Circulating monocyte chemoattractant protein-1 (MCP-1) is associated with cachexia in treatment-naïve pancreatic cancer patients.

BACKGROUND: Cancer-associated wasting, termed cancer cachexia, has a profound effect on the morbidity and mortality of cancer patients but remains difficult to recognize and diagnose. While increases in circulating levels of a number of inflammatory cytokines have been associated with cancer cachexia, these associations were generally made in patients with advanced disease and thus may be associated with disease progression rather than directly with the cachexia syndrome. Thus, we sought to assess potential biomarkers of cancer-induced cachexia in patients with earlier stages of disease. METHODS: A custom multiplex array was used to measure circulating levels of 25 soluble factors from 70 pancreatic cancer patients undergoing attempted tumour resections. A high-sensitivity multiplex was used for increased sensitivity for nine cytokines. RESULTS: Resectable pancreatic cancer patients with cachexia had low levels of canonical pro-inflammatory cytokines including interleukin-6 (IL-6), interleukin-1ß (IL-1ß), interferon-γ (IFN-γ), and tumour necrosis factor (TNF). Even in our more sensitive analysis, these cytokines were not associated with cancer cachexia. Of the 25 circulating factors tested, only monocyte chemoattractant protein-1 (MCP-1) was increased in treatment-naïve cachectic patients compared with weight stable patients and identified as a potential biomarker for cancer cachexia. Although circulating levels of leptin and granulocyte-macrophage colony-stimulating factor (GM-CSF) were found to be decreased in the same cohort of treatment-naïve cachectic patients, these factors were closely associated with body mass index, limiting their utility as cancer cachexia biomarkers. CONCLUSIONS: Unlike in advanced disease, it is possible that cachexia in patients with resectable pancreatic cancer is not associated with high levels of classical markers of systemic inflammation. However, cachectic, treatment-naïve patients have higher levels of MCP-1, suggesting that MCP-1 may be useful as a biomarker of cancer cachexia.

Perioperative cytokine levels portend early death after pancreatectomy for ductal adenocarcinoma.

BACKGROUND: Soluble signaling molecules may play an important role in malignant pathogenesis. We hypothesize that perioperative cytokine levels are associated with outcomes in patients with pancreatic adenocarcinoma (PDAC) undergoing surgical resection. METHODS: One hundered and eighteen patients with benign or malignant pancreatic disease were enrolled in a prospective study through a protocol for banking biologic samples. Peripheral blood was drawn at time of operation, and a multiplex cytokine assay was performed. Statistical analysis was via χ2 and Kaplan Meier methods. RESULTS: Of 118 patients enrolled, 85 (72%) had a diagnosis of PDAC, and 60 (70%) ultimately underwent partial pancreatectomy. Cytokine levels were not associated with postoperative complications in this initial cohort. A plasma level of monocyte chemoattractant protein-1 (MCP-1) pg/mL ≤118 was associated with better overall survival (OS) (median survival 21 months vs 12.8 months, P = 0.023), as was non-detectable interleukin-8 (IL-8) (19 months) versus detectable IL-8 (12.8 months, P = 0.05). Patients with both MCP-1 >118 pg/mL and detectable IL-8 had a median survival of 10.6 months (P = 0.028). CONCLUSIONS: MCP-1 and IL-8 cytokine levels are associated with decreased survival following pancreatectomy for PDAC, and may be useful biomarkers. Measurement of these cytokine levels at different time points in future investigations will be important to validate these findings.

Current Management of Perihilar Cholangiocarcinoma and Future Perspectives.

Perihilar cholangiocarcinoma is the most common type of biliary tract cancer and is associated with a high mortality, usually due to late presentation. High-resolution cross-sectional imaging modalities are necessary for diagnosis and preoperative planning. Although surgical resection with negative margins offers the only hope for cure, only a small subset of patients are amenable for surgery at the time of diagnosis. Portal vein embolization and biliary tract decompression are important in some patients prior to surgical resection. Liver transplantation in combination with neoadjuvant therapy has resulted in excellent 5-year recurrence-free survival rates in highly selected patients with inoperable disease. Gemcitabine plus cisplatin constitute the backbone of chemotherapy in patients with inoperable metastatic perihilar cholangiocarcinoma. Recent advances in understanding the molecular pathogenesis of CCA have created a growing interest in identifying novel therapies targeting key molecular pathways. Herein, we provide an overview of the most current principles of management of patients with perihilar cholangiocarcinoma.

Hepatic Artery Infusional Chemotherapy.

Hepatic artery infusion (HAI) therapy is a well-studied and viable regional therapy for patients with hepatic metastases. Implantable pump devices may be safely placed intraarterially with minimal morbidity and HAI treatments can be used as an adjunct to systemic therapy. Future trials may address sequencing of regional and systemic therapies. However, HAI is not without complications and requires close monitoring and attention to detail but can offer reasonable control of liver tumor burden when managed jointly between medical and surgical oncologists. Herein we describe the technical aspects of HAI pump placement and review pertinent studies in primary and secondary liver tumors.