Comparative oncology: The paradigmatic example of canine and human mast cell neoplasms

In humans, advanced mast cell (MC) neoplasms are rare malignancies with a poor prognosis. Only a few preclinical models are available, and current treatment options are limited. In dogs, MC neoplasms are the most frequent malignant skin tumours. Unlike low-grade MC neoplasms, high-grade MC disorders usually have a poor prognosis with short survival. In both species, neoplastic MCs display activating KIT mutations, which are considered to contribute to disease evolution. Therefore, tyrosine kinase inhibitors against KIT have been developed. Unfortunately, clinical responses are unpredictable and often transient, which remains a clinical challenge in both species. Therefore, current efforts focus on the development of new improved treatment strategies. The field of comparative oncology may assist in these efforts and accelerate human and canine research regarding diagnosis, prognostication, and novel therapies. In this article, we review the current status of comparative oncology approaches and perspectives in the field of MC neoplasms

Proposed Diagnostic Criteria and Classification of Canine Mast Cell Neoplasms: A Consensus Proposal

Mast cell neoplasms are one of the most frequently diagnosed malignancies in dogs. The clinical picture, course, and prognosis vary substantially among patients, depending on the anatomic site, grade and stage of the disease. The most frequently involved organ is the skin, followed by hematopoietic organs (lymph nodes, spleen, liver, and bone marrow) and mucosal sites of the oral cavity and the gastrointestinal tract. In cutaneous mast cell tumors, several grading and staging systems have been introduced. However, no comprehensive classification and no widely accepted diagnostic criteria have been proposed to date. To address these open issues and points we organized a Working Conference on canine mast cell neoplasms in Vienna in 2019. The outcomes of this meeting are summarized in this article. The proposed classification includes cutaneous mast cell tumors and their sub-variants defined by grading- and staging results, mucosal mast cell tumors, extracutaneous/extramucosal mast cell tumors without skin involvement, and mast cell leukemia (MCL). For each of these entities, diagnostic criteria are proposed. Moreover, we have refined grading and staging criteria for mast cell neoplasms in dogs based on consensus discussion. The criteria and classification proposed in this article should greatly facilitate diagnostic evaluation and prognostication in dogs with mast cell neoplasms and should thereby support management of these patients in daily practice and the conduct of clinical trials

Identification of heat shock protein 32 (Hsp32) as a novel target in acute lymphoblastic leukemia

Heat shock proteins (Hsp) are increasingly employed as therapeutic targets in oncology. We have shown that Hsp32, also known as heme oxygenase-1 (HO-1), serves as survival factor and potential target in Ph+ chronic myeloid leukemia. We here report that primary cells and cell lines derived from patients with acute lymphoblastic leukemia (ALL) express Hsp32 mRNA and the Hsp32 protein in a constitutive manner. Highly enriched CD34+/CD38- ALL stem cells also expressed Hsp32. Two Hsp32-targeting drugs, pegylated zinc protoporphyrine (PEG-ZnPP) and styrene maleic acid-micelle-encapsulated ZnPP (SMA-ZnPP), induced apoptosis and growth arrest in the BCR/ABL1+ cell lines, in Ph- lymphoblastic cell lines and in primary Ph+ and Ph- ALL cells. The effects of PEG-ZnPP and SMA-ZnPP on growth of leukemic cells were dose-dependent. In Ph+ ALL, major growth-inhibitory effects of the Hsp32-targeting drugs were observed in imatinib-sensitive and imatinib-resistant cells. Hsp32-targeting drugs were found to synergize with imatinib, nilotinib, and bendamustine in producing growth inhibition and apoptosis in Ph+ ALL cells. A siRNA against Hsp32 was found to inhibit growth and survival of ALL cells and to synergize with imatinib in suppressing the growth of ALL cells. In conclusion, Hsp32 is an essential survival factor and potential new target in ALL.Sabine Cerny-Reiterer, Renata A. Meyer, Harald Herrmann, Barbara Peter, Karoline V. Gleixner, Gabriele Stefanzl, Emir Hadzijusufovic, Winfried F. Pickl, Wolfgang R. Sperr, Junia V. Melo, Hiroshi Maeda, Ulrich Jäger, Peter Valen

Minimally invasive esophagectomy: clinical evidence and surgical techniques

Background!#!Surgical esophagectomy plays a crucial role in the curative and palliative treatment of esophageal cancer. Thereby, minimally invasive esophagectomy (MIE) is increasingly applied all over the world. Combining minimal invasiveness with improved possibilities for meticulous dissection, robot-assisted minimal invasive esophagectomy (RAMIE) has been implemented in many centers.!##!Purpose!#!This review focuses on the development of MIE as well as RAMIE and their value based on evidence in current literature.!##!Conclusion!#!Although MIE and RAMIE are highly complex procedures, they can be performed safely with improved postoperative outcome and equal oncological results compared with open esophagectomy (OE). RAMIE offers additional advantages regarding surgical dissection, lymphadenectomy, and extended indications for advanced tumors

Robot-assisted and conventional minimally invasive esophagectomy are associated with better postoperative results compared to hybrid and open transthoracic esophagectomy

Background: Currently 4 surgical techniques are performed for transthoracic esophagectomy (open esophagectomy (OE), hybrid esophagectomy (HE), conventional minimally invasive esophagectomy (MIE) and robot assisted minimally invasive esophagectomy (RAMIE). Aim of this study was to compare these 4 different esophagectomy approaches regarding postoperative complications and short term oncologic outcomes. Methods: Between 2008 and 2019, consecutive patients who underwent esophagectomy with gastric conduit reconstruction were included in this single center study. The primary outcome of this study was the incidence of postoperative complications. Results: Overall 422 patients (OE (n = 107), HE (n = 101), MIE (n = 91) and RAMIE (n = 123)) were evaluated. Uncomplicated postoperative course was observed in 27% (OE), 34% (HE), 53% (MIE), and 63% (RAMIE) of patients (p < 0.001). Pulmonary complications were observed in 57% (OE), 44% (HE), 28% (MIE), and 21% (RAMIE) of patients (p < 0.001). Cardiac complications were present in 25% (OE), 23% (HE), 9% (MIE), and 11% (RAMIE) of patients (p < 0.001). MIE and RAMIE were associated with fewer wound infections (p < 0.001). Median hospital stay after MIE (13 days) and RAMIE (12 days) was shorter compared to OE (20 days) and HE (17 days) (p < 0.001). A median number of 21 (OE), 23 (HE), 23 (MIE), and 31 (RAMIE) lymph nodes was harvested (p < 0.001). Conclusion: Total minimally invasive esophagectomy (MIE, RAMIE) was associated with a lower overall, pulmonary, cardiac and wound complication rate as well as a shorter hospital stay compared to open or hybrid approach (OE, HE). RAMIE resulted in higher lymph node harvest than MIE

Robot-assisted minimally invasive esophagectomy (RAMIE) compared to conventional minimally invasive esophagectomy (MIE) for esophageal cancer : a propensity-matched analysis

Robot-assisted minimally invasive esophagectomy (RAMIE) is increasingly being applied as treatment for esophageal cancer. In this study, the results of 50 RAMIE procedures were compared with 50 conventional minimally invasive esophagectomy (MIE) operations, which had been the standard treatment for esophageal cancer prior to the robotic era. Between April 2016 and March 2018, data of 100 consecutive patients with esophageal carcinoma undergoing modified Ivor Lewis esophagectomy were prospectively collected. All operations were performed by the same surgeon using an identical intrathoracic anastomotic reconstruction technique with the same perioperative management and pain control regimen. Intra-operative and postoperative complications were graded according to definitions stated by the Esophagectomy Complications Consensus Group. Data analysis was carried out with and without propensity score matching. Baseline characteristics did not show significant differences between the RAMIE and MIE group. Propensity score matching of the initial group of 100 patients resulted in two equal groups of 40 patients for each surgical approach. In the RAMIE group, the median total lymph node yield was 27 (range 13-84) compared to 23 in the MIE group (range 11-48), P = 0.053. Median intensive care unit (ICU) stay was 1 day (range 1-43) in the RAMIE group compared to 2 days (range 1-17) in the MIE group (P = 0.029). The incidence of postoperative complications was not significantly different between the two groups (P = 0.581). In this propensity-matched study comparing RAMIE to MIE, ICU stay was significantly shorter in the RAMIE group. There was a trend in improved lymphadenectomy in RAMIE