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"Weir, Justin"
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Malignant Melanoma of the Gastrointestinal Tract: Symptoms, Diagnosis, and Current Treatment Options
Malignant melanoma (MM) has become the fifth most frequent cancer in the UK. It is the most common carcinoma to metastasize to the gastrointestinal (GI) tract. MM particularly has an affinity to spread to the small bowel, which is followed by the involvement of the stomach and large intestine. Excellent endoscopic options including video capsule endoscopy and enteroscopy are available for a precise diagnosis of GI involvement by a metastatic MM. The complete surgical resection of GI metastatic MM in carefully selected patients not only provides symptom control, but has also been associated with an increase in overall survival. The approval of BRAF-targeted therapies and immune checkpoint inhibitors has transformed therapeutic approaches for patients with metastatic MM over the past decade. Currently, the overall survival of patients with advanced metastatic MM who have been treated with a combination of immunotherapeutic agents reaches 52% at five years. The role of surgery for patients with the metastatic involvement of the GI tract with MM is evolving in the era of effective systemic treatments.
Journal Article
Lactate dehydrogenase activity staining demonstrates time-dependent immune cell infiltration in human ex-vivo burn-injured skin
Burn injuries constitute one of the most serious accidental injuries. Increased metabolic rate is a hallmark feature of burn injury. Visualising lactate dehydrogenase (LDH) activity has been previously used to identify metabolic activity differences, hence cell viability and burn depth in burn skin. LDH activity was visualised in injured and uninjured skin from 38 sub-acute burn patients. LDH activity aided the identification of spatially correlating immunocompetent cells in a sub-group of six patients. Desorption Electrospray Ionisation Mass Spectrometry Imaging (DESI MSI) was used to describe relative lactate and pyruvate abundance in burned and uninjured tissue. LDH activity was significantly increased in the middle and deep regions of burnt skin compared with superficial areas in burnt skin and uninjured tissue and positively correlated with post-burn time. Regions of increased LDH activity showed high pyruvate and low lactate abundance when examined with DESI-MSI. Areas of increased LDH activity exhibited cellular infiltration, including CD3 + and CD4 + T-lymphocytes and CD68 + macrophages. Our data demonstrate a steady increase in functional LDH activity in sub-acute burn wounds linked to cellular infiltration. The cell types associated are related to tissue restructuring and inflammation. This region in burn wounds is likely the focus of dysregulated inflammation and hypermetabolism.
Journal Article
Primary Immunoglobulin G4-Related Laryngeal Disease: A Case Series and Review of Literature
Objective:
Immunoglobulin G4-related disease (IgG4-RD) is an increasingly recognised cause of various systemic fibro-inflammatory conditions. However, laryngeal involvement as a primary feature is extremely rare. We aimed to report on a case series of such patients and examine the global literature relating to laryngeal involvement.
Methods:
Having previously reported a case of IgG4-RD laryngeal pseudotumour, we describe a case series of further 4 patients with primary laryngeal IgG4-RD managed by our UK quaternary airway service and provide a brief overview of laryngeal IgG4-RD.
Results:
Including our cases, 14 cases of primary laryngeal IgG4-RD have been reported. Vocal cord involvement is relatively uncommon. Repeat biopsies may be required to achieve histological diagnosis. Remission is achievable by commencement of immunomodulatory treatment, following which laryngeal reconstruction may be necessary.
Conclusion:
Laryngeal involvement is a rare presentation of IgG4-RD, itself a rare and difficult-to-diagnose condition. A high and prolonged index of suspicion is necessary from both surgical and pathological specialists for correct diagnosis and management.
Journal Article
Leo Tolstoy and the Alibi of Narrative
One hundred years after his death, Tolstoy still inspires controversy with his notoriously complex narrative strategies. This original book explores how and why Tolstoy has mystified interpreters and offers a new look at his most famous works of fiction.
eBook
Surgical Management of Primary Anorectal Melanoma: Is Less More?
Purpose
Ano-uro-genital (AUG) Mucosal Melanoma UK guidelines recommended a less radical surgical strategy for anorectal melanoma (ARM) where possible. We report our experience of ARM consistent with that approach including clinical presentation, intervention undertaken and prognosis.
Methods
We present a retrospective study of 15 consecutive patients with ARM surgically treated between November 2014 and April 2023. Patients were divided into the two surgery types: wide local excision (WLE,
n
= 9) and abdominoperineal resection (APR,
n
= 6). Data on demographics, diagnosis, treatment and oncological outcomes were assessed between the groups.
Results
The mean age was 65.3 ± 17.4 years and 6 (40.0%) were female patients. Nine patients (60.0%) were diagnosed with stage I and six patients (40.0%) with stage II disease. R0 margins were achieved in all cases. The overall mean length of stay was lower following WLE compared to APR (2.6 ± 2.4 days versus 14.0 ± 9.8 days,
p
= 0.032). Two complications were observed in the WLE group compared to four complications after APR (
p
= 0.605). Five patients (55.5%) developed local/distant recurrence in the WLE group compared to three patients (50.0%) in the APR group (
p
= 0.707), with a median overall survival of 38.5 (12–83) months versus 26.5 (14–48) months, respectively.
Conclusions
Achieving clear margins by the least radical fashion may have equivalent oncological outcomes to radical surgery, potentially reducing patient morbidity and preserving function. In our experience, the surgical management of ARM consistent with the ‘less is more’ approach adhering to AUG guidelines has acceptable outcomes.
Journal Article
Skull base pathology – a diagnostic conundrum
BackgroundMyoepithelioma is a rare benign neoplasm, most commonly derived from salivary glands, but there are limited cases of extra salivary gland involvement too. There is little knowledge on typical investigative findings and, instead, diagnosis relies on immunohistochemistry analysis. To our knowledge, this paper reports the 13th case of sinonasal myoepithelioma in the English literature.Case reportThis paper presents a 25-year-old man who complained of chronic nasal obstruction. A sinonasal mass was noted on examination that appeared benign on imaging. Biopsy revealed a grade 2 chondrosarcoma that was endoscopically resected; however, excisional margins were positive. On histopathological review at the multidisciplinary team meeting, the lesion was more in keeping with chondromyxoid fibroma, but immunohistochemistry analysis confirmed a myoepithelioma lesion. In light of this revised diagnosis, quorate opinion was for follow up with active monitoring.ConclusionSinonasal tumours require a thorough history, examination and investigation before a treatment plan can be formulated. If there is diagnostic uncertainty, it is important to keep a wide differential list and seek a second specialist opinion where possible.
Journal Article
Turgenev as Institution: Sketches from a Hunter's Album in Tolstoi's Early Aesthetics
[...] a cycle of events based on the non-existent dream of his mother's death has been set in motion; these events acquire their own reality. [...] one concludes, the fictional Childhood is composed of events which, though they may never have existed, are meant to evoke genuine emotion.
Journal Article