Y. A. Rossi, Letícia C. Ribeiro, Regina Mendes Medeiros, E. Spugnini, C. E. Fonseca-Alves, D. D. dos Anjos
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Electrochemotherapy (ECT) is an effective local treatment which combines chemotherapeutic drugs mainly bleomycin or cisplatin followed by the delivery of permeabilizing electrical pulses However, other hydrophilic drugs seem to present an increase cytotoxic effect such as carboplatin.Case: A 9-year-old mixed-breed neutered dog was referred to a private clinic with a mass in the perianal region diagnosed as perianal melanoma. No metastasis was observed on abdominal ultrasound nor chest x-ray (3 views). Clinical signs noted were tenesmus, hemorrhagic discharge, weight loss and hyporexia. Considering the tumor volume (16.0 x 10.0 cm), a neoadjuvant ECT session was proposed. The authors opted for carboplatin (300 mg/m², intravenously), administered over 20 min and cisplatin intratumorally (1 mg/cm³, equivalent to 1 mL/1cm³; total volume 20 mL) administered in the upper parts of the mass that could be reached while avoiding drug leakage. After administration, sequences of eight biphasic pulses, (100 microseconds), with a voltage ranging from 650-1,000V/cm (pulse generator Onkodisruptor®) using a hexagonal/single pair and plate electrode were delivered. At day 30th, a partial response was observed accordingly to RECIST system, with tumor size of 5.0 x 5.0 cm (65.4 cm³). A second ECT session was performed with the same previous protocol, but with a decreased dosage of carboplatin (240 mg/m² consistent with 20% reduction) due to adverse effects in the first session, resulting in stable disease at day 60th (30 days after second ECT). Then, we proposed a surgical excision of the mass including partial resection of ventral rectum with intraoperative ECT. Afterwards, it was observed fecal incontinence that did not resolved after time but did not significant cause a morbidity in the patient. Patient achieved a disease-free interval (DFI) of 700 days and survival time of 730 days. Unfortunately, patient died due to distant metastasis.Discussion: Surgery is still the cornerstone treatment for MM in dogs, regardless anatomic site. However, in perianal region, wide or radical local surgical excision is a challenge due to anatomic region which precluded most of the time to achieve complete margins. In this report, the origin of the tumors was not defined since no normal tissue was found surrounding tumors cells probably due to tumor invasion and destruction of surrounding tissue. Thus, based on the previous literature, this tumor could have been arisen from rectum wall or anal sac. The longer DFI and survival time from this patient is superior from the most veterinary cases in literature which combined different types of treatment such as surgery, chemotherapy, immunotherapy, palliative care or ECT. Neoadjuvant ECT leaded to a reliable approach for partial remission in order to perform a better surgical approach in this case report. To conclude, ECT may be an option for partial remission and local control in regions which anatomic limitation is a challenge for wide excision.Keywords: bleomycin, carboplatin, cisplatin, electroporation, melanocytic tumor.","PeriodicalId":7182,"journal":{"name":"Acta Scientiae Veterinariae","volume":" ","pages":""},"PeriodicalIF":0.2000,"publicationDate":"2022-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Primary Perianal Malignant Melanoma in a Dog - Combination Therapy\",\"authors\":\"Y. A. Rossi, Letícia C. Ribeiro, Regina Mendes Medeiros, E. Spugnini, C. E. Fonseca-Alves, D. D. dos Anjos\",\"doi\":\"10.22456/1679-9216.117948\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Background: Melanocytic neoplasm can arise from melanocytes in any location of the body. Malignant melanoma (MM) has a poor prognosis in dogs and presence of lymphvascular invasion, distant metastasis, or mitotic activity present prognostic value. Primary melanoma affecting the gastrointestinal tract has been rarely reported in veterinary literature, thus the prognosis affecting gastrointestinal tract is unknown. Electrochemotherapy (ECT) is an effective local treatment which combines chemotherapeutic drugs mainly bleomycin or cisplatin followed by the delivery of permeabilizing electrical pulses However, other hydrophilic drugs seem to present an increase cytotoxic effect such as carboplatin.Case: A 9-year-old mixed-breed neutered dog was referred to a private clinic with a mass in the perianal region diagnosed as perianal melanoma. No metastasis was observed on abdominal ultrasound nor chest x-ray (3 views). Clinical signs noted were tenesmus, hemorrhagic discharge, weight loss and hyporexia. Considering the tumor volume (16.0 x 10.0 cm), a neoadjuvant ECT session was proposed. The authors opted for carboplatin (300 mg/m², intravenously), administered over 20 min and cisplatin intratumorally (1 mg/cm³, equivalent to 1 mL/1cm³; total volume 20 mL) administered in the upper parts of the mass that could be reached while avoiding drug leakage. After administration, sequences of eight biphasic pulses, (100 microseconds), with a voltage ranging from 650-1,000V/cm (pulse generator Onkodisruptor®) using a hexagonal/single pair and plate electrode were delivered. At day 30th, a partial response was observed accordingly to RECIST system, with tumor size of 5.0 x 5.0 cm (65.4 cm³). A second ECT session was performed with the same previous protocol, but with a decreased dosage of carboplatin (240 mg/m² consistent with 20% reduction) due to adverse effects in the first session, resulting in stable disease at day 60th (30 days after second ECT). Then, we proposed a surgical excision of the mass including partial resection of ventral rectum with intraoperative ECT. Afterwards, it was observed fecal incontinence that did not resolved after time but did not significant cause a morbidity in the patient. Patient achieved a disease-free interval (DFI) of 700 days and survival time of 730 days. Unfortunately, patient died due to distant metastasis.Discussion: Surgery is still the cornerstone treatment for MM in dogs, regardless anatomic site. However, in perianal region, wide or radical local surgical excision is a challenge due to anatomic region which precluded most of the time to achieve complete margins. In this report, the origin of the tumors was not defined since no normal tissue was found surrounding tumors cells probably due to tumor invasion and destruction of surrounding tissue. Thus, based on the previous literature, this tumor could have been arisen from rectum wall or anal sac. 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引用次数: 0
摘要
背景:黑色素细胞肿瘤可由身体任何部位的黑色素细胞引起。狗的恶性黑色素瘤(MM)预后较差,淋巴管浸润、远处转移或有丝分裂活性的存在具有预后价值。影响胃肠道的原发性黑色素瘤在兽医文献中很少报道,因此影响胃肠道预后尚不清楚。电化学治疗(ECT)是一种有效的局部治疗方法,它结合了化疗药物,主要是博来霉素或顺铂,然后输送可渗透的电脉冲。然而,其他亲水性药物似乎表现出增加的细胞毒性作用,如卡铂。病例:一只9岁的混血绝育狗被转诊到一家私人诊所,其肛周区域的肿块被诊断为肛周黑色素瘤。在腹部超声和胸部x线片上均未观察到转移(3个视图)。注意到的临床症状有里急后重、出血性放电、体重减轻和低热。考虑到肿瘤体积(16.0x10.0cm),建议采用新辅助ECT治疗。作者选择了卡铂(300 mg/m²,静脉注射),在20分钟内给药,并选择在肿瘤上部给药顺铂(1 mg/cm³,相当于1 mL/1cm³;总体积20 mL),同时避免药物渗漏。给药后,使用六边形/单对和平板电极输送电压范围为650-1000V/cm的八个双相脉冲序列(100微秒)(脉冲发生器Onkodisruptor®)。在第30天,观察到RECIST系统的部分反应,肿瘤大小为5.0 x 5.0 cm(65.4 cm³)。第二次ECT治疗采用相同的先前方案,但由于第一次治疗的不良反应,卡铂剂量减少(240 mg/m²,减少20%),导致第60天(第二次ECT30天后)病情稳定。然后,我们提出了一种肿块的外科切除术,包括腹侧直肠部分切除术和术中ECT。之后,观察到粪便失禁在一段时间后没有解决,但没有显著导致患者发病。患者实现了700天的无病间隔(DFI)和730天的生存时间。不幸的是,患者死于远处转移。讨论:手术仍然是治疗犬MM的基石,无论解剖部位如何。然而,在肛周区域,由于解剖区域的原因,广泛或彻底的局部手术切除是一个挑战,这使得大部分时间无法获得完整的边缘。在本报告中,肿瘤的起源没有明确,因为在肿瘤细胞周围没有发现正常组织,这可能是由于肿瘤侵袭和破坏了周围组织。因此,根据先前的文献,这种肿瘤可能来自直肠壁或肛门囊。与文献中结合不同类型治疗(如手术、化疗、免疫疗法、姑息治疗或ECT)的大多数兽医病例相比,该患者的DFI和生存时间更长。新辅助ECT为部分缓解提供了可靠的方法,以便在本病例报告中进行更好的手术方法。总之,ECT可能是部分缓解和局部控制的一种选择,因为解剖限制对广泛切除是一个挑战。关键词:博来霉素,卡铂,顺铂,电穿孔,黑色素细胞瘤。
Primary Perianal Malignant Melanoma in a Dog - Combination Therapy
Background: Melanocytic neoplasm can arise from melanocytes in any location of the body. Malignant melanoma (MM) has a poor prognosis in dogs and presence of lymphvascular invasion, distant metastasis, or mitotic activity present prognostic value. Primary melanoma affecting the gastrointestinal tract has been rarely reported in veterinary literature, thus the prognosis affecting gastrointestinal tract is unknown. Electrochemotherapy (ECT) is an effective local treatment which combines chemotherapeutic drugs mainly bleomycin or cisplatin followed by the delivery of permeabilizing electrical pulses However, other hydrophilic drugs seem to present an increase cytotoxic effect such as carboplatin.Case: A 9-year-old mixed-breed neutered dog was referred to a private clinic with a mass in the perianal region diagnosed as perianal melanoma. No metastasis was observed on abdominal ultrasound nor chest x-ray (3 views). Clinical signs noted were tenesmus, hemorrhagic discharge, weight loss and hyporexia. Considering the tumor volume (16.0 x 10.0 cm), a neoadjuvant ECT session was proposed. The authors opted for carboplatin (300 mg/m², intravenously), administered over 20 min and cisplatin intratumorally (1 mg/cm³, equivalent to 1 mL/1cm³; total volume 20 mL) administered in the upper parts of the mass that could be reached while avoiding drug leakage. After administration, sequences of eight biphasic pulses, (100 microseconds), with a voltage ranging from 650-1,000V/cm (pulse generator Onkodisruptor®) using a hexagonal/single pair and plate electrode were delivered. At day 30th, a partial response was observed accordingly to RECIST system, with tumor size of 5.0 x 5.0 cm (65.4 cm³). A second ECT session was performed with the same previous protocol, but with a decreased dosage of carboplatin (240 mg/m² consistent with 20% reduction) due to adverse effects in the first session, resulting in stable disease at day 60th (30 days after second ECT). Then, we proposed a surgical excision of the mass including partial resection of ventral rectum with intraoperative ECT. Afterwards, it was observed fecal incontinence that did not resolved after time but did not significant cause a morbidity in the patient. Patient achieved a disease-free interval (DFI) of 700 days and survival time of 730 days. Unfortunately, patient died due to distant metastasis.Discussion: Surgery is still the cornerstone treatment for MM in dogs, regardless anatomic site. However, in perianal region, wide or radical local surgical excision is a challenge due to anatomic region which precluded most of the time to achieve complete margins. In this report, the origin of the tumors was not defined since no normal tissue was found surrounding tumors cells probably due to tumor invasion and destruction of surrounding tissue. Thus, based on the previous literature, this tumor could have been arisen from rectum wall or anal sac. The longer DFI and survival time from this patient is superior from the most veterinary cases in literature which combined different types of treatment such as surgery, chemotherapy, immunotherapy, palliative care or ECT. Neoadjuvant ECT leaded to a reliable approach for partial remission in order to perform a better surgical approach in this case report. To conclude, ECT may be an option for partial remission and local control in regions which anatomic limitation is a challenge for wide excision.Keywords: bleomycin, carboplatin, cisplatin, electroporation, melanocytic tumor.
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