scholarly journals Intratumoural Treatment of 18 Cytologically Diagnosed Canine High-Grade Mast Cell Tumours With Tigilanol Tiglate

2021 ◽  
Vol 8 ◽  
Author(s):  
Graham K. Brown ◽  
Justine E. Campbell ◽  
Pamela D. Jones ◽  
Thomas R. De Ridder ◽  
Paul Reddell ◽  
...  

Canine high-grade mast cell tumours (HGMCT) are associated with a poor prognosis, are inherently more invasive, and have higher rates of local recurrence. The primary aim of this retrospective study was to assess the efficacy of intratumoural tigilanol tiglate (TT) as a local treatment option. Eighteen dogs with mast cell tumours (MCT) cytologically diagnosed by veterinary pathologists as either high-grade or suspected high-grade MCT were treated with TT. The TT dose was based on tumour volume (0.5 mg TT/cm3 tumour volume) and delivered intratumourally using a Luer lock syringe and a fanning technique to maximise distribution throughout the tumour mass. Efficacy was assessed on the presence/absence of a complete response (CR) to therapy at days 28 and 84 using response evaluation criteria in solid tumours (RECIST). For dogs not achieving a CR after 28 days, the protocol was repeated with a second intratumoural TT injection. Ten out of 18 dogs (56%) in this study achieved and maintained a CR to at least 84 days after their first or second treatment. Six patients were alive and available for evaluation at 2 years, three of those were recurrence free, and a further three patients were recurrence free following a second treatment cycle. Tigilanol tiglate shows efficacy for local treatment of HGMCT, with higher efficacy noted with a second injection if a CR was not achieved following the first treatment. In the event of treatment site recurrence (TSR), the tumour may be controlled with additional treatment cycles. Tigilanol tiglate provides an alternative local treatment approach to dogs with HGMCT that would either pose an unacceptable anaesthetic risk or the tumour location provides a challenge when attempting surgical excision.

2018 ◽  
Vol 56 (1) ◽  
pp. 43-49 ◽  
Author(s):  
Silvia Sabattini ◽  
Giuliano Bettini

Cutaneous mast cell tumors (cMCTs) account for approximately 20% of skin neoplasms in cats. As there is no grading system for these tumors, prognosis is difficult to estimate. Although the typical presentation is a benign tumor that can be cured by surgical excision, a small but important proportion of feline cMCTs is biologically aggressive and can spread to local lymph nodes, precede the onset of disseminated cutaneous disease, or be associated with visceral involvement. A number of macroscopic and histologic features were retrospectively evaluated in cases of feline cMCTs treated with surgical excision with or without medical therapy. Cats were divided into 2 groups based on the clinical outcome. Group 1 included cats alive with no mast cell tumor–related disease at 1000 days from surgery; group 2 included cats developing histologically confirmed metastatic or cutaneous disseminated disease. The criteria allowing the best differentiation between the groups were used to develop a grading scheme. Groups 1 and 2 were composed by 48 (76%) and 15 (24%) cases, respectively. Tumors were classified as high grade if there were >5 mitotic figures in 10 fields (400×) and at least 2 of the following criteria: tumor diameter >1.5 cm, irregular nuclear shape, and nucleolar prominence/chromatin clusters. According to this scheme, the 15 (24%) high-grade cMCTs had significantly reduced survival time (median, 349 days; 95% CI, 0–739 days) as compared with the 48 low-grade tumors (median not reached; P < .001). Further studies are warranted to validate this grading system and test reproducibility on a larger case series.


1991 ◽  
Vol 6 (4) ◽  
pp. 247-252 ◽  
Author(s):  
D.J. Cruickshank ◽  
P.B. Terry ◽  
W.T. Fullerton

Seventy four consecutive patients with epithelial ovarian cancer have been followed up longitudinally with serial serum CA125 for up to 48 months. From this database, the CAl25 changes in small volume disease have been evaluated. For long term complete responders (n = l2), the mean plateau level of CA125 was 7.2 U/ml (95% confidence interval; 5.6 to 9.2 U/ml). The natural half-life of CA125 at 5.1 days (range 3.8 to 7 days) was calculated from five patients with Stage I and II disease who underwent complete surgical excision. A mean lead time of 99 days (range 14 to 255 days) was demonstrated between marker detection of disease progression and clinically apparent progressive disease in 12 out of 13 patients (92%) who relapsed after chemotherapy induced complete remission. The threshold of tumour volume detection with CA125 is unlikely to be determined by an arbitrary cut-off level. The kinetics of CA125 provide more useful information and the potential to define complete response or indeed cure with CA125 parameters requires further investigation.


2021 ◽  
Vol 8 ◽  
Author(s):  
Thomas De Ridder ◽  
Paul Reddell ◽  
Pamela Jones ◽  
Graham Brown ◽  
Justine Campbell

Tigilanol tiglate (TT) is a novel small molecule registered as a veterinary pharmaceutical for intratumoural treatment of canine mast cell tumours (MCTs). The drug has a multifactorial mode of action resulting in rapid destruction of the treated tumour by haemorrhagic necrosis and subsequent slough of the necrotic tumour to reveal a tissue deficit that is left to heal by second intention with minimal to no veterinary intervention. Here we introduce the concept of TT-mediated margins, the calculated margin of tissue loss analogous to surgically applied margins to help clinicians conceptualise tissue deficits formed following tumour destruction by TT relative to surgical excision. We used data from 51 dogs that were recurrence-free 12 months after a single administered TT dose into a single target MCT &lt;10 cm3 in volume in a randomised, controlled clinical trial in the USA. We calculated TT-mediated margins based on length of the longest axis of (i) the tumour prior to treatment and (ii) the maximum tissue deficit formed 7–14 days after TT treatment. We compared these TT-mediated margins for each tumour to two surgical approaches to MCT excision in general practise: modified proportional margins (with 2 cm upper limit) and 3 cm fixed margins. For most dogs, TT-mediated margins were less than half the length of the margins calculated for the two surgical approaches in removing the same tumour. There was a trend for TT-mediated margins to increase with increasing tumour volume. Nonetheless, even for the larger tumours in this study (&gt;2 cm3 volume), 50% of TT-mediated margins were less than half the length of the two surgical margins. Eighteen cases were lower limb MCTs, sites often surgically challenging in veterinary practise. On these lower limbs, TT-mediated margins were less than half the length of the corresponding proportional margins in 56% of cases and larger than proportional margins in only two cases. This study suggests that, in many cases, smaller and more targeted margins could be expected when treating MCTs &lt;10 cm3 volume with TT compared with surgical excision. TT-mediated margins are a novel approach to conceptualise tissue deficits after intratumoural TT treatment.


2021 ◽  
pp. 221049172198908
Author(s):  
Lam Wei Sze Yvette ◽  
Fong Sin Tak ◽  
Mak Ka Lok

Introduction: Fibromatosis is a benign disease yet prone to recurrence. The best treatment option remains controversial. The purpose of this study was to analyse the management approach in our musculoskeletal tumour centre. Materials and Methods: Thirty-four patients with extra-abdominal fibromatosis referred to our centre between 2000 to 2018 were included. Patients’ demographics, tumour location and size, year of diagnosis, treatment modalities, surgical margins, recurrence, and subsequent management were analysed. Results: Patients mostly presented in the second and third decade, with female predominance. Twenty-seven patients underwent excision. Other management options included ‘watchful waiting’, pharmacological treatment and radiotherapy. Recurrence rate was 51.9%. There was no statistically significant relationship between marginal status and recurrence. Conclusion: We report our experiences on management of fibromatosis, with strategy shifted from early excision to a conservative approach over the years. Surgical excision is still indicated in some situations. Tumour recurrence is not rare but second excision is not always necessary.


2021 ◽  
pp. 030098582098513
Author(s):  
Mafalda Casanova ◽  
Sandra Branco ◽  
Inês Berenguer Veiga ◽  
André Barros ◽  
Pedro Faísca

Canine cutaneous mast cell tumors (ccMCTs) are currently graded according to Patnaik and Kiupel grading schemes. The qualitative and semiquantitative parameters applied in these schemes may lead to inter- and intraobserver variability. This study investigates the prognostic value of volume-weighted mean nuclear volume ([Formula: see text]), a stereological estimation that provides information about nuclear size and its variability. [Formula: see text] of 55 ccMCTs was estimated using the “point-sampled intercept” method and compared with histological grade and clinical outcome. The clinical history of dogs treated with surgical excision alone was available for 30 ccMCTs. Statistical differences in [Formula: see text] were found between grade II ([Formula: see text]= 115 ± 29 µm3) and grade III ccMCTs ([Formula: see text]= 197 ± 63 µm3), as well as between low-grade ([Formula: see text]= 113 ± 28 µm3) and high-grade ccMCTs ([Formula: see text]= 184 ± 63 µm3). An optimal cutoff value of [Formula: see text] ≥ 150 µm3 and [Formula: see text] ≥ 140 µm3 was determined for grade III and high-grade ccMCTs, respectively. In terms of prognosis, [Formula: see text] was not able to predict the clinical outcome in 42% of the cases; however, cases with [Formula: see text]<125 µm3 had a favorable outcome. These results indicate that, despite having limited prognostic value when used as a solitary parameter, [Formula: see text] is highly reproducible and is associated with histological grade as well as with benign behavior.


2022 ◽  
pp. 000348942110694
Author(s):  
Holden W. Richards ◽  
Caitlin Bertelsen ◽  
Bronwyn Hamilton ◽  
David Sauer ◽  
Joshua Schindler

Objectives: Discussions regarding the specific management and outcomes for laryngeal MEC are limited to very small, single-institution case series. To look further into the diagnosis and management of these uncommon non-squamous cell carcinomas of the larynx, we present 3 recent cases of laryngeal MEC treated at our institution. Methods: Patients at a tertiary hospital treated for MEC between October 2019 and December 2020 were retrospectively identified. Chart review, imaging analysis, and histologic slide creation were completed for all patients. Results: We identified and treated 2 patients with high-grade supraglottic and 1 patient with intermediate-grade glottic MEC. These patients presented to our clinic with a primary complaint of either gradual, worsening dysphonia, dysphagia, or both. All patients underwent laryngovideostroboscopy as well as panendoscopy with directed submucosal biopsy, which was consistent with MEC. MRI was performed in 2 of the cases further elucidating the extent of submucosal spread. PET-CT was performed in all 3 cases, and none demonstrated evidence of regional or distal metastases. Surgically, high-grade MEC lesions were treated with a total laryngectomy. The intermediate MEC lesion was managed with a supracricoid partial laryngectomy (SCPL). Surgical margins were free of tumor in all cases with no nodal metastases by modified radical neck dissection. Radiation therapy was offered to both high-grade MEC patients and declined by one. Radiation was not recommended to the patient with intermediate-grade MEC as we believed that the risk of additional treatment outweighed the benefit. Conclusion: We believe that MEC of the larynx should be considered in patients with atypical submucosal laryngeal masses. Laryngovideostroboscopy, MRI, and PET imaging may be valuable in determining the extent of the lesions and planning appropriate surgery. Postoperative radiation therapy should be considered a per tumor grade in other more studied sites, as there is no data on efficacy in laryngeal MEC.


Author(s):  
Muhammed Fatih Simsekoglu ◽  
İslim Kaleler ◽  
Bulent Onal ◽  
Cetin Demirdag ◽  
Sinharib Citgez ◽  
...  

Background: Mast cells play a critical role in tumor-associated immune pathways. We aimed to determine whether the urinary mast cell mediators predict the immune response in patients with non-muscle invasive bladder cancer (NMIBC) treated with Bacillus Calmette-Guérin (BCG) immunotherapy. Methods: Nineteen patients who have received immunotherapy due to NMIBC and 19 healthy participants were enrolled. Urine samples were collected to assay N-methylhistamine, histamine, and tryptase levels immediately before the first BCG instillation, immediately after the third and sixth instillations, and four weeks after the sixth instillation in patients with NMIBC and at a single visit in healthy participants. Cystoscopic examinations were performed on the patient with NMIBC at three-month intervals for two years. The changes in urinary markers due to BCC response, BCG instillation, and the presence of NMIBC were assessed. Results: The average age was 56.1 ± 10.5 years in patients with NMIBC. Fourteen patients had high-grade Ta tumors, and 5 had high-grade T1 tumors. While 12 patients responded, 6 presented with recurrence and 1 with progression. There was no correlation between the levels of mast cell mediators and BCG response. The N-methylhistamine and histamine levels were increased significantly with the onset of immunotherapy, and N-methylhistamine levels were significantly decreased when immunotherapy was terminated. Pre-BCG estimated marginal means of N-methylhistamine were significantly higher in patients with NMIBC than healthy participants. Conclusions: Our study is the first study to identify the changes in mast cell mediators with the onset of immunotherapy and with the presence of bladder cancer. However, these mediators were not found to predict the patients’ response to immunotherapy.


2021 ◽  
Author(s):  
Wing Nam Yuen ◽  
Joshua Jing Xi Li ◽  
Man Yi Chan ◽  
Gary M Tse

Abstract BackgroundPhyllodes tumour is a rare biphasic neoplasm of the breast that mostly affects middle aged women. Ductal carcinoma in-situ and microcalcifications occurring within phyllodes tumours are documented but are rare findings. Primary surgical excision with adjuvant therapies remains the mainstay of treatment.Case presentationWe report a case of a 42-year-old woman with high-grade ductal carcinoma in-situ within a borderline phyllodes tumour. Radiologically, clumps of microcalcification were detected within the lesion. Local excision followed by total mastectomy with axillary dissection was then performed. No tumour recurrence was detected up to a period of 8 years.ConclusionPresence of microcalcifications within a phyllodes tumour should alert clinicians and pathologists of possible coexisting carcinoma components. Stromal and epithelial components of these lesions should be evaluated separately when formulating a management plan.


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