Radiation Proctitis: A Review of Pathophysiology and Treatment Strategies.

Radiotherapy (RT) has become an integral part of cancer treatment worldwide; it aims to arrest the uncontrolled growth of tumor cells by using high-energy rays. Radiation proctitis is a known clinical manifestation after the RT regime for pelvic malignancies. Radiation proctitis can have a variable presentation, and there are a lot of patient-related factors that can affect the eventual outcome. In most instances, it is self-limiting; however, it can become chronic in some cases and can affect the quality of life. Many treatment options are recommended, but there has been no consensus on the treatment protocols for managing this known clinical condition. We have tried to briefly describe its pathogenesis, important factors affecting the outcome, and available treatment strategies.

Clinical Trial-Ready Patient Cohorts for Multiple System Atrophy: Coupling Biospecimen and iPSC Banking to Longitudinal Deep-Phenotyping.

Multiple system atrophy (MSA) is a fatal neurodegenerative disease of unknown etiology characterized by widespread aggregation of the protein alpha-synuclein in neurons and glia. Its orphan status, biological relationship to Parkinson's disease (PD), and rapid progression have sparked interest in drug development. One significant obstacle to therapeutics is disease heterogeneity. Here, we share our process of developing a clinical trial-ready cohort of MSA patients (69 patients in 2 years) within an outpatient clinical setting, and recruiting 20 of these patients into a longitudinal "n-of-few" clinical trial paradigm. First, we deeply phenotype our patients with clinical scales (UMSARS, BARS, MoCA, NMSS, and UPSIT) and tests designed to establish early differential diagnosis (including volumetric MRI, FDG-PET, MIBG scan, polysomnography, genetic testing, autonomic function tests, skin biopsy) or disease activity (PBR06-TSPO). Second, we longitudinally collect biospecimens (blood, CSF, stool) and clinical, biometric, and imaging data to generate antecedent disease-progression scores. Third, in our Mass General Brigham SCiN study (stem cells in neurodegeneration), we generate induced pluripotent stem cell (iPSC) models from our patients, matched to biospecimens, including postmortem brain. We present 38 iPSC lines derived from MSA patients and relevant disease controls (spinocerebellar ataxia and PD, including alpha-synuclein triplication cases), 22 matched to whole-genome sequenced postmortem brain. iPSC models may facilitate matching patients to appropriate therapies, particularly in heterogeneous diseases for which patient-specific biology may elude animal models. We anticipate that deeply phenotyped and genotyped patient cohorts matched to cellular models will increase the likelihood of success in clinical trials for MSA.

Circulating neurofilament is linked with morbid obesity, renal function, and brain density.

Neurofilament light chain (NfL) is a novel biomarker reflecting neuroaxonal damage and associates with brain atrophy, and glial fibrillary acidic protein (GFAP) is a marker of astrocytic activation, associated with several neurodegenerative diseases. Since obesity is associated with increased risk for several neurodegenerative disorders, we hypothesized that circulating NfL and GFAP levels could reflect neuronal damage in obese patients. 28 morbidly obese and 18 lean subjects were studied with voxel based morphometry (VBM) MRI to assess gray and white matter densities. Serum NfL and GFAP levels were determined with single-molecule array. Obese subjects were re-studied 6 months after bariatric surgery. Morbidly obese subjects had lower absolute concentrations of circulating NfL and GFAP compared to lean individuals. Following bariatric surgery-induced weight loss, both these levels increased. Both at baseline and after weight loss, circulating NfL and GFAP values correlated inversely with eGFR. Cross-sectionally, circulating NfL levels correlated inversely with gray matter (GM) density, and this association remained significant also when accounting for age and total eGFR. GFAP values did not correlate with GM density. Our data suggest that when determining circulating NfL and GFAP levels, eGFR should also be measured since renal function can affect these measurements. Despite the potential confounding effect of renal function on NfL measurement, NfL correlated inversely with gray matter density in this group of subjects with no identified neurological disorders, suggesting that circulating NfL level may be a feasible biomarker of cerebral function even in apparently neurologically healthy subjects.

Cortical and Subcortical Dysmetabolism Are Dynamic Markers of Clinical Disability and Course in Anti-LGI1 Encephalitis.

BACKGROUND AND OBJECTIVES: This [18F]fluorodeoxyglucose (FDG) PET study evaluates the accuracy of semiquantitative measurement of putaminal hypermetabolism in identifying anti-leucine-rich, glioma-inactivated-1 (LGI1) protein autoimmune encephalitis (AE). In addition, the extent of brain dysmetabolism, their association with clinical outcomes, and longitudinal metabolic changes after immunotherapy in LGI1-AE are examined. METHODS: FDG-PET scans from 49 age-matched and sex-matched subjects (13 in LGI1-AE group, 15 in non-LGI1-AE group, 11 with Alzheimer disease [AD], and 10 negative controls [NCs]) and follow-up scans from 8 patients with LGI1 AE on a median 6 months after immunotherapy were analyzed. Putaminal standardized uptake value ratios (SUVRs) normalized to global brain (P-SUVRg), thalamus (P/Th), and midbrain (P/Mi) were evaluated for diagnostic accuracy. SUVRg was applied for all other analyses. RESULTS: P-SUVRg, P/Th, and P/Mi were higher in LGI1-AE group than in non-LGI1-AE group, AD group, and NCs (all p < 0.05). P/Mi and P-SUVRg differentiated LGI1-AE group robustly from other groups (areas under the curve 0.84-0.99). Mediotemporal lobe (MTL) SUVRg was increased in both LGI1-AE and non-LGI1-AE groups when compared with NCs (both p < 0.05). SUVRg was decreased in several frontoparietal regions and increased in pallidum, caudate, pons, olfactory, and inferior occipital gyrus in LGI1-AE group when compared with that in NCs (all p < 0.05). In LGI1-AE group, both MTL and putaminal hypermetabolism were reduced after immunotherapy. Normalization of regional cortical dysmetabolism associated with clinical improvement at the 6- and 20-month follow-up. DISCUSSION: Semiquantitative measurement of putaminal hypermetabolism with FDG-PET may be used to distinguish LGI1-AE from other pathologies. Metabolic abnormalities in LGI1-AE extend beyond putamen and MTL into other subcortical and cortical regions. FDG-PET may be used in evaluating disease evolution in LGI1-AE. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that semiquantitative measures of putaminal metabolism on PET can differentiate patients with LGI1-AE from patients without LGI1-AE, patients with AD, or NCs.

Extent of infectious SARS-CoV-2 aerosolisation as a result of oesophagogastroduodenoscopy or colonoscopy.

BACKGROUND: COVID-19 has caused an unprecedented pandemic and medical emergency that has changed routine care pathways. This article discusses the extent of aerosolisation of severe acute respiratory syndrome coronavirus 2, the virus that causes COVID-19, as a result of oesophagogastroduodenoscopy and colonoscopy. METHODS: PubMed and Google Scholar were searched for relevant publications, using the terms COVID-19 aerosolisation, COVID-19 infection, COVID-19 transmission, COVID-19 pandemic, COVID-19 and endoscopy, Endoscopy for COVID-19 patients. RESULTS: A total of 3745 articles were identified, 26 of which were selected to answer the question of the extent of SARS-CoV-2 aerosolisation during upper and lower gastrointestinal endoscopy. All studies suggested high infectivity from contact and droplet spread. No clinical study has yet reported the viral load in the aerosol and therefore the infective dose has not been accurately determined. However, aerosol-generating procedures are potentially risky and full personal protective equipment should be used. CONCLUSIONS: As it is a highly infectious disease, clinicians treating patients with COVID-19 require effective personal protective equipment. The main routes of infection are direct contact and droplets in the air and on surfaces. Aerosolisation carries a substantial risk of infection, so any aerosol-producing procedure, such as endoscopy, should be performed wearing personal protective equipment and with extra caution to protect the endoscopist, staff and patients from cross-infection via the respiratory system.

The PET Sandwich: Using Serial FDG-PET Scans with Interval Burst Suppression to Assess Ictal Components of Disease.

BACKGROUND: Determining the cause of refractory seizures and/or interictal continuum (IIC) findings in the critically ill patient remains a challenge. These electrographic abnormalities may represent primary ictal pathology or may instead be driven by an underlying infectious, inflammatory, or neoplastic pathology that requires targeted therapy. In these cases, it is unclear whether escalating antiepileptic therapy will be helpful or harmful. Herein, we report the use of serial [F-18] fluorodeoxyglucose positron emission tomography (FDG-PET) coupled with induced electrographic burst suppression to distinguish between primary and secondary ictal pathologies. We propose that anesthetic suppression of hypermetabolic foci suggests clinical responsiveness to escalating antiepileptic therapy, whereas non-suppressible hypermetabolic foci are suggestive of non-ictal pathologies that likely require multimodal therapy. METHODS: We describe 6 patients who presented with electrographic findings of seizure or IIC abnormalities, severe neurologic injury, and clinical concern for confounding pathologies. All patients were continuously monitored on video electroencephalography (cvEEG). Five patients underwent at least two sequential FDG-PET scans of the brain: one in a baseline state and the second while under electrographic burst suppression. FDG-avid loci and EEG tracings were compared pre- and post-burst suppression. One patient underwent a single FDG-PET scan while burst-suppressed. RESULTS: Four patients had initially FDG-avid foci that subsequently resolved with burst suppression. Escalation of antiepileptic therapy in these patients resulted in clinical improvement, suggesting that the foci were related to primary ictal pathology. These included clinical diagnoses of electroclinical status epilepticus, new-onset refractory status epilepticus, stroke-like migraine attacks after radiotherapy, and epilepsy secondary to inflammatory cerebral amyloid angiopathy. Conversely, two patients with high-grade EEG abnormalities had FDG-avid foci that persisted despite burst suppression. The first presented with a poor examination, fever, and concern for encephalitis. Postmortem pathology confirmed suspicion of herpes simplex virus encephalitis. The second patient presented with concern for checkpoint inhibitor-induced autoimmune encephalitis. The persistence of the FDG-avid focus, despite electrographic burst suppression, guided successful treatment through escalation of immunosuppressive therapy. CONCLUSIONS: In appropriately selected patients, FDG-PET scans while in burst suppression may help dissect the underlying pathophysiologic cause of IIC findings observed on EEG and guide tailored therapy.

Neurosarcoidosis.

Sarcoidosis is an idiopathic multisystem granulomatous disorder. Neurologic manifestations in sarcoidosis are varied and making a diagnosis of neurosarcoidosis can be difficult as it mimics various other neurologic diseases. Knowledge of the syndromes associated with neurosarcoidosis can help guide the diagnostic evaluation. Definitive diagnosis requires neurologic tissue evidence of noncaseating granuloma, but in practice probable diagnosis is often made through nonneurologic biopsy and a characteristic syndrome and imaging. Treatment remains empiric, but new advances in immunologic therapy hold promise for effective and less-toxic regimens.

Brain: positron emission tomography tracers beyond [¹8F]fluorodeoxyglucose.

Several PET radiopharmaceuticals beyond FDG have been used to study the physiology and pathophysiology in neurosciences. This article provides a broad overview of some of the commonly studied radiopharmaceuticals for PET imaging in selected neurologic conditions, particularly attempting to study their clinical relevance. Future studies on the use of advanced PET imaging in delineating neural pathophysiology, drug development, and altering patient management and outcomes across the disciplines of neurosciences are needed.

11C-methionine PET for grading and prognostication in gliomas: a comparison study with 18F-FDG PET and contrast enhancement on MRI.

UNLABELLED: The aim of this study was to compare the grading and prognostic value of l-[methyl-(11)C]-methionine ((11)C-MET) PET in glioma patients with (18)F-FDG PET and contrast-enhanced MRI. METHODS: Patients (n = 102) with histopathologically confirmed gliomas were followed up for an average of 34.6 ± 3.8 mo after PET. The median survival was 18 ± 4.7 mo in the high-grade glioma group and 58 ± 27 mo in the low-grade glioma group. Patients underwent (18)F-FDG PET, (11)C-MET PET, and MRI in the diagnostic and preoperative stage. The ratio of the mean standardized uptake value in the tumor to mean standardized uptake value in contralateral normal cortex (T/N ratio) was calculated. Kaplan-Meier survival analysis and ANOVA were performed. RESULTS: T/N ratios for (11)C-MET PET and (18)F-FDG PET were significantly higher in high-grade gliomas than in low-grade gliomas (2.15 ± 0.77 vs. 1.56 ± 0.74, P < 0.001, and 0.85 ± 0.61 vs. 0.63 ± 0.37, P < 0.01, respectively). Median survival was 19 ± 5.4 mo in patients with a T/N ratio greater than 1.51 for (11)C-MET PET and 58 ± 26.7 mo in those with a T/N ratio less than 1.51 (P = 0.03). Among the LGGs, median survival was lower in patients with a mean T/N ratio greater than 1.51 for (11)C-MET PET (16 ± 10 mo; 95% confidence interval, 1-36 mo) than in those with a T/N ratio less than 1.51 (P = 0.04). No significant difference in survival in LGGs was based on (18)F-FDG uptake and MRI contrast enhancement. CONCLUSION: (11)C-MET PET can predict prognosis in gliomas and is better than (18)F-FDG PET and MRI in predicting survival in LGGs.

Positron emission tomography applications in clinical neurology.

Positron emission tomography (PET) is a molecular imaging technique for developing maps of functional and biochemical activity in target tissues in vivo. PET has led to significant insights into nervous system biology, physiology, and pathophysiology in health and disease. Several of these insights and applications have a direct usefulness for the clinical neurologist. Although [F-18]fluorodeoxyglucose (FDG-) PET has remained a workhorse of PET imaging, many other radiolabeled biomolecules have been studied using PET. This article aims to provide an overview of current clinical usefulness of PET across the neurologic subspecialties including dementias, movement disorders, epilepsy, brain tumors, and neurologic infectious and inflammatory diseases.

Upper gastrointestinal bleeding due to gastric stromal tumour: a case report.

INTRODUCTION: Gastro-intestinal stromal tumours are the most common mesenchymal tumours of the gastro-intestinal tract. This case report highlights the necessity of early surgical intervention in such cases to avoid mortality due to rebleeding and to raise the awareness of rare causes of upper gastrointestinal bleed and their management. CASE PRESENTATION: A 61-year-old male presented to the accident and emergency department with a one-day history of haemetemesis with coffee ground vomiting. After initial resuscitation, he underwent upper gastrointestinal endoscopy under sedation which demonstrated a large, bleeding, gastric mass with a central crater along the greater curvature of the stomach. A partial gastrectomy was performed taking a wedge of the stomach with clearance from the tumour, with no signs of extraperitoneal disease. CONCLUSION: Early surgical intervention, either open or laparoscopic resection, is the treatment of choice to prevent rebleeds. In general, complete surgical resection is accomplished in 40-60% of all gastro-intestinal stromal tumours patients, and in >70% of those with primary non- metastatic gastro-intestinal stromal tumour. In our case we had completely excised the tumour. Following surgery, all patients must be referred to centres which have more experience in treating gastro-intestinal stromal tumours. Imatinib is proven to be the first effective systemic therapy in cases of unresectable or metastatic disease. All gastro-intestinal stromal tumours have the potential for aggressive behaviour with the risk being estimated from tumour size and mitotic count.

Failed laparoscopic anti-reflux surgery and indications for revision. A retrospective study.

UNLABELLED: Revisional anti-reflux surgery is required in certain patients for either early post-operative complications or recurrence of their original symptoms. The aim of this study is to review our revisional surgeries, learn the lessons and to highlight the treatment options for recurrent gastrooesophageal symptoms. MATERIALS AND METHODS: Three hundred and fifty one patients underwent laparoscopic anti-reflux surgery through January 2000 to March 2006 at our minimal access unit. Thirty-seven patients were diagnosed with failure of anti-reflux surgery. Patient's data and follow up were retrieved from medical records. All recurrences were investigated for underlying cause and their managements were planned accordingly. RESULTS: Thirty-seven (10.54%) patients who developed early post-operative complications or recurrence of gastroesophageal symptoms were 25 women and 12 men. Heartburn was the commonest recurrent symptom. The majority of failures occurred in the first two years. Fourteen patients underwent revisional surgery while 23 patients were treated with acid reducing medications and showed a good response. The re-operation rate is 3.98%. There was no mortality and the total morbidity rate for revisional surgery is 7.14%. CONCLUSION: Early surgical complications of the initial procedures are managed by revisional surgery and the results were satisfactory provided these complications are detected early. Chronic failure of anti-reflux surgery can be managed by revisional surgery or medications depending on clinical symptoms and patients preference.

Management of an incidentally found large adrenal myelolipoma: a case report.

Adrenal myelolipoma is a rare benign neoplasm composed of mature adipose and hematopoietic tissue. Most lesions are small, unilateral and asymptomatic, discovered incidentally at autopsy or on imaging studies performed for other reasons. We would like to present a case report of this rare tumour. Cross-sectional imaging is helpful in making a pre-operative diagnosis. The size of the lesion should be a criterion for surgical intervention.

Long-term study of port-site incisional hernia after laparoscopic procedures.

BACKGROUND: Laparoscopic surgery is widely practiced and offers realistic benefits over conventional surgery. There is considerable variation in results between surgeons, concerning port-site complications. The aim of this study was to evaluate the laparoscopic port closure technique and to explore the factors associated with port-site incisional hernia. METHODS: Between January 2000 and January 2007, 5541 laparoscopic operations were performed by a single consultant surgeon for different indications. The ports were closed by the classical method using a J-shaped needle after release of pneumoperitoneum. The incidence of port-site incisional hernias was calculated. All patients were followed up by outpatient clinic visits and by their general practitioners. RESULTS: During a 6-year period, 5541 laparoscopic operations were performed. Eight patients (0.14%) developed port-site hernia during a mean follow-up period of 43 months (range, 25 to 96) and required elective surgery to repair their hernias. No major complications or mortality was reported. CONCLUSION: Laparoscopic port closure using the classical method was associated with an acceptable incidence of port-site hernia. Modification of the current methods of closure may lead to a new technique to prevent or reduce the incidence of port-site incisional hernias.

Laparoscopic treatment of early small bowel obstruction after laparoscopic ventral hernia repair.

PURPOSE: The aim of presenting this case is to highlight the importance of early diagnosis and laparoscopic treatment of bowel obstruction following laparoscopic ventral hernia repair. METHOD: A 45-years old patients underwent laparoscopic exploration for bowel obstruction following laparoscopic repair of ventral hernia. The early adhesions were divided and the mesh was re-fixed using different ticker. RESULTS: The patient had uneventful recovery and was discharged in good health. CONCLUSIONS: Early small bowel obstruction following laparoscopic ventral hernia repair was managed using minimal access. High index of suspicior and early laparoscopic exploration is important to avoid catastrophic complications following laparoscopic ventral hernia repair.