Sarcoma

Electrochemotherapy (ECT) is a novel anticancer therapy that combines the delivery of trains of appropriate waveforms with the local administration of chemotherapy agents. The purpose of this investigation was to assess the adjuvant potentials of ECT for the treatment of incompletely excised mast cell tumors (MCT). Twenty-eight privately-owned dogs with incompletely removed MCT were treated with intralesional bleomycin (1.5 IU/cm2) followed by the application of trains of biphasic pulses (8 pulses, 1300 V/cm, 50 + 50 micros duration, 1 Hz frequency). The overall response rate was 85% with a mean estimated time to recurrence of 52.76 +/- 6.5 months (range: 39.99 to 65.54 months, 95% CI). At the time of writing this report, the median survival time was not reached. Three dogs died of metastatic disease that they developed at the same time of local recurrence, one developed multiple cutaneous nodules at different locations and one with recurrence was re-treated and is currently disease...

Cancer-associated isocitrate dehydrogenase (IDH) 1 and 2 mutations gain a new activity of reducing α-KG to produce D-2-hydroxyglutarate (D-2-HG), which is proposed to function as an oncometabolite by inhibiting α-KG dependent dioxygenases. We investigated the function of D-2-HG in tumorigenesis using IDH1 and IDH2 mutant cancer cell lines. Inhibition of D-2-HG production either by specific deletion of the mutant IDH1-R132C allele or overexpression of D-2-hydroxyglutarate dehydrogenase (D2HGDH) increases α-KG and related metabolites, restores the activity of some α-KG-dependent dioxygenases, and selectively alters gene expression. Ablation of D-2-HG production has no significant effect on cell proliferation and migration, but strongly inhibits anchorage independent growth in vitro and tumor growth in xenografted mouse models. Our study identifies a new activity of oncometabolite D-2-HG in promoting tumorigenesis.

Aggressive surgery has been suggested for improving local tumor control in patients with retroperitoneal sarcoma (RS). This study aimed at investigating local disease-free and overall survival after complete surgery, in patients with RS. Retrospective data of patients submitted to complete surgery for RS were extracted from a prospectively-maintained database. Forty-three out of 78 patients (55%) presented with primary RS. Infiltrated organs were resected in 42 patients (54%). Patients presenting with recurrent (hazard ratio (HR)=5.57, p=0.002) and high-grade (HR 3.47, p=0.041) tumors were at higher risk of local recurrence. Microscopically-involved tumor resection margins (HR=3.47, p=0.04) and recurrent tumor at presentation (HR=2.49, p=0.008) were independent predictors of poor survival. Patients presenting with primary RS had longer local disease-free survival and overall survival than those with recurrent tumor after complete surgery. Complete surgery remains the standard-of-car...

Background: Soft tissue dedifferentiated leiomyosarcoma with heterologous osteosarcomatous component is an extremely rare entity described in only few cases in the literature. Case presentation: We report the case of a 65-year-old male patient who, after initial inadequate surgery of a tumor of the left forearm, developed local recurrence that was treated with neoadjuvant chemotherapy, surgery and postoperative radiation therapy. Histologically the tumor showed an abrupt separation of two different patterns. One component consisted of interlacing fascicles of spindle cells with cigar-shaped nuclei strongly positive for smooth muscle actin, desmin and H-caldesmon. The other component consisted of a high-grade pleomorphic sarcoma with osteoid and chondroid matrix production, which positive for SATB2. Thus, a final diagnosis of dedifferentiated leiomyosarcoma was rendered. Fifteen months after treatment, the patient presented further local and distant relapse with pulmonary metastases and died 23 months after the first presentation. Discussion and conclusions: Dedifferentiated leiomyosarcoma is a highly malignant neoplasm with a poor outcome. Extensive sampling of soft tissue leiomyosarcomas is recommended to detect possible dedifferentiated areas as they represent a crucial prognostic parameter.

Gastro-intestinal stromal tumours (GIST) are primary mesenchymal tumours arising from the gastro-intestinal tract. They are uncommon visceral tumours, preferentially located in the stomach and small intestine. The present paper will discuss the clinical presentation of GIST in a 32-year-old female (Case 1) and in a 72-year-old female (Case 2). In both cases the tumour is located in the duodenum which appears to be a rather unusual location (4%) for GIST. This work will illustrate that duodenal GIST can occur in extreme presentations, diverging from vague complaints to directly life threatening symptoms.

Treatment of soft tissue tumors in young patients relies on the diagnostic information conveyed in the pathology report. We examined pathology reports from Children's Oncology Group ARST0332 for inclusion of data elements required in published guidelines. Pathology reports for 551 eligible patients were examined for required data elements defined by the College of American Pathologists, including tissue type, procedure, tumor site, tumor maximum diameter, macroscopic extent of tumor, histologic type, mitotic rate, extent of necrosis, tumor grade, margin status, use of ancillary studies, and pathologic stage. Only 65 (12%) of 551 reports included all required data elements. Of reports containing synoptic templates, 57% were complete. This study reveals significant opportunity to improve the quality of pathology reports in young patients with soft tissue tumors. Use of templates or checklists improves completeness of reports.

OBJECTIVE: The aim of the CWS 96 Study was to achieve an optimal treatment in children and adolescents with soft tissue sarcoma (STS) implementing a further refinement of risk-adapted allocation to chemotherapy, surgery and radiotherapy. METHODS: Treatment stratification was based on tumour histology, TNM status, postsurgical stage, localisation and age. Local tumour control was ensured by surgery and risk-adapted radiotherapy. RESULTS: From 1995 to 2002, 89 patients were registered in Austria. The 3-year event-free survival (EFS) and overall survival rates (OS) were 63% ± 6% and 71% ± 6%, respectively. 59/89 patients had localised RMS-like (rhabdomayosarcoma) STS (EFS 73% ± 7%), 14 had localised Non-RMS STS (EFS, 54% ± 16%) and 15 patients had metastatic disease at diagnosis (EFS, 33% ± 12%), 1 patient had fibromatosis. The EFS rates at 3 years in patients with localised RMS-like tumours according to risk group were 92% ± 8% for low and standard risk (12 patients) and 67% ± 8% for high risk (47 patients). Favourable primary tumour sites of nonmetastatic RMS-like STS i.e. orbit, head/neck nonparameningeal or genitourinary non-bladder/prostate were diagnosed in 15 patients (1 of 15 patients died). In 44 patients with unfavourable localisation such as parameningeal, genitourinary bladder/prostate, extremity and others, 7 deceased. The 3-year EFS according to histology in patients with RMS-like STS was 61% ± 11% for RME (embryonal RMS ) (28 patients) and 71% ± 15% for RMA (alveolar RMS) (10 patients). The most common treatment failure was local relapse occurring in 21% of patients in the high-risk group. CONCLUSION: Risk-adapted individualisation of treatment led to a reduction of chemotherapy in the low- and standard-risk group without compromising survival. The outcome of RME and RMA was similar in this cohort of patients. These preliminary results after a median observation time of 2.5 years confirm the CWS 96 strategy. ZIEL: Die CWS-96-Studie für Behandlung von Weichteilsarkomen (WS) im Kindes- und Jugendalter verfolgte eine maximale Tumorkontrolle bei Minimierung von Spätfolgen durch eine verbesserte risikoadaptierte Chemo-, Operations- und Radiotherapie. METHODEN: Die Stratifikation der Patienten erfolgte nach Histologie, TNM-Status, postchirurgischem Stadium, Lokalisation und Alter. Die Lokalkontrolle wurde durch Chirurgie und risikoadaptierte Bestrahlung angestrebt. ERGEBNISSE: Im Zeitraum von 1995 bis 2002 wurden 89 Patienten registriert. Das ereignisfreie (EFS) und das absolute Überleben (OS) nach 3 Jahren lag bei 63% ± 6% bzw. 71% ± 6%. 59 von 89 Patienten hatten lokalisierte RMS-(Rhabdomysoarkom-)artige WS (EFS, 73% ± 7%), 14 lokalisierte Non-RMS-artige WS (EFS, 54% ± 16%), 15 initial disseminierte WS (EFS, 33% ± 12%) und 1 Fibromatose. Das 3-Jahres-Überleben bei lokalisierten RMS-artigen nach Risikogruppe ergab 92% ± 8% EFS für niedriges und Standard-Risiko (12 Patienten), sowie 67% ± 8% EFS für hohes Risiko (47 Patienten). Die Lokalisation der 59 nicht metastasierten RMS-artigen WS war bei 15 Patienten in als günstig definierten Regionen (Orbita, Kopf/Hals – nicht parameningeal oder urogenital – nicht Blase/Prostata: 1 von 15 Patienten verstorben), während bei 44 Patienten ungünstige Lokalisationen vorlagen (Kopf/Hals – parameningeal, urogenital – Blase/Prostata, Extremitäten und andere: 7 von 44 Patienten verstorben). Das EFS nach Histologie in der Kategorie der lokalisierten RMS-artigen lag für embryonale RMS (RME) (28 Patienten) bei 61% ± 11% und für alveoläre RMS (RMA) (10 Patienten) bei 71% ± 15%. Das Hauptproblem war das lokale Rezidiv, das bei 21% aller Patienten im Hochrisikoarm auftrat. SCHLUSSFOLGERUNG: Die risikoadaptierte Individualisierung der Therapie als oberstes Ziel führte zu Einsparungen an Chemotherapie in der Niedrig- und Standard-Risiko-Gruppe bei erhaltener guter Prognose. In dieser Patientenkohorte war das Überleben für RME und RMA ähnlich. Nach einer medianen Beobachtungszeit von 2,5 Jahren bestätigen diese ersten Ergebnisse die erfolgreiche Umsetzung des CWS-Konzeptes.

RESUMO Tumores gástricos em animais domésticos são raros, e a literatura pertinente é escassa. Em humanos, esse tumor representa 80% dos tumores mesenquimais do trato digestivo, sendo mais comum no estômago (70%). Indivíduos de meia-idade e idosos, principalmente do gênero masculino, são os mais afetados, e o diagnosticado é feito com base em suas manifestações clínicas associadas à morfologia celular típica e à imuno-histoquímica positiva. O presente trabalho objetiva descrever um sarcoma gástrico em cão, assim como o diagnóstico, o tratamento cirúrgico e o pós-cirúrgico do animal. Foi atendido no Hospital Veterinário da Universidade Metropolitana de Santos (Unimes) um cão macho, SRD, 10 anos, 8,3kg, castrado, com bom estado geral, com queixa de emese há um ano. Na ultrassonografia abdominal foi observada a presença de uma formação arredondada no estômago que media 3,20 x 2,61cm, localizada na região epigástrica em contiguidade com a parede. O cão foi submetido a endoscopia gástrica, em que se observou a presença de uma massa arredondada na região pilórica, confirmada na laparotomia e na gastrotomia. O tumor retirado foi enviado para avaliação anatomopatológica, e os achados foram compatíveis com sarcoma estromal gástrico. ABSTRACT Gastric tumors in domestic animals are rare and the literature is scarce. In humans this tumor represents 80% of mesenchymal tumors of the digestive tract, most commonly in the stomach (70%). Affected individuals are middle-aged and elderly, especially males, diagnosed from its clinical manifestations in association with typical cell morphology and positive immunohistochemistry. The aim of this report was to describe a gastric sarcoma in a dog, as well as the diagnosis, surgical and post surgical treatment. The experiment was conducted in the Veterinary Hospital of the Metropolitan University of Santos (UNIMES) on a male dog, SRD, 10 years old, 8.3kg, castrated, in a good general condition, with complaint of emesis for year. In the abdominal ultrasound exam we observed the presence of a round formation in the stomach which measured 3.20 x 2.61cm, located in the epigastric region contiguous with the wall. The dog was submitted to gastric endoscopy, in which the presence of a rounded mass in the pyloric region was observed, and laparotomy and gastrostomy were performed. The removed tumor was sent for pathologic evaluation, where the findings were compatible with gastric stromal sarcoma.

Opinion statement Malignancies of the nasal cavity and paranasal sinuses represent a wide spectrum of histologies, tissues of origin, and anatomic primary sites. The inherent difficulty in generalizing treatment approaches is obvious, given the numerous variables associated with the broadly-based term, paranasal sinus malignancy (PNSCa). Nevertheless, the majority of epithelial and salivary malignancies of this region (ie, squamous cell carcinoma, adenocarcinoma, adenoid cystic carcinoma, sinonasal undifferentiated carcinoma, and esthesioneuroblastoma) require surgical intervention as part of any treatment regimen. Recent trends have broadened the indications for chemotherapeutic and radiotherapeutic options in the management of advanced PNSCa. Nonepithelial malignancies, including the wide variety of sarcomas arising in this region, most commonly require multimodality treatment including chemotherapy, radiation, and/or surgery for definitive treatment. Moreover, the proximity of the nasal cavity and paranasal sinuses to structures including the orbit, dura, brain, cranial nerves, and carotid arteries mandates careful radiologic and neurologic evaluations throughout the course of the disease. Surgical advances now permit complex tumor removal and reconstruction surrounding these structures resulting in functional and cosmetic improvements when compared to earlier techniques. However, additional clinical trials are necessary to systematically evaluate the locoregional control, organ-preservation strategies, and survival related to the variety of treatments currently available.

Prostate sarcomas are rare entity, the most common is leiomyosarcoma which account for 0.1% of all prostate malignancies. The presenting symptoms are mainly obstructive urinary symptoms. Surgery with chemo- or radiotherapy are the mainstay treatment options. The overall survival rate remains poor regardless of initial tumour size, grade or histological subtype. Immunohistochemistry reveals tumour cells diffusely positive for vimentin, smooth muscle actin, focally positive for progesterone receptor, whilst keratins are usually negative. We describe a case of a patient affected by sarcoma of prostate. Furthermore, we reviewed the cases of prostate sarcomas available in literature to clarify the best therapeutic options to be applied. In the case described leiomyosarcoma diagnosed by an ultrasound guided biopsy was characterized by fascicles of spindle-shaped cells with a variable degree of nuclear atypia. The immunohistochemistry showed positive staining for smooth muscle actin, vimen...

Introducción: El leiomiosarcoma primario localizado en extremidades es un sarcoma raro en frecuencia, y se debe a la proliferación de células mesenquimales. Reporte de caso: el presente caso describe a un varón de 62 años diagnosticado de leiomiosarcoma primario en las partes blandas de la pierna, tras presentar una prolongada clínica de dolor de características osteomusculares; esta localización es infrecuente, describiéndose la clínica, las pruebas diagnósticas, anatomopatológicos, el tratamiento y su posterior evolución. Conclusión: los mejores resultados en enfermedad localizada se consiguen con un tratamiento multidisciplinar, en el que la cirugía es imprescindible y la radioterapia postoperatoria contribuye a disminuir de forma significativa las recidivas locales, aunque sin haber demostrado beneficio en supervivencia. El papel de la quimioterapia como tratamiento adyuvante es controvertido.

Endometrial stromal sarcomas originate in the endometrial cavity. These tumors represent between 15-27.9% of uterine sarcomas. We present the case of a 41-year-old woman who underwent surgical hysteroscopy for metrorrhagia over a period of one month who had an intrauterine polypoid mass detected by ultrasonography. Histologic analysis of the polypoid mass removed by hysteroscopy was a high-grade endometrial stromal sarcoma of the uterus. The description of this case provides an opportunity to review the literature on uterine sarcomas diagnosed by surgical hysteroscopy.

The approval of cancer drugs by the United States Food and Drug Administration have increased progressively over the past
two decades with a trend towards the adoption of targeted drugs which are more precise in their mechanisms of action.
Advances in genetic profiling, immunohistochemical analysis of tumors, biomarker development, and a renewed appreciation
of the tumor microenvironment have produced a new generation of targeted chemical and biological therapies. These
innovations are the fruits of basic research in molecular and cellular biology, biochemistry, and immunology.
Purpose: To elucidate the paradigm shift in cancer drug development that has impacted the lives of patients in terms of
quality of life, tumor responses, over-all survival, and potential cures.
Methods: This review is based on an examination of published literature using the National Center for Biotechnology Information
(NCBI), the USFDA/National Institutes of Health (NIH) websites, USFDA approved product literature, Center Watch,
industry-sponsored websites, and clinicaltrials.gov websites. Cancer drugs are classified and described based on their proposed
mechanisms of action.
Results: The last two decades witnessed a paradigm shift in cancer drug development toward molecular targeted therapies
and targeted drug delivery. Molecular targets include tyrosine kinase receptors, serinethreonine kinase signaling pathways,
and growth factors. An increasing number of antibody-based therapies have emerged. Improvements in drug delivery include
the use of albumin-bound nanoparticles for targeting the enhanced permeability and retention effects seen in tumors.
Recent developments in the fields of cancer immunotherapy and gene therapy are exceedingly encouraging.
Conclusions: A review of USFDA-approved drugs and cancer drugs in clinical development, based on their mechanisms of
action, is presented. The progressive shift in cancer drug development towards targeted therapies and cancer immunotherapy
raises hope for improved outcomes for many types of cancer in the future.

The thoracodorsal artery perforator flap is considered a technically difficult flap because of significant anatomical variations in perforator location. The authors' strategy to facilitate the harvest of these flaps includes careful preoperative mapping of perforators and a standardized planning and harvesting technique. The authors evaluated 99 pedicled thoracodorsal artery perforator flaps, with an emphasis on preoperative planning, surgical technique, and analysis of complications. Between May of 2000 and October of 2006, 99 patients underwent pedicled thoracodorsal artery perforator flaps in the authors' department. Their charts and postoperative results were reviewed retrospectively. A thoracodorsal artery perforator flap was harvested in 90 cases. The perforators were unsuitable in the other 10 flaps; therefore, a muscle-sparing technique was used (type I or type II). Unidirectional Doppler imaging was used exclusively in 92 percent of cases to map the perforator preop...