Size Of Liver Metastases Research Articles

D05 - FOLFOXIRI plus bevacizumab (bev) as upfront treatment for metastatic colorectal cancer (mCRC) patients (pts) with initially unresectable liver-limited disease (LLD)

Background: Surgical resection of colorectal liver metastases is a potentially curative option for a subgroup of initially unresectable mCRC pts. Active upfront regimens may increase the percentage of pts converted to resection and positively affect their survival. The aim of the present study was to assess the activity and efficacy of FOLFOXIRI plus bev in mCRC pts with LLD. Patients and Methods: Pts with unresectable LLD treated with FOLFOXIRI plus bev in FOIB, TRIBE and MOMA studies were selected. Baseline clinical and molecular characteristics and outcome parameters were collected. Results: 205 pts with LLD were identified. 184 (90%) pts presented with synchronous disease, 119 (61%) had = 4 metastases, liver metastases were bilobar in 140 (79%) cases, and primary tumor was unresected in 74 (36%). 137 (67%) pts responded, and 124 (60%) achieved early response. 91 (44%) pts underwent resection: R0, R1 and R2 resections were performed in 63 (69%), 11 (12%) and 17 (19%) cases, respectively. Having less than 6 involved segments (p = 0.014), achieving RECIST response (p < 0.001), early response (p = 0.002), and deeper response (p = 0.063) were associated with higher probability to undergo resection in the multivariable model. As compared to unresected pts, those achieving resection had longer PFS (median PFS: 18.1 vs 10.6 mos, HR: 0.47 [0.34-0.65], p < 0.001) and OS (median OS: 44.3 vs 22.5 mos, HR: 0.29 [0.20-0.44], p < 0.001). At a median follow up of 36.5 mos, the estimated 5ys-PFS and 5ys-OS in resected pts were 10% and 38%, respectively. Neither number and size of liver metastases, nor their distribution, nor number of involved segments, nodal status, CEA levels, Fong and Nordlinger score predicted RFS and OS of resected pts. Notably, BRAF mut pts resected after FOLFOXIRI plus bev achieved survival results comparable with RAS/BRAF wt and RAS mut. Radiological (p = 0.047) and pathological response (TRG 1-2 vs 3-4, p = 0.088) was associated with longer OS. Conclusion: FOLFOXIRI plus bev allowed to obtain high resection rate and remarkable survival results in a population of mCRC pts with extensive LLD, not selected for a conversion intent. Radiological and pathological response to FOLFOXIRI plus bev predict survival in resected pts, differently from traditional clinical risk scores and RAS/BRAF status.

Peritoneal carcinomatosis with synchronous liver metastases from colorectal cancer: Who will benefit from complete cytoreductive surgery?

PurposeSelection of patients for resection of synchronous liver metastases (LM) and peritoneal carcinomatosis (PC) of colorectal cancer (CRC) remains a debated issue since morbidity of this surgery is not negligible. We aimed to define overall survival (OS) prognostic criteria in patients undergoing PC surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) and LM resection. MethodsThis monocentric and comparative study included all consecutive patients operated for LM (LM group, n = 77), PC (HIPEC group, n = 18) and PC + LM (LM + HIPEC group, n = 9) from January 2007 to May 2011. Characteristics of the 3 groups were prospectively collected and retrospectively compared. ResultsMedian follow-up was 56,5 months. Major morbidity and mortality were respectively 14% and 3%. Two-year disease free and overall survival rates were respectively 23% and 76%. There were significantly more Dindo grade III-IV complications in LM + HIPEC group. In multivariate analysis, grade II and III preoperative chemotherapy-induced toxicity and size of LM were identified as poor OS prognostic factors whereas response to preoperative chemotherapy significantly increases OS. OS was not different (p = 0.235) between the 3 groups. ConclusionToxicity to preoperative chemotherapy and size of LM were identified as poor prognostic factors in patients undergoing simultaneous PC and LM surgery. These criteria could help in better selecting patients for such extensive surgery.

Anti-metastatic action of FAK inhibitor OXA-11 in combination with VEGFR-2 signaling blockade in pancreatic neuroendocrine tumors.

The present study sought to determine the anti-tumor effects of OXA-11, a potent, novel small-molecule amino pyrimidine inhibitor (1.2 pM biochemical IC(50)) of focal adhesion kinase (FAK). In studies of cancer cell lines, OXA-11 inhibited FAK phosphorylation at phospho-tyrosine 397 with a mechanistic IC(50) of 1 nM in TOV21G tumor cells, which translated into functional suppression of proliferation in 3-dimensional culture with an EC(50) of 9 nM. Studies of OXA-11 activity in TOV21G tumor-cell xenografts in mice revealed a pharmacodynamic EC(50) of 1.8 nM, indicative of mechanistic inhibition of pFAK [Y397] in these tumors. OXA-11 inhibited TOV21G tumor growth in a dose-dependent manner and also potentiated effects of cisplatin on tumor cell proliferation and apoptosis in vitro and on tumor growth in mice. Studies of pancreatic neuroendocrine tumors in RIP-Tag2 transgenic mice revealed OXA-11 suppression of pFAK [Y397] and pFAK [Y861] in tumors and liver. OXA-11 given daily from age 14 to 17 weeks reduced tumor vascularity, invasion, and when given together with the anti-VEGFR-2 antibody DC101 reduced the incidence, abundance, and size of liver metastases. Liver micrometastases were found in 100 % of mice treated with vehicle, 84 % of mice treated with OXA-11, and 79 % of mice treated with DC101 (19-24 mice per group). In contrast, liver micrometastases were found in only 52 % of 21 mice treated with OXA-11 plus DC101, and those present were significantly smaller and less numerous. Together, these findings indicate that OXA-11 is a potent and selective inhibitor of FAK phosphorylation in vitro and in vivo. OXA-11 slows tumor growth, potentiates the anti-tumor actions of cisplatin and--when combined with VEGFR-2 blockade--reduces metastasis of pancreatic neuroendocrine tumors in RIP-Tag2 mice.

Complications following liver resection for colorectal metastases do not impact on longterm outcome

BackgroundIt has been suggested that adverse postoperative outcomes may have a negative impact on longterm survival in patients with colorectal liver metastases. ObjectivesThis study was conducted to evaluate the prognostic impact of postoperative complications in patients submitted to a potentially curative resection of colorectal liver metastases. MethodsA retrospective analysis of outcomes in 199 patients submitted to hepatic resection with curative intent for metastatic colorectal cancer during 1999–2008 was conducted. ResultsThe overall complication rate was 38% (n = 75). Of all complications, 79% were minor (Grades I or II). There were five deaths (3%). The median length of follow‐up was 39 months. Rates of 5‐year overall and disease‐free survival were 44% and 27%, respectively. Univariate analysis demonstrated that an elevated preoperative level of carcinoembryonic antigen (CEA), intraoperative blood loss of >300 ml, multiple metastases, large (≥35 mm) metastases and resection margins of <1 mm were associated with poor overall and disease‐free survival. In addition, male sex and synchronous metastases were associated with poor disease‐free survival. Postoperative complications did not have an impact on either survival measure. The multivariate model did not include complications as a predictive factor. ConclusionsPostoperative complications were not found to influence overall or disease‐free survival in the present series. The number and size of liver metastases were confirmed as significant prognostic factors.

Overexpression of Nodal induces a metastatic phenotype in pancreatic cancer cells via the Smad2/3 pathway.

Metastasis is the major cause for the high mortality rate of pancreatic cancer. Human embryonic stem cell (hESC) associated genes frequently correlate with malignant disease progression. Recent studies have demonstrated that the embryonic protein Nodal, which plays a critical role during embryonic development, is re-expressed in several types of tumors and promotes cancers progression. However, little is known about the role of Nodal in pancreatic cancer. Here, we show that Nodal expression is upregulated in human pancreatic cancer tissues. Moreover, Nodal expression levels correlate well with the grade of pancreatic cancer differentiation. In addition, we present clear evidence that Nodal induces signal transduction through the Smad2/3-dependent pathway in vitro. Furthermore, we show that Nodal promotes pancreatic cancer cell migration and invasion, induces epithelial-mesenchymal transition (EMT) and enhances the expression of matrix metalloproteinase-2 (MMP2) and CXC chemokine receptor 4 (CXCR4). Using an in vivo liver metastasis model of pancreatic cancer, we observed that blocking Nodal signaling activity with the small-molecule inhibitor SB431542 decreases the number and size of liver metastases. Taken together, our results suggest that Nodal overexpression induces a metastatic phenotype in pancreatic cancer cells, and that targeting Nodal signaling may be a promising therapeutic strategy for pancreatic cancer.

The Evolving Use of Prognostic Factors After Resection of Colorectal Liver Metastases

The expanding use of surgical therapy for patients with colorectal liver metastases (CRLM) and developments in chemotherapeutic regimens have led to a significant improvement in survival. However, outcomes can vary substantially and criteria for determining the prognosis of individual patients are lacking. Traditionally, clinicopathologic factors, for example primary tumor stage, number and size of liver metastases, preoperative carcinoembryonic antigen levels, presence of extrahepatic disease, and others, have been used to determine which patients are more likely to experience recurrence and poor survival. However, these factors, both separately and as part of scoring systems, have been inconsistent and conflicting in determining prognosis. Recently, molecular and biological indicators have emerged as potential prognosticators for CRLM patients undergoing hepatic resection. Tumor response to chemotherapy, both on imaging and on pathology, mutation status of such oncogenes as KRAS and BRAF, and expression patterns of proliferative markers including MACC1 and Ki-67, have all furnished promising results in prediction of patient outcomes. Moreover, circulating tumor cells and tumor DNA may not only be a useful prognostic instrument but also an excellent means of screening for early detection of recurrence.

All-trans-retinoic acid counteract the tumor-stimulating effect of hepatectomy and increases survival of rats bearing liver metastases

BackgroundWe previously demonstrated a stimulating effect of hepatectomy on residual tumor cells after resection of liver metastases. The aim of this study was to analyze the effect of all-trans-retinoic acid (ATRA) on the protumor effect of hepatectomy and survival of hepatectomized rats bearing liver metastases. We also explored whether ATRA interfered with the tumor promoting effect of hepatotropic growth factors (GFs). MethodsThe in vitro effect of ATRA on proliferation of S4MH rhabdomyosarcoma tumor cells was assessed when cultured with laparotomized or hepatectomized rat serum (HRS), or in the presence of GFs (hepatocyte growth factor, insulin growth factor 2, Platelet Derived Growth Factor (PDGF)-BB, and vascular endothelial growth factor). For the in vivo studies, rats were partially hepatectomized on day 10 after metastasis induction, one group being treated with ATRA from day 7 to 14, and a second receiving cyclophosphamide (CY; on days 10 and 14) alone or with ATRA. We determined the size and number of liver and lung metastases. Finally, we analyzed the effect of treatments on rat survival. ResultsHepatotropic GFs increased cell proliferation in a similar manner to HRS. In vitro, ATRA blocked the protumor effect of both HRS and GFs. In vivo, ATRA reduced the size and number of liver and lung metastases, and significantly increased rat survival. Furthermore, adding ATRA to CY significantly increased survival compared with CY alone. ConclusionsIn our model, ATRA minimizes the tumor-stimulating effect of hepatectomy, reducing the number and size of liver metastases and improving survival. The results suggest that the ATRA may be useful for blocking the growth-promoting effect of hepatotropic GFs released after liver metastasis resection.

Benefits of simultaneous laparoscopic resection of primary colorectal cancer and liver metastases

Recently, consensus on the optimal strategy for resectable synchronous colorectal liver metastases (LM) seems to have shifted toward simultaneous resection. However, there are still relatively few reports about simultaneous laparoscopic resection. The aim of this study is to evaluate the outcomes of patients who underwent simultaneous laparoscopic resection. We evaluated 14 patients who underwent simultaneous resection of primary colorectal cancer and LM in our hospital from 2004 to 2012. Patients were selected by matched pair analysis based on the number of LM (≤4) and tumor size (≤5 cm). We divided them into two groups: the simultaneous laparoscopic resection of primary colorectal cancer and LM (Lap-S) group (n = 7) and the simultaneous open resection of primary colorectal cancer and LM (Open-S) group (n = 7). Clinical and oncologic outcomes were compared between the groups. The Lap-S patients were significantly older than the Open-S patients. The mean operative times of Lap-S and Open-S were 472 min and 466 min, respectively. The mean blood loss was significantly smaller in the Lap-S group (153 mL) than in the Open-S group (496 mL). There was no surgical mortality in either group. The incidence of postoperative complications in the Lap-S and Open-S groups was 12.3% and 33.0%, respectively. The mean postoperative hospital stay was significantly shorter in the Lap-S group (16 days) than in the Open-S group (36 days). There was no significant difference in long-term survival between the two groups. Lap-S patients had equivalent long-term outcomes to Open-S patients. Therefore, given its technical feasibility and safety, Lap-S may be one of the most promising options in selected patients.

Outcomes of Open Versus Laparoscopic Procedure for Synchronous Radical Resection of Liver Metastatic Colorectal Cancer

The laparoscopic resection of colorectal cancer (CRC) along with synchronous liver metastases has been attempted and reported in multiple single series. In this study, we aimed to examine the feasibility, procedural safety, and oncological integrity of 1-stage totally laparoscopic procedure for the radical resection of liver metastatic CRC in a head-to-head comparison with the 1-stage open procedure simultaneously. The patients who underwent selective 1-stage concomitant resection of CRC and synchronous liver metastases between January 2004 and December 2008 (laparoscopy group, n=13) were retrospectively enrolled in the study. Patients receiving open 1-stage resection (laparotomy group) were retrospectively included at the ratio of 1:1 (n=13 out of 71), matching the laparoscopy group in sex, age, body mass index, site and stage of primary tumor, location and size of liver metastases, and adjuvant therapies. All the thirteen 1-stage laparoscopic procedures were successfully completed, without conversion to open procedure or additional incision. The operative duration of laparoscopic procedure was shorter than that of open procedure (313 ± 44 vs. 350 ± 46 min, P<0.05). The volume of blood loss was comparable between the 2 groups (259 ± 111 vs. 273 ± 95 mL, P>0.05). Patients undergoing laparoscopic procedure resumed off-bed activities, bowel movement, and oral intake earlier than those undergoing open procedure, and also had a shorter hospitalization stay (8.5 ± 1.9 vs. 11.2 ± 1.8 d, P<0.05). Only 1 clinically significant adverse event occurred in a patient who developed bile leak after the laparoscopic resection. The 1-, 3-, and 5-year survival rates were comparable between the 2 groups (P>0.05). One-stage synchronous laparoscopic resection of liver metastatic CRC is a feasible, effective, and safe modality in specifically indicated patients, both accelerating postoperative recovery and shortening hospitalization time.

Impact of Simultaneous Diaphragm Resection During Hepatectomy for Treatment of Metastatic Colorectal Cancer

IntroductionFor colorectal cancer patients with liver metastases involving the hepatic dome or invading the diaphragm, a concomitant diaphragm resection is often required to achieve negative surgical margins. The purpose of this study is to determine whether diaphragm resection during partial hepatectomy for metastatic colorectal cancer influences short-term perioperative outcomes and overall survival. MethodsDemographics, treatments, and outcomes of 442 patients who underwent hepatic resection for metastatic colorectal cancer from 1996 to 2010 at a high-volume center were reviewed. Recurrence and survival were measured from the date of metastectomy. Actuarial curves were generated using the Kaplan–Meier method and compared using log–ranks testing. Multivariate predictors of worse survival were compared using a Cox-proportional hazards model. ResultsA total of 442 patients underwent hepatectomy for metastatic colorectal cancer. Of these, 34 required simultaneous diaphragm resection (DR) and 408 did not (LR). No significant differences existed in patient demographics or comorbidities. The DR group had longer median operative times (336 vs. 267 min, p = 0.0008) but had comparable rates of perioperative morbidity and mortality. Median overall survival was shorter in the DR group compared to the LR group (18.8 vs. 36 months, p = 0.0017). When controlling for potential cofounders, liver metastases size > 5 cm (HR 1.45 95 % CI (1.08–1.99), p = 0.015) and diaphragm resection (HR = 1.72 95 % CI (1.03–2.86), p = 0.038) predicted worse survival. ConclusionsSimultaneous diaphragm resection during partial hepatectomy does not significantly influence perioperative morbidity or mortality despite longer operative times. However, patients who require diaphragm resection have less favorable survival rates as compared to those who do not.

Outcome of patients with colorectal liver metastasis: Analysis of 1,613 consecutive cases.

e14000 Background: To evaluate the long-time outcome of patients with colorectal liver metastasis (CRLM) undergoing different types of therapy and identify factors associated with prognosis. Methods: From 2000 to 2010, a total of 1,613 patients with CRLM were identified in Zhongshan Hospital. Clinicopathological and outcome data were collected and analyzed by univariate and multivariate analyses. Results: Of 1,613 patients the median survival was 23.1 months and the five-year survival rate was 23%. Synchronous liver metastasis (SLM), female, grade III-IV, T4 and N + of primary tumor, bilobar disease, number of liver metastases ≥ 4, size of largest liver metastases ≥ 5 cm, CEA ≥5 ng/ml and CA19-9 ≥ 37u/ml were the predictors of adverse outcome using univariate analysis. The median survival and five-year survival rate for patients after resection of liver metastases was 49.8 months and 47%, compared with 22.2 months and 19% for those after systemic chemotherapy alone, 19.0 months and 13% for those after hepatic arterial chemotherapy alone, 22.8 months and 10% for those after systemic chemotherapy combined with hepatic arterial chemotherapy, and 28.5 months and 6% for those after local regional treatment alone (p&lt; 0.010). In addition, patients without treatment had the poorest survival rate (9.6 months and 0%). 64 initially unresectable patients underwent surgery after convertible therapy and had a median survival of 36.9 months and a five-year survival of 30%, which was better than that of unresectable patients who did not undergo surgery (18.2 months and 10%). By multivariate analysis, SLM, poorly differentiated primary tumor, number of liver metastases ≥ 4, size of largest liver metastases ≥ 5 cm, and no surgical treatment of liver metastases were found to be independent predictors of poor survival. Conclusions: Patients with CRLM could get long-term survival benefit from different types of therapy, and resection of resectable and initially unresectable liver metastases was the optimal strategy. The disease-free interval from primary to liver metastases, the differentiation of the primary tumor, the number and size of liver metastases and the types of therapy used to treat liver metastases were independent prognostic factors.

Parallel hierarchical sampling: A general-purpose interacting Markov chains Monte Carlo algorithm

A novel class of interacting Markov chain Monte Carlo (MCMC) algorithms, hereby referred to as the Parallel Hierarchical Sampler (PHS), is developed and its mixing properties are assessed. PHS algorithms are modular MCMC samplers designed to produce reliable estimates for multi-modal and heavy-tailed posterior distributions. As such, PHS aims at benefitting statisticians whom, working on a wide spectrum of applications, are more focused on defining and refining models than constructing sophisticated sampling strategies. Convergence of a vanilla PHS algorithm is proved for the case of Metropolis–Hastings within-chain updates. The accuracy of this PHS kernel is compared with that of optimized single-chain and multiple-chain MCMC algorithms for multi-modal mixtures of multivariate Gaussian densities and for ‘banana-shaped’ heavy-tailed multivariate distributions. These examples show that PHS can yield a dramatic improvement in the precision of MCMC estimators over standard samplers. PHS is then applied to two realistically complex Bayesian model uncertainty scenarios. First, PHS is used to select a low number of meaningful predictors for a Gaussian linear regression model in the presence of high collinearity. Second, the posterior probability of survival trees approximated by PHS indicates that the number and size of liver metastases at the time of diagnosis are predictive of substantial differences in the survival distributions of colorectal cancer patients.

Transcatheter Arterial Chemoembolization for Liver Metastases in Patients with Adrenocortical Carcinoma

To retrospectively evaluate the effectiveness, tolerance, and predictors of response to transcatheter arterial chemoembolization for treatment of liver metastases from adrenocortical carcinoma. Twenty-nine patients with progressive liver metastases from adrenocortical carcinoma were treated with transcatheter arterial chemoembolization. Rate and duration of tumor response were defined according to Response Evaluation Criteria In Solid Tumors. The size of liver metastases, percentage of liver involvement, and Lipiodol uptake were studied as potential predictive factors of response. Time to liver and metastatic lesion progression were considered as endpoints. Three months after transcatheter arterial chemoembolization, a liver morphologic response was observed in six of 29 patients (21%), stabilization in 18 (62%), and progression in five (17%). According to per-lesion analysis (n = 103), a morphologic response was observed in 23 lesions (22%), stabilization in 67 (65%), and progression in 13 (13%). Higher response rates were observed in cases in which the diameter of the target metastasis was 3 cm or smaller (P = .002) and in cases of high Lipiodol uptake (> 50%; P < .0001). On per-patient and per-lesion bases, progression rates were 32% and 55% at 6 months and 23% and 38% at 12 months. The median time to progression was 9 months and median survival was 11 months after the first procedure. Transcatheter arterial chemoembolization should be considered as part of the therapeutic arsenal to treat liver metastases from adrenocortical carcinoma. The size of liver metastases and the percentage of Lipiodol uptake may help identify patients likely to benefit most from transcatheter arterial chemoembolization.

Prognostic analysis of 77 cases of rectal cancer with synchronous liver metastases

To explore the prognostic factors for rectal cancer patients with synchronous liver metastases. Data from a total of 77 cases of rectal cancer with synchronous liver metastases treated in our center from January 2002 to December 2008 were collected and reviewed. The total survival rate was analyzed by Kaplan-Meier method. Log-rank test and Cox regression model with SPSS 17.0 software were used to analyze 13 factors including clinicopathological factors and treatment choices. The median survival time of the 77 cases was 12 months. The 1-, 2-, 3- and 5-year survival rates were 47.7%, 28.0%, 13.1%, and 1.5%, respectively. Univariate analysis with Kaplan-Meier method revealed that the differentiation of the primary tumor, T-stage, N status, the distribution, number and size of liver metastases, extrahepatic disease, serum CEA level at diagnosis and treatment modality were prognostic factors (P < 0.05). Multivariate analysis showed that the differentiation of the primary tumor (P = 0.007), T-stage (P = 0.027), the size of liver metastases (P = 0.003), serum CEA value at diagnosis (P = 0.000) were independent prognostic factors for rectal cancer patients with synchronous liver metastases. The factors affecting the prognosis for rectal cancer patients with synchronous liver metastases are the differentiation of the primary tumor, T-stage, N status, the distribution, number and size of liver metastases, extrahepatic disease, serum CEA level at diagnosis and treatment modality. The differentiation of the primary tumor, T-stage, the size of liver metastases, and serum CEA value at diagnosis are independent prognostic factors.

Impact of Octreotide and SOM-230 on liver metastasis and hepatic lipidperoxidation in ductal pancreatic adenocarcinoma in Syrian Hamster

Octreotide is a somatostatin analogue binding on two receptor subtypes. In previous trials Octreotide showed inhibitory effects on tumour growth and liver metastasis in experimental pancreatic cancer. Thus we evaluated whether the new somatostatin analogue SOM-230 binding on 4 receptor subtypes has superior effects on carcinogenesis in pancreatic carcinoma. About 120 Syrian hamsters were randomised into six groups (n = 20): Gr.1: Aqua/Aqua, Gr.2: BOP/Aqua, Gr.3: Aqua/Octreotide, Gr.4: BOP/Octreotide, Gr.5: Aqua/SOM-230, Gr.6: BOP/SOM-230. Tumour groups 2,4,6 subcutaneously received 10 mg/kg body weight N-nitrosobis-2-oxopropylamin (BOP) weekly for 10 weeks, healthy control Gr.1,3,5 were given aqua. In the 17th week therapy started with Octreotide and SOM-230 for 16 weeks, after 32 weeks animals were sacrificed. Pancreas and liver were histopathologically analysed. Hepatic lipidperoxidation was determined by activities of antioxidative enzymes gluthation-peroxidase (GSH-Px) and superoxiddismutase (SOD) as well as concentration of thiobarbituric-acid reactive substances (TBARS). Incidence of liver metastases was 88.2% in Gr.2 (BOP/Aqua), it was decreased in Gr.4 (BOP/Octreo: 40%) and Gr.6 (BOP/SOM-230: 50%) (P < 0.05). Mean number/animal and mean-2-dimensional size of liver metastases did not differ between tumour groups. Comparing GSH-Px-activity in intrametastatic and extrametastatic hepatic tissue revealed a significant increase extrametastatically in Gr.2 (BOP/Aqua) and Gr.6 (BOP/SOM-230). SOD-activity in liver metastases was decreased in Gr.2 (1,801) (P < 0.05) versus Gr.4 (8,304) and Gr.6 (7,038). Intrametastatic TBARS concentration was increased in Gr.2 compared to Gr.4 (BOP/Octreotid) and Gr.6 (BOP/SOM-230) (P < 0.05). Octreotide and SOM-230 equally reduced liver metastasis in ductal pancreatic adenocarcinoma probably by a reduction of lipidperoxidation.

Analysis of prognostic factors in 300 colorectal cancer patients with liver metastases

To analyse the clinical characteristics and potential prognostic factors of colorectal cancer patients with liver metastases. The clinical and pathological data of 300 colorectal cancer patients with liver metastases were retrospectively reviewed and analyzed. The median survival time of these patients was 19.0 months. The 1-, 2- and 5-year survival rates after liver metastases were 79.0%, 29.0% and 3.0%, respectively. Univariate analysis revealed that performance status (KPS), histological grading, primary tumor, N status, lymphatic and vascular invasion, stage at diagnosis, the number, size and distribution of liver metastases and other accompanied metastases were prognostic factors. Multivariate analysis showed that KPS, lymphatic and vascular invasion, the number and size of liver metastases were independent prognostic factors of colorectal cancer with liver metastases. Performance status, lymphatic and vascular invasion, the number and size of liver metastases are independent prognostic factors of colorectal cancer with liver metastases.

Five-year survival in 309 patients with colorectal liver metastases treated with radiofrequency ablation

There is little published long-term survival data for patients with colorectal liver metastases treated with radiofrequency ablation (RFA). We present a multivariate analysis of 5-year survival in 309 patients (198 male, aged 64 (24-92)) treated at 617 sessions. Our standard protocol used internally cooled electrodes introduced percutaneously under combined US and CT guidance/monitoring. The number and size of liver metastases, the presence and location of extrahepatic disease, primary resection, clinical, chemotherapy and follow-up data were recorded. Data analysis was performed using SPSS v.10. On multivariate analysis, significant survival factors were the presence of extrahepatic disease (p < 0.001) and liver tumour volume (p = 0.001). For 123 patients with five or less metastases of 5 cm or less maximum diameter and no extrahepatic disease median survival was 46 and 36 months from liver metastasis diagnosis and ablation, respectively; corresponding 3- and 5-year survival rates were 63%, 34% and 49%, 24%. Sixty-nine patients had three or less tumours of below 3.5 cm in diameter and their 5-year survival from ablation was 33%. There were 23/617(3.7%) local complications requiring intervention. Five-year survival of 24-33% post ablation in selected patients is superior to any published chemotherapy data and approaches the results of liver resection.

Effective treatment of a hormonally inactive carcinoid tumour with somatostatin analogues: application of serum chromogranin A for clinical follow-up

Hormonally inactive carcinoids represent a significant proportion of all carcinoids tumours. Classical biochemical and hormonal parameters are not suitable for the diagnosis and follow-up of these tumours. However, the tumour marker chromogranin A that is characteristic for several neuroendocrine tumours and secreted by the majority of these tumours as well, may offer a better means of diagnosis and follow-up. Somatostatin receptors are expressed by hormonally inactive carcinoids and the presence of these receptors has important diagnostic and therapeutic consequences. The authors present the history of a patient with a hormonally inactive bronchial carcinoid tumour. After surgical removal of the bronchial carcinoid, liver metastases developed which were found to be somatostatin receptor positive. Somatostatin analogue treatment was introduced, followed by Yttrium-isotope labelled somatostatin analogue therapy. Serum chromogranin A was elevated before somatostatin treatment, and gradually decreased in parallel with therapy. The size of liver metastases remained unchanged during treatment. Chromogranin A can be efficiently applied for the clinical follow-up of hormonally inactive carcinoid tumours. Somatostatin analogues may be effective for preventing tumour progression not only in hormone-secreting but also in hormonally inactive carcinoid tumours.

Prognostic factors in metastatic colorectal carcinoma at initial diagnosis, MCCID

14548 Background: Despite several studies have evaluated the role of prognostic factors (PF) in metastatic colorectal cancer, results are controversial. The aim of the present study was to assess PF in a homogeneous population with MCCID treated with biochemical modulation of 5- Fluorouracil-based regimens. Methods: Analyses were based on individual data of 318 patients (P) with MCCID treated in different prospective trials at GOCS Institutions since May 1984 to Jun 2001. The following variables (V) were considered: a) Clinical variables (CV): age, sex, family history of CC, hypertension, diabetes, tabaquism, weight loss, and performance status (PS), b) Tumor variables (TV): histologic grade, size and location of primary tumor; number of metastatic sites, number and size of liver metastases, uni- bilateral liver involvement; and c) Laboratory variables (LV): CEA, lactate dehydrogenase (LDH), alkaline phosphatase, ALT, AST, and hemoglobin. Overall survival (OS) was analyzed since date of diagnosis by means of Kaplan-Meier and the Log-rank test was used to assess the differences. A Cox’s proportional hazard modeling was used for multivariate analyses. Results: The OS for the entire group was 18.1 months (IC95, 15.0–22.7). Univariate analysis showed statistical significance in the following; a) CV: family history CC (p=0.001), PS (p=0.04), diabetes (P=0.003); b) TV: histologic grade (p=0.01), uni-bilateral liver involvement (p&lt;0.0001), number of liver metastases (p&lt;0.0001) and size of liver metastases (p&lt;0.0001); and c) LV: hemoglobin (p=0.05), ALT (P=0.0006), AST (p&lt;0.0001), alkaline phosphatase (p&lt;0.0001), LDH (p=0.0004); Cox’s analyses showed statistical significance only for PS and alkaline phosphatase (p= 0.01 and p=0.0001, respectively). Conclusions: In this setting of P with MCCID the PS remains the most important PF for OS. High value of alkaline phosphatase may reflect liver involvement. No others PF considered in the analyses had prognostic influence. No significant financial relationships to disclose.

The impact of metastatic sites in metastatic colorectal cancer at initial diagnosis (MCCID)

14536 Background: The role of metastatic site in MCCID is unclear. The goal of this study is to evaluate if metastatic site influence survival in this setting of patients (P). Methods: Analyses were based on individual data of 300 P with MCCID treated with biochemical modulation of 5- Fluorouracil by Methotrexate regimens in different prospective trials conducted at GOCS Institutions since May 1984 to Aug 2000. P with surgical resection of liver metastases were not included in the analyses. 38 P were excluded for incomplete data. P were grouped according to metastatic sites into group A= Liver metastases only (n=161), group B= Liver and other metastatic sites (n=61) and group C= Non liver metastases (n=40) (lung, peritoneal, others). Different prognostic variables were considered: age, sex, PS, weight loss, size of liver metastases, unilateral or bilateral liver involvement, number of liver metastases, histologic differentiation of primary tumor, location of primary tumor, lactate dehydrogenase, alkaline phosphatase, ALT, AST and hemoglobin. Overall survival (OS) was analyzed since date of diagnosis by means of Kaplan-Meier and the Log-rank test was used to assess the differences. Results: The average follow-up time was 14.4 months (0–73.4). Clinical, laboratory and tumor characteristics were similar among groups A, B and C respectively. However P in group A had bigger size of liver metastases, higher number of them and more bilateral liver involvement respect to group B (p=0.02, p=0.03, p=0.05 respectively). Median OS in group A=21.0 months, group B=13.1 months and group C=15 months (p= 0.02). Statistical difference in OS was observed between group A and group B (p= 0.015). No difference was observed between groups A plus B vs the heterogeneous group C (p= 0.83) Conclusions: P with liver only metastatic site had better prognosis respect to those with other coexisting site of metastases despite presenting higher tumor burden in the liver. No factors analysed in the study explaine this difference. The subset of P with liver only metastatic site would be considered as a distinctive group and deserve further molecular studies. No significant financial relationships to disclose.