Steven C. Katz

Dermatofibrosarcoma protuberans: A clinicopathologic analysis of patients treated and followed at a single institution.

Despite optimal surgical therapy for patients with dermatofibrosarcoma protuberans (DFSP), some patients still continue to develop local recurrence. The authors objective was to identify and analyze clinicopathologic factors for disease free survival in a large group of patients who were followed prospectively at a single institution.

Combined Stimulation with Interleukin-18 and CpG Induces Murine Natural Killer Dendritic Cells to Produce IFN-γ and Inhibit Tumor Growth

Natural killer dendritic cells (NKDC) are a novel subtype of dendritic cells with natural killer (NK) cell properties. IFN-gamma is a pleiotropic cytokine that plays an important role in the innate immune response to tumors. Based on our previous finding that the combination of Toll-like receptor 9 ligand CpG and interleukin (IL)-4 stimulates NKDC to produce IFN-gamma, we hypothesized that NKDC are the major IFN-gamma-producing dendritic cell subtype and may play a significant role in the host antitumor response. We found that under several conditions in vitro and in vivo NKDC accounted for the majority of IFN-gamma production by murine spleen CD11c(+) cells. IL-18 alone induced NKDC to secrete IFN-gamma, and the combination of IL-18 and CpG resulted in a synergistic increase in IFN-gamma production, both in vitro and in vivo. NK cells made 26-fold less IFN-gamma under the same conditions in vitro, whereas dendritic cells produced a negligible amount. The mechanism of IFN-gamma secretion by NKDC depended on IL-12. NKDC selectively proliferated in vitro and in vivo in response to the combination of IL-18 and CpG. Systemic treatment with IL-18 and CpG reduced the number of B16F10 melanoma lung metastases. The mechanism depended on NK1.1(+) cells, as their depletion abrogated the effect. IL-18 and CpG activated NKDC provided greater tumor protection than NK cells in IFN-gamma(-/-) mice. Thus, NKDC are the major dendritic cell subtype to produce IFN-gamma. The combined use of IL-18 and CpG is a viable strategy to potentiate the antitumor function of NKDC.

Randomized Clinical Trials in Soft Tissue Sarcoma

Soft tissue sarcomas (STS) are rare, but potentially lethal, extraskeletal mesenchymal neoplasms. It is estimated that approximately 12,000 cases of STS are reported annually in the United States, with 3,500 STS deaths. Few randomized controlled trials (RCTs) have been conducted since the previous issue of this publication. The current understanding of STS biology and, hence, ability to provide safe, effective therapy is predicated upon seminal trials performed in the 1980s and 1990s. The authors briefly summarize the trials presented in the previous issue and then critically assess the more recent publications that have addressed the management of STS.

Laparoscopic spleen-preserving distal pancreatectomy in elderly subjects: splenic vessel sacrifice may be associated with a higher rate of splenic infarction

BACKGROUNDnLaparoscopic spleen-preserving distal pancreatectomy has gained popularity in recent years. Splenic preservation can be achieved with or without splenic vessel preservation (SVP). The potential morbidity of this approach in patients aged >70 years has not been well defined.nnnMETHODSnTen patients aged >70 years underwent attempted laparoscopic spleen-preserving distal pancreatectomy within a 2-year period. Multiple patient parameters were examined and chi-squared analysis was used to evaluate the association between the operative technique (SVP or splenic vessel division [SVD]) and splenic infarction. The Mann-Whitney test was used to compare the SVP and SVD groups with regard to age, estimated blood loss (EBL), operating time, splenic volume and length of stay (LoS).nnnRESULTSnMedian age was 81 years (range: 71-92 years). Operating room time, LoS, EBL and complication rates were similar to those reported in published series of younger patients. In four patients, the splenic vessels were divided in a manner relying on short gastric collateral flow; SVP was achieved in all other patients. All four patients who underwent SVD developed splenic infarcts and three required splenectomy to manage this (P=0.002). Median LoS was increased in the SVD group (9.3 days vs. 4.3 days; P=0.053). Estimated blood loss was higher in the SVP group (200 ml vs. 100 ml; P=0.091). One pancreatic leak occurred. There were no mortalities.nnnCONCLUSIONSnSpleen-preserving laparoscopic distal pancreatectomy can be performed safely in elderly patients, with results comparable with those achieved in younger subjects. However, elderly patients undergoing division of the splenic artery and vein may be at higher risk for splenic infarct and the aetiology of this is unclear.

Regional hepatic therapies: an important component in the management of colorectal cancer liver metastases.

The treatment of colorectal cancer liver metastases (CRLM) has evolved significantly in the last 15 years. Currently, complete surgical resection remains the only potentially curative option; unfortunately, approximately 80% of patients with CRLM are not candidates for complete tumor resection. For patients with unresectable CRLM the available treatment options were historically limited; however, the development of regional hepatic therapies (RHT) and improvement of systemic chemotherapeutic regimens have emerged as viable options to improve overall survival and quality of life for this group of patients. The selection, sequence and integration of interventions into a multi-modal approach is a complex and evolving discipline. In this article, the currently available RHT modalities for CRLM are presented as a guide to the options for clinical treatment decisions.

Bipolar radiofrequency ablation of liver tumors: Technical experience and interval follow-up in 22 patients with 33 ablations

Bipolar radiofrequency ablation (BRFA) of hepatic tumors has short ablation times and may avoid convective heat loss from high‐flow vessels. We evaluated the technical feasibility of and local recurrence following BRFA.

Mincle Signaling Promotes Con A Hepatitis

Con A hepatitis is regarded as a T cell–mediated model of acute liver injury. Mincle is a C-type lectin receptor that is critical in the immune response to mycobacteria and fungi but does not have a well-defined role in preclinical models of non-pathogen–mediated inflammation. Because Mincle can ligate the cell death ligand SAP130, we postulated that Mincle signaling drives intrahepatic inflammation and liver injury in Con A hepatitis. Acute liver injury was assessed in the murine Con A hepatitis model using C57BL/6, Mincle−/−, and Dectin-1−/− mice. The role of C/EBPβ and hypoxia-inducible factor-1α (HIF-1α) signaling was assessed using selective inhibitors. We found that Mincle was highly expressed in hepatic innate inflammatory cells and endothelial cells in both mice and humans. Furthermore, sterile Mincle ligands and Mincle signaling intermediates were increased in the murine liver in Con A hepatitis. Most significantly, Mincle deletion or blockade protected against Con A hepatitis, whereas Mincle ligation exacerbated disease. Bone marrow chimeric and adoptive transfer experiments suggested that Mincle signaling in infiltrating myeloid cells dictates disease phenotype. Conversely, signaling via other C-type lectin receptors did not alter disease course. Mechanistically, we found that Mincle blockade decreased the NF-κβ–related signaling intermediates C/EBPβ and HIF-1α, both of which are necessary in macrophage-mediated inflammatory responses. Accordingly, Mincle deletion lowered production of nitrites in Con A hepatitis and inhibition of both C/EBPβ and HIF-1α reduced the severity of liver disease. Our work implicates a novel innate immune driver of Con A hepatitis and, more broadly, suggests a potential role for Mincle in diseases governed by sterile inflammation.

Thermal tumor ablation therapy for colorectal cancer hepatic metastasis

Surgical resection for colorectal hepatic metastases (CRHM) is the preferred treatment for suitable candidates, and the only potentially curative modality. However, due to various limitations, the majority of patients with CRHM are not candidates for liver resection. In recent years, there has been an increasing interest in the role of thermal tumor ablation (TTA) as a component of combined resection-ablation strategies, staged hepatic resections, or as standalone adjunct treatment for patients with CRHM. Thus, ablative approaches have expanded the group of patients with CRHM that may benefit from liver-directed treatment strategies.

Age-related trends in utilization of the internet and electronic communication devices for coordination of cancer care in elderly patients

OBJECTIVESnIn this rapidly changing electronic era, we implemented a study to define age dependent variations in access and use of internet and electronic devices in the exchange of healthcare related information (HRI) and coordination of clinical care (CCC) among elderly patients with cancer.nnnMATERIALS AND METHODSnData was collected through independently completed surveys after obtaining IRB approval in a single institution cancer center over a 4-month period. Questions regarding internet access and use of electronic media to obtain health information and coordinate care were distributed. The sample was divided in two groups based upon the World Health Organization (WHO) definition of geriatric patients: <65 y/o (group A) and ≥65 y/o (group B).nnnRESULTSnOne hundred and twenty-six surveys were analyzed with 70 patients in group A and 56 patients in group B. Access to the internet and use of email was higher in the group A (77% and 71%) vs. group B (36% and 33%, p < 0.001). The younger group felt more comfortable using the internet when compared to the older group (70% vs. 40%, p = 0.01). Patients in group B demonstrated a strong preference for paper copy based HRI and phone calls to CCC than text messages or emails (73% and 95%, p < 0.001). A transition zone between the ages of 65 and 70 years was defined to identify patients with increased reluctance to use internet and electronic devices to exchange HRI and CCC.nnnCONCLUSIONnThe data supports that there is an age-defined underutilization of internet and electronic devices to exchange HRI and CCC. Characterization of this age-dependent transition zone will enable clinicians to identify patients who may not interface well with electronic communication strategies, and to improve delivery of HRI and CCC for the elderly.

Hepatic PEComa: a potential pitfall in the evaluation of hepatic neoplasms

Perivascular epithelioid cell tumour (PEComa) of the liver is very uncommon and may be overlooked in the clinical and histological differential diagnosis of a liver tumour. We report the case of an incidentally discovered liver mass suspicious for hepatocellular carcinoma, which on biopsy was suggestive of a pseudocyst but after resection was found to be hepatic PEComa with some of the usual characteristics of this neoplasm as well as several less familiar features. We have also reviewed cases of hepatic PEComa from the literature in order to provide insight into recognising possible PEComa preoperatively and assessing its risk of malignancy after diagnosis.