Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. They can occur anywhere in the gastrointestinal tract, and rarely outside the digestive tract. We herein report a case of primary gastrointestinal stromal tumor that was resected from the liver of a 56-year-old male, which is the sixth description of a primary hepatic gastrointestinal stromal tumor. The tumor was shown to be completely limited within the liver by radiological, intraoperative and pathological examinations. The pathological results demonstrated an intermediate risk gastrointestinal stromal tumor, and immunohistochemical expression of CD117 was positive. Although rare, we suggested that GISTs should be considered in the differential diagnosis of hepatic nodules, and that not all hepatic gastrointestinal stromal tumors should automatically be considered to be metastases from a primary gastrointestinal site.

Chromogranin A (CgA) is widely used as an immunohistochemical marker of neuroendocrine neoplasms and has been measurable in plasma of patients. We assessed the clinical role of plasma CgA in diagnosing pancreatic neuroendocrine neoplasm (PNEN). CgA was checked in 44 patients with pancreatic mass who underwent surgical resection from 2009 through 2011. The cutoff value for diagnosing PNEN and the relationships between CgA and clinicopathologic variables were analyzed. Twenty-six patients were PNENs and 18 patients were other pancreatic disorders. ROC analysis showed a cutoff of 60.7 ng/mL with 77% sensitivity and 56% specificity, and the area under the curve (AUC) was 0.679. Among PNEN group, the sensitivity and specificity of diagnosing metastasis were 100% and 90% respectively when CgA cutoff was 156.5 ng/mL. The AUC was 0.958. High Ki-67 index (160.8 vs 62.1 ng/mL, P = 0.001) and mitotic count (173.5 vs 74.6 ng/mL, P = 0.044) were significantly correlated with plasma CgA, but the tumor size was not. In conclusion, CgA has a little value in diagnosing PNEN. However, the high level of CgA (more than 156.5 ng/mL) can predict the metastasis. Also, plasma CgA level correlates with Ki-67 index and mitotic count which represents prognosis of PNENs.

Background:

Limited clinical data are available regarding the safety of docetaxel in metastatic breast cancer patients with liver dysfunction.

METHODS:

Eligible patients had breast cancer with impaired liver function secondary to hepatic metastases and were candidates for docetaxel therapy. They were assigned to one of five groups on the basis of total bilirubin, alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase levels. All other causes of liver dysfunction were excluded, and bile duct obstruction was corrected, if possible, prior to study entry. Patients received docetaxel every three weeks. The chemotherapy dose was chosen on the basis of the patient's level of hepatic dysfunction and escalated as tolerated. The primary outcome of this study was safety. The secondary outcomes were pharmacokinetic data and efficacy in terms of time to disease progression.

RESULTS:

Twenty-three patients were enrolled. No unexpected toxicities occurred. Grade 3/4 fatigue (65%), neutropenia (30%), myalgias (26%), neutropenic fever (26%), vomiting (9%), and rash (9%) were the most common serious adverse events. The median time to progression was three months (range 1-18 months). Pharmacokinetic results indicated that patients with more severe hepatic dysfunction may have been underdosed based on our conservative dosing strategy.

CONCLUSIONS:

Docetaxel can be administered to patients with metastatic breast cancer and liver dysfunction after dose attenuation. However, because of a narrow therapeutic index in this clinical setting, therapy should be closely monitored with subsequent dose escalation when possible.

Male breast cancer comprises only about 1% of all breast cancers. Commonly, sites of metastases include the central nervous system, lungs, bones, and even liver. In females, extrahepatic gastrointestinal metastases are unusual but have been reported with various clinical presentations. We are reporting the first case of a male patient with a history of ductal breast carcinoma that developed colonic metastasis and presented with mechanical large bowel obstruction masquerading as primary colon cancer.

PURPOSE:

recent developments of second generation Hsp90 inhibitors suggested a potential for development of this class of molecules also in tumors that have become resistant to molecular targeted agents. Disease progression is often due to brain metastases, sometimes related to insufficient drug concentrations within the brain. Our objective was to identify and characterize a novel inhibitor of Hsp90 able to cross the blood-brain barrier (BBB). EXPERIMENTAL

DESIGN:

here is described a detailed biochemical and crystallographic characterization of NMS-E973. Mechanism based anticancer activity was described in cell models, including models of resistance to kinase inhibitors. Pharmacokinetics properties were followed in plasma, tumor, liver and brain. In vivo activity and pharmacodynamics, as well as the PK/PD relationships, were evaluated in xenografts, including an intracranially implanted melanoma model.

RESULTS:

NMS-E973, representative of a novel isoxazole-derived class of Hsp90 inhibitors, binds Hsp90α with subnanomolar affinity and high selectivity towards kinases, as well as other ATPases. It possesses potent antiproliferative activity against tumor cell lines and a favorable pharmacokinetic profile, with selective retention in tumor tissue and ability to cross the blood brain barrier. NMS-E973 induces tumor shrinkage in different human tumor xenografts, and is highly active in models of resistance to kinase inhibitors. Moreover, consistent with its brain penetration, NMS-E973 is active also in an intracranially implanted melanoma model.

CONCLUSIONS:

overall, the efficacy profile of NMS-E973 suggests a potential for development in different clinical settings, including tumors that have become resistant to molecular targeted agents, particularly in cases of tumors which reside beyond the BBB.

OBJECTIVE::

To examine the prognostic factors and outcomes after several types of treatments in patients with hepatocellular carcinoma (HCC) negative for hepatitis B surface antigen and hepatitis C antibody, so-called "non-B non-C HCC" using the data of a nationwide survey.

BACKGROUND::

The proportion of non-B non-C HCC is rapidly increasing in Japan.

METHODS::

A total of 4741 patients with non-B non-C HCC, who underwent hepatic resection (HR, n = 2872), radiofrequency ablation (RFA, n = 432), and transcatheter arterial chemoembolization (TACE, n = 1437) as the initial treatment, were enrolled in this study. The exclusion criteria included extrahepatic metastases and/or Child-Pugh C. Significant prognostic variables determined by a univariate analysis were subjected to a multivariate analysis using a Cox proportional hazard regression model.

RESULTS::

The degree of liver damage in the HR group was significantly lower than that in the RFA and TACE groups. The HR and TACE groups had significantly more advanced HCC than the RFA group. The 5-year survival rates after HR, RFA, and TACE were 66%, 49%, and 32%, respectively. Stratifying the survival rates, according to the TNM stage and the Japan Integrated Staging (JIS) score, showed the HR group to have a significantly better prognosis than the RFA group in the stage II and in the JIS scores "1" and "2." The multivariate analysis showed 12 independent prognostic factors. HR offers significant prognostic advantages over TACE and RFA.

CONCLUSIONS::

The findings of this large prospective cohort study indicated that HR may be recommended, especially in patients with TNM stage II and JIS scores "1" and "2" of non-B non-C HCC.

BACKGROUND:

Laparoscopic liver resection is growing in popularity, but the long-term outcome of patients undergoing laparoscopic liver resection for malignancy has not been established. This paper is a meta-analysis and compares the long-term survival of patients undergoing laparoscopic (LHep) versus open (OHep) liver resection for the treatment of malignant liver tumours.

METHODS:

A PubMed database search identified comparative human studies analysing LHep versus OHep for malignant tumours. Clinical and survival parameters were extracted. The search was last conducted on 18 March 2012.

RESULTS:

In total, 1002 patients in 15 studies were included (446 LHep and 556 OHep). A meta-analysis of overall survival showed no difference [1-year: odds ratio (OR) 0.71, 95% confidence interval (CI) 0.42 to 1.20, P = 0.202; 3-years: OR 0.76, 95% CI 0.56 to 1.03, P = 0.076; 5-years: OR 0.8, 95% CI 0.59 to 1.10, P = 0.173]. Subset analyses of hepatocellular carcinoma (HCC) and colorectal metastases (CRM) were performed. There was no difference in the 1-, 3-, and 5-year survival for HCC or in the 1-year survival for CRM, however, a survival advantage was found for CRM at 3 years (LHep 80% versus OHep 67.4%, P = 0.036).

CONCLUSIONS:

Laparoscopic surgery should be considered an acceptable alternative for the treatment of malignant liver tumours.

To evaluate outcomes in resectable cholangiocarcinoma patients and to determine prognostic factors.A retrospective study was conducted among newly-diagnosed cholangiocarcinoma patients from January 2009 to December 2011 who underwent curative resection in Srinakarind Hospital (a 1000-bed university hospital). Two hundred and sixty-three cholangiocarcinoma patients with good performance were enrolled. These patients had pathological reports with clear margins or microscopic margins. Prognostic factors which included clinical factors, serum liver function test as well as serum tumor makers at presentation, tumor data, and receiving adjuvant chemotherapy were determined by uni- and multivariate analysis.The median overall survival time was 17 mo (95%CI: 13.2-20.7); and 1-, 2-, and 3- year survival rates were 65.5%, 45.2% and 35.4%. Serum albumin levels, serum carcinoembryonic antigen (CEA) levels, staging classifications by American Joint Committee on cancer, pathological tumor staging, lymph node metastases, tumor grading, surgical margin status, and if adjuvant chemotherapy was administered, were shown to be significant prognostic factors of resectable cholangiocarcinoma by univariate analysis. Multivariate analysis, however, established that only abnormal serum CEA [hazard ratio (HR) 1.68; P = 0.027] and lymph node metastases (HR 2.27; P = 0.007) were significantly associated with a decrease in overall survival, while adjuvant chemotherapy (HR 0.71; P = 0.067) and surgical margin negative (HR 0.72; P = 0.094) tended to improve survival time.Serum CEA and lymph node metastases which were associated with advanced stage tumors become strong negative prognostic factors in cholangiocarcinoma.

Radiofrequency ablation (RFA) uses high frequency alternating current to heat a volume of tissue around a needle electrode to induce focal coagulative necrosis with minimal injury to surrounding tissues. RFA can be performed via an open, laparoscopic, or image guided percutaneous approach and be performed under general or local anesthesia. Advances in delivery mechanisms, electrode designs, and higher power generators have increased the maximum volume that can be ablated, while maximizing oncological outcomes. In general, RFA is used to control local tumor growth, prevent recurrence, palliate symptoms, and improve survival in a subset of patients that are not candidates for surgical resection. It's equivalence to surgical resection has yet to be proven in large randomized control trials. Currently, the use of RFA has been well described as a primary or adjuvant treatment modality of limited but unresectable hepatocellular carcinoma, liver metastasis, especially colorectal cancer metastases, primary lung tumors, renal cell carcinoma, boney metastasis and osteoid osteomas. The role of RFA in the primary treatment of early stage breast cancer is still evolving. This review will discuss the general features of RFA and outline its role in commonly encountered solid tumors.

PURPOSE:

This prospective study evaluated the effectiveness and safety of TACE using irinotecan loaded superabsorbent polymer (SAP) microspheres for treatment of colorectal cancer liver metastases (CCLM) in a salvage setting of patients.

METHODS:

A total of 71 TACE procedures were performed in 29 patients with liver only or liver-dominant CCLM. In all patients, systemic chemotherapy before TACE had failed. Two hundred milligrams of irinotecan were loaded into 50-100 mg of SAP microspheres (HepaSphere™ Microspheres) considering tumor size and vascularization. TACE was performed selectively with respect to tumor distribution. Response was evaluated following RECIST and EASL criteria, respectively. Median follow-up after last TACE was 8 (range 1-54) months. All patients had died at time of analysis.

RESULTS:

All TACE procedures were performed successfully; 35-400 mg (mean 168.3 mg) of irinotecan loaded in 13-100 mg (mean 48.3 mg) SAP microspheres were injected during individual sessions. No major complications occurred. Three, 6, and 12 months after first TACE complete and partial response was present in 72, 32 %, 0 of patients by EASL criteria and stable disease was seen in 86, 48, and 8 % with no complete and no partial response by RECIST criteria. Median overall survival after first TACE was 8 months, and median time to progression was 5 months. Median overall survival was longer in patients with limited (<25 %) compared with extensive (>50 %) intrahepatic disease (21 vs. 5 months, p < 0.005).

CONCLUSIONS:

TACE using irinotecan loaded SAP microspheres is safe and effective in terms of tumor necrosis. Survival benefit in a salvage setting seems to be limited in patients with advanced intrahepatic tumor load.