暂无摘要。

Hemangiosarcoma is an aggressive tumour that most frequently occurs in larger, middle-aged dogs of certain breeds. The spleen is the most commonly affected organ. The aim of this prospective therapy study was to evaluate the clinical effect of autologous, monocyte-derived dendritic cell (DC) therapy in canine hemangiosarcoma stage II after splenectomy. Dogs (n=452) diagnosed with splenic hemangiosarcoma that underwent splenectomy were enrolled. Of these, 42 dogs with stage II entered the DC therapy study. The median survival time for the total group of 42 dogs was 203 days. The median survival for the group (n=34) that received the full DC therapy (≥3 vaccines) was 256 days, with a 29 % one-year survival rate and a hazard ratio of 0.30, adjusted to age and bodyweight (P=0.010). We further observed a significant increase in DC yield after each application and demonstrated that DC yield at the beginning of treatment is significantly related to patient survival. While further evidence is needed, we conclude that autologous, monocyte-derived DC therapy is a viable alternative to standard treatment methods of canine splenic stage II hemangiosarcoma.

BACKGROUND: Dogs with retroperitoneal hemangiosarcoma (HSA) exhibit variable postoperative median survival times (MST).
OBJECTIVE: To retrospectively evaluate the prognostic value of selected tumour-related factors, such as tumour size, rupture, invasion into adjacent tissue, involvement of lymph node and distant metastasis, they were analysed in dogs with retroperitoneal HSA.
METHODS: Ten dogs with retroperitoneal HSA managed solely with surgical excision were reviewed and compared with spleen (71) and liver (9) HSA. The Kaplan-Meier method and log-rank analysis were used compare MSTs between factors. Multivariable Cox proportional-hazard analysis was used to compare differences between arising sites.
RESULTS: Retroperitoneal HSA showed comparatively longer postoperative MST compared with that of spleen and liver HSA and demonstrated significantly longer MST (p = 0.003) for tumours ≥5 cm (195 days) than <5 cm (70 days). Spleen HSA revealed significantly shorter MSTs in involvement of distant lymph nodes (23 days) and distant metastasis (39 days) than those in negative (83 days, p = 0.002 and 110 days, p < 0.001, respectively). Liver HSA also revealed significantly shorter MST (16.5 days compared with 98 days, p = 0.003) for distant metastasis. Additionally, hazard ratios (HRs) and their forest plot for overall HSA revealed as poor prognostic factors, arising sites (spleen; HR 2.78, p = 0.016 and liver; HR 3.62, p = 0.019), involvement of distant lymph nodes (HR 2.43, p = 0.014), and distant metastasis (HR 2.86, p < 0.001), and as better prognostic factor of tumour size ≥5 cm (HR 0.53, p = 0.037).
CONCLUSIONS: In combination with overall HSA, retroperitoneal HSA shows comparatively longer postoperative MST compared to spleen and liver HSA, associated with tumour size ≥5 cm suggesting better prognostic factor.

Vascular neoplasms, including hemangiosarcoma (HSA) and hemangioma (HMA), are more common in dogs than other domestic animal species; however, comprehensive laboratory screening tests for early diagnosis are currently limited. The aims of this study were to investigate general signalments, anatomic locations, and clinicopathological abnormalities of dogs diagnosed with vascular neoplasms and to determine the diagnostic significance of these abnormalities. Retrospective data of dogs with HMA, HSA, and healthy dogs were analyzed. Dogs with HMA and HSA were seniors, with mixed breeds being most affected. HMA affected predominantly non-visceral sites, while HSA was more common in visceral sites, particularly the spleen. In multivariate model analyses, the odds of HMA diagnosis were 5.5 times higher in anemic dogs and 33.0 times higher in lymphopenic dogs compared to dogs without the abnormalities. The odds of HSA diagnosis were 42.5 times higher in anemic dogs, 343 times higher in lymphopenic dogs and 92.7 times higher in dogs with hyperfibrinogenemia compared to dogs without the abnormalities. The study suggested that these identified abnormalities were nonspecific and commonly observed in various chronic diseases, and hence their combination with clinical information, such as diagnostic imaging and histopathology, is important to facilitate a more precise diagnosis of canine vascular neoplasms.

OBJECTIVE: To assess the predictability of the hemangiosarcoma likelihood prediction (HeLP) score and the Tufts Splenic Tumor Assessment Tool (T-STAT) for hemangiosarcoma and malignancy, respectively.
METHODS: 261 dogs undergoing splenectomy for a splenic mass.
METHODS: Medical records were retrospectively reviewed; variables for the HeLP score and T-STAT were collected, and scores were assigned. Area under the curve (AUC) was calculated for each score.
RESULTS: The HeLP score included 141 dogs; hemangiosarcoma was diagnosed in 87 (61.7%) dogs. The median cumulative HeLP score was 51 (range, 17 to 82; IQR, 39 to 58) for dogs with hemangiosarcoma and 28 (range, 0 to 70; IQR, 17 to 41) for dogs without hemangiosarcoma. The categorical HeLP score was low (28; 32.2%), medium (31; 35.6%), and high (28; 32.2%) for dogs with hemangiosarcoma and was low (41; 75.9%), medium (9; 16.7%), and high (4; 7.4%) for dogs without hemangiosarcoma. The AUC of the cumulative and categorical HeLP scores for diagnosis of hemangiosarcoma were 0.79 (95% CI, 0.71 to 0.86) and 0.73 (95% CI, 0.65 to 0.82), respectively. The T-STAT included 181 dogs. Lesions were benign in 95 (52.5%) and malignant in 86 (47.5%) dogs. The median T-STAT score was 62% (range, 5% to 98%; IQR, 36% to 77%) for dogs with malignant lesions and 38% (range, 5% to 91%; IQR, 24% to 59%) for dogs with benign lesions. The T-STAT had an AUC of 0.68 (0.60 to 0.76) for diagnosis of malignancy.
CONCLUSIONS: The HeLP score had acceptable performance, and the T-STAT had poor performance for diagnosis prediction. A tool with excellent or outstanding discrimination is needed to more reliably predict the presence of hemangiosarcoma or a malignant lesion preoperatively.

BACKGROUND: AS is a malignant tumor that originates from vascular endothelial cells and is known for a high rate of local recurrence and metastasis.
METHODS: A 48-year-old male presented with cutaneous epithelioid AS. Cutaneous AS of the foot is quite rare, especially in the absence of predisposing factors, and in this patient it was previously misdiagnosed as a DFU.
CONCLUSIONS: Physicians should be aware of this rare presentation of cutaneous AS. The authors of the current report advise regular clinical reassessment of chronic ulcers and biopsies of nonhealing wounds, even when adequate wound treatment has been administered, with the goal of identifying ulcerated skin malignancies and preventing delay in providing appropriate treatment.

BACKGROUND: Angiosarcoma is a rare and aggressive cancer of the endothelial cells. Propranolol, a non-selective β-blocker, was able to initiate apoptosis in angiosarcoma cell lines and its anti-tumor activity has been described in several case reports. The aim of this trial was to prospectively evaluate the anti-tumor activity of propranolol monotherapy in patients with angiosarcoma before proceeding to standard of care treatment.
METHODS: Propranolol was dosed 80 mg to 240 mg/day for 3 to 6 weeks according to a dose titration schedule. The primary endpoint was clinical response (response according to RECIST 1.1 or stable disease with improvement of cutaneous lesions) in at least three patients. Exploratory objectives included histologic response (>30% decrease in Ki-67), FDG PET response, and β-receptor expression levels.
RESULTS: Fourteen patients were enrolled. The median duration of treatment was 26 days (range 21-42 days). The median highest propranolol dose was 160 mg/day (range 80 - 240 mg). Two patients showed clinical response (14%, 95% CI 3-100%). One of these patients showed a partial metabolic response on PET-CT. None of the tumors showed histologic response. The most common adverse event was grade 1/2 bradycardia (86%). There were no grade ≥ 3 adverse events. ADRB2 was overexpressed in 16 out of 18 tumors, in both responders and non-responders. None of the tumors showed ADRB1 overexpression.
CONCLUSIONS: This window-of-opportunity trial did not show clinical efficacy of propranolol monotherapy. However, two out of 14 patients did show clinical benefit. ADRB1/2 expression did not correlate with clinical response.

OBJECTIVE: Angiosarcoma (AS) is a rare malignant vascular tumor that phenotypically and functionally recapitulate normal endothelium. They constitute approximately 2-4% of soft tissue sarcomas. We present 36 cases of head and neck AS diagnosed for 11 years at a tertiary care hospital in South India to analyze the clinical, pathological, and immunophenotypic profiles with special emphasis on their differential diagnoses and diagnostic pitfalls.
METHODS: Head and neck AS diagnosed from January 2006 to December 2017 were included. Clinical characteristics, treatment received, and follow-up data were obtained from electronic medical records. Hematoxylin and eosin (H&E)-stained slides and immunohistochemistry (IHC) slides were reviewed, and the histomorphological features, immunohistochemical staining, and their utility in resolving differential diagnosis were assessed.
RESULTS: Twenty-two females and 14 males were diagnosed with head and neck AS in the study period. Histomorphological patterns observed were mixed vasoformative and solid ( n = 22), pure vasoformative ( n = 13), and pure solid ( n = 1). Neoplastic cells showed epithelioid, spindly, signet cell-like, clear cell, and rhabdoid morphology. CD31 was positive in 100% of cases, and CD34 was positive in 40% of cases. Differential diagnoses included melanoma, rhabdomyosarcoma, and large-cell lymphoma. Surgery, radiotherapy, and chemotherapy were the treatment modalities used. Twelve patients developed local recurrence, and 12 patients developed metastasis on follow-up. Twenty-five patients died of disease, on an average of 24 months after diagnosis.
CONCLUSIONS: Head and neck AS pose a significant diagnostic challenge due to their broad morphologic spectrum. Proper clinicopathologic correlation is necessary to avoid misdiagnosis.

UNASSIGNED: Eribulin modulates the tumor-immune microenvironment via cGAS-STING signaling in preclinical models. This non-randomized phase II trial evaluated the combination of eribulin and pembrolizumab in patients with soft-tissue sarcomas (STS).
UNASSIGNED: Patients enrolled in one of three cohorts: leiomyosarcoma (LMS), liposarcomas (LPS), or other STS that may benefit from PD-1 inhibitors, including undifferentiated pleomorphic sarcoma (UPS). Eribulin was administered at 1.4 mg/m2 i.v. (days 1 and 8) with fixed-dose pembrolizumab 200 mg i.v. (day 1) of each 21-day cycle, until progression, unacceptable toxicity, or completion of 2 years of treatment. The primary endpoint was the 12-week progression-free survival rate (PFS-12) in each cohort. Secondary endpoints included the objective response rate, median PFS, safety profile, and overall survival (OS). Pretreatment and on-treatment blood specimens were evaluated in patients who achieved durable disease control (DDC) or progression within 12 weeks [early progression (EP)]. Multiplexed immunofluorescence was performed on archival LPS samples from patients with DDC or EP.
UNASSIGNED: Fifty-seven patients enrolled (LMS, n = 19; LPS, n = 20; UPS/Other, n = 18). The PFS-12 was 36.8% (90% confidence interval: 22.5-60.4) for LMS, 69.6% (54.5-89.0) for LPS, and 52.6% (36.8-75.3) for UPS/Other cohorts. All 3 patients in the UPS/Other cohort with angiosarcoma achieved RECIST responses. Toxicity was manageable. Higher IFNα and IL4 serum levels were associated with clinical benefit. Immune aggregates expressing PD-1 and PD-L1 were observed in a patient that completed 2 years of treatment.
UNASSIGNED: The combination of eribulin and pembrolizumab demonstrated promising activity in LPS and angiosarcoma.

Canine splenic hemangiosarcoma has a high metastatic rate and short survival time. Currently, the main prognostic parameters are tumor stage and therapy, while data on histologic parameters, such as grade and Ki-67 expression, are scarce. The aims of this study were to compare two methods of assessment of Ki-67, verify their prognostic impact, and define a threshold value based on survival. Thirty-one cases of histologically diagnosed canine splenic hemangiosarcoma, which were treated with splenectomy and had full staging and follow-up information, were collected. Three were stage I, 17 stage II, and 11 stage III. The mean mitotic count (MC) was 23.9 (standard deviation [SD]: 22.1) and the median was 15 (range, 1-93). Immunohistochemistry for Ki-67 was performed, the Ki-67 labeling index (Ki-67LI) was assessed as a percentage of positive neoplastic nuclei per ≥500 cell, and the Ki-67 count (KI-67C) was defined as the average number of positive nuclei using a 1 cm2 optical grid performed in 5, 40× fields. The mean Ki-67LI and Ki-67C were 56.4% (SD: 38.7) and 27.2 (SD: 12.9) and medians were 51% (range, 8.2-55.2) and 26 (range, 5.5-148), respectively. Using a cut-off of 56% and 9, respectively, Kaplan-Meier survival curves showed an association of overall survival with Ki-67LI and MC. In addition to clinical stage, Ki-67LI maintained its prognostic value on multivariate analysis, supporting the role of Ki-67LI as an independent prognostic parameter. Based on these results, we propose a diagnostically applicable cut-off value of 56% for Ki-67LI as a prognostic parameter for canine splenic hemangiosarcoma.