets of Langerhans. The presented technique can serve as a bioengineering platform to generate implantable and functional endocrine Neo-Pancreata.

Pharmacology of reflex blinks in the rat: a novel model for headache research.

BACKGROUND: Migraineurs are highly sensitive to the nitric oxide donor glyceryl trinitrate which triggers attacks in many sufferers. In animal studies, glyceryl trinitrate increases neuronal activity in the trigeminovascular pathway and elevates neurotransmitter levels in the brainstem. Many migraineurs also display alterations in blink reflexes, known to involve brainstem circuits. We investigated the effect of GTN on evoked blinks in the anaesthetised rat to determine whether such reflexes may prove useful as the basis for a novel animal model to evaluate potential anti-migraine therapeutic agents. METHOD: In anaesthetised rats the electromyogram associated with the reflex blink evoked by corneal airpuff was recorded. Rats were infused with glyceryl trinitrate, sumatriptan plus glyceryl trinitrate or vehicle control. Changes in the magnitude of the reflex blink-associated electromyogram following these treatments were measured. RESULTS: Glyceryl trinitrate potentiated the evoked reflex blink-associated EMG response from 2 h after infusion. That effect was abolished by simultaneous infusion of sumatriptan with glyceryl trinitrate. CONCLUSIONS: These results show that simple skin surface measurements of evoked electromyographic activity in the rat can reliably detect the evoked blink reflex that can be potentiated by nitric oxide donors. This novel model may be an effective tool for evaluating putative anti-migraine therapeutic agents.

[The Impact of Tumor Cell Proliferation on Occult Micrometastases, Tumor Recurrence and Patient Outcome Following Resection for Liver Malignancies]. / Stellenwert des Proliferationsreizes auf die okkulte Mikrometastasierung sowie Rezidivhäufigkeit und Prognose nach Resektion von Lebermalignomen.

Liver resection is currently considered to be essential part of the curative treatment of primary and secondary liver malignancies. However, long-term survival in these patients is limited by the high incidence of tumor recurrence. Recent clinical and experimental studies have indicated that cellular and molecular mechanisms associated with liver regeneration after partial hepatectomy may have a proliferative effect on occult micrometastases and circulating tumor cells and are thus responsible for recurrent disease. Growth factors and cytokines involved in liver regeneration have also been shown to influence tumour growth and metastasis. However, the underlying mechanisms explaining the interactions between regenerating liver tissue and tumour cell proliferation remain unclear. The development of modern agents specifically targeting these processes may improve disease-free and overall survival rates after oncological hepatectomy.

The prognostic significance of MRI-detected extramural venous invasion in rectal carcinoma.

AIM: To assess whether there is a significant difference in the incidence of patients with metastases of rectal carcinoma at 1 year follow-up between magnetic resonance imaging (MRI)-detected extramural venous invasion (EMVI) and those without. MATERIALS AND METHODS: A search of our institution's cancer registry revealed 788 patients with rectal carcinoma between January 2007 and April 2012. Those who were initially staged using MRI and computed tomography (CT) chest/abdomen/pelvis, and followed-up with a CT chest/abdomen/pelvis examination at 1 year were included in this retrospective study. Patients with synchronous metastases were excluded, leaving a cohort of 202 cases. Two consultant radiologists reviewed all MRI images and gave a consensus opinion regarding EMVI grade and vessel size involved. All CT images were reviewed for metastases. Results were analysed using chi-squared and Fisher's exact tests. RESULTS: There were 53 cases (26.2%) of EMVI-positive rectal carcinoma. Of the patients with EMVI, 24.5% developed metastases at 1 year follow-up, compared to 6.7% of those without. There is a significant difference in prognosis between those patients with and those without MRI-detected EMVI (χ(2) = 12.29, p < 0·001). Those with EMVI have a 3.7 times increased relative risk of developing metachronous metastases within 1 year of diagnosis. CONCLUSION: MRI-detected EMVI-positive rectal carcinomas are associated with an increased risk of metachronous metastases within 1 year of diagnosis. Currently, EMVI status does not directly influence the initial management of rectal carcinoma. This available and potentially prognostic feature could be used to guide treatment pathways to increase disease-free survival.