Queen Elizabeth Hospital Birmingham Charity

Abstract Background & Aim Gastrointestinal stromal tumours (GISTs) require individualised surgical strategies based on tumour biology and anatomical complexity. We assessed real-world outcomes from a high-volume tertiary centre, including the use of minimally invasive approaches and complex resections. Method A retrospective study of 152 primary GIST resections performed between 2012 and 2024 was conducted. Demographics, tumour characteristics, surgical approach, recurrence, and survival outcomes were analysed. A Subgroup analysis of the multi-visceral resections was also analysed. SPSS v24 was used for statistical analysis, with significance set at p<0.05. Results Most tumours were gastric 75%, spindle-cell type 77.6%, and >5 cm in 63.8%. Minimally invasive surgery (MIS) was performed in 48% of cases, including one-third of large tumours. R0 resection was achieved in 96.1%, with an overall 5-year survival of 91.4% and recurrence in 9.9%. In multi-visceral resections (n =18), recurrence was significantly higher (27.8%, p =0.020), although 5-year survival remained high (94.4%). Postoperative complication rates were acceptable in the entire cohort: VTE, 9.5%; leak, 3.3%; reoperation, 2.6%; readmission rate, 2.6%; and surgical site infections (SSIs), 2%, with higher rates in multi-visceral cases. Conclusions This is one of the largest regional GIST series evaluating MIS use in GIST >5cm. Post op complications, namely leaks and SSI, are within the globally accepted range. Multi-visceral resections were shown to predict recurrence. Recurrence and 5-year disease free survival reflects favourable outcomes in a well-managed tertiary setting. These findings, along with other data, support the importance of effective multidisciplinary management in GIST; evident in our high-volume centre.

This systematic review and meta-analysis evaluated the role of neoadjuvant systemic therapy in enabling partial nephrectomy (PN) for patients with high-complexity or locally advanced non-metastatic renal cell carcinoma (RCC). Thirteen studies, including 359 patients, were analysed, with most investigating vascular endothelial growth factor receptor-targeted tyrosine kinase inhibitors (VEGFR-TKIs), while some assessed immune checkpoint inhibitors (IO) alone or in combination. The pooled results showed that neoadjuvant therapy increased the feasibility of PN, achieving high rates of tumour shrinkage and negative surgical margins. Perioperative outcomes, including blood loss and complications, were comparable to upfront surgery, and severe complications were uncommon. Renal function generally declined following treatment, but nephron-sparing approaches preserved kidney function better than radical surgery. Early survival outcomes, including recurrence-free and overall survival, were favourable across studies. These findings suggest that neoadjuvant therapy may be a safe and effective strategy to expand surgical options in complex renal tumours. However, larger prospective trials are needed to validate these results.

To investigate the effect of topical cyclosporine (0.05%) on the ocular surface and corneal sub-basal nerve plexus in patients with chronic Ocular Graft-versus-Host Disease (oGVHD). This prospective study included 24 eyes from 24 patients with chronic oGVHD. All patients were treated twice daily with topical cyclosporine (0.05%). Ophthalmic examinations were performed at baseline and at the 1st, 3rd, and 6th months of treatment, including the evaluation of corneal fluorescein staining (CFS).The Ocular Surface Disease Index (OSDI) questionnaire was administered. Non-invasive tear break-up time (NIBUT) (Sirius, CSO, Italy), central corneal epithelial thickness (ET) (AS-OCT, Topcon 3D OCT-1 Maestro, Japan), upper eyelid non-contact meibography (Sirius, CSO, Italy), and in vivo confocal microscopy (ConfoScan4, Nidek, Japan) measurements were performed.A paired t-test was used for comparative analysis. Significant improvements were observed in CFS, NIBUT, and OSDI scores at the 1st, 3rd, and 6th months, as well as in upper eyelid meiboscores at the 3rd and 6th months compared to baseline (p < 0.05).However, no significant changes were found in ET, corneal sub-basal nerve fiber density, nerve fiber count, or fiber tortuosity throughout the study period (p > 0.05). While topical cyclosporine significantly improved the ocular surface and symptoms in patients with oGVHD, it did not alter the morphology of the corneal sub-basal nerve plexus. Its anti-inflammatory effects were evident at the epithelial level, but the treatment did not appear to affect the subepithelial region in the short term. Further research is needed to assess the long-term impact of topical cyclosporine on corneal innervation.

The DIPLOMA trial showed comparable radical resection rates after minimally invasive left pancreatectomy (MILP) and open left pancreatectomy (OLP) in patients with upfront resectable pancreatic cancer. Data on long-term overall survival (OS) and disease-free survival (DFS) are currently lacking, but are required before the oncological efficacy of MILP can be confirmed. To determine the long-term oncological outcome, including OS and DFS, of MILP vs OLP in patients with upfront resectable left-sided pancreatic cancer in the DIPLOMA trial. The randomized, patient-blinded and pathologist-blinded DIPLOMA trial was conducted between 2018 and 2021, with a follow-up duration of at least 36 months. It was a multicenter international trial that took place in 35 centers in 12 countries worldwide. Patients with upfront resectable pancreatic ductal adenocarcinoma of the body or tail of the pancreas were included. Participants were randomly assigned to undergo MILP (laparoscopic and robotic) or OLP. Patients were blinded for the surgical approach. Main outcomes included OS and DFS. Other outcomes include receipt of adjuvant therapy and time to start of adjuvant therapy. Between May 2018 and May 2021, 258 patients were randomized to the MILP (131 patients) and OLP (127 patients) groups. After a median follow-up of 38 (IQR 36-46) months, 134 patients (52%) had died and 127 patients (55%) experienced disease recurrence. OS did not differ significantly between the MILP and OLP groups (median, 32 vs 34 months; stratified hazard ratio, 1.02; 95% CI, 0.72-1.44; P = .92). Also, DFS did not significantly differ between the MILP and OLP groups (median, 21 vs 17 months; stratified hazard ratio, 0.96; 95% CI, 0.68-1.35; P = .81). Adjuvant therapy was administered in 79 patients after MILP (79 of 113 [70%]) and 79 patients after OLP (79 of 110 [72%]) (P = .63). Time to adjuvant therapy was comparable between groups (median 59 vs 56 days; P = .92). In this long-term follow-up of the randomized DIPLOMA trial in patients with upfront resectable pancreatic cancer, oncological outcomes after MILP and OLP did not differ significantly, confirming the oncological safety of MILP. International Standard Registered Clinical/Social Study Number Registry Identifier: ISRCTN44897265.

Facial nerve palsy (FNP) is a common neurological disorder. There are multiple causes of FNP, and Bell’s palsy is defined as an idiopathic cause of FNP. If a patient presents with facial palsy, a full investigation workup should be performed. Lyme disease can present with erythema migrans, fever, headache, muscle and joint pain, and facial palsy. We present a case of a 47-year-old man who presented with progression from unilateral to bilateral FNP. After a series of investigations, he was diagnosed with LNB. Even if MRI findings are normal, cerebrospinal fluid (CSF) analysis and Lyme serology (enzyme-linked immunosorbent assay followed by Western blot) in serum and/or CSF can confirm the diagnosis of neuroborreliosis. We have administered the patient IV ceftriaxone 2 g daily, as per the guidelines. He showed gradual improvement in FNP from House-Brackmann Grade V to Grade II on subsequent follow-ups. This case emphasizes the importance of broad clinical evaluation in diagnosing FNP. Early detection of LNB and initiation of treatment can ensure patients have a favorable outcome.

Introduction: There is limited local data comparing the outcomes of core decompression and fibular strut grafting in early-stage avascular necrosis (AVN) of the hip. International findings may not be directly applicable due to population-specific factors such as genetics, lifestyle, and healthcare access. Early identification of the optimal surgical option is essential for improving patient counseling, postoperative recovery, and overall clinical outcomes.Objective: To compare postoperative pain and functional outcomes of core decompression versus fibular strut grafting in patients with early-stage AVN of the hip.Methodology: This prospective, randomized comparative cohort study was conducted at the Department of Orthopedic Surgery, Khyber Teaching Hospital, Peshawar, from 14th March 2023 to 13th September 2023. A total of 112 patients aged 18-50 years with Ficat and Arlet stage I-II AVN were enrolled and equally allocated into the core decompression or fibular strut graft groups using blocked randomization. Postoperative pain was assessed at 12 weeks using the visual analog scale (VAS), with a score >3 considered significant. Functional status was evaluated using the Hip Disability and Osteoarthritis Outcome Score (HOOS). Data were analyzed using chi-square tests for categorical variables and appropriate tests for functional scores, with p ≤ 0.05 considered statistically significant.Results: Significant postoperative pain (VAS > 3) was observed in 11 (19.6%) patients in the core decompression group and 17 (30.4%) in the fibular strut graft group (χ² = 1.708, p = 0.190). Stratification by age, gender, and BMI consistently showed lower pain rates in the core decompression group, though differences were not statistically significant. HOOS functional scores demonstrated a similar trend favoring core decompression, but these differences also did not reach statistical significance.Conclusion: Core decompression was associated with fewer patients experiencing significant postoperative pain and showed a trend toward better short-term functional outcomes compared to fibular strut grafting. Its minimally invasive nature may make it a preferable option for early pain management in patients with early-stage AVN of the hip. However, the lack of statistical significance and the short follow-up period warrant further studies with larger sample sizes and inclusion of long-term functional and radiological outcomes before definitive clinical recommendations can be made.

Abstract AIMS Gliomas and other primary brain tumours remain a significant cause of cancer-related mortality, with lim- ited predictive biomarkers to guide therapy selection. The PEAR-GLIO trial investigates Pear Bio’s AI-driven ex vivo platform to evaluate the therapeutic sensitivity of FDA-approved and experimental treatments on patient- derived 3D immune-microtumours. This observational study aims to validate the platform’s ability to provide actionable insights for patient stratification and treatment optimisation. The trial also integrates patient and public involvement (PPIE) to improve study design and accessibility. METHODS PEAR-GLIO (NCT06038760) is a UK-based observational study enrolling 50 patients with operable primary brain tumours, including grades 2-4 gliomas. Inclusion criteria include histologically confirmed malignancy, avail- ability of ≥0.4g of tumour tissue and 40mL of whole blood, and consent for sample and data use. Patients re- ceiving pre-surgical chemotherapy or radiotherapy within 30 days or with inoperable disease are excluded. Tumour-derived and immune cells are co-cultured as physiologically relevant 3D immune-microtumours and exposed to FDA-approved and experimental treatments. Phenotypic and molecular responses, including changes in tumour viability, cell death, migration, and immune cell infiltration, are assessed using live imag- ing and computer vision. Real-time confocal imaging and omics analyses evaluate drug mechanisms of action, correlating responses with biomarkers like MGMT methylation, IDH mutation, and 1p/19q co-deletion. RESULTS Recruitment began in October 2023, with 12 patients enrolled to date. Data from the first cohort will guide plat- form optimization and scalability. All samples are anonymised, with outcomes monitored per RANO guidelines. CONCLUSION Early PPIE efforts have enhanced trial design. The platform is concurrently being validated in other high- unmet-need indications, including early-stage breast cancer (NCT05435352) and metastatic kidney cancer (NCT06264479), aiming to advance precision treatment selection and transform clinical oncology.

ZusammenfassungHintergrund und ZielsetzungDie Mycosis fungoides (MF) ist das häufigste kutane Lymphom (CL). Ihre Diagnosestellung erfolgt im Frühstadium nachweislich verzögert. Eine rechtzeitige Diagnose ist wichtig, um ungeeignete Therapien und eine unnötige Belastung der Patienten zu vermeiden. Ziel der Studie war es, die Ansichten von Experten und Nicht‐Experten für kutane T‐Zell‐Lymphome (CTCL) hinsichtlich der Diagnose der MF im Frühstadium zu erfassen und miteinander zu vergleichen, um den klinischen Bedarf in diesem Bereich aufzuzeigen.MethodikZwei unterschiedliche Fragebögen wurden an Ärzte mit potenziellem oder keinem besonderen Interesse an kutanen Lymphomen (Nicht‐Experten) sowie an solche mit besonderem Interesse an CL (Experten) versendet. Letztere wurden durch ihre Teilnahme an der PROCLIPI‐Studie (PROspective Cutaneous Lymphoma International Prognostic Index) identifiziert.ErgebnisseAn der Umfrage nahmen 382 Personen teil – 86 Experten und 296 Nicht‐Experten. Insgesamt waren 82% der Befragten der Ansicht, dass die Diagnose der frühen MF verzögert erfolgt. Ihre häufige Fehlinterpretation als benigne entzündliche Dermatose wurde als wichtigster ursächlicher Faktor genannt.SchlussfolgerungenNicht‐Experten gehen davon aus, dass eine verzögerte Diagnose die therapeutische Wirksamkeit und Prognose der MF beeinträchtigt, während Experten vor allem negative Auswirkungen auf die Lebensqualität vermuten. Unsere Studie zeigt einen bislang ungedeckten klinischen Bedarf auf. Die Aufklärung über die Diagnose der MF im Frühstadium sowie das Bewusstsein für deren Auswirkungen auf das Patientenmanagement sollten gezielt gefördert werden.

Abstract Aims Colorectal surgery outcomes are better when performed by dedicated surgeons at dedicated centres. No established colorectal cancer service exists in any public sector hospitals in Lahore, Pakistan. We developed a referral unit for colorectal cancers in our hospital. Methods All colorectal cancer patients operated from Jan 2018 to Dec 2024 included. Patient’s demographics, Area of presentation (Emergency/Elective), Type of Surgery were recorded. Early Post-Op Outcomes including margins, CRM positivity, LN yield and post op complications were recorded. Results 72 months. 183 cases. 84 colon cancers and 99 cases of rectal cancer. 179 out of 183 cases were operated of which are 24 laparoscopic colonic resection and 60 are open colonic resection. Among rectal cancer 40 are laparoscopic resection and 59 are open rectal cancer resections. In terms of oncological out comes 19 cases were at stage 2 disease, 160 cases were at stage 3 , median lymph node retrieved 13, proximal margin positive 0, distal margin positive 2 and CRM positive In terms of Complications Superficial SSI 24, Deep SSI 4, Bleeding 2, Anastamotic Leak 6 Mortality 6. Colon cancerN=84Rectal cancersN=99Sigmoid Colectomy23Anterior resection29Right Hemicolectomy32Hartman15Left Hemicolectomy9APR23Total Colectomy7Extra Levator APR8Stoma formation only11Posterior Pelvic exenteration7Diagnostic lap and abandoned2stoma only10Resection of recurrent Rectal cancer3 Conclusion We have established dedicated referral centre for colorectal cancers. Next step is to start a Training program for colorectal surgery in future.

<h3>Introduction</h3> Inclisiran is a novel small interfering RNA (siRNA)-based therapy designed to inhibit the expression of the PCSK9 (Proprotein Convertase Subtilisin/Kexin type 9) gene. By doing so, it enhances the recycling and membrane expression of LDL receptors in hepatocytes, leading to a reduction in LDL cholesterol (LDL-c) levels. Despite its promising mechanism, there is limited real-world data on its safety and effectiveness in achieving LDL-c reduction targets. <h3>Objective</h3> This study aimed to assess the efficacy of Inclisiran in lowering LDL cholesterol levels and to evaluate its safety profile over a one-year period in patients with hyperlipidaemia. <h3>Methodology</h3> A total of 77 patients (mean age 66.5 ± 10.2 years, 72.7% male, 27.3% female, 30 Asians, 47 Caucasians) were enrolled and followed from September 2023 to September 2024. Baseline characteristics included medical histories of hypertension, diabetes, chronic kidney disease (CKD), smoking status, and prior acute coronary syndrome (ACS). Lipid profiles were assessed three months after a single dose of Inclisiran to evaluate changes in LDL-c levels. The study compared LDL-c reductions across various treatment regimens, including Inclisiran monotherapy and combinations with low-dose statins, high-dose statins, ezetimibe, or other lipid-lowering drugs. Statistical analyses, including paired t-tests, ANOVA, and independent sample t-tests, were performed using IBM SPSS Statistics version 25 to determine significant differences. <h3>Results</h3> Of the 77 patients, 71 completed the study, with one death and five lost to follow-up. Inclisiran treatment resulted in a significant mean LDL-c reduction of 53.8% (from 3.4 ± 0.8 mmol/L to 1.57 ± 0.77 mmol/L, p &lt; 0.05). Total cholesterol levels also decreased significantly (from 5.39 ± 1.10 mmol/L to 3.64 ± 1.05 mmol/L, p &lt; 0.05), while changes in HDL cholesterol and triglycerides were mild and not statistically significant. Ethnic differences were observed, with Asians achieving a greater mean LDL-c reduction (61.58%) compared to Caucasians (50.41%, p &lt; 0.05). Subgroup analysis revealed significant variations in LDL-c reduction based on treatment regimens. The greatest reduction was seen in patients receiving Inclisiran combined with statins and ezetimibe (69.03%), followed by Inclisiran with high-dose statins (64.40%) and low-dose statins (52.20%). In contrast, Inclisiran monotherapy achieved a 41.12% reduction, and combinations with other lipid-lowering drugs resulted in a 46.04% reduction. These differences were statistically significant (p &lt; 0.05), highlighting the superior efficacy of combination therapies. %. This difference was statistically significant (<i>p</i> &lt; 0.05), which highlights the superior efficacy of combination therapies involving Inclisiran (figure&nbsp;1). Patients on baseline statin therapy showed a greater mean LDL-c reduction (61.4%) compared to those not on statins (43.77%, p &lt; 0.05). Three patients experienced an increase in LDL-c post-treatment, potentially due to drug resistance. The safety profile of Inclisiran was favourable, with only three patients reporting mild local injection site irritation. <h3>Conclusion</h3> Inclisiran significantly reduces LDL cholesterol levels, with the greatest efficacy observed when used in combination with statins and ezetimibe. Efficacy varied by ethnicity and was enhanced in patients already on statin therapy. The drug demonstrated a favourable safety profile with minimal adverse effects. These findings emphasize the importance of optimizing lipid-lowering regimens to achieve superior LDL-c reductions in clinical practice.