Improving resectability of hepatic colorectal metastases: expert consensus statement.
Explore the source record for details and available documents.
Catheter Ablation↗
Biomedical subjects
Anton J Bilchik
Publications and source records attributed to Anton J Bilchik.
The clinical significance of MAGEA3 expression in pancreatic cancer.
The MAGEA gene family that encodes cancer testis antigens is differentially expressed in many cancers. Though MAGEA3 expression has been detected in gastrointestinal malignancies, its role in pancreatic ductal adenocarcinoma (PDAC) has not been well established. We assessed 57 patients who underwent intent-to-cure surgery for PDAC. Total RNA from paraffin-embedded pancreatic tumors was extracted and assessed for MAGEA3 gene expression by an optimized probe-based quantitative real-time RT-PCR (qRT) assay. MAGEA3 gene expression was detected by qRT in 25 (44%) patients. For the entire cohort, detection of MAGEA3 expression was associated with significantly decreased overall survival (median, 16 vs 33 months; log-rank, p = 0.032). When clinicopathologic factors, including age, gender, stage, tumor extent, lymph node metastasis, tumor grade, perineural invasion and lymphovascular invasion were assessed by univariate analysis, MAGEA3 gene expression and tumor grade were significant prognostic factors for poor survival (HR 2.1, 95% CI: 1.0-4.4, p = 0.041; and HR 3.7, 95% CI: 1.8-7.6, p = 0.0004, respectively). Immunohistochemistry (IHC) was performed and confirmed MAGEA3 protein in PDAC specimens. In conclusion, MAGEA3 is differentially expressed in patients with PDAC; its expression correlates with significantly worse survival. Molecular assessment for MAGEA3 should be considered to improve prognostic evaluation and to identify eligible patients for potential immune-based therapy.
Adult↗
Colorectal cancer screening and surveillance: current standards and future trends.
Its prevalence, long premalignant course, and favorable response to early intervention make colorectal cancer an ideal target for screening regimens. The success of these regimens depends on accurate assessment of risk factors, patient compliance with scheduled visits and tests, and physician knowledge of screening strategies. We review the current recommendations for colorectal cancer screening in general and at-risk populations, comment on surveillance methods in high-risk patients, and examine current trends that will likely influence screening regimens in the future.
Barium Sulfate↗
Prospective multicenter trial of staging adequacy in colon cancer: preliminary results.
HYPOTHESIS: Lymph node evaluation is an important prognostic factor in colorectal cancer (CRC). A 25% recurrence rate in patients with node-negative CRC suggests that current staging practices are inadequate. Focused analysis of the sentinel node (SN) by multiple sectioning and immunohistochemistry improves staging accuracy. DESIGN: Prospective phase 2 multicenter trial. SETTING: Tertiary referral cancer centers. PATIENTS: Between March 2001 and June 2005, 132 patients were enrolled with clinical stage I and II CRC in a prospective multicenter trial (R01-CA90484). INTERVENTION: During a standard oncologic resection, lymphatic mapping was performed and the SN identified either by the surgeon or the pathologist. Hematoxylin-eosin staining was performed on all lymph nodes and immunohistochemistry, on lymph nodes negative by hematoxylin-eosin staining. MAIN OUTCOME MEASURES: Micrometastases greater than 0.2 mm but less than 2 mm and isolated tumor cells less than 0.2 mm were defined according to the sixth edition of the American Joint Committee on Cancer Cancer Staging Manual. RESULTS: The 63 men and 69 women had a median age of 74 years. Sixty-eight patients (52%) underwent a right hemicolectomy; 3 (2.3%), a transverse colectomy; 9 (7%), a left colectomy; 15 (11%), a sigmoid colectomy; 34 (26%), a low anterior resection; 1 (1%), an abdominal perineal resection; and 2 (2%), a total colectomy. Of the 111 evaluable primary tumors, 19 (17%) were T1 lesions; 17 (15%), T2; 72 (65%), T3; and 3 (2.7%), T4 tumors. Thirty-three patients (30%) were classified as stage I; 46 (41%), stage II, and 32 (29%), stage III. The SN was identified by the surgeon in 127 patients (96%) and by the pathologist in 5 patients (4%). The median number of SNs and total lymph nodes examined were 3 and 14.5, respectively. The sensitivity of lymphatic mapping and SN analysis was 88.2% and the false-negative rate, 7.4% (6/81). Of the 6 false-negative results, 4 were attributed to lymphatic channels obliterated by tumor. Upstaging occurred in 28 patients (23.6%). CONCLUSIONS: In a multicenter trial, ultrastaging of colon cancer is feasible and accurate. In stage II CRC, 24% of patients had nodal carcinoma cells not detected by conventional staging methods. Surgical technique (adequate lymph node retrieval) and focused pathological analysis may improve staging accuracy and the selection of patients for chemotherapy. The unnecessary toxicity and expense of chemotherapy may be avoided in those patients who are truly node negative.
Aged↗
Long-term survival after radiofrequency ablation of complex unresectable liver tumors.
HYPOTHESIS: Radiofrequency ablation (RFA) may improve survival of high-risk patients with unresectable and refractory tumors. DESIGN: Retrospective analysis of a prospective database. SETTING: A tertiary referral cancer center. PATIENTS AND METHODS: Between November 1, 1997, and January 31, 2005, we performed 219 RFA procedures to ablate 521 hepatic tumors in 181 patients. RESULTS: Of the 181 patients, 52% were male and 48% were female, and the mean age was 61.3 years (age range, 27-91 years). Radiofrequency ablation was performed via celiotomy (n = 135), via laparoscopy (n = 48), or percutaneously (n = 36). In 106 patients (79%), RFA was used in combination with surgical resection. The most common tumors included colorectal cancer (40.9%), hepatocellular carcinoma (14.9%), carcinoid tumor (13.8%), melanoma (9.4%), and breast cancer (5.0%). The average number of tumors per patient was 3.3 tumors. The average number of RFA-treated lesions per procedure was 2.38 lesions; the mean lesion size was 3.56 cm (lesion size range, 0.8-9.0 cm). At a mean follow-up of 33.2 months (follow-up range, 12-91 months), overall survival was 48.3 months for carcinoid tumors, 25.2 months for hepatocellular carcinoma, 18.5 months for melanoma, 29.7 months for colorectal cancer, and 30.1 months for breast cancer. Seventy-eight patients (43%) developed recurrences. Of 521 tumors that were treated, 125 (24%) recurred; the incidence of local recurrence was 28% for tumors larger than 3 cm vs 18% for tumors 3 cm or smaller (P = .04). Twenty-nine patients underwent serial ablations. Seventy-one patients (39%) were disease free at last follow-up. CONCLUSION: A significant number of patients whose hepatic malignancies are unresectable or refractory to chemotherapy may be considered for RFA as part of a multimodality therapeutic regimen. In these patients, RFA is safe and may prolong survival.
Adult↗
Sentinel lymph node mapping with GI cancer.
Precise evaluation of lymph node status is one of the most important factors in determining clinical outcome in treating gastro-intestinal (GI) cancer. Sentinel lymph node (SLN) mapping clearly has become highly feasible and accurate in staging GI cancer. The lunchtime symposium focused on the present status of SLN mapping for GI cancer. Dr. Kitigawa proposed a new strategy using sentinel node biopsy for esophageal cancer patients with clinically early stage disease. Dr. Uenosono reported on whether the SLN concept is applicable for gastric cancer through his analysis of more than 180 patients with cT1-2, N0 tumors. The detection rate was 95%, the false negative rate of lymph node metastasis including micro-metastasis was 4%, and accuracy was 99% in gastric cancer patients with cT1N0. Dr. Bilchik recommended the best technique for identifying SLNs in colorectal cancer: a combination of radiotracer and blue dye method, emphasizing that this technique will become increasingly popular because of the SLN concept, with improvement in staging accuracy. He stressed that this novel procedure offers the potential for significant upstaging of GI cancer. Dr. Saha emphasized that SLN mapping for colorectal cancer is highly successful and accurate in predicting the presence or absence of nodal disease with a relatively low incidence of skip metastases. It provided the "right nodes" to the pathologists for detailed analysis for appropriate staging and treatment with adjuvant chemotherapy. Although more evidence from large-scale multicenter clinical trials is required, SLN mapping may be very useful for individualizing multi-modal treatment for esophageal cancer and might be widely acceptable even for GI cancer.
Antineoplastic Agents↗
The utility of estrogen receptor, progesterone receptor, and Her-2/neu status to predict survival in patients undergoing hepatic resection for breast cancer metastases.
BACKGROUND: Hepatic metastases from breast cancer signal a dismal prognosis, with a median survival of 9.5 months. METHODS: Twenty breast cancer patients with liver metastases underwent hepatic resection, biopsy, or ablation between 1995 and 2004. Hormone receptor status and Her-2/neu expression of primary and metastatic tumors were correlated with overall survival. RESULTS: At a mean follow-up of 39 months after hepatic resection, median survival was 32 months. Patients undergoing anatomic resection with or without ablation lived significantly longer than those undergoing more limited resections (46 vs. 25 months, P = .016). Survival was significantly greater in patients with estrogen receptor (ER)-positive primary (P = .02) and metastatic (P < .004) tumors, Her-2/neu-positive metastases (P = .02), </=2 hepatic metastases (P < .002), and age >50 years at metastasectomy (P = .02). CONCLUSIONS: The ER status of the primary tumor and ER and Her-2/neu status of hepatic metastases, in addition to other clinical factors, may help select patients who would benefit from hepatic metastasectomy.
Breast Neoplasms↗
Chemokine receptor CXCR4 expression in patients with melanoma and colorectal cancer liver metastases and the association with disease outcome.
OBJECTIVE: To determine the role of chemokine receptor (CR) expression in patients with melanoma and colorectal cancer (CRC) liver metastases. SUMMARY BACKGROUND DATA: Murine and in vitro models have identified CR as potential factors in organ-specific metastasis of multiple cancers. Chemokines via their respective receptors have been shown to promote cell migration to distant organs. METHODS: Patients who underwent hepatic surgery for melanoma or CRC liver metastases were assessed. Screening cDNA microarrays of melanoma/CRC cell lines and tumor specimens were analyzed to identify CR. Microarray data were validated by quantitative real-time RT-PCR (qRT) in paraffin-embedded liver metastases. Migration assays and immunohistochemistry were performed to verify CR function and confirm CR expression, respectively. RESULTS: Microarray analysis identified CXCR4 as the most common CR expressed by both cancers. qRT demonstrated CXCR4 expression in 24 of 27 (89%) melanoma and 28 of 29 (97%) CRC liver metastases. In vitro treatment of melanoma or CRC cells with CXCL12, the ligand for CXCR4, significantly increased cell migration (P < 0.001). Low versus high CXCR4 expression in CRC liver metastases correlated with a significant difference in overall survival (median 27 months vs. 10 months, respectively; P = 0.036). In melanoma, low versus high CXCR4 expression in liver metastases demonstrated no difference in overall survival (median 11 months vs. 8 months, respectively; P = not significant). CONCLUSIONS: CXCR4 is expressed and functional on melanoma and CRC cells. The ligand for CXCR4 is highly expressed in liver and may specifically attract melanoma and CRC CXCR4 (+) cells. Quantitative analysis of CXCR4 gene expression in patients with liver metastases has prognostic significance for disease outcome.
Adult↗
More extensive nodal dissection improves survival for stages I to III of colon cancer: a population-based study.
OBJECTIVE: To determine whether analyzing more lymph nodes in colon cancer specimens improves survival. SUMMARY BACKGROUND DATA: Increasing the number of lymph nodes analyzed has been reported to correlate with improved survival in patients with node-negative colon cancer. METHODS: The Surveillance, Epidemiology, and End Results database was queried for all patients undergoing resection for histologically confirmed colon cancer between the years 1988 and 2000. Patients were excluded for distant metastases or if an unknown number of nodes was sampled. The number of nodes sampled was categorized into 0, 1 to 7, 8 to 14, and > or =15 nodes. Survival curves constructed using the Kaplan-Meier method were compared using log rank testing. A Cox proportional hazard model was created to adjust for year of diagnosis, age, race, gender, tumor grade, tumor size, TNM stage, and percent of nodes positive for tumor. RESULTS: The median number of lymph nodes sampled for all 82,896 patients was 9. For all stages examined, increasing nodal sampling was associated with improved survival. Multivariate regression demonstrated that patients who had at least 15 nodes sampled as compared with 1 to 7 nodes experienced a 20.6% reduction in mortality independent of other patient and tumor characteristics. CONCLUSIONS: Adequate lymphadenectomy, as measured by analysis of at least 15 lymph nodes, correlates with improved survival, independent of stage, patient demographics, and tumor characteristics. Currently, most procedures do not meet this guideline. Future trials of adjuvant therapy should include extent of lymphadenectomy as a stratification factor.
Aged↗
Increased integrity of free circulating DNA in sera of patients with colorectal or periampullary cancer: direct quantitative PCR for ALU repeats.
BACKGROUND: Cell-free DNA circulating in blood is a candidate biomarker for malignant tumors. Unlike uniformly truncated DNA released from apoptotic nondiseased cells, DNA released from dead cancer cells varies in size. We developed a novel method to measure the ratio of longer to shorter DNA fragments (DNA integrity) in serum as a potential biomarker for patients with colorectal cancer (CRC) or periampullary cancers (PACs). METHODS: Sera from 32 patients with CRC (3 stage I, 14 stage II, 6 stage III, and 9 stage IV patients), 19 patients with PACs (2 stage I, 9 stage II, 1 stage III, and 7 stage IV patients), and 51 healthy volunteers were assessed by quantitative real-time PCR of ALU repeats (ALU-qPCR) with 2 sets of primers (115 and 247 bp) amplifying different lengths of DNA. We used serum directly as a template for ALU-qPCR without DNA purification. DNA integrity was determined as ratio of qPCR results of 247-bp ALU over 115-bp ALU. RESULTS: ALU-qPCR had a detection limit of 0.01 pg of DNA. Eliminating DNA purification reduced technical artifacts and reagent/labor costs. Serum DNA integrity was significantly increased for stage I/II and III/IV CRC and stage I/II and III/IV PACs (P = 0.002, P = 0.006, P = 0.022, and P <0.0001, respectively). ROC curves for detecting CRC and PACs had areas under the curves of 0.78 and 0.80, respectively. CONCLUSIONS: Direct ALU-qPCR is a robust, highly sensitive, and high-throughput method to measure serum DNA integrity. DNA integrity is a potential serum biomarker for detection and evaluation of CRC and PACs.
Aged↗
Radiofrequency ablation of hepatic metastases from colorectal cancer: are newer generation probes better?
Second-generation radiofrequency ablation (RFA) probes and their successors have more power, shorter ablation times, and an increased area of ablation compared with the first-generation probes used before 2000. We examined whether the use of the newer probes has improved the clinical outcome of RFA for hepatic metastases of colorectal cancer at our tertiary cancer center. Of 160 patients who underwent RFA between 1997 and 2003, 52 had metastases confined to the liver: 21 patients underwent 46 ablations with the first-generation probes and 31 patients underwent 58 ablations with the newer probes. The two groups had similar demographic characteristics. At a median follow-up of 26.2 months, patients treated with the newer probes had a longer median disease-free survival (16 months vs 8 months, P < 0.01) and a lower rate of margin recurrence (5.2% vs 17.4%); eight patients had no evidence of disease and one patient was alive with disease. By contrast, of the 46 patients treated with the first-generation probes, 2 patients had no evidence of disease and 1 patient was alive with disease. Newer-generation probes are associated with lower rates of margin recurrence and higher rates of disease-free survival after RFA of hepatic metastases from colorectal cancer.
Aged↗
Treatment disparities in Hispanic rectal cancer patients: a SEER database study.
Although Hispanics demonstrate a low overall incidence of rectal cancer, mortality rates have not decreased relative to non-Hispanic whites. To determine if this was in part due to racial disparities in care, we compared rates of neoadjuvant therapy and sphincter-preserving surgery between Hispanics and non-Hispanic whites diagnosed with rectal cancer using the Surveillance, Epidemiology, and End Results (SEER) database. The study population was comprised of 2,573 Hispanics (55.4% male) and 28,395 non-Hispanic whites (56.6% male). Rates of neoadjuvant radiation were 13.5 per cent for Hispanics compared with 10.4 per cent for non-Hispanic whites (P < 0.001). In a Cox proportional hazards model adjusting for nodal status, tumor size, and T stage, non-Hispanic whites were significantly less likely to have received neoadjuvant therapy (hazard ratio, 0.72; P < 0.001; 95% confidence interval 0.63-0.83). Rates of sphincter preservation were 67 per cent for Hispanics and 70 per cent for non-Hispanic whites (P = 0.003). Non-Hispanic whites were significantly more likely to have received a sphincter-preserving operation than Hispanics (hazard ratio, 1.076; P = 0.019; 95% confidence interval 1.02-1.27). We conclude that Hispanics are significantly more likely to receive neoadjuvant therapy but are less likely to receive sphincter-sparing operations for rectal cancer compared with non-Hispanic whites. Further studies are required to assess the impact of these treatment disparities on patient outcome.
Aged↗
Neoadjuvant chemotherapy for metastatic colon cancer: a cautionary note.
Explore the source record for details and available documents.
Antineoplastic Combined Chemotherapy Protocols↗
Chemokine receptor CXCR4 expression in colorectal cancer patients increases the risk for recurrence and for poor survival.
PURPOSE: Liver metastasis is the predominant cause of colorectal cancer (CRC) related mortality. Chemokines, soluble factors that orchestrate hematopoetic cell movement, have been implicated in directing cancer metastasis, although their clinical relevance in CRC has not been defined. Our hypothesis was that the chemokine receptor CXCR4 expressed by CRC is a prognostic factor for poor disease outcome. METHODS: CRC cell lines (n = 6) and tumor specimens (n = 139) from patients with different American Joint Committee on Cancer (AJCC) stages of CRC were assessed. Microarray screening of select specimens and cell lines identified CXCR4 as a prominent chemokine receptor. CXCR4 expression in tumor and benign specimens was assessed by quantitative real-time reverse transcription polymerase chain reaction and correlated with disease recurrence and overall survival. RESULTS: High CXCR4 expression in tumor specimens (n = 57) from AJCC stage I/II patients was associated with increased risk for local recurrence and/or distant metastasis (risk ratio, 1.35; 95% CI, 1.09 to 1.68; P = .0065). High CXCR4 expression in primary tumor specimens (n = 35) from AJCC stage IV patients correlated with worse overall median survival (9 months v 23 months; RR, 2.53; 95% CI, 1.19 to 5.40; P = .016). CXCR4 expression was significantly higher in liver metastases (n = 39) compared with primary CRC tumors (n = 100; P < .0001). CONCLUSION: CXCR4, a well-characterized chemokine receptor for T-cells, is differentially expressed in CRC. CXCR4 gene expression in primary CRC demonstrated significant associations with recurrence, survival, and liver metastasis. The CXCR4-CXCL12 signaling mechanism may be clinically relevant for patients with CRC and represents a potential novel target for disease-directed therapy.
Adult↗
Lymphatic mapping and sentinel node analysis in colon cancer.
Accurate staging of colon cancer is prognostically and therapeutically important. By identifying those patients who would most benefit from adjuvant chemotherapy, accurate staging should decrease recurrence rates and improve overall survival. Lymphatic mapping and sentinel node analysis allow for a focused review of the lymph nodes, which are most likely to harbor a metastasis and may make ultrastaging techniques, such as immunohistochemistry and reverse-transcriptase polymerase chain reaction, more practical. The prognostic significance of micrometastatic disease detected via ultrastaging techniques remains controversial.
Colonic Neoplasms↗
Epigenetic inactivation of ID4 in colorectal carcinomas correlates with poor differentiation and unfavorable prognosis.
PURPOSE: ID4 gene is a member of the inhibitor of DNA binding (ID) family proteins that inhibit DNA binding of basic helix-loop-helix transcription factors. The epigenetic inactivation of ID4 gene on colorectal cancer (CRC) development and its clinical significance was assessed. EXPERIMENTAL DESIGN: In CRC cell lines, ID4 methylation status of the promoter region was assessed by methylation-specific PCR and bisulfite sequencing. The mRNA expression level was assessed by quantitative real-time reverse transcription-PCR. The methylation status of 9 normal epithelia, 13 adenomas, 92 primary CRCs, and 26 liver metastases was assessed by methylation-specific PCR. ID4 protein expression was assessed by immunohistochemistry analysis of tissue specimen. RESULTS: CRC cell lines were shown to be hypermethylated, and mRNA expression was suppressed and could be restored by 5-aza-cytidine treatment. In clinical specimens from normal epithelia, adenomas, primary CRCs, and liver metastases, the frequency of ID4 hypermethylation was 0 of 9 (0%), 0 of 13 (0%), 49 of 92 (53%), and 19 of 26 (73%), respectively, with a significant elevation according to CRC pathological progression. Methylation status of primary CRCs significantly correlated with histopathological tumor grade (P = 0.028). Immunohistochemistry analysis showed ID4 expression of normal colon epithelia, adenomas, and unmethylated primary CRCs but not hypermethylated CRC specimens. Among 76 American Joint Committee on Cancer stage I to IV patients who had undergone curative surgical resection, overall survival was significantly poorer in patients with hypermethylated ID4 bearing tumors (P = 0.0066). CONCLUSIONS: ID4 gene is a potential tumor suppressor gene for which methylation status may play an important role in the CRC progression.
Adult↗
Allelic imbalance of APAF-1 locus at 12q23 is related to progression of colorectal carcinoma.
APAF-1 gene, located at chromosome locus 12q23, is a key factor in the mitochondrial apoptotic pathway downstream of p53, and is a potential tumor suppressor gene. We hypothesized that APAF-1 gene dysfunction due to allelic imbalance (AI) contributes to the development and progression of colorectal carcinoma (CRC). AI at APAF-1 locus and microsatellite instability (MIN) in CRCs and adenomas were assessed by multiple microsatellite markers. The frequency of AI significantly increased with tumor progression; 0 of 33 (0%) adenomas, 14 of 49 (29%) primary CRCs, and 18 of 34 (53%) liver metastases had AI. A total of 12 metastases were matched with corresponding primary CRCs; in 11 of 12 (92%) pairs, the metastasis had same AI status as the corresponding primary tumor. APAF-1 mRNA transcription level was significantly decreased with AI in liver metastases (P=0.009). Promoter hypermethylation was found in three of 35 (9%) primary CRCs and one of 15 (7%) liver metastases by methylation-specific PCR but was not correlated with AI. MIN was observed in 11 of 49 (23%) primary CRCs and was a favorable prognostic factor. Our results suggest that APAF-1 gene haploinsufficiency caused by AI increases with tumor progression, and relates to hepatic metastasis.
Alleles↗
Peptide nucleic acid clamp PCR: a novel K-ras mutation detection assay for colorectal cancer micrometastases in lymph nodes.
Inaccurate staging of colorectal cancer (CRC) has been attributed to the failure to detect lymph node metastases by conventional pathology. We have previously reported the use of lymphatic mapping to accurately identify those lymph nodes most likely to harbor micrometastatic disease and permit focused pathologic examination. Mutation of K-ras allele at codons 12 or 13 occurs frequently in early stages of CRC development. The purpose of our study was to assess sentinel lymph nodes (SLN) for occult CRC micrometastases using a unique peptide nucleic acid (PNA) clamp PCR assay specific for K-ras mutations. Seventy-two paraffin-embedded primary CRC and paired SLN were evaluated by PNA clamp PCR for K-ras mutations. Thirty primary tumors (42%) were positive for K-ras mutations, and in 5 of these cases the SLN were positive for metastases by Hematoxylin and Eosin staining. PNA clamp PCR identified occult metastases in an additional 6 patients, upstaging 24% of K-ras positive primary CRCs (p = 0.014). No K-ras mutations were detected among the 20 noncancer lymph nodes assessed. This study demonstrates the utility, specificity and sensitivity of PNA clamp PCR assay in identifying occult micrometastases in the SLN of CRC patients by single-base mutation analysis.
Adult↗