CD1a-autoreactive T cells recognize natural skin oils that function as headless antigens.

T cells autoreactive to the antigen-presenting molecule CD1a are common in human blood and skin, but the search for natural autoantigens has been confounded by background T cell responses to CD1 proteins and self lipids. After capturing CD1a-lipid complexes, we gently eluted ligands while preserving non-ligand-bound CD1a for testing lipids from tissues. CD1a released hundreds of ligands of two types. Inhibitory ligands were ubiquitous membrane lipids with polar head groups, whereas stimulatory compounds were apolar oils. We identified squalene and wax esters, which naturally accumulate in epidermis and sebum, as autoantigens presented by CD1a. The activation of T cells by skin oils suggested that headless mini-antigens nest within CD1a and displace non-antigenic resident lipids with large head groups. Oily autoantigens naturally coat the surface of the skin; thus, this points to a previously unknown mechanism of barrier immunity.

Response and acquired resistance to everolimus in anaplastic thyroid cancer.

Everolimus, an inhibitor of the mammalian target of rapamycin (mTOR), is effective in treating tumors harboring alterations in the mTOR pathway. Mechanisms of resistance to everolimus remain undefined. Resistance developed in a patient with metastatic anaplastic thyroid carcinoma after an extraordinary 18-month response. Whole-exome sequencing of pretreatment and drug-resistant tumors revealed a nonsense mutation in TSC2, a negative regulator of mTOR, suggesting a mechanism for exquisite sensitivity to everolimus. The resistant tumor also harbored a mutation in MTOR that confers resistance to allosteric mTOR inhibition. The mutation remains sensitive to mTOR kinase inhibitors.

Characteristics of contralateral carcinomas in patients with differentiated thyroid cancer larger than 1 cm.

PURPOSE: Traditionally, total thyroidectomy has been advocated for patients with tumors larger than 1 cm. However, according to the ATA and NCCN guidelines (2015, USA), patients with tumors up to 4 cm are now eligible for lobectomy. A rationale for adhering to total thyroidectomy might be the presence of contralateral carcinomas. The purpose of this study was to describe the characteristics of contralateral carcinomas in patients with differentiated thyroid cancer (DTC) larger than 1 cm. METHODS: A retrospective study was performed including patients from 17 centers in 5 countries. Adults diagnosed with DTC stage T1b-T3 N0-1a M0 who all underwent a total thyroidectomy were included. The primary endpoint was the presence of a contralateral carcinoma. RESULTS: A total of 1313 patients were included, of whom 426 (32 %) had a contralateral carcinoma. The contralateral carcinomas consisted of 288 (67 %) papillary thyroid carcinomas (PTC), 124 (30 %) follicular variant of a papillary thyroid carcinoma (FvPTC), 5 (1 %) follicular thyroid carcinomas (FTC), and 3 (1 %) Hürthle cell carcinomas (HTC). Ipsilateral multifocality was strongly associated with the presence of contralateral carcinomas (OR 2.62). Of all contralateral carcinomas, 82 % were ≤10 mm and of those 99 % were PTC or FvPTC. Even if the primary tumor was a FTC or HTC, the contralateral carcinoma was (Fv)PTC in 92 % of cases. CONCLUSIONS: This international multicenter study performed on patients with DTC larger than 1 cm shows that contralateral carcinomas occur in one third of patients and, independently of primary tumor subtype, predominantly consist of microPTC.

The variable phenotype and low-risk nature of RAS-positive thyroid nodules.

BACKGROUND: Oncogenic mutations are common in thyroid cancers. While the frequently detected RAS-oncogene mutations have been studied for diagnostic use in cytologically indeterminate thyroid nodules, no investigation has studied such mutations in an unselected population of thyroid nodules. No long-term study of RAS-positive thyroid nodules has been performed. METHODS: We performed a prospective, blinded cohort study in 362 consecutive patients presenting with clinically relevant (>1 cm) thyroid nodules. Fine needle aspiration cytology and mutational testing were obtained for all nodules. Post-operative histopathology was obtained for malignant or indeterminate nodules, and benign nodules were sonographically followed. Histopathological features were compared between RAS- and BRAF-positive malignancies. RAS-positive benign nodules were analyzed for growth or cellular change from prior aspirations. RESULTS: Overall, 17 of 362 nodules were RAS-positive. Nine separate nodules were BRAF-positive, of which eight underwent surgery and all proved malignant (100%). Out of the 17 RAS-positive nodules, ten underwent surgery, of which eight proved malignant (47%). All RAS-positive malignancies were low risk - all follicular variants of papillary carcinoma, without extrathyroidal extension, metastases, or lymphovascular invasion. RAS-positivity was associated with malignancy in younger patients (P = 0.028). Of the nine RAS-positive benign nodules, five had long-term prospective sonographic follow-up (mean 8.3 years) showing no growth or signs of malignancy. Four of these nodules also had previous aspirations (mean 5.8 years prior), all with similar benign results. CONCLUSIONS: While RAS-oncogene mutations increase malignancy risk, these data demonstrate a low-risk phenotype for most RAS-positive cancers. Furthermore, cytologically benign, yet RAS-positive nodules behave in an indolent fashion over years. RAS-positivity alone should therefore not dictate clinical decisions.

Efficacy of Neoadjuvant Versus Adjuvant Therapy for Resectable Pancreatic Adenocarcinoma: A Decision Analysis.

BACKGROUND: Neoadjuvant therapy-based protocols for potentially resectable pancreatic adenocarcinoma (PAC) have not been directly compared with adjuvant protocols in large prospective randomized trials. This study aimed to compare the efficacy of neoadjuvant versus adjuvant therapy-based management by using a formal decision analytic model. METHODS: A decision analytic model was created with a Markov process to compare neoadjuvant and adjuvant chemo- and/or chemoradiation therapy-based strategies for simulated cohorts of patients with potentially resectable PAC. Base-case probabilities were derived from the published data of 21 prospective phases 2 and 3 trials (3708 patients) between 1997 and 2014. The primary outcome measures determined in an intent-to-treat fashion were overall and quality-adjusted survival rates. One- and two-way sensitivity analyses were performed to assess the effects of model uncertainty on outcomes. RESULTS: The median overall survival and 2-year survival rates for the patients in the standard adjuvant therapy arm of the study were 20 months and 42.2 % versus 22 months and 46.8 % for those in the neoadjuvant strategy arm. Quality-adjusted survival was 18.4 and 19.8 months, respectively. Sensitivity analysis demonstrated that when recurrence-free survival after completion of neoadjuvant therapy and resection is less than 13.9 months or when the rate for progression of disease precluding resection during neoadjuvant therapy is greater than 44 %, the neoadjuvant strategy is no longer the favored option. CONCLUSIONS: The decision analytic model suggests that neoadjuvant therapy-based management improves the outcomes for patients with potentially resectable pancreatic cancer. However, the benefits in terms of overall and quality-adjusted survival are modest.

False negative cytology in large thyroid nodules.

BACKGROUND: Controversy exists regarding the accuracy of fine-needle aspiration (FNA) in large thyroid nodules. Recent surgical series have documented false-negative rates ranging from 0.7 to 13 %. We examined the accuracy of benign FNA cytology in patients with thyroid nodules ≥3 cm who underwent surgical resection and identified features characteristic of false-negative results. METHODS: We retrospectively studied all thyroidectomy specimens between January 2009 and October 2011 and identified nodules ≥3 cm with corresponding benign preoperative FNA cytology. We collected clinical information regarding patient demographics, nodule size, symptoms, sonographic features, FNA results, and final surgical pathology. For comparison, we analyzed nodules <3 cm from this cohort also with benign FNA cytology. RESULTS: A total of 323 nodules with benign preoperative cytology were identified. Eighty-three nodules were <3 cm, 94 nodules were 3-3.9 cm, and 146 nodules were ≥4 cm in size. The false-negative rate was 11.7 % for all nodules ≥3 cm and 4.8 % for nodules <3 cm (p = 0.03). Subgroup analysis of nodules ≥3 cm revealed a false-negative rate of 12.8 % for nodules 3-3.9 cm and 11 % for nodules ≥4 cm. Age ≥55 years and asymptomatic clinical status were the only patient characteristics that reached statistical significance as risk factors. Final pathology of the false-negative specimens consisted mainly of follicular variant of papillary thyroid cancer and follicular thyroid cancer. CONCLUSIONS: When referred for thyroidectomy, patients with large thyroid nodules demonstrate a modest, yet significant, false-negative rate despite initial benign aspiration cytology. Therefore, thyroid nodules ≥3 cm may be considered for removal even when referred with benign preoperative cytology.

Surgeons and patients disagree on the potential consequences from hypoparathyroidism.

OBJECTIVE: To test the hypothesis that surgeons and their patients underestimate the potential negative impact that permanent hypoparathyroidism has on quality of life (QOL). METHODS: We used a modified SF-36 assessment tool to compare the perceptions of patients with permanent hypoparathyroidism to the perceptions of control subjects who were given a standardized preoperative statement about the complications of hypoparathyroidism. We also elicited the perceptions of endocrine surgeons regarding the QOL impacts of hypoparathyroidism using a subset of questions from the modified SF-36. RESULTS: A total of 340 postsurgical patients with permanent hypoparathyroidism, 200 controls, and 102 surgeons participated in the study. Both surgeons and controls underestimated the negative impact of hypoparathyroidism on QOL when compared to patients living with permanent hypoparathyroidism. Forty-seven percent of hypoparathyroid patients believed that their health was "much worse" than before surgery, compared with 16% of surgeons (P<.001) and 7% of controls (P<.001). Postoperative hypoparathyroid patients also reported far more negative effects on QOL, from interference with social activities, paresthesias, muscle cramping, and medications than were anticipated by surgeons or controls (P<.05 for all comparisons). In each of the 8 dimensions of QOL, including physical functioning, role limitations due to physical health, role limitations due to emotional problems, energy/fatigue, emotional well-being, social functioning, pain, and general health, hypoparathyroid patients reported a significantly lower mean score compared to the control group (P<.001 for all comparisons). CONCLUSION: The impact of postoperative hypoparathyroidism on patient QOL is consistently and significantly underestimated by surgeons and subjects receiving surgical consultation.

Bilateral neck exploration decreases operative time compared to minimally invasive parathyroidectomy in patients with discordant imaging.

BACKGROUND: Unilateral parathyroidectomy for primary hyperparathyroidism (PHPT) has a high success rate in patients with concordant imaging by sestamibi and ultrasound. However, the optimal procedure when imaging is discordant remains controversial; therefore we compared unilateral exploration with intraoperative parathyroid hormone (IOPTH) monitoring to bilateral neck exploration without IOPTH monitoring in patients with discordant localization studies. METHODS: We conducted a retrospective study of 324 consecutive patients with PHPT treated at our institution from October 2005 to September 2009. We collected information regarding imaging, localization site, procedure performed, operative time, and calcium/PTH measurements. RESULTS: Of the 324 patients in the study, 79 (24 %) had discordant imaging by sestamibi and ultrasound. Of these, 62 patients (78 %) underwent bilateral neck exploration without IOPTH monitoring, and 14 patients (18 %) had unilateral exploration with IOPTH monitoring. IOPTH monitoring during unilateral exploration correctly predicted removal of single adenomas in 10/14 patients (71 %) and altered operative management in 4/14 cases (29 %), resulting in conversion to bilateral neck exploration. Operative time for unilateral exploration with IOPTH [median time: 96 min (range: 51-153 min)] was significantly increased relative to bilateral exploration [median time: 52 min (range: 28-149 min)]; p = 0.0027. We identified single-gland disease in 53/76 patients (70 %), double adenomas in 13/76 patients (17 %), and multiglandular hyperplasia in 10/76 patients (13 %). There was no difference in cure rate between these two surgical approaches (p = 1.0) CONCLUSIONS: In contrast with prior studies, we found that operative time for unilateral exploration with IOPTH was significantly increased compared to bilateral neck exploration. In patients with discordant imaging, IOPTH is a useful adjunct in limiting exploration to a single side despite a high false negative rate.

Global tyrosine kinome profiling of human thyroid tumors identifies Src as a promising target for invasive cancers.

BACKGROUND: Novel therapies are needed for the treatment of invasive thyroid cancers. Aberrant activation of tyrosine kinases plays an important role in thyroid oncogenesis. Because current targeted therapies are biased toward a small subset of tyrosine kinases, we conducted a study to reveal novel therapeutic targets for thyroid cancer using a bead-based, high-throughput system. METHODS: Thyroid tumors and matched normal tissues were harvested from twenty-six patients in the operating room. Protein lysates were analyzed using the Luminex immunosandwich, a bead-based kinase phosphorylation assay. Data was analyzed using GenePattern 3.0 software and clustered according to histology, demographic factors, and tumor status regarding capsular invasion, size, lymphovascular invasion, and extrathyroidal extension. Survival and invasion assays were performed to determine the effect of Src inhibition in papillary thyroid cancer (PTC) cells. RESULTS: Tyrosine kinome profiling demonstrated upregulation of nine tyrosine kinases in tumors relative to matched normal thyroid tissue: EGFR, PTK6, BTK, HCK, ABL1, TNK1, GRB2, ERK, and SRC. Supervised clustering of well-differentiated tumors by histology, gender, age, or size did not reveal significant differences in tyrosine kinase activity. However, supervised clustering by the presence of invasive disease showed increased Src activity in invasive tumors relative to non-invasive tumors (60% v. 0%, p<0.05). In vitro, we found that Src inhibition in PTC cells decreased cell invasion and proliferation. CONCLUSION: Global kinome analysis enables the discovery of novel targets for thyroid cancer therapy. Further investigation of Src targeted therapy for advanced thyroid cancer is warranted.

Adrenal artery aneurysm encountered during laparoscopic adrenalectomy for pheochromocytoma.

Adrenal artery aneurysms are an extremely rare clinical entity. Only six previous case reports of adrenal artery aneurysms exist, all of which were discovered after rupture. Herein, we describe the discovery of an unruptured adrenal artery aneurysm found during laparoscopic adrenalectomy for pheochromocytoma.

Prospective evaluation of the rate and impact of hemolysis on intraoperative parathyroid hormone (IOPTH) assay results.

BACKGROUND: Intraoperative parathyroid hormone (IOPTH) is commonly used during minimally invasive parathyroidectomy. Retrospective evidence suggested that hemolysis may artificially lower IOPTH results. Falsely decreased IOPTH measurements could result in either failed parathyroidectomy or unnecessary bilateral neck exploration. METHODS: A total of 130 IOPTH specimens from 30 patients were assayed before and after induction of mechanical hemolysis using a vortex and inert sterile glass beads. Free hemoglobin (Hg) was measured as a surrogate for extent of hemolysis. Paired sample t test was used for comparison of matched prehemolysis and posthemolysis specimens. RESULTS: Of the samples, 16.9% were hemolyzed at the baseline (11 of 72 pre-excision, 11 of 55 postexcision). We successfully induced moderate hemolysis (ΔHg 0.1-1.0 mg/DL) in 66 samples that had minimal hemolysis at baseline. In these, mechanical hemolysis increased free Hg by an average of 0.37 mg/DL (533%; mean posthemolysis free Hg = 0.43; moderate hemolysis) and lowered PTH values by an average of 39% (median = 36%, SD = 11%; P = .002). The decrease in PTH was related to the extent of hemolysis induced (r = 0.51; P < .001), but was unrelated to the specimen's baseline (true) PTH (P = .24). In 12 of 30 patients, the experimentally hemolyzed pre-excision PTH value would have reduced the 50% threshold sufficiently to cause a false-negative result. In 6 of the 30 parathyroidectomies, a hemolyzed postexcision PTH value would have decreased PTH value sufficiently to cause a false-positive result. CONCLUSIONS: Hemolysis of IOPTH specimens occurs commonly and falsely reduces PTH results. In 18 of 30 patients, this effect was sufficient to have contributed to either a false-positive or false-negative IOPTH result.

Galectin-3 regulates apoptosis and doxorubicin chemoresistance in papillary thyroid cancer cells.

A subset of patients with papillary thyroid cancer (PTC) present with aggressive disease that is refractory to conventional treatment. Novel therapies are needed to treat this group of patients. Galectin-3 (Gal-3) is a beta-galactoside-binding protein with anti-apoptotic activity. Over 30 studies in the last 3 years have reported that Gal-3 is highly expressed in PTC relative to normal thyrocytes. In this study, we show that Gal-3 silencing with RNA interference stimulates apoptosis, while Gal-3 overexpression protects against both TRAIL- and doxorubicin-induced apoptosis in PTC cells. The anti-apoptotic activity and chemoresistance related to Gal-3 function can be partially reversed through the inhibition of the PI3K-Akt pathway, suggesting that Gal-3 acts, at least in part, on the PI3K-Akt axis. These observations support further evaluation of Gal-3 as a potential therapeutic target in patients with aggressive PTC.

Have Recent Modifications of Operating Room Attire Policies Decreased Surgical Site Infections? An American College of Surgeons NSQIP Review of 6,517 Patients.

BACKGROUND: After a Department of Health site visit, 2 teaching hospitals imposed strict regulations on operating room attire, including full coverage of ears and facial hair. We hypothesized that this intervention would reduce superficial surgical site infections (SSIs). STUDY DESIGN: We compared NSQIP data from all patients undergoing operations in the 9 months before implementation (n = 3,077) to time-matched data 9 months post-implementation (n = 3,440). Univariate and multivariable analyses were used to examine patient, clinical, and operative factors associated with SSIs. Power analysis was performed using pre-intervention SSI rates. RESULTS: Despite a shift toward more clean cases, there were more SSIs post-implementation (33 vs 30 [1%]; p = 0.95). There were no differences in length of stay, complications, or mortality between the 2 time periods. Overall, SSI increased with wound class: 0.6%, 0.9%, 2.3%, and 3.8% in clean, clean-contaminated, contaminated, and infected cases, respectively. Limiting the review to clean or clean-contaminated cases, incisional SSIs increased from 0.7% (20 of 2,754) to 0.8% (24 of 3,115) (p = 0.85). A multivariable analysis showed that implementation of these policies was not associated with decreased SSIs (odds ratio 1.2; 95% CI 0.70 to 1.96; p = 0.56). The largest predictors of SSIs were preoperative infection, operative time >75th percentile, open wounds, and dirty/contaminated wounds. A hypothetical analysis revealed that a sample size of 485,154 patients would be required to demonstrate a 10% SSI reduction among patients with clean or clean-contaminated wounds. CONCLUSIONS: Implementation of stringent operating room attire policies do not reduce SSI rates. A study to prove this principle further would be impractical to conduct.

Open adrenalectomy through a makuuchi incision: A single institution's experience.

BACKGROUND: Surgical techniques for adrenalectomy have evolved substantially over the last century. Although minimally invasive approaches are favored for benign disease, open adrenalectomy remains the gold standard for large tumors and those concerning for malignancy. Most reports describe the use of midline, subcostal, or thoracoabdominal incisions for open adrenalectomy. We studied our experience with the Makuuchi incision, designed to optimize exposure and minimize denervation of the abdominal wall. METHODS: All open adrenalectomies at the University of Rochester from 2009 to 2017 were retrospectively reviewed. Patient demographic characteristics, intraoperative details, and postoperative complications were investigated. Surgical site infection and hernia rates of Makuuchi incision were compared with non-Makuuchi incision patients and with published standards. The study was approved by the university Institutional Review Board. RESULTS: A total of 41 adrenalectomies were performed via Makuuchi incision. Population statistics included a mean age of 51.7 (19-86) years, a mean body mass index of 29.7 (17.3-45.8), and a mean tumor diameter of 8 cm (3.1-26 cm). Fourteen (34%) required multivisceral resection. Twenty-one (51%) were previous or current smokers, and 9 (22%) had hypercortisolemia. Median duration of stay was 6 days (4-73). Incisional hernia occurred in 5 patients (12%) and surgical site infection in 3 patients (7%), 2 patients had Cushing syndrome and 1 was immunosuppressed. Pain was managed with patient-controlled epidural anesthesia or patient-controlled anesthesia with postoperative day 1 daily morphine equivalents equating to 0.5 mg of hydromorphone q2h. Among 15 non-Makuuchi incision patients, there were 2 hernias (13%), 2 surgical site infections (13%), and 1 case of postoperative pneumonia. CONCLUSION: The Makuuchi incision is well tolerated and affords outstanding exposure of the adrenals and adjacent viscera. Incisional hernia and surgical site infection rates were favorable compared with published rates for midline or subcostal incisions, despite an obese population with a high incidence of hypercortisolism and immunosuppression.

Prevalence of Contralateral Tumors in Patients with Follicular Variant of Papillary Thyroid Cancer.

BACKGROUND: Thyroid lobectomy alone is being performed increasingly for patients with encapsulated follicular variant of papillary thyroid carcinoma (fvPTC). However, the prevalence of contralateral disease in these patients is unknown. We investigated the presence of synchronous disease in fvPTC to improve decision making about the extent of surgical resection and need for surveillance. STUDY DESIGN: We performed a retrospective review of patients who underwent thyroid surgery from October 2009 to February 2013 with a diagnosis of fvPTC as their primary lesion. We collected information on patient demographics, nodule size, multifocality, fine-needle aspiration results, lymphovascular invasion, extrathyroidal extension, and lymph node metastasis. Tumors were divided into noninvasive and invasive/infiltrative fvPTC categories. Characteristics of solitary and bilateral fvPTC were compared. RESULTS: We identified 124 patients with final pathology demonstrating fvPTC. The most common fine-needle aspiration diagnosis was "suspicious for malignancy" (n = 53). Sixty-five contralateral tumors were identified in 44 of 124 patients (35.5%) and included fvPTC (n = 40), classical PTC (n = 22), tall cell PTC (n = 2), and follicular carcinoma (n = 1). Fifty contralateral tumors were 1 to 5 mm, 10 measured 6 to 9 mm, and 5 were ≥10 mm. Contralateral disease correlated significantly with lymphovascular invasion (p = 0.037) and larger primary lesions (p = 0.020). There was no significant difference noted in extrathyroidal extension or lymph node metastasis. Both noninvasive and invasive/infiltrative fvPTC demonstrated similar rates of contralateral disease. CONCLUSIONS: Bilateral disease is common in fvPTC, primarily in the form of papillary microcarcinomas. Future monitoring of the contralateral lobe should be discussed with fvPTC patients who do not undergo completion thyroidectomy.

Genomic Heterogeneity and Exceptional Response to Dual Pathway Inhibition in Anaplastic Thyroid Cancer.

Purpose: Cancers may resist single-agent targeted therapies when the flux of cellular growth signals is shifted from one pathway to another. Blockade of multiple pathways may be necessary for effective inhibition of tumor growth. We document a case in which a patient with anaplastic thyroid carcinoma (ATC) failed to respond to either mTOR/PI3K or combined RAF/MEK inhibition but experienced a dramatic response when both drug regimens were combined.Experimental Design: Multi-region whole-exome sequencing of five diagnostic and four autopsy tumor biopsies was performed. Meta-analysis of DNA and RNA sequencing studies of ATC was performed.Results: Sequencing revealed truncal BRAF and PIK3CA mutations, which are known to activate the MAPK and PI3K/AKT pathways, respectively. Meta-analysis demonstrated 10.3% cooccurrence of MAPK and PI3K pathway alterations in ATC. These tumors display a separate transcriptional profile from other ATCs, consistent with a novel subgroup of ATC.Conclusions: BRAF and PIK3CA mutations define a distinct subset of ATC. Blockade of the MAPK and PI3K pathways appears necessary for tumor response in this subset of ATC. This identification of synergistic activity between targeted agents may inform clinical trial design in ATC. Clin Cancer Res; 23(9); 2367-73. ©2016 AACR.

Fractional genomic alteration detected by array-based comparative genomic hybridization independently predicts survival after hepatic resection for metastatic colorectal cancer.

PURPOSE: Although liver resection is the primary curative therapy for patients with colorectal hepatic metastases, most patients have a recurrence. Identification of molecular markers that predict patients at highest risk for recurrence may help to target further therapy. EXPERIMENTAL DESIGN: Array-based comparative genomic hybridization was used to investigate the association of DNA copy number alterations with outcome in patients with colorectal liver metastasis resected with curative intent. DNA from 50 liver metastases was labeled and hybridized onto an array consisting of 2,463 bacterial artificial chromosome clones covering the entire genome. The total fraction of genome altered (FGA) in the metastases and the patient's clinical risk score (CRS) were calculated to identify independent prognostic factors for survival. RESULTS: An average of 30 +/- 14% of the genome was altered in the liver metastases (14% gained and 16% lost). As expected, a lower CRS was an independent predictor of overall survival (P = 0.03). In addition, a high FGA also was an independent predictor of survival (P = 0.01). The median survival time in patients with a low CRS (score 0-2) and a high (> or =20%) FGA was 38 months compared with 18 months in patients with a low CRS and a low FGA. Supervised analyses, using Prediction Analysis of Microarrays and Significance Analysis of Microarrays, identified a set of clones, predominantly located on chromosomes 7 and 20, which best predicted survival. CONCLUSIONS: Both FGA and CRS are independent predictors of survival in patients with resected hepatic colorectal cancer metastases. The greater the FGA, the more likely the patient is to survive.