Localized and systemic bacterial infections in necrotizing pancreatitis submitted to surgical necrosectomy or percutaneous drainage of necrotic secretions.

BACKGROUND: Infectious complications are observed in 40-70% of all patients with severe acute pancreatitis. Infections are associated with a significant increase in mortality rates. METHODS: We evaluated the prevalence and characteristics of pancreatic and systemic infections in 46 patients with necrotizing pancreatitis submitted to surgical procedures during their hospital stay as well as the impact of such infectious complications on patient clinical outcome. Samples for microbiological cultures were taken at hospital admission from blood and bile and 2 days after invasive procedure from blood, drainage fluid, bile and necrotic tissues. RESULTS: 74% patients with necrotizing pancreatitis had a localized or systemic infection. At admission, 15% of subjects had positive blood cultures whereas 13% had evidence of bacterial growth from bile cultures. Two days after the invasive procedures for removal of necrotic materials and fluids, blood cultures became positive in 30% of patients in spite of antibiotic prophylaxis and bile cultures resulted positive in 22% of cases. Furthermore, bacterial growth from drainage fluids was found in 30% and from homogenized necrotic material in 44% of cases. As refers to bacterial isolates, all patients had a monomicrobial infection. Carbapenems were the drugs with the best sensitivity profile. CONCLUSIONS: Infectious complications significantly increase mortality in patients with necrotizing pancreatitis. In addition, subjects with systemic infections developed more complications and demonstrated a higher mortality rate in comparison with those having a localized infection. In our study, the sensitivity pattern of the isolated microorganisms suggests to consider carbapenems as the best option for empirical treatment in patients with necrotizing pancreatitis who develop a clear-cut evidence of systemic or localized bacterial infection.

Nutrition in oncologic patients during antiblastic treatment.

Cancer may induce weight loss and cachexia, and cancer treatment may contribute to nutritional impairment. Here, we review the literature on the mechanisms of cancer cachexia and the pharmacological interventions both in use in clinical practice and currently under development. Based on this analysis, several nutritional proposals for cancer patients are suggested and the importance of good nutritional status in candidates for hematopoietic stem cell transplantation is highlighted.

Pancreatic cancer in HIV-positive patients: a clinical case-control study.

OBJECTIVES: Pancreatic cancer (PC) is the fourth and fifth most common cause of cancer-related death among men in United States and in Europe, respectively. No data are available for HIV-positive patients. The aim of this study was to investigate and to compare clinical presentation and outcome between HIV-positive and HIV-negative PC patients. METHODS: From April 1988 to June 2010, the Italian Cooperative Group on AIDS and Tumors identified 16 cases of HIV-positive PC patients. Each HIV-positive patient from our institution was randomly matched (ratio 1:2) with HIV-negative patients (32 controls) based on sex and year of PC diagnosis. Differences in clinical presentation, treatment, and overall survival were assessed. RESULTS: At multivariate analysis, HIV-positive patients compared with HIV-negative patients had a higher risk of an unfavorable performance status (PS ≥ 2) and a younger age (<50 years) at cancer diagnosis. At multivariate analysis, HIV-positive status and PS of 2 or greater were the only 2 features that significantly reduced PC patients' survival. CONCLUSIONS: Our data show, for the first time, that HIV-positive PC patients, compared with HIV-negative patients, are younger at cancer diagnosis. Furthermore, they share a more unfavorable PS and a shorter survival.

Extramedullary intracranial localization of multiple myeloma and treatment with novel agents: a retrospective survey of 50 patients.

BACKGROUND: Intracranial involvement in multiple myeloma is extremely rare. The effect of new drugs (eg, thalidomide, bortezomib, lenalidomide) with respect to old drugs (eg, alkylators, steroids) has not been reported. METHODS: We collected clinical and biological data of patients presenting with an osteo-dural or primary dural multiple myeloma (OD-DMM) or a central nervous system myelomatosis (CNS-MM) by sending a questionnaire to the centers of the Gruppo Italiano Malattie Ematologiche dell'Adulto (GIMEMA). RESULTS: A total of 50 patients were registered. New therapies were used in 35 patients, whereas 15 patients received old treatments. Twenty-five out of 50 patients obtained a complete remission or a very good partial remission (CR+VGPR). Overall survival (OS) for CNS-MM was 6 months, for OD-DMM 25 months. OS was 25 months for patients treated with new agents versus 8 months with old agents. Improved OS and progression-free survival were predicted by response (CR+VGPR) and by patients who underwent stem cell transplantation versus chemotherapy. ß2-Microglobulin >5 mmol/L was a poor prognostic factor. Multivariate analysis showed poor survival for patients with ß2-microglobulin >5 mmol/L and better survival for patients achieving CR+VGPR. CONCLUSIONS: The overall data highlight the relevance of therapy with new drugs in intracranial myeloma, providing a framework for future clinical trials.

Oxaliplatin-based chemotherapy in the treatment of elderly patients with metastatic colorectal cancer (CRC).

Elderly patients constitute a subpopulation with special clinical features that differ from those of the general population and are under-represented in clinical trials. We retrospectively analyzed the toxicity and efficacy of oxaliplatin-based chemotherapy in the treatment of elderly patients affected by metastatic (m) CRC. Seventy-five consecutive patients aged 65-75 years (median age 71 years), 51 males and 24 females, with mCRC and measurable disease, were analyzed. The primary site of metastases was the liver (38.6% of patients). The majority of patients had a performance status (PS) according to the Eastern Cooperative Oncology Group (ECOG) PS before treatment of 0-1 (96%). The overall response rate was 57.3%, median progression-free survival was 7 months and median overall survival was 27 months. The main hematological and extra-hematological toxicities (grade 3 or 4) were neutropenia (20.0%), and neurological toxicity or diarrhea (6.7%), respectively. No toxic death occurred. Oxaliplatin-based chemotherapy maintains its efficacy, and safety in elderly patients with mCRC and good PS. This regimen should be considered in the treatment of this particular setting of patients.

Adjuvant radiotherapy on older and oldest breast cancer patients after conservative surgery: a retrospective analysis.

Purpose of this study was to evaluate the impact of adjuvant radiotherapy, in terms of feasibility and activity, in women aged ≥ 75 years with early (stage) breast cancer. From January 2000 to December 2007, 131 consecutive patients aged 75 years or older received adjuvant radiotherapy after breast conserving surgery. Eighty-two patients received radiotherapy in combination with 5 years of hormone therapy with tamoxifen or aromatase inhibitor. Thirty out of 131 received chemotherapy. Variables considered were age, stage, co-morbidity, performance status, radiation dose (boost), hormone therapy and chemotherapy. The mean age was 78.3 years (range 75-88 years). A total of 19.1% of the patients had no co-morbidity, 57.38% mild, 19.8% moderate, and 3.8% had severe co-morbidities. All patients but one completed the planned radiation schedule. At a median follow-up of 56 months, the 5-year overall survival rate was 78.8%. There was a better survival for patients with no or mild co-morbidities (p<0.0001). The disease-free survival at 5 years was 89.6%. No difference in acute and late toxicity rates was found between patients with different ACE-27 (Adult Comorbidity Evaluation-27) indexes and for different age. We conclude that compliance with adjuvant radiotherapy is good and rate of toxicity is acceptable in elderly patients. Patients with no or mild co-morbidities have a significantly better survival. Increasing severity of co-morbidity may sufficiently shorten remaining life expectancy to cancel gains with adjuvant radiotherapy. Further prospective trials are needed to confirm these results.

The role of diet in gastric cancer: still an open question.

The risk of gastric cancer is often related to lifestyle and diet. There have been several studies on correlation between Nutrition and the risk of gastric cancer with different and sometimes contradictory results. Here we reviewed the role of nutrition as risk/protective factor in the development of gastric cancer.

The role of nutrition in the development of esophageal cancer: what do we know?

Cancer of the esophagus is the eighth most common cancer by incidence worldwide and ranks sixth as the most common cause of cancer death. It is unique among the gastrointestinal tract malignancies because it embodies two distinct histopatologic types, squamous cell carcinoma and adenocarcinoma. Which type of cancer occurs in a given patient or predominates in a given geographic area depends on many variables, including individual lifestyle, socioeconomic pressures, environmental factors and diet and nutrition. Generally for both squamous cell carcinoma and adenocarcinoma of the esophagus case-control studies provide evidence of a protective effect of fruits and vegetables. Here we review the role of nutrition in the etiology of esophageal cancer.

Hepatocellular carcinoma in HIV-infected patients: check early, treat hard.

PURPOSE: Hepatocellular carcinoma (HCC) is an increasing cause of mortality in HIV-infected patients in the highly active antiretroviral therapy (HAART) era. The aims of this study were to describe HCC tumor characteristics and different therapeutic approaches, to evaluate patient survival time from HCC diagnosis, and to identify clinical prognostic predictors in patients with and without HIV infection. PATIENTS AND METHODS: A multicenter observational retrospective comparison of 104 HIV-infected patients and 484 uninfected patients was performed in four Italian centers. HCC was staged according to the Barcelona Clinic Liver Cancer (BCLC) criteria. RESULTS: Tumor characteristics of patients with and without HIV were significantly different for age, Eastern Cooperative Oncology Group performance status (PS) score ≤1, and etiology of chronic liver disease. Despite the similar potentially curative option rate and better BCLC stage at diagnosis, the median survival time was significantly shorter in HIV(+) patients. HIV(+) patients were less frequently retreated at relapse. Independent predictors of survival were: BCLC stage, potentially effective HCC therapy, tumor dimension ≤3 cm, HCC diagnosis under a screening program, HCC recurrence, and portal vein thrombosis. Restricting the analysis to HIV(+) patients only, all positive prognostic factors were confirmed together with HAART exposure. CONCLUSION: This study confirms a significantly shorter survival time in HIV(+) HCC patients. The less aggressive retreatment at recurrence approach does not balance the benefit of younger age and better BCLC stage and PS score of HIV(+) patients. Thus, considering the prognosis of HIV(+) HCC patients, effective screening techniques, programs, and specific management guidelines are urgently needed.

Anal cancer: Focus on HIV-positive patients in the HAART-era.

Anal cancer represents an increasing health problem, especially in immune-compromised patients, as HIV-positive patients. Notably, a significant higher incidence rate is reported among HIV infected patients with the advent of highly active antiretroviral therapy (HAART). To date, no randomised trial supports the correlation between existing screening strategies and reduced progression of anal intraepithelial neoplasia (AIN) to anal cancer or improved survival. Nevertheless, screening and treatment of AIN by topical agents should be implemented in high risk population. Data on invasive anal cancer treatment show that combined modality treatment (CMT) is the treatment of choice. Early reports on HIV-positive patients describe higher treatment toxicity and a relation with lower CD4 count and higher HIV viral load. More recently, reported outcomes seem to be similar in HIV-positive population and general population. Reports on a rise in local recurrence rates and in acute side effects along with a correlation with pre-treatment CD4 counts in HIV-positive patients, are not confirmed by all authors. The development of the first approved vaccine is a milestone in the field of anogenital cancers. However, many questions are still unresolved especially as concerns immunization in the setting of HIV infection.

FOLFOX4 in the treatment of metastatic colorectal cancer in elderly patients: a prospective study.

Elderly patients constitute a subpopulation with special characteristics that differ from those of the general population and have been under-represented in clinical trials. We, prospectively, analyzed the toxicity and efficacy of the original FOLFOX4-regimen in the treatment of elderly patients affected by metastatic (m) colorectal cancer (CRC). Thirty-six consecutive patients aged 67-82 years (median age 72 years), 22 males and 14 females, with mCRC and measurable disease, were enrolled in the study. The primary site of metastases was the liver (36.1% of patients). The median ECOG Performance Status (PS) was 1. The main hematological and extra-hematological (grade 3 or 4) toxicities were neutropenia (38.9%) and neurological (13.9%), respectively. A total of 36 patients, aged 67-82 years were included. Twenty-two and 14 patients were male and female, respectively. The median age was 72 years (range 67-82). The primary site of metastases was the liver (36.1% of patients). The median ECOG Performance Status (PS) was 1. The overall response rate (ORR) was 44.4% and similar to original study. Median progression-free survival (PFS) was 7.5 months and median overall survival (OS) was 16 months. The main hematological and extra-hematological (grade 3 or 4) toxicities were neutropenia (38.9%) and neurological (13.9%), respectively. Tolerability, however, was manageable and no toxic death occurred. FOLFOX4-regimen maintains its efficacy, and safety ratio in elderly patients with mCRC and good performance status. It would be considered the treatment of choice in the treatment of this particular setting of patients.

Oxaliplatin based chemotherapy and concomitant highly active antiretroviral therapy in the treatment of 24 patients with colorectal cancer and HIV infection.

BACKGROUND: Although FOLFOX4 is considered the standard chemotherapy regimen for colorectal cancer (CRC), few data are available on its results in human immunodeficiency (HIV)-related CRC. The results were analyzed to evaluate feasibility and activity of FOLFOX4 plus highly active antiretroviral therapy (HAART) in metastatic CRC (mCRC) HIV-seropositive patients. PATIENTS AND METHODS: From January 2002 to March 2007, 24 patients were selected among the CRC HIV-seropositive patients treated with FOLFOX4 and concomitant HAART within the Italian Cooperative Group on AIDS and Tumors (GICAT). RESULTS: Four median cycles of chemotherapy were administered; the most common severe toxicity was neutropenia (37.5%). An overall response rate of 50% was observed; 4.2% of patients achieved complete response and 45.8% partial response. No opportunistic infections occurred during or immediately after chemotherapy. The median CD4+ count was 380 (range 220-570) at diagnosis. CONCLUSIONS: To our knowledge, this is the largest study describing activity and tolerability of FOLFOX4 and HAART, in this setting. FOLFOX4 plus concomitant HAART resulted feasible and active also in HIV-seropositive patients. Moreover, the concomitant use of HAART did not to seem to increase the FOLFOX4 toxicity. This study suggests the good tolerability of the FOLFOX4, making it a reasonable option for combination with HAART.

Biomarkers in neuroendocrine tumors.

Here, we review the role of clinical biomarkers (tissue and circulating markers) in the management of neuroendocrine tumors. These tumors may originate in different organs, from cells embriologically different but expressing common phenotypic characteristics, such as the immuno-reactivity for markers of neuro endocrine differentiation (defined as "pan-neuroendocrine"), the capacity to sec rete specific or aspecific peptide and hormones, and the expression of some receptors, that are at the basis of the current diagnostic and therapeutic approach.

Clinical presentation and outcome of colorectal cancer in HIV-positive patients: a clinical case-control study.

BACKGROUND: Data on colorectal cancer (CRC) in HIV-positive patients are limited. The study objective was to investigate and compare clinical presentation and outcome between HIV-positive and HIV-negative CRC patients. PATIENTS AND METHODS: Between September 1985 and November 2003 we identified 27 cases of HIV-positive CRC patients from the cancer registry database - Italian Cooperative Group AIDS and Tumours (GICAT); the clinical presentation/outcome information was retrieved. Each HIV-positive patient from our institution was randomly matched (ratio 1:2) with HIV-negative patients (54 controls) based on age, sex, and year of diagnosis in the same time period. Differences in clinical presentation, treatment, and overall survival were assessed. RESULTS: Of 1130 HIV-negative CRC patients, 54 were identified and matched with 27 HIV-positive patients. Compared with the HIV-negative patients, the HIV-positive patients had a higher risk of lower performance status (PS: > or =2) (odds ratio (OR) = 14.4; 95% confidence interval (CI): 3.6-57.7), a higher risk of unfavorable Dukes' stage (D) (OR = 4.9; 95% CI: 1.8-13.5), and a higher risk of poor grading (G3-G4) (OR = 5.0; 95% CI: 1.9-13.4). Median overall follow-up was 27 months (range: 2-212). At multivariate analysis, the only characteristics that significantly reduced the survival of the CRC patients were: HIV-positive status (hazard ratio (HR): 2.4; 95% CI: 1.1-5.2) and Dukes' stage D (HR: 3.7; 95% CI: 1.9-7.1). CONCLUSION: Our data show that HIV-positive CRC patients compared to HIV-negative patients have a poorer PS, an unfavorable Dukes' stage, higher grading and shorter survival.

Aberrant phenotypic expression of the T-cell-associated antigen CD8 on B-cell chronic lymphocytic leukemia cells.

B-cell chronic lymphocytic leukemia (B-CLL) is a heterogeneous hematologic malignancy caused by a clonally expanded B-cell population that recirculates between the blood and tissues. Described is the case of an 81-year-old female B-CLL patient with aberrant expression of a T-cell-associated antigen, CD8, on CD19+ B-CLL cells. Despite chlorambucil therapy and a subsequent salvage regimen, the patient rapidly entered progressive disease and died 9 months later. Flow cytometric immunophenotyping of the B-CLL cells for a number of antigens ruled out a mixed-lineage disorder. The implications of CD8 expression in B-CLL are discussed, and its expression in this case probably reflects an aberrant lineage infidelity. CD8 expression might be considered as a marker of aggressive disease.

Effects of imatinib mesylate in osteoblastogenesis.

Imatinib mesylate (IM), a tyrosine kinase inhibitor currently used in chronic myeloid leukemia (CML), may also affect the growth of other cellular systems besides CML cells. Because it has been reported that IM may affect bone tissue remodeling, we evaluated the effects of IM on osteoblastic differentiation of human bone marrow mesenchymal stem cells (hBM-MSCs). After 21 days of culture, hBM-MSCs treated with IM (1 microM) alone or osteogenic medium (OM) + IM showed changes in morphology with evidence of extracellular mineralization and increased mRNA expression of osteogenic markers, such as RUNX2, osteocalcin (OCN), and bone morphogenetic protein (BMP-2). We also observed that levels of OCN and the osteoprotegerin (OPG)/receptor activator of nuclear factor-kappa B ligand (RANKL) ratio (OPG/RANKL ratio) were increased in the surnatant of the 21-day culture with IM or OM + IM compared to controls (p<0.005). In addition, we found that in 46 serum samples collected from CML patients treated with IM for 3 to 24 months, the OPG/RANKL ratio increased after 3 and 6 months (p<0.004) returning back to the basal level after 24 months of IM treatment. In these patients, OCN levels were low at diagnosis but they increased throughout the IM treatment, approaching normal levels at 24 months of IM therapy. In summary, our data show that IM increases mRNA expression of osteogenic markers in hBM-MSCs and increases the OPG/RANKL ratio and the OCN levels both in surnatant of hBM-MSCs cultured with IM and in serum of patients treated with IM, thus indicating that IM potentially favors osteoblastogenesis.

Correlation between leukocytosis and thrombosis in Philadelphia-negative chronic myeloproliferative neoplasms.

The evidence that leukocytes may contribute to the pathogenesis of thrombosis in Chronic Myeloproliferative Neoplasms is increasing but not definitive. To further enforces whether an increased leukocyte count is associated with thrombosis and whether this effect can be modulated by cytoreductive therapy, we analyzed the clinical course of 187 patients with Polycythemia Vera (PV) and Essential Thrombocythemia (ET) followed at two Italian Institutions over a period of 7 years. The association was measured at diagnosis or before thrombotic events: a multivariable analysis was carried out using data at baseline and time-dependent covariates. We found that white blood cells (WBC) count above 9.5 x 10(9)/L at diagnosis (baseline analysis) was associated with thrombosis during the follow-up (Hazard Ratio [HR] of 1.8, p 0.03). At the time-dependent analysis, therapy with hydroxyurea (HU), lowering by 35% the baseline WBC level, reduced such strength of association giving a HR of 1.3 (p value non significant). We found a trend between WBC level and thrombosis in untreated low-risk patients (RR of 1.9, 95% CI 0.9 to 3.1); in high-risk patients treated with HU this correlation was clearly lost (RR 1.1, 95% CI 0.2 to 2.7). Finally, we could not identify the presence of JAK2 (V617F) as a risk factor for thrombosis. Properly designed prospective studies should corroborate such results.