Strong expression of chemokine receptor CXCR4 by pancreatic cancer correlates with advanced disease.

Certain chemokines have been proposed to distinctly contribute to tumor growth, dissemination and local immune escape. Expression of the chemokine receptor CXCR4 has been linked to tumor progression in diverse tumor entities. The aim of this study was to evaluate if the expression of CXCR4 influences progression of human pancreatic cancer. CXCR4 expression of pancreatic cancer was retrospectively assessed by immunohistochemistry in 103 patients with pancreatic cancer. Intensity of CXCR4 expression was correlated with both tumor and patient characteristics. Human pancreatic cancer revealed variable intensities of CXCR4 expression. Strong CXCR4 expression was significantly associated with advanced UICC stages (P=0.03) and revealed a trend for hematogenous metastasis (P=0.09) and progressed local tumor stages (P=0.15). In summary, strong expression of CXCR4 was significantly associated with advanced pancreatic cancer.

Liver resection or cryotherapy for colorectal liver metastases: a prospective case control study.

BACKGROUND AND AIMS: While there is promising survival data for cryosurgery of colorectal liver metastases, local recurrence following cryoablation remains a problem. We aimed to compare morbidity and mortality, as well as the recurrence pattern and survival after liver resection and cryotherapy (alone or in combination with resection) for liver metastases. PATIENTS AND METHODS: Between 1996 and 2002, 168 patients underwent liver resection alone and 55 patients had cryotherapy (25 in combination with liver resection) for colorectal liver metastases. The patient, tumour and operative details were recorded prospectively and the two patient groups were compared regarding morbidity, survival and recurrence. RESULTS: More patients had a prior liver resection, liver metastases were smaller and less frequently synchronous, morbidity was significantly lower and hepatic recurrence was significantly more frequent in the cryotherapy group. Five-year survival rates following resection and cryotherapy were comparable (23 and 26% respectively), while overall and hepatic recurrence-free survival was inferior following cryotherapy. CONCLUSION: Cryotherapy is a valuable treatment option for some patients with non-resectable colorectal liver metastases. While survival is comparable to that after resection, higher hepatic recurrence rates following cryotherapy should caution against the use of cryotherapy for resectable disease until the results of randomized controlled trials are available.

A pig model of hepatic cryotherapy. In vivo temperature distribution during freezing and histopathological changes.

We aimed to assess the temperature distribution in the cryolesion during hepatic cryotherapy and the association with postoperative histological changes to optimise the technique and allow better preoperative planning. Hepatic cryolesions were produced in 22 pigs following laparotomy using a CMS-cryosystem and 8mm-AccuProbe-Cryoprobes. The temperature was measured in 1 min intervals at different distances from the probe during freezing. The animals were treated in 5 groups: (i) single freezing of 20 min; (ii) double freezing of 20 min each; (iii) single freezing of 40 min; (iv) single freezing of 20 min (n=4), histology at 1 week p.o., and (v) single freezing of 20 min and Pringle manoeuvre; [(i)-(iii) and (v): histology at 24 h p.o.]. The mean diameter of the -38 degrees C isotherm, i.e., the zone of effective treatment for colorectal metastases was 37 mm for group (i) with a mean iceball diameter of 59 mm and about 46 mm for groups (ii, iii, and v) with mean iceball diameters of 78, 75, and 75 mm, respectively. At 7 days postoperatively secondary necrosis was seen in the largest central part of the lesion, wherever temperatures of -15 degrees C or lower were achieved during cryosurgery. Under the hypothesis that -38 degrees C is the effective temperature for the destruction of colorectal liver metastases, a lesion of 37-mm diameter may be effectively treated with a single 8mm-AccuProbe-Cryoprobe and a 20 min single freeze cycle and a lesion of 46 mm may be effectively treated when a double freeze-thaw cycle of 20 min each, a single freeze cycle of 40 min, or a 20 min single freeze cycle with additional Pringle manoeuvre is used, when it is perfectly placed in the lesion.

Large volume hepatic freezing: association with significant release of the cytokines interleukin-6 and tumor necrosis factor a in a rat model.

Although cryotherapy of liver tumors is generally considered a safe procedure, a syndrome of coagulopathy and fatal multiorgan failure has been observed in some patients and is called the cryoshock phenomenon. Our aim was to establish an animal model of this phenomenon and examine the effects of the basic parameters of freezing or cryotherapy on it. A group of 75 female Sprague-Dawley rats were allocated randomly to five groups: (1) sham laparotomy (n = 15); (2) small (25% liver volume) single freeze (n = 15); (3) small (25% liver volume) double freeze (n = 15); (4) large (50% liver volume) single freeze (n = 15); (5) large (50% liver volume) double freeze (n = 15). Blood samples were collected at different postoperative times, and organs were harvested for histopathology. There was a significant release of tumor necrosis factor-a (TNFa) and interleukin 6 (IL-6) following hepatic freezing, which was greatest in group 5. Postoperative serum cytokine levels were significantly associated with hepatocellular injury, as measured by postoperative serum aspartate transaminase (AST) concentrations. Severe hemoglobinuria and renal injury, as demonstrated by the serum creatinine level and the glomerular neutrophil count, were observed and were greatest in group 5. Hepatic cryosurgery is associated with release of IL-6 and TNFa and renal injury in a rat model. It is likely that the cryoshock phenomenon is another form of the systemic inflammatory response syndrome. Based on the results of this study, it is possibly mediated by cytokines released from the frozen liver tissue. We therefore caution against cryotherapy of large tumor volumes.