Botulinum-toxin-A injection following conservative management in patients with dyssynergic defaecation only improves symptoms in the short term: a retrospective study

Objective: Dyssynergic defaecation (DD) is an important cause of chronic constipation. In patients where conservative treatments fail, injections of botulinum toxin A (BTX-A) into the puborectalis and anal sphincter muscles can be effective. Complications of this procedure are reported to be rare and generally mild. This study aimed to identify the complication rates and short- to medium-term success rates of BTX-A injections as a treatment for DD. Methods: A retrospective review was conducted on patients diagnosed with DD who had undergone BTX-A injections at a functional colorectal unit. Patient demographics, manometric assessment, conservative management, and injection technique were collected through a chart review. Subjective patient reports and comparison of pre- and postprocedure symptom scores were used to determine efficacy. Results: The 21 patients included (24 procedures, with 3 patients receiving BTX-A on two separate occasions) all received stool modification and dietary advice, and 20 patients underwent pelvic floor physiotherapy, averaging 8 sessions. The injections were universally applied under general anesthetic, primarily targeting the anal sphincter and/or puborectalis muscles. There were 6 reports of faecal urge/incontinence, with all but one being resolved within weeks. The BTX-A injection was subjectively reported as beneficial in 19 cases, averaging 4.7 months (range 1-32) of improvement. Only 2 were sustained beyond 12 months. Despite overall improvements in symptom scores from pre- to postprocedure, none were statistically significant. Conclusion: Following a course of conservative management, the BTX-A injection appears to be a safe treatment for DD, but only has short term efficacy. (AU)

Late diagnosis of a giant, pedunculated, cutaneous melanoma: a rare case study in an Australian tertiary centre.

Giant melanomas are uncommon tumours that still occur in Australia despite extensive public health messaging on the importance of early detection of skin cancers. We present the case of a 49-year-old female with a giant melanoma of her left arm measuring 101 × 71 × 22 mm, which had been growing for over 1 year and was metastatic on presentation. In this interesting case, we identify reasons for delayed presentation and highlight the importance of multi-disciplinary care in the management of such large tumours, with reference to other cases in the literature.

Elevated frequencies of CD8 T cells expressing PD-1, CTLA-4 and Tim-3 within tumour from perineural squamous cell carcinoma patients.

Perineural spread of tumour cells along cranial nerves is a severe complication of primary cutaneous squamous cell carcinomas of the head and neck region. While surgical excision of the tumour is the treatment of choice, removal of all the tumour is often complicated by the neural location and recurrence is frequent. Non-invasive immune treatments such as checkpoint inhibitor blockade may be useful in this set of tumours although little is understood about the immune response to perineural spread of squamous cell carcinomas. Immunohistochemistry studies suggest that perineural tumour contains a lymphocyte infiltrate but it is difficult to quantitate the different proportions of immune cell subsets and expression of checkpoint molecules such as PD-1, Tim-3 and CTLA-4. Using flow cytometry of excised perineural tumour tissue, we show that a T cell infiltrate is prominent in addition to less frequent B cell, NK cell and NKT cell infiltrates. CD8 T cells are more frequent than other T cells in the tumour tissue. Amongst CD8 T cells, the frequency of Tim-3, CTLA-4 and PD-1 expressing cells was significantly greater in the tumour relative to the blood, a pattern that was repeated for Tim-3, CTLA-4 and PD-1 amongst non-CD8 T cells. Using immunohistochemistry, PD-1 and PD-L1-expression could be detected in close proximity amongst perineural tumour tissue. The data suggest that perineural SCC contains a mixture of immune cells with a predominant T cell infiltrate containing CD8 T cells. Elevated frequencies of tumour-associated Tim-3+, CTLA-4+ and PD-1+ CD8 T cells suggests that a subset of patients may benefit from local antibody blockade of these checkpoint inhibitors.