Genome-wide association study identifies high-impact susceptibility loci for HCC in North America.

Background And Aims: Despite the substantial impact of environmental factors, individuals with a family history of liver cancer have an increased risk for HCC. However, genetic factors have not been studied systematically by genome-wide approaches in large numbers of individuals from European descent populations (EDP).

Approach And Results: We conducted a 2-stage genome-wide association study (GWAS) on HCC not affected by HBV infections.

Phase II Trial Using a Combination of Oxaliplatin, Capecitabine, and Celecoxib with Concurrent Radiation for Newly Diagnosed Resectable Rectal Cancer.

Lessons Learned: Colorectal cancers exhibit a high level of cyclooxygenase-2 (COX-2) expression with strong preclinical rationale for improved clinical outcomes with COX-2 inhibition. Celecoxib is a COX-2 inhibitor and we have shown that it can be safely combined with capecitabine and oxaliplatin as part of neoadjuvant treatment with radiation therapy (RT) in rectal cancer.There was a significant improvement in skin toxicity with this combination as compared with historical data.

INST OX-05-024: first line gemcitabine, oxaliplatin, and erlotinib for primary hepatocellular carcinoma and bile duct cancers: a multicenter Phase II trial.

Hepatocellular Carcinoma (HCC) incidence is increasing in the USA. Gemcitabine (G) and oxaliplatin (O) are active in HCC and biliary duct cancer (BDC). Erlotinib (E) is an EGFR tyrosine kinase inhibitor (TKI) with known activity against both.

Phase II Trial of Sorafenib in Combination with Capecitabine in Patients with Hepatocellular Carcinoma: INST 08-20.

Lessons Learned: There continues to be a lack of systemic options for advanced hepatocellular carcinoma (HCC); sorafenib and, very recently, regorafenib are the only approved options. There exists a potential to combine sorafenib with chemotherapeutic agents shown to be active in HCC, such as capecitabine, safely.Good tumor response was observed, with objective improvement in a few patients seldom seen by single agent sorafenib; however, because of the limited number of patients, meaningful conclusions on survival cannot be drawn.

Estrogen Replacement Reduces Risk and Increases Survival Times of Women With Hepatocellular Carcinoma.

Background & Aims: Environmental factors have been identified that affect risk of hepatocellular carcinoma (HCC), but little is known about the effects of sex hormones on liver cancer development or outcome. The authors investigated whether menopause hormone therapy (MHT) affects risk, age at onset, or outcome of HCC.

Methods: We performed a case-control study of 234 female patients treated for HCC at a tertiary medical center and with 282 healthy women (controls) from January 1, 2004 through May 31, 2015.

Treatment of hepatocellular carcinoma in the community: disparities in standard therapy.

Background And Aims: Hepatocellular carcinoma (HCC) incidence is expected to rise dramatically over the next decades because of increasing hepatitis C infections and obesity-related comorbidities. However, little information exists regarding the treatment of patients with HCC in the community setting. The purpose of this article was to characterize patterns of diagnosis, treatment, and survival for HCC in the community.

Modified cisplatin/interferon α-2b/doxorubicin/5-fluorouracil (PIAF) chemotherapy in patients with no hepatitis or cirrhosis is associated with improved response rate, resectability, and survival of initially unresectable hepatocellular carcinoma.

Background: The purpose of this study was to evaluate the factors associated with response rate, resectability, and survival after cisplatin/interferon α-2b/doxorubicin/5-fluorouracil (PIAF) combination therapy in patients with initially unresectable hepatocellular carcinoma.

Methods: The study included 2 groups of patients treated with conventional high-dose PIAF (n = 84) between 1994 and 2003 and those without hepatitis or cirrhosis treated with modified PIAF (n = 33) between 2003 and 2012. Tolerance of chemotherapy, best radiographic response, rate of conversion to curative surgery, and overall survival were analyzed and compared between the 2 groups, and multivariate and logistic regression analyses were applied to identify predictors of response and survival.

Genetic variation in the PNPLA3 gene and hepatocellular carcinoma in USA: risk and prognosis prediction.

Nonalcoholic fatty liver disease (NAFLD) is an emerging epidemic with high prevalence in Western countries. Genome-wide association studies had reported that a variation in the patatin-like phospholipase domain containing 3 (PNPLA3) gene is associated with high susceptibility to NAFLD. However, the relationship between this variation and hepatocellular carcinoma (HCC) has not been well established.

A randomized, phase II trial of standard triweekly compared with dose-dense biweekly capecitabine plus oxaliplatin plus bevacizumab as first-line treatment for metastatic colorectal cancer: XELOX-A-DVS (dense versus standard).

Background: Capecitabine administered for 7 days biweekly with oxaliplatin (XELOX) biweekly has been reported to have activity and safety profiles similar to those of standard capecitabine given for 14 days triweekly. Multiple studies have shown that the addition of bevacizumab to 5-fluorouracil-based chemotherapy is active and well tolerated.

Methods: Patients with metastatic colorectal cancer (mCRC) were randomized to XELOX plus bevacizumab using a standard triweekly cycle (Q3W) or a dose-dense biweekly cycle (Q2W) schedule.

A phase I study of imexon plus gemcitabine as first-line therapy for advanced pancreatic cancer.

Purpose: Imexon is an aziridine-derived iminopyrrolidone which has synergy with gemcitabine in pancreatic cancer cell lines. Gemcitabine is a standard therapy for pancreatic cancer. We performed a phase I trial of imexon and gemcitabine to evaluate safety, dose-limiting toxicity (DLT), and maximum tolerated dose (MTD) in patients with advanced pancreatic cancer.

The association of family history of liver cancer with hepatocellular carcinoma: a case-control study in the United States.

Background/aims: The study aimed at addressing the connection between positive family history of liver cancer and hepatocellular carcinoma (HCC) development in the USA.

Methods: At The University of Texas M.D.

Effect of different types of smoking and synergism with hepatitis C virus on risk of hepatocellular carcinoma in American men and women: case-control study.

The International Agency for Research on Cancer has declared smoking to be a risk factor for hepatocellular carcinoma (HCC). However, passive exposure to cigarette smoke and use of noncigarette tobacco products on the risk of HCC has not been examined. Therefore, we evaluated the independent effects of different types of smoking exposure along with multiple risk factors for HCC and determined whether the magnitude of smoking was modified by other risk factors in men and women.

A phase I/II trial of TAC-101, an oral synthetic retinoid, in patients with advanced hepatocellular carcinoma.

Purpose: Preclinical models showed TAC-101 (4-[3,5-bis(trimethylsilyl) benzamide] benzoic acid), an oral synthetic retinoid, has anti-tumor activity in hepatocellular carcinoma (HCC). A phase I/II study was performed in advanced HCC patients (pts).

Patients And Methods: Thirty-three patients were enrolled.

Capecitabine plus 3-weekly irinotecan (XELIRI regimen) as first-line chemotherapy for metastatic colorectal cancer: phase II trial results.

Background: Capecitabine results in superior response rate, improved safety, and improved convenience compared with 5-fluorouracil (FU)/leucovorin (LV) in metastatic colorectal cancer (MCRC). Irinotecan in combination with 5-FU/LV has been shown to improve efficacy compared with 5-FU/LV alone in MCRC. Therefore, we evaluated the efficacy and safety of capecitabine plus irinotecan every 3 weeks (XELIRI regimen) as first-line treatment.

Risk factors for intrahepatic and extrahepatic cholangiocarcinoma: a hospital-based case-control study.

Background: The risk factors for cholangiocarcinoma are poorly defined in the United States. We evaluated hepatitis C virus (HCV), hepatitis B virus (HBV), and liver cirrhosis as risk factors for intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC).

Methods: A case-control study in which cases were cholangiocarcinoma patients referred to the M.

OncoSurge: a strategy for improving resectability with curative intent in metastatic colorectal cancer.

Purpose: Most patients with colorectal liver metastases present to general surgeons and oncologists without a specialist interest in their management. Since treatment strategy is frequently dependent on the response to earlier treatments, our aim was to create a therapeutic decision model identifying appropriate procedure sequences.

Methods: We used the RAND Corporation/University of California, Los Angeles Appropriateness Method (RAM) assessing strategies of resection, local ablation and chemotherapy.

A Phase II study of intravenous exatecan administered daily for 5 days, every 3 weeks to patients with biliary tract cancers.

Purpose: Exatecan is a hexacyclic topoisomerase-1 inhibitor that has broad in vitro and in vivo activity. A multicenter phase II study to determine the antitumor activity of exatecan was conducted in patients with advanced cholangiocarcinoma and gallbladder carcinoma.

Methods: Patients with 0 to 1 prior chemotherapy regimens, adequate major organ function, and metastatic disease were eligible.

Thalidomide in the treatment of patients with hepatocellular carcinoma: a phase II trial.

Background: The treatment of patients with hepatocellular carcinoma (HCC) presents a major challenge, because associated cirrhosis limits the choice of chemotherapeutic agents. However, the abundant vascularity of HCC presents an attractive target for antiangiogenic therapy that potentially may be tolerated by cirrhotic patients. The current study was conducted to assess the antitumor activity, treatment tolerance, treatment-related toxicity, and patient survival after the administration of thalidomide in a Phase II trial.

Novel systemic therapy options for hepatocellular carcinoma.

Hepatocellular carcinoma, a common malignancy globally, has been increasing in incidence in the United States, mostly due to the rising incidence of Hepatitis C viral (HCV) infection. The prognosis of patients with this cancer has been poor and even tumor resection has rarely been curative. However, orthotopic liver transplantation (OLT) has been associated with long-term survival benefit and cures, provided rigorous patient-selection criteria were adhered to.

Feasibility of adjuvant hepatic arterial infusion of chemotherapy after radiofrequency ablation with or without resection in patients with hepatic metastases from colorectal cancer.

Background: The safety of combined hepatic artery infusion chemotherapy (HAI) and radiofrequency ablation (RFA) for liver metastases has not been assessed. We conducted a study to determine the feasibility of using HAI after RFA for colorectal cancer (CRC) liver metastases.

Methods: Between 1996 and 2001, patients with hepatic metastases from CRC were enrolled onto a prospective study of RFA plus HAI consisting of continuous-infusion floxuridine and bolus fluorouracil.

Recombinant human interleukin-11 improves thrombocytopenia in patients with cirrhosis.

To elucidate the hematopoietic activity of recombinant human interleukin-11 (rhIL-11, [Neumega, Cambridge, MA]) in patients with cirrhosis and thrombocytopenia, we administered rhIL-11 at 50 microg/kg/d subcutaneously to 10 patients for 10 days with a 30-day follow-up period. All treated patients (n = 9) experienced a gradual, yet significant increase in their platelet count above the baseline value (P < or =.01) reaching the peak value (median, 93,000/microL; range, 60,000-206,000/microL) at a median of 13 days (range, 6-23 days).

Phase II trial of systemic continuous fluorouracil and subcutaneous recombinant interferon Alfa-2b for treatment of hepatocellular carcinoma.

Purpose: Because cirrhosis is extremely common in hepatocellular carcinoma (HCC) in the United States, and it precludes the use of several chemotherapy agents, this phase II trial of fluorouracil (FU) and recombinant interferon alfa-2b (rIFNalpha2b) in HCC was launched with the assumption that it could be tolerated by cirrhotics.

Patients And Methods: Forty-three patients with HCC (34), and fibrolamellar HCC (FLHCC; nine) were treated with continuous intravenous (IV) FU (200 mg/m2/d x 21 every 28 days) and subcutaneous (SC) rIFNalpha2b (4 million U/m2) three times weekly. Survival was determined in all 43 patients, and response could be assessed in 28 HCC and 8 FLHCC patients.

Risk factors for hepatocellular carcinoma: synergism of alcohol with viral hepatitis and diabetes mellitus.

Risk factors associated with hepatocellular carcinoma (HCC) are well documented, but the synergisms between these risk factors are not well examined. We conducted a hospital-based, case-control study among 115 HCC patients and 230 non-liver cancer controls. Cases and controls were pathologically diagnosed at The University of Texas M.