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Background: In this series from the Transatlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG), the authors examined longitudinal outcomes of patients with a second recurrence of retroperitoneal sarcoma (RPS) after complete resection of a first local recurrence (LR). Methods: Data from patients undergoing resection of a first LR from January 2002 to December 2011were collected from 22 sarcoma centers. The primary outcome was overall survival (OS) after second recurrence. Results: Second recurrences occurred in 400 of 567 patients (70.5%) after an R0/R1 resection of a first locally recurrent RPS. Patterns of disease recurrence were LR in 323 patients (80.75%), distant metastases (DM) in 55 patients (13.75%), and both LR and DM in 22 patients (5.5%). The main subtype among the LR group was liposarcoma (77%), whereas DM mainly were leiomyosarcomas (43.6%). In patients with a second LR only, a total of 200 patients underwent re‐resection (61.9%). The 5‐year OS rate varied significantly based on the pattern of failure (P <.001): 45.6% for the LR group, 25.5% for the DM group, and 0% for the group with LR and DM. The only factors found to be associated with improved OS on multivariable analysis were both time between second surgery and the development of the second recurrence (32 months vs 8 months: hazard ratio, 0.44 [P <.001]) and surgery for second recurrence (yes vs no: hazard ratio, 3.25 [P <.001]). The 5‐year OS rate for patients undergoing surgery for a second LR was 59% versus 18% in the patients not deemed suitable for surgical resection. Conclusions: Survival rates after second recurrence of RPS varied based on patterns of disease recurrence and treatment. Durable disease‐free survivors were identified after surgery for second LR in patients selected for this intervention. The current series, derived from 22 sarcoma centers from the Transatlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG) collaborative, describes the outcomes of patients experiencing a second recurrence of retroperitoneal sarcoma. Second recurrences are reported in approximately 70.5% of patients, with a 5‐year overall survival rate of between 0% and 45%, but durable disease‐free survivors are identified after surgery for second local recurrence among selected patients. [ABSTRACT FROM AUTHOR]

Epigenetic transformations may provide early indicators for cancer and other disease. Specifically, the amount of genomic 5‐hydroxymethylcytosine (5‐hmC) was shown to be globally reduced in a wide range of cancers. The integration of this global biomarker into diagnostic workflows is hampered by the limitations of current 5‐hmC quantification methods. Here we present and validate a fluorescence‐based platform for high‐throughput and cost‐effective quantification of global genomic 5‐hmC levels. We utilized the assay to characterize cancerous tissues based on their 5‐hmC content, and observed a pronounced reduction in 5‐hmC level in various cancer types. We present data for glioblastoma, colorectal cancer, multiple myeloma, chronic lymphocytic leukemia and pancreatic cancer, compared to corresponding controls. Potentially, the technique could also be used to follow response to treatment for personalized treatment selection. We present initial proof‐of‐concept data for treatment of familial adenomatous polyposis. What's new? The amount of genomic 5‐hydroxymethylcytosine (5‐hmC) was shown to be globally reduced in a wide range of cancerous tissues. The utility of such an epigenetic transformation as a clinical biomarker is hampered by the limitations of existing detection assays, however. The authors present a simple‐to‐perform fluorescence‐based platform for high‐throughput and cost‐effective quantification of global genomic 5‐hmC levels. They demonstrate the assay's sensitivity in detecting various cancers and its applicability for colorectal cancer diagnosis. Potentially, the technique could also be used to follow response to treatment for personalized treatment selection, with the authors providing initial proof‐of‐concept data for familial adenomatous polyposis. [ABSTRACT FROM AUTHOR]

Background: Our aim was to evaluate the association between visceral fat content with soft tissue sarcoma (STS) local recurrence and survival. Methods: One hundred and one computed tomography imaging studies of primary STS patients who had complete macroscopic resection at our institution between 2002 and 2012 were reviewed, and retroperitoneal and circumferential fat contents were measured. Correlations between imaging findings and clinical data were analyzed. Results: Fifty-seven STS tumors (56.4 %) were retroperitoneal; of them, 65 % were high grade, median size was 15 cm (range 3-49), and the most common histological subtype was high grade liposarcoma (31.6 %). Median follow-up length for the entire cohort was 64 months (range 6-95). High visceral fat (VF) content ≥15 versus <15 mm was identified as a risk factor for retroperitoneal STS local recurrence; 65.1 versus 26.7 %, respectively ( p = 0.04); VF content did not correlate with distant metastasis. Median overall survival (OS) length of patients with VF ≥15 versus <15 mm was 57 months (range 2-144) versus not reached, respectively ( p = 0.007). Multivariable analysis identified VF ≥15 mm as an independent risk factor for decreased OS (HR: 4.2, 95 % CI 1.07-16.67). In contrast, circumferential fat content did not correlate with retroperitoneal STS patient outcomes. Conclusion: High VF content is an independent adverse prognosticator associated with significantly higher rates of retroperitoneal STS local recurrence and decreased patients survival. Local tumor biology may be affected by the presence of adipose cells. Further clinical and molecular research is needed to establish this premise. [ABSTRACT FROM AUTHOR]

Objectives To evaluate long-term morbidity, mortality, and quality of life ( Qo L) after pancreaticoduodenectomy ( PD) in elderly adults. Design Retrospective cohort study. Setting Tel- Aviv Sourasky Medical Center, Tel- Aviv, Israel. Participants One hundred and sixty-eight individuals aged 70 and older who underwent PD between 1995 and 2010. Measurements A prospective pancreatic surgery database was analyzed for postoperative morbidity; mortality; intensive care unit ( ICU), hospital, and rehabilitation facility stay; and readmissions after surgery. Qo L was assessed using a validated questionnaire completed 3, 6, and 12 months after surgery. Results Seventy-two percent of the participants had an American Society of Anesthesiologists score of 3 or greater. There was no intraoperative death. Thirty- and 60-day postoperative mortality rates were 5.9% and 6.5%, respectively. Median ICU stay was 2 days, and median hospital stay was 22 days. Sixty-four participants (37.5%) were discharged to a rehabilitation facility. The first-year readmission rate was 31%. One- and 2-year overall survival rates were 58% and 36%, respectively. Global Qo L scores 3 and 12 months after surgery were 68% and 73%, respectively. Scores were lower yet comparable with those of matched individuals undergoing laparoscopic cholecystectomy. Conclusion Most elderly adults with pancreatic cancer survive longer than 1 year after PD; 36% survive longer than 2 years. These individuals are likely to have acceptable long-term morbidity and overall good Qo L, corresponding with their age. [ABSTRACT FROM AUTHOR]

Lahat G, Zhang P, Zhu Q-S, Torres K, Ghadimi M, Smith K D, Wang W-L, Lazar A J & Lev D (2011) Histopathology 59, 556-561 The expression of c-Met pathway components in unclassified pleomorphic sarcoma/malignant fibrous histiocytoma (UPS/MFH): a tissue microarray study Aims: Subclassification of undifferentiated pleomorphic sarcoma/malignant fibrous histiocytoma (UPS/MFH) into distinct biological cohorts based on the expression patterns of molecular markers can identify patient subsets with especially unfavourable clinical outcomes. Identification of molecular prognosticators amenable for drug targeting can facilitate rational development of UPS/MFH tailored therapies. The aim was to evaluate expression of c-Met pathway components in a large cohort of UPS/MFH samples. Methods and results: An immunohistochemical analysis for hepatocyte growth factor (HGF), c-Met, phospho-c-Met (pc-Met), phospho-mitogen-activated protein kinase kinase (MAPKK) also known as mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) kinase (p-MEK) and phospho-protein kinase B (p-AKT) was performed on a clinically annotated tissue microarray of 158 UPS/MFH samples. Univariable and multivariable analyses were conducted to evaluate the correlation of molecular variables with UPS/MFH disease specific survival. All evaluated markers were expressed in UPS/MFH to varying levels. Most importantly, strong HGF, pc-Met, p-MEK and p-AKT expression correlated significantly with dismal patient outcome on univariable statistical analysis. Expression of p-MEK and p-AKT remained statistically significant independent prognosticators on multivariable analysis. Conclusions: c-Met pathway components and especially p-MEK and p-AKT are potential prognostic biomarkers for UPS/MFH; their inclusion in future molecular-based staging systems should be evaluated. Furthermore, novel approaches targeting HGF, c-Met, MEK/extracellular-regulated kinase (ERK) and/or AKT should be considered for a subset of UPS/MFH patients. [ABSTRACT FROM AUTHOR]

Preoperative diagnosis of malignancy within intraductal papillary mucinous neoplasm of the pancreas (IPMN) solely by clinical or radiological findings is not always possible. We sought a correlation between preoperative clinico-radiological findings and outcome. A prospective database of pancreatic resections for IPMN (2002–2008) and a retrospective pathological revision of all pancreatic cancer specimens (1995–2001) were analyzed. The patients were grouped into asymptomatic with preoperative diagnosis of IPMN (group 1), symptomatic with a preoperative diagnosis of IPMN (group 2), and those with a preoperative diagnosis of pancreatic cancer whose specimen revealed a background of IPMN (group 3). The groups were compared for demographics, clinical presentation, pathological findings, and outcome. Of the 62 patients with IPMN, 19 were in group 1, 23 in group 2, and 20 in group 3. Their median age (range) was 65.6 (46–80), 67 (50–84), and 73.4 (57–86) years, respectively. The clinical presentation for groups 2 and 3 included abdominal pain (56% vs. 32 %), weight loss (8% vs. 52%), obstructive jaundice (4% vs. 57%), pancreatitis (22% and 5%), and new onset of diabetes (14% and 44%). Invasive cancer was found in one patient in group 1 (5.2%), two patients in group 2 (8.7%), and all patients in group 3. IPMN was present in 23 of 217 (10.6%) of all resected pancreatic cancer specimens. Five year survival for patients with invasive disease was 47% and 92% for patients with noninvasive disease (mean follow-up 37.6 months). Benign IPMN can usually be differentiated from adenocarcinoma preoperatively. The clinical presentation is highly indicative of disease course. [ABSTRACT FROM AUTHOR]

Aims: The molecular signature of alveolar soft part sarcoma (ASPS) is a specific der(17)t(X;17)(p11.2;q25) translocation, resulting in a chimeric transcription factor (ASPSCR1–TFE3). When this disease is no longer amenable to surgical curative intervention, uniformly efficacious therapies are lacking. The aim of this study was to evaluate the expression of potential molecular therapeutic targets in a cohort of ASPS tumour samples. Methods and results: Immunohistochemical analysis for hepatocyte growth factor, c-Met, phosphorylated c-Met, phosphorylated AKT, phosphorylated MEK, epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), p53 and vimentin was performed on an ASPS tissue microarray, yielding complete data from 26 tumours. Activation of c-Met and its downstream effectors was noted, whereas only limited EGFR expression was seen. VEGF was expressed to varying degrees. Only one sample exhibited strong nuclear p53 expression, while 10 expressed low levels. Vimentin expression was negative in the vast majority of samples (96%). Conclusions: There is a crucial need for better anti-ASPS therapies. Activated c-Met and the phosphorylation of its downstream effectors validate an intact signalling cascade probably induced by the ASPSCR1–TFE3 chimeric transcription factor. The angiogenic phenotype of these tumours is supported by increased angiogenic factor expression. Combination therapies targeting both tumour cells and angiogenesis merit further investigation. [ABSTRACT FROM AUTHOR]

The article focuses on a report that evaluates whether computed tomography (CT) differentiates well differentiated (WD) from dedifferentiated (DD) retroperitoneal liposarcoma (RPLS). It reviews imaging studies from 78 RPLS patients who underwent surgery at the University of Texas M. D. Anderson Cancer Center (UTMDACC) in Houston, Texas between 2001-2007. It concludes that further diagnostic tests are not needed to characterize tumors when CT suggests WD.