Early and late outcome after surgery for colorectal cancer: elective versus emergency surgery

AIMS AND BACKGROUND: Emergency surgery for colorectal cancer is associated with a higher postoperative morbidity and mortality rate and a poor long-term outcome compared with elective surgery. The aim of the present study was to compare early and late outcome after elective and emergency surgery for malignant colorectal cancer, looking for the principal determinants of a worse outcome after emergency colorectal surgery. METHODS: A retrospective study of 236 patients presenting with colorectal cancer over an 8-year period was undertaken. Of these, 118 presented as emergencies, whereas 118 patients, well matched for age, sex, site of tumor and TNM admitted as elective, were included in the study. Data reviewed included postoperative mortality and morbidity and long-term outcome. RESULTS: The 30-day operative mortality rate was significantly higher in the emergency group than in the electively treated group (11.9% versus 3.4%, P < 0.01). The higher mortality rate was observed in the perforation group. The 30-day operative morbidity was higher in the emergency group (27.1% versus 12.7%, P < 0.05). Anastomotic failure was a serious complication: following primary resection, we observed 4 non-fatal (5.4%) and two fatal (2.7%) anastomotic leaks after 74 primary anastomoses. Among emergency-treated patients, the procedures characterized by the highest percentage of postoperative complications were three-stage resections (63.6%). The 5-year survival rate was greater after elective surgery (59% versus 39%). CONCLUSIONS: The early and long-term outcome following emergency colorectal surgery was significantly lower than that after elective surgery. Although medical complications in patients with end-stage cancer played an important role, surgical failures still had an important impact on outcome.     

High-dose sequential chemotherapy and peripheral blood progenitor cell autografting in patients with refractory and/or recurrent Hodgkin lymphoma: a multicenter study of the intergruppo Italiano Linfomi showing prolonged disease free survival in patients treated at first recurrence

BACKGROUND: The objective of the current study was to evaluate in a multicenter setting the feasibility and efficacy of a high-dose sequential (HDS) chemotherapy regimen that combined intensive debulking and high-dose therapy (HDT) with peripheral blood progenitor cell (PBPC) autografting in patients with refractory or recurrent Hodgkin lymphoma (HL). METHODS: Data were collected from 102 patients with HL who were treated with the HDS regimen at 14 centers associated with the Intergruppo Italiano Linfomi. Twenty-four patients had primary refractory HL, 59 patients had their first recurrence of HL (within 1 year in 32 patients and > 1 year in 27 patients), and 19 patients had multiple disease recurrences. The HDS regimen included the sequential delivery of high-dose (hd) cyclophosphamide with PBPC harvesting, methotrexate, etoposide, then HDT (usually hd mitoxantrone plus L-phenylalanine mustard) with PBPC autografting. In addition, radiotherapy was delivered to 36 patients at sites of bulky or persistent disease. RESULTS: Ninety-two patients (90%) completed the HDS program. There were five toxic deaths (treatment-related mortality rate, 4.9%) and six secondary malignan cies (five patients developed myelodysplastic syndrome/acute myelogenous leukemia, and one patient developed colorectal carcinoma). At a median follow-up of 5 years, the 5-year overall survival (OS) and event-free survival (EFS) projections were 64% (95% confidence interval [95% CI], 54-74%) and 53% (95% CI, 43-63%), respectively. Patients with their first recurrence had the most favorable outcome, with 5-year OS and EFS projections of 77% (95% CI, 66-88%) and 63% (95% CI, 50-76%), respectively. There were no significant differences between patients with early first recurrence and late first recurrence. The poorest outcome was observed in patients with refractory HL, with 5-year OS and EFS projections of 36% (95% CI, 16-55%) and 33% (95% CI, 14-52%), respectively. Patients who received HDS chemotherapy after multiple recurrences had an intermediate outcome. Multivariate analysis showed that refractory disease and systemic symptoms at the time of initial presentation were associated significantly associated with poor OS and EFS. CONCLUSIONS: The use of HDS chemotherapy for patients with refractory and/or recurrent HL is feasible at the multicenter level. The combination of intensive debulking and HDT with PBPC autografting offers a good chance of prolonged disease free survival for patients with their first recurrence of HL.     

Treatment of colon and breast carcinoma cells with 5-fluorouracil enhances expression of carcinoembryonic antigen and susceptibility to HLA-A(*)02.01 restricted,CEA-peptide-specific cytotoxic T cells in vitro

Cancer vaccines directed against tumor associate antigen (TAA) have produced encouraging results in preclinical models but not in cancer patients. A major limitation of this strategy is the relative degree of tolerance to these antigens and the low and heterogeneous tumor cell expression of TAA and major histocompatibility complex (MHC). Previous studies have shown that 5-fluorouracil (5-FU) can upregulate the expression of membrane-associated carcino-embryonic antigen (CEA), and MHC molecules in colon and breast carcinoma cell lines. We have investigated whether this drug can also enhance their sensitivity to the lytic effects of CEA-peptide specific Cytotoxic T cell lymphocytes (CTL). The CEA peptide-specific CTLs generated in our laboratory from normal HLA-A(*)02.01(+) donor PBMCs, were able to kill HLA-A(*)02.01(+)/CEA(+) breast (MCF-7-T103) and colon (HLA-A(*)02.01 gene-transfected HT-29 and C22.20) carcinoma cells in HLA-A(*)02.01 restricted manner. The treatment of target cells with 5-FU, enhanced their CEA expression and susceptibility to CTL-mediated lysis. Cold competition assays confirmed these results, thus supporting the hypothesis that immune target cell lysis and 5-FU mediated enhancement were dependent on CEA peptide presentation by cancer cells. 5-FU treatment of functionally "mature" CTL after in vitro expansion, did not reduce their cytolytic activity against MT-2 target cells but, when the anti-metabolite was added during the immune-sensitization phase, CTL generation was significantly inhibited. These results provide a rationale for investigating a possible new role of 5-FU as an immuno targeting amplifier agent in breast and colorectal cancer patients immunized with CEA-directed cancer vaccines.     

Mucilage in the Adriatic Sea: role of possible causal agents and environmental factors

The massive accumulation of gelatinous material at and below the seawater surface occurred in Northern Adriatic, at a frequency and with such an extension to cause serious environmental and economic damages. The present review describes the updated knowledge and considers the main hypotheses on mucilage formation. They focus, in turn, on organisms that produce mucilage, on the particular hydrodynamic of the North Adriatic basin, on the role of nutrients, but the trigger mechanism has not yet been really understood. Finally, the theoretical framework recently proposed by Azam et al. is presented. In the organic matter continuum view, organisms of the microbial loop just represent a part of the whole picture from which specific mechanisms of interactions are examined and few important pathways are outlined for future research.     

Experimentelle Studien über Keratohyalin,Eleidin und Parakeratose

Ohne ZusammenfassungHiezu Taf. IV.     

Patient satisfaction after endoscopic retrograde cholangiopancreatography for biliary stones: A prospective multicenter study in Lombardy

Aims:  To measure patients' satisfaction after endoscopic retrograde cholangiopancreatography (ERCP) for biliary stones in a large number of unselected endoscopy units.
Methods:  A prospective study using a questionnaire (Group Health Association of America—9 [GHAA-9], modified) was administered 24 h and 30 days after the procedure. Patients undergoing endoscopy for biliary stones for the first time were enrolled in a large number of endoscopy units, regardless of their size and workload.
Results:  In all, 700 patients were enrolled in 15 units. A high proportion of patients expressed satisfaction (80%). Satisfaction was less extensive for pain control and the quality of information provided before the procedure. There were no differences in the replies to questionnaires at 24 h and 30 days.
Conclusion:  It is feasible to record patients' satisfaction and in this series most patients were very satisfied. Criticisms concerned pain control and explanations provided before the procedure.     

Lamivudine and alpha-interferon in combination long term for precore mutant chronic hepatitis B

BACKGROUND/AIMS: Alpha-interferon (alpha-IFN) and lamivudine are the two licensed drugs for patients with chronic hepatitis B, however, their efficacy in precore mutant chronic hepatitis B is limited. The aim of this study was to investigate the efficacy of 1 year alpha-IFN-lamivudine combination therapy for anti-HBe/hepatitis B virus- (HBV)-DNA positive patients. METHODS: Between 1997 and 1999, 29 consecutive anti-HBe/HBV-DNA positive patients entered this prospective pilot study. Patients received 100mg lamivudine orally daily and alpha-IFN 6 million units (MU) three times weekly for 52 weeks. All patients were followed-up for 12 months after stopping therapy. Primary end points were loss of serum HBV-DNA and alanine transaminase normalization at week 52. RESULTS: Overall, the end-treatment biochemical and virological response was 93% while the sustained response at week 104 was 14%. HBV-DNA negative patients did not experience a viral breakthrough during treatment; no tyrosine-methionine-aspartate-aspartate amino acid motif of HBV polymerase (YMDD) variant emerged. At week 52, 46% of patients with paired liver biopsies slides available, showed an histological improvement (histological activity index > or =2). CONCLUSIONS: Combination of lamivudine and interferon for 1 year is followed by high end-treatment virological and biochemical response rates, by improvement of liver histology and by the prevention of the emergence of YMDD mutation; however, the sustained response rate remains low.     

Is it possible to automatically distinguish resting EEG data of normal elderly vs. mild cognitive impairment subjects with high degree of accuracy?

OBJECTIVE: It has been shown that a new procedure (implicit function as squashing time, IFAST) based on artificial neural networks (ANNs) is able to compress eyes-closed resting electroencephalographic (EEG) data into spatial invariants of the instant voltage distributions for an automatic classification of mild cognitive impairment (MCI) and Alzheimer's disease (AD) subjects with classification accuracy of individual subjects higher than 92%. METHODS: Here we tested the hypothesis that this is the case also for the classification of individual normal elderly (Nold) vs. MCI subjects, an important issue for the screening of large populations at high risk of AD. Eyes-closed resting EEG data (10-20 electrode montage) were recorded in 171 Nold and in 115 amnesic MCI subjects. The data inputs for the classification by IFAST were the weights of the connections within a nonlinear auto-associative ANN trained to generate the instant voltage distributions of 60-s artifact-free EEG data. RESULTS: The most relevant features were selected and coincidently the dataset was split into two halves for the final binary classification (training and testing) performed by a supervised ANN. The classification of the individual Nold and MCI subjects reached 95.87% of sensitivity and 91.06% of specificity (93.46% of accuracy). CONCLUSIONS: These results indicate that IFAST can reliably distinguish eyes-closed resting EEG in individual Nold and MCI subjects. SIGNIFICANCE: IFAST may be used for large-scale periodic screening of large populations at risk of AD and personalized care.