Prognosis of mucinous histology for patients with radically resected stage II and III colon cancer.

BACKGROUND: Previous studies investigating the prognostic role of mucinous histology of colorectal cancer produced conflicting results. This retrospective analysis was carried out in order to explore whether mucinous adenocarcinoma (MC) is associated with a comparatively worse prognosis than that of nonmucinous adenocarcinoma (NMC) for patients undergoing curative resection for stage II and III colon cancer. PATIENTS AND METHODS: This study involved 1025 unselected patients who underwent curative surgery for sporadic colon cancer and follow-up procedures at six different oncology departments. RESULTS: MCs accounted for 17.4% (n=178) of tumours. Patients with MC had 5- and 8-year overall survival rates of 78.6% and 68.8%, respectively, compared with 72.3% and 63.8%, respectively, for patients with nonmucinous tumours. Multivariate analysis using the Cox proportional hazards model showed that the clinically significant prognostic factors were stage of disease and adjuvant chemotherapy. No statistically significant interaction between mucinous histology and adjuvant chemotherapy was found. CONCLUSIONS: For patients with stage II and III colon cancer who underwent curative surgery, mucinous histology has no significant correlation with prognosis compared with NMC. This retrospective analysis suggests a comparable benefit from adjuvant chemotherapy for MC compared with NMC.

Dual-source CT coronary angiography: prospective versus retrospective acquisition technique.

PURPOSE: The aim of our work was to compare image quality and radiation dose in a group of patients who underwent cardiac dual-source computed tomography (DSCT) with prospective electrocardiographic (ECG) gating with those of a control group studied with retrospective gating. MATERIALS AND METHODS: Sixty patients were randomly assigned to two groups of 30 individuals each. Patients with heart rates >70 bpm and body mass index (BMI) >30 kg/m(2) were excluded. Group A was examined with prospective ECG gating and group B with retrospective gating. The dose-length product (DLP) was recorded to calculate the radiation dose, whereas the effective dose was normalised to a standard 12-cm scan of the heart. RESULTS: Applying the best reconstruction interval, 98.6% of segments in the prospective group and 99.3% in the retrospective group were diagnostic. No significant difference (p>0.05) in image quality was observed between groups. Mean normalised radiation dose was 4.91 ± 0.4 mSv in the prospective-gating group and 14.62 mSv ± 4.36 in the retrospective-gating group (p<0.01). CONCLUSIONS: Coronary CT with prospective ECG gating, a standard feature on new scanners, allows for a significant reduction in radiation dose without causing any significant decrease in image quality or in the number of segments assessed. The prospective technique is thus recommended for patients with heart rates £70 bpm and BMI £30 kg/m(2).

Nonlinearity-generated resilience in large complex systems.

We consider a generic nonlinear extension of May's 1972 model by including all higher-order terms in the expansion around the chosen fixed point (placed at the origin) with random Gaussian coefficients. The ensuing analysis reveals that as long as the origin remains stable, it is surrounded by a "resilience gap": there are no other fixed points within a radius r_{*}>0 and the system is therefore expected to be resilient to a typical initial displacement small in comparison to r_{*}. The radius r_{*} is shown to vanish at the same threshold where the origin loses local stability, revealing a mechanism by which systems close to the tipping point become less resilient. We also find that beyond the resilience radius the number of fixed points in a ball surrounding the original point of equilibrium grows exponentially with N, making systems dynamics highly sensitive to far enough displacements from the origin.

Preliminary experience with abdominal dual-energy CT (DECT): true versus virtual nonenhanced images of the liver.

PURPOSE: The aim of this work was to compare the quality and noise of true non-enhanced (TNE) and virtual non-enhanced (VNE) images in patients undergoing dual-energy computed tomography (DECT) of the liver. MATERIALS AND METHODS: Twenty consecutive patients (mean age 54.7±19.9 years) prospectively underwent abdominal DECT to assess the liver using a triphasic protocol consisting of precontrast, arterial-phase and portal-phase acquisitions. Exclusion criteria were allergy to iodinated contrast material, impaired renal function and a body mass index (BMI) >35 kg/m(2). The DE portal-phase acquisition was performed with automatic dose modulation (CARE Dose 4D). Nonionic iodinated contrast material (Iomeron 400) was administered at 0.625 gI/kg with a flow rate of 3.5 ml/s. Axial VNE images were reconstructed based on the portal data set using a collimation and an increment of 5 mm and were compared with TNE images reconstructed with the same parameters. The average image quality and noise were analysed by two radiologists in separate reading sessions. RESULTS: No statistically significant difference (p>0.05) in image quality was observed between VNE (4.00±0.85) and TNE images (4.35±0.58). A sufficient diagnostic quality was found in 95.0% (19/20) of VNE images and in 100% of TNE images. No statistically significant difference (p<0.05) was observed in the average image noise of VNE (9.5±0.7) and TNE (12.3±1.1) images. CONCLUSIONS: Abdominal DECT allows acquisition of liver VNE images with similar image quality and lower noise than TNE. Nevertheless, a few technical limitations related to the small field of view of the second detector in patients with a high BMI and heterogeneous iodine subtraction restrict the application of this technique to selected patients only.

Preoperative coronary risk assessment with dual-source CT in patients undergoing noncoronary cardiac surgery.

PURPOSE: The aim of our work was to assess the role of dual-source computed tomography (DSCT) in the preoperative evaluation of coronary artery disease in patients scheduled for noncoronary cardiac surgery. MATERIALS AND METHODS: One hundred patients were prospectively evaluated. Patients negative for coronary disease at DSCT (n=81) underwent surgery without coronary angiography. Patients positive for significant lesions or with nondiagnostic image quality due to artefacts or severe calcifications underwent coronary angiography (n=19) and were excluded from the study. In patients who underwent surgery with only a DSCT diagnosis, we evaluated the frequency of major adverse cardiac events (MACEs) during the perioperative period and at 3 months follow-up. RESULTS: No MACEs were recorded during the perioperative period; three noncardiac complications (one surgical revision for bleeding, one cardiac tamponade and one respiratory insufficiency) and one death related to severe respiratory insufficiency were observed. None of the 80 patients had MACEs during the 3-month follow-up period. CONCLUSIONS: Coronary evaluation with DSCT is able to rule out the presence of coronary disease in patients scheduled for cardiac surgery, without the need for coronary angiography confirmation. Patients with significant stenosis or nondiagnostic image quality should be referred for coronary angiography.

Mucinous histology predicts for poor response rate and overall survival of patients with colorectal cancer and treated with first-line oxaliplatin- and/or irinotecan-based chemotherapy.

The objective of this study was to investigate the efficacy of first-line chemotherapy containing irinotecan and/or oxaliplatin in patients with advanced mucinous colorectal cancer. Prognostic factors associated with response rate and survival were identified using univariate and multivariate logistic and/or Cox proportional hazards analyses. The population included 255 patients, of whom 49 (19%) had mucinous and 206 (81%) had non-mucinous colorectal cancer. The overall response rates for mucinous and non-mucinous tumours were 18.4 (95% CI, 7.5-29.2%) and 49% (95% CI, 42.2-55.8%), respectively (P=0.0002). After a median follow-up of 45 months, median overall survival for the mucinous patients was 14.0 months compared with 23.4 months for the non-mucinous group (hazard ratio (HR), 1.74; CI 95%, 1.27-3.31; P=0.0034). After adjustment for significant features by multivariate Cox regression analysis, mucinous histology was associated with poor overall survival (HR, 1.593, 95% CI, 1.05-2.40; P=0.0267), together with performance status ECOG 2, number of metastatic sites > or =2, and peritoneal metastases. This retrospective analysis shows that patients with mucinous colorectal cancer have poor responsiveness to oxaliplatin/irinotecan-based first-line combination chemotherapy and an unfavourable prognosis compared with non-mucinous colorectal cancer patients.

Impact of cumulative anthracycline dose, preparative regimen and chronic graft-versus-host disease on pulmonary and cardiac function in children 5 years after allogeneic hematopoietic stem cell transplantation: a prospective evaluation on behalf of the EBMT Pediatric Diseases and Late Effects Working Parties.

This prospective study focused on risk factors and clinical outcome of pulmonary and cardiac late effects after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We prospectively evaluated 162 children by pulmonary function tests (PFTs) and cardiac shortening fraction (SF) before allo-HSCT and yearly up to the 5th year of follow-up. The 5-year cumulative incidence of lung and cardiac impairment was 35 (hazard rate=0.03) and 26% (hazard rate=0.06), respectively. Patients presenting abnormal PFTs and SF at last follow-up were 19 and 13%, respectively, with a median Lansky performance status of 90% (70-100). Chronic graft-versus-host disease (c-GVHD) was the major risk factor for reduced lung function in univariate (P=0.02) and multivariate analysis (P=0.02). Total body irradiation (TBI) alone and TBI together with pre-transplant anthracycline administration were significant risk factors for reduced cardiac function in univariate analysis, only (P=0.04 and 0.004, respectively). In conclusion, our prospective study demonstrates an asymptomatic post-allo-HSCT deterioration of pulmonary and cardiac function in some long-term survivors, who had been transplanted in childhood, and thus emphasizes the need for lifelong cardiopulmonary monitoring and the development of new strategies both to reduce pre-transplant cardiotoxic regimens and to treat more efficiently c-GVHD.

Toward sensitive immuno-based detection of tau protein by surface plasmon resonance coupled to carbon nanostructures as signal amplifiers.

Interest on Tau protein is fast increasing in Alzheimer's disease (AD) diagnosis. There is the urgent need of highly sensitive and specific diagnostic platforms for its quantification, also in combination with the other AD hallmarks. Up to now, SPR has been poorly exploited for tau detection by immunosensing, due to sensitivity limits at nanomolar level, whereas the clinical requirement is in the picomolar range. Molecular architectures built in a layer-by-layer fashion, biomolecules and nanostructures (metallic or not) may amplify the SPR signal and improve the limit of detection to the desired sensitivity. Mostly gold nanostructures are widely employed to this aim, but great interest is also emerging in Multi Walled Carbon Nanotubes (MWCNTs). Here MWCNTs are modified and then decorated with the secondary antibody for tau protein. Eventually we took advantage from MWCNTs-antibody conjugate to obtain a sandwich-based bioassay with the capability to increase the SPR signal of about 102 folds compared to direct detection and conventional unconjugated sandwich. With respect to these results, we hope to give a strong impulse for further investigation on studying possible roles of carbon nanotubes in optical-based biosensing.

Octreotide versus loperamide in the treatment of fluorouracil-induced diarrhea: a randomized trial.

PURPOSE: Diarrhea is a prominent feature of fluorouracil (5FU) gastrointestinal toxicity, especially when 5FU is combined with leucovorin (LV) or interferon (IFN). No treatment for this condition has been well defined, although drugs, such as diphenoxylate or loperamide, generally are used. The efficacy of octreotide in the treatment of 5FU-induced diarrhea recently has been reported. We performed a randomized trial that compared octreotide with loperamide, the drug most commonly used for therapy for this disorder. PATIENTS AND METHODS: Forty-one patients with grade 2 (four to six stools per day) or grade 3 (seven to nine stools per day; National Cancer Institute toxicity criteria) diarrhea after chemotherapy with a 5FU-containing regimen for colorectal cancer in 28 cases, gastric cancer in six cases, pancreatic cancer in five cases, and breast cancer in two cases, were entered onto the study. Twenty-one patients received octreotide at a dosage of 0.1 mg subcutaneously twice per day for 3 days, and 20 patients received loperamide 4 mg orally initially and then 2 mg every 6 hours for 3 days. The two arms were comparable for age, sex, and primary tumor. Patients were evaluated for response each treatment day; all patients were assessable. RESULTS: Diarrhea resolved in 19 patients in the octreotide arm (one within the first day; four within the second day; and 14 within the third day) versus only three (all after the third day of therapy) in the loperamide arm (P < .005). Median frequency of stools in the 3 days of therapy was four, three, and zero in the octreotide arm and five, five, and five in the loperamide arm. No side effects were observed in both arms. Ten patients on the loperamide arm and only one on the octreotide arm required hospitalization for parenteral replenishment of fluids and electrolytes. CONCLUSION: Octreotide seems to be more effective than loperamide in control of diarrhea and elimination of the need for replenishment of fluids and electrolytes.

Recombinant human erythropoietin treatment in cisplatin-associated anemia: a randomized, double-blind trial with placebo.

PURPOSE: To evaluate the effect of exogenous recombinant human erythropoietin (rHuEPO) on the increase of hemoglobin levels and on the transfusion requirements in patients with cisplatin (CDDP)-induced anemia, we performed a double-blind randomized trial with placebo. PATIENTS AND METHODS: One hundred patients with CDDP-associated anemia (hemoglobin level < 90 g/L) were randomized to receive either placebo (saline solution) or rHuEPO (100 U/kg body weight subcutaneously) three times per week. The end points of this study were the increase in hemoglobin levels to greater than 100 g/L after 3, 6, and 9 weeks and the effect on transfusion requirements. RESULTS: Ninety-nine of 100 patients were assessable for response and toxicity. In the rHuEPO arm, mean hemoglobin levels were statistically significantly increased after the third, sixth, and ninth weeks of therapy (101.1 +/- 9.0, 102.4 +/- 6.6, and 105.1 +/- 9.4 g/L, respectively) compared with the mean baseline value (86.3 +/- 6.2 g/L). In the placebo arm, there were no increases in mean hemoglobin levels at the third, sixth, and ninth weeks (81.0 +/- 5.2, 81.3 +/- 9.2, and 81.2 +/- 11 g/L, respectively) compared with the mean baseline value (87.3 +/- 5.2 g/L). Furthermore only 20% of patients required blood transfusions in the rHuEPO arm versus 56% of patients in the placebo arm (P = .01), with a mean units of blood transfused per patient of 0.30 in the rHuEPO arm and 1.8 in the placebo arm (P = .01). Treatment was well tolerated, with no significant side effects. CONCLUSION: CDDP-induced anemia is corrected by rHuEPO, which results in reduced blood transfusion requirements.

Control of chemotherapy-induced diarrhoea with octreotide in patients receiving 5-fluorouracil.

Chemotherapy treatment with combination of 5-fluorouracil and leucovorin or interferon alpha determined an incidence of severe diarrhoea of 10 and 20%, respectively. Up to date no treatment for this condition has been defined. 21 patients affected by advanced colorectal cancer and 6 patients affected by advanced pancreatic cancer received octreotide as treatment for severe diarrhoea following chemotherapy with 5-fluorouracil/leucovorin (Machover's regimen) or 5-fluorouracil/interferon (Wadler's regimen) combination. Octreotide was administered by subcutaneous injection of 50 micrograms twice daily on the first day and 100 micrograms twice daily on the second and third day. 26 patients had total cessation of diarrhoea: 4 patients within the first day, 6 within the second day and 16 within the third day. 1 patient had no change and after the last administration of octreotide he was treated with loperamide and intravenous hydration. Side effects have been mild. In summary octreotide seems to be an effective agent in the management of chemotherapy related diarrhoea.

Intensive weekly chemotherapy for advanced gastric-cancer using 5-Fluorouracil, Cisplatin, epi-Doxorubicin, 6s-leucovorin and granulocyte-colony-stimulating factor.

Thirty-four advanced gastric cancer patients received, every week for nine weeks, 5-fluorouracil 500 mg/m2 iv; epi-doxorubicin 35 Mg/M2 iv; cisplatin 40 Mg/M2 iv; 6S-leucovorin 250 mg/M2 in 4 hour infusion. Granulocyte-colony stimulating factor, at the dose of 5 mug/kg, was administered daily from the day after to the day before each chemotherapy administration. 5 patients achieved a complete response and 20 a partial response, resulting in an overall response rate of 72% (95% confidence interval, 59% to 88%). Median survival time was 12 months for all the patients and 13 months for responding patients. Toxicity was mild. In conclusion, this regimen seems to be promising and suitable for further studies in gastric cancer.

Carboplatin associated anemia treated with subcutaneous erythropoietin - a pilot-study.

In nineteen patients with carboplatin-induced anemia (hemoglobin less than 90 g/l), recombinant human erythropoietin was administered subcutaneously three times a week on an outpatient basis. The initial dose was 50 Units/kg of body weight. If response was not achieved within 3 weeks, dose was increased to 75 Units/kg. Using the same criteria further escalations to 100 and 150 Units/kg were performed. If there was no response erythropoietin was terminated. Two patients obtained an increase of hemoglobin levels greater than 100 g/l, which was considered as a clinical response in this study, with a dose of 75 U/kg; eleven patients needed an erythropoietin dose of 100 U/kg and three a dose of 150 U/kg. The other three patients required hemotransfusions and were considered non responders. Hemoglobin increases occurred despite continuation of carboplatin chemotherapy. In conclusion, subcutaneous eryhtropoietin is effective and safe in the treatment of carboplatin-induced anemia.

A new cisplatin/gemcitabine schedule in locally advanced (IIIB) and metastatic (IV) non-small cell lung cancer: relationship between dose-intensity and efficacy. A phase II study.

BACKGROUND: Cisplatin/gemcitabine are one of the "standard" chemotherapy schedules in locally advanced and metastatic NSCLC cancer. A number of trials documented that omission of gemcitabine on day 15 and reduction of cisplatin up to 70 mg/mq are equivalent in term of response rates to "classic" administrations on days 1, 8 and 15 with cisplatin 100 mg/mq. The aim of this study was to confirm this evidence and to demonstrate that a further reduction of gemcitabine dose-intensity may be performed with the same efficacy on response. PATIENTS AND METHODS: Fifty untreated patients with locally advanced and metastatic NSCLC entered the study: 24 stage IIIB and 26 stage IV. The median age was 65 years (range 32-76); 44 males and 6 females Genicitabine was administered 1000 mg/mq weekly on days 1 and 8 followed by a 2-week rest and cisplatin 80 mg/mq on day 2 of each 28-day-cycle. RESULTS: Forty-five patients were evaluable for response and all for toxicity. The overall response rates were 35.5% with 16 partial responses (95% Confidence Interval: 32%-61%). Most of the objective responses were seen in IIIB patients (56% of the stage IIIB and 44% of the stage IV patients responded). According to the intent-to-treat-principle, the response rates were 32% (16 out of 50 patients). The median dose-intensity of gemcitabine and cisplatin was respectively 477.6 mg/mq/week (481.4 for responders) and 19.5 mg/mq/week (19.9 mg/mq for responders). The median response duration was 5 months (range 1-18) and the median time to progression was 5 months (1-21); median survival was 9 months (range 2-31). The main toxicity was haematological: thrombocytopenia grade IV in 5 patients (10%) and grade III in 11 patients (22%); neutropenia grade III-IV in 4 patients (8%); grade III anemia in 3 (6%). Asthenia was the most significant non-haematological toxicity and was observed in 19 patients (38%). CONCLUSION: This trial confirmed the efficacy of a schedule with 2 administrations of gemcitabine (on days 1, 8) and a cisplatin dose on day 2 lower than 100 mg/mq. Moreover, the same efficacy was obtained with a median-dose intensity of cisplatin and gemcitabine lower than planned in a 21-day-schedule. For safety and low toxicity, we think that this schedule provides another chance to treat patients with non-small cell lung cancer, especially the elderly or patients with coexistent medical illnesses.

5-Fluorouracil dose intensity increase in 5-fluorouracil and leucovorin combination: results of a phase II study.

It was our intention to verify if in the combination of 5-fluorouracil and leucovorin, the fluoropyrimidine dose intensity is an important determinant of response as noted by Hryniuk when 5-fluorouracil was given alone. By employing the Machover regimen but with cycles repeated every three weeks, a 5-fluorouracil projected dose intensity of 616 mg/m2/wk was obtained. It approximates the maximum tolerated dose for this drug when used alone by i.v. bolus. 50 patients entered this study and 48 were evaluable for response and toxicity. The overall response rate was 29% (five complete responses and nine partial responses). The dose limiting toxicity was gastrointestinal rather than myelosuppression. 5-fluorouracil dose reduction was needed in seven patients. The mean delivered dose intensity of 5-fluorouracil was 610 mg/m2/wk (582 mg/m2/wk in patients in whom 5-fluorouracil was reduced for toxicity and 616 mg/m2/wk in the others). Our results do not seem to show any advantage in the maximization of 5-fluorouracil dose intensity. Furthermore, in an analysis of data from the literature we did not find any difference in response rate in relation to dose intensity in the 5-fluorouracil/leucovorin combination.

Treatment of elderly advanced gastric cancer patients with 5-fluorouracil and leucovorin combination.

In September 1987 a phase II study was begun to verify if elderly symptomatic patients affected by advanced gastric cancer could benefit from a combination of 5-fluorouracil (5FU) and leucovorin (LV). We employed Machover's regimen: 5FU 370 mg/m2 i.v. infusion daily for 5 days; LV 200 mg/m2 i.v. bolus daily for 5 days; cycles were repeated every 3 weeks. 23 patients entered the study and 22 were evaluable for response and toxicity. We obtained only one partial response; 9 had stable disease and 12 progressed on therapy. The median duration of survival was 6 months. Symptoms were not affected by treatment. These data reflect the absence of significant improvement in the quality of life, which was further lessened by the presence of treatment side effects. Because of this we think that this regimen cannot be recommended for the treatment of elderly advanced gastric cancer patients.

Salvage chemotherapy in colorectal cancer patients with good performance status and young age after failure of 5-fluorouracil/leucovorin combination.

Forty-one patients with metastatic colorectal cancer were treated every four weeks with methotrexate 25 mg/m2 i.v. days 1, 8, 15; vincristine 1 mg/m2 i.v. day 1; lomustine 100 mg/m2 p.o. day 1. Inclusion criteria were: failure of previous 5-fluorouracil/leucovorin treatment; performance status (ECOG) 0-2; age less than 60 years; presence of symptoms; absence of concomitant diseases. Metastatic sites were: liver 30, lung 4, abdominal/pelvic mass 7. Three patients achieved partial responses (2 liver, 1 lung metastases); 4 showed stable disease and 34 progressed on therapy. The median survival of patients with partial response, stable disease and progression was comparable (24, 21, 22 weeks respectively). The most common toxicity was hematologic (thrombocytopenia and leukopenia). Other side effects included nausea and vomiting, stomatitis and diarrhea. Symptoms were not affected by treatment. We conclude that salvage chemotherapy is not recommended in colorectal cancer after 5-fluorouracil/leucovorin treatment even in patients with generally considered favorable characteristics for response to chemotherapy.

Gastric metastases from breast cancer: a case report.

We describe a case of a 50 year old woman with a secondary involvement of the stomach from breast carcinoma. She complained of nausea, vomiting and epigastric pain resistant to gastroprotective drugs. Initially symptoms were attributed to the side effects of chemotherapeutic agents. Correct diagnosis led to effective treatment of gastrointestinal symptoms with consequent improvement in her quality of life.

Experience with intrapleural natural beta interferon in the treatment of malignant pleural effusions.

Malignant pleural effusion is a common complication of cancer. Intrapleural beta interferon has been recently tested, and responses were obtained in about 1/3 of the patients without considerable side effects. We treated 22 patients with recurrent symptomatic malignant pleural effusions with intrapleural beta interferon at increasing doses (5-15 million units) for a maximum of three courses and obtained only two responses. In our opinion, this schedule cannot be recommended for routine use.

Feasibility of a cell kinetic-based adjuvant chemotherapy trial in axillary node-negative breast cancer.

AIMS AND BACKGROUND: Accumulated information on biologic prognostic indicators and predictors of response to different types of treatment in patients with different tumor characteristics has made it possible to design clinical protocols on biologic bases. Among cell proliferation indices, the thymidine labelling index (TLI) has proved to be an independent and consistent prognostic indicator over time. Moreover, experimental and retrospective analyses of clinical studies have revealed a direct relation between TLI and response to chemotherapy. On the basis of the results, a prospective clinical protocol on axillary node-negative breast cancer was activated in Italy in 1989. METHODS: Patients with low TLI tumors were treated with local-regional therapy alone, whereas patients with high TLI tumors were randomized to receive local-regional therapy followed or not by adjuvant chemotherapy consisting of 6 cycles of CMF. RESULTS AND CONCLUSIONS: The present paper reports on the feasibility of a prospective clinical protocol based on a subgroup of patients with specific pathologic (node negative) and biologic (rapidly proliferating) breast cancers. However, patient eligibility was only 11%.