Pancreatic Cancer: Beyond Brca Mutations.

Pancreatic cancer is the fourth-leading cause of cancer-related deaths worldwide. The outcomes in patients with pancreatic cancer remain unsatisfactory. In the current review, we summarize the genetic and epigenetic architecture of metastatic pancreatic cancer beyond the BRCA mutations, focusing on the genetic alterations and the molecular pathology in pancreatic cancer. This review focuses on the molecular targets for the treatment of pancreatic cancer, with a correlation to future treatments. The potential approach addressed in this review may lead to the identification of a subset of patients with specific biological behaviors and treatment responses.

Adjuvant zoledronic acid and letrozole plus ovarian function suppression in premenopausal breast cancer: HOBOE phase 3 randomised trial.

AIM: The aim of the study is to analyse whether letrozole (L) and zoledronic acid plus L (ZL) are more effective than tamoxifen (T) as adjuvant endocrine treatment of premenopausal patients with breast cancer with hormone receptor-positive (HR+) tumours. PATIENTS AND METHODS: In a phase 3 trial, 1065 premenopausal patients with HR + early breast cancer received triptorelin to suppress ovarian function and were randomly assigned (1:1:1) to adjuvant T, L or ZL for 5 years. Cancer recurrence, second breast or non-breast cancer and death were considered events for the intention-to-treat disease-free survival (DFS) analysis. RESULTS: With a 64-month median follow-up and 134 reported events, the disease-free rate at 5 years was 85.4%, 93.2% and 93.3% with T, L and ZL, respectively (overall P = 0.008). The hazard ratio for a DFS event was 0.52 (95% confidence interval [CI], 0.34 to 0.80; P = 0.003) with ZL vs T, 0.72 (95% CI, 0.48 to 1.07; P = 0.06) with L vs T and 0.70 (95% CI, 0.44 to 1.12; P = 0.22) with ZL vs L. With 36 deaths, there was no significant difference in overall survival (P = 0.14). Treatment was stopped for toxicity or refusal in 7.3%, 7.3% and 16.6% patients, and in the safety population, grade 3-4 side-effects were reported in 4.2%, 6.9% and 9.1% patients treated with T, L or ZL, respectively. CONCLUSION: HOBOE study shows that in premenopausal patients with early breast cancer undergoing ovarian function suppression with triptorelin, ZL significantly improves DFS, while worsening compliance and toxicity, as compared with T. (NCT00412022).

Cancer of the Liver Italian Program (CLIP) score for staging hepatocellular carcinoma.

AIM: To assess the prognostic ability of the Cancer of the Liver Italian Program (CLIP) score in patients with hepatocellular carcinoma after a longer follow up. METHODS: The updated survival data were derived from an analysis that was performed on two joined sets of data. The first set was collected retrospectively in 1995 and was used to perform an exploratory prognostic factor analysis (the CLIP-03 study), that produced the CLIP score. The second set of data was collected prospectively for the CLIP-01 randomized clinical trial. RESULTS: Out of 912 overall patients, analysis was performed on 650 patients whose records contained all informationregarding prognostic factors. The median survival of the whole group of patients was 17.7 months and the 5-year survival rate was 10.7%. The median survival of the patients was inversely proportional to the CLIP score: the higher the CLIP score the worse the survival. CONCLUSIONS: The CLIP score keeps good prognostic and discriminative abilities after a longer follow up and remains one the most useful prognostic system for hepatocellular carcinoma.

Long-term survival in a patient with metastatic squamous cell lung carcinoma: A case report.

Non-small-cell lung cancer (NSCLC) is the most common malignancy in industrialized countries, with a 5-year survival rate of only ~15%, as the majority of the patients have advanced-stage disease at diagnosis and the treatment options are limited. Squamous cell carcinoma the second most frequent type of NSCLC and is closely associated with cigarette smoking. We herein present the case of a 72-year-old male smoker, diagnosed with stage IV squamous cell lung carcinoma, with a solitary brain metastasis. After the diagnosis, stereotactic radiotherapy was performed on the brain metastasis. Following radiotherapy, chemotherapy with carboplatin + paclitaxel was initiated. However, after 2 cycles of chemotherapy, disease progression in the lung was observed. Therefore, second-line treatment with pemetrexed was started, which was discontinued after 2 cycles due to further disease progression. Third-line treatment with erlotinib was then administered, with notable benefit, as the patient remains alive after 6 years of treatment with a good performance status. The mutation status of EGFR was unknown.

[Thrombotic thrombocytopenic purpura in patient with metastatic occult adenocarcinoma. A case report]. / Un caso di porpora trombotica trombocitopenica in paziente con adenocarcinoma metastatico.

In the past two decades, in addition to idiopathic thrombotic thrombocytopenic purpura (TTP) more cases of secondary TTP have been identified, perhaps due to an enthusiasm for cure potential with an availability of exchange-plasmapheresis. An early diagnosis is important, because the evaluation of patients with suspected thrombotic thrombocytopenic purpura is difficult since the diagnostic criteria, thrombocytopenia, microangiopathic haemolytic anemia and no other clinically apparent etiology are not specific.

[Screening of hepatocellular carcinoma: role of the alpha-fetoprotein (AFP) and ultrasonography]. / Lo screening del carcinoma epatocellulare.

Even if there are no definitive evidence that hepatocellular carcinoma (HCC) screening in high-risk groups improves survival, many physicians screen high-risk population by various strategies, alpha-fetoprotein (AFP) and liver ultrasonography are the most widely used tools. AFP sensitivity and specificity depend on the cut-off value chosen. In cirrhotic patients, using a cut-off level of 20 ng/mL, sensitivity is only around 60% and positive predictive value ranges from 9% to 50%, depending on HCC prevalence. Sensitivity and specificity are much higher (94.1% and 99.9%, respectively) in hepatitis B carriers, but positive predictive value is only 5%. The performance of ultrasonography as a screening tool varies widely depending on the experience of the examiner and the technology used. Recent studies generally indicate a 60% sensitivity or higher, a specificity greater than 90%, and a positive predictive value of 70%. Based on the estimated HCC doubling time, the recommended screening interval is 6 months, although a 1 year interval seems as effective. Currently, HCC screening with AFP only is not recommended except when ultrasonography is either not available or of poor quality. Ultrasonography seems more efficient as a screening tool. Pathology assessment of liver explants in living donor transplantation programs will provide more precise and reliable information regarding the value of AFP and ultrasonography as HCC screening tools.

Alpha-fetoprotein and ultrasonography screening for hepatocellular carcinoma.

Although there is no definitive evidence that hepatocellular carcinoma (HCC) screening in high-risk groups improves survival, many physicians screen high-risk populations with various strategies. alpha-fetoprotein (AFP) and liver ultrasonography (US) are the most widely used tools. AFP sensitivity and specificity depend on the cut-off value chosen. In cirrhotic patients, using a cut-off level of 20 ng/mL, sensitivity is only around 60% and positive predictive value ranges from 9% to 50%, depending on HCC prevalence. Sensitivity and specificity are much higher (94.1% and 99.9%, respectively) in hepatitis B carriers, but positive predictive value is only 5%. The performance of US as a screening tool varies widely depending on the experience of the examiner and the technology used. Recent studies generally indicate a 60% sensitivity or higher, a specificity greater than 90%, and a positive predictive value of 70%. The cost effectiveness of screening strategies using AFP, US, or both have been estimated retrospectively or using decision models. In general, HCC screening using both AFP and US appears to be of borderline cost effectiveness or not cost effective at all. Based on the estimated HCC doubling time, the recommended screening interval is 6 months, although a 1-year interval seems as effective. Currently, HCC screening with AFP only is not recommended except when US is either not available or of poor quality. US seems more efficient as a screening tool. Pathology assessment of liver explants in living-donor transplantation programs will provide more precise and reliable information regarding the value of AFP and US as HCC screening tools.

Supportive care in patients with advanced non-small-cell lung cancer.

The present study describes supportive care (SC) in patients with advanced non-small-cell lung cancer (NSCLC), evaluating whether it is affected by concomitant chemotherapy, patient's performance status (PS) and age. Data of patients enrolled in three randomised trials of first-line chemotherapy, conducted between 1996 and 2001, were pooled. The analysis was limited to the first three cycles of treatment. Supportive care data were available for 1185 out of 1312 (90%) enrolled patients. Gastrointestinal drugs (45.7%), corticosteroids (33.4%) and analgesics (23.8%) were the most frequently observed categories. The mean number of drugs per patient was 2.43; 538 patients (45.4%) assumed three or more supportive drugs. Vinorelbine does not produce substantial variations in the SC pattern, while cisplatin-based treatment requires an overall higher number of supportive drugs, with higher use of antiemetics (41 vs 27%) and antianaemics (10 vs 4%). Patients with worse PS are more exposed to corticosteroids (42 vs 30%). Elderly patients require drugs against concomitant diseases significantly more than adults (20 vs 7%) and are less frequently exposed to antiemetics (12 vs 27%). In conclusion, polypharmacotherapy is a relevant issue in patients with advanced NSCLC. Chemotherapy does not remarkably affect the pattern of SC, except for some drugs against side effects. Elderly patients assume more drugs for concomitant diseases and receive less antiemetics than adults.