Blockage of interleukin-1ß with canakinumab in patients with Covid-19.

There is the urgent need to study the effects of immunomodulating agents as therapy for Covid-19. An observational, cohort, prospective study with 30 days of observation was carried out to assess clinical outcomes in 88 patients hospitalized for Covid-19 pneumonia and treated with canakinumab (300 mg sc). Median time from diagnosis of Covid-19 by viral swab to administration of canakinumab was 7.5 days (range 0-30, IQR 4-11). Median PaO2/FiO2 increased from 160 (range 53-409, IQR 122-210) at baseline to 237 (range 72-533, IQR 158-331) at day 7 after treatment with canakinumab (p < 0.0001). Improvement of oxygen support category was observed in 61.4% of cases. Median duration of hospitalization following administration of canakinumab was 6 days (range 0-30, IQR 4-11). At 7 days, 58% of patients had been discharged and 12 (13.6%) had died. Significant differences between baseline and 7 days were observed for absolute lymphocyte counts (mean 0.60 vs 1.11 × 109/L, respectively, p < 0.0001) and C-reactive protein (mean 31.5 vs 5.8 mg/L, respectively, p < 0.0001).Overall survival at 1 month was 79.5% (95% CI 68.7-90.3). Oxygen-support requirements improved and overall mortality was 13.6%. Confirmation of the efficacy of canakinumab for Covid-19 warrants further study in randomized controlled trials.

Sixty-Day Mortality Among 520 Italian Hospitalized COVID-19 Patients According to the Adopted Ventilatory Strategy in the Context of an Integrated Multidisciplinary Clinical Organization: A Population-Based Cohort Study.

PURPOSE: Although the decision of which ventilation strategy to adopt in COVID-19 patients is crucial, yet the most appropriate means of carrying out this undertaking is not supported by strong evidence. We therefore described the organization of a province-level healthcare system during the occurrence of the COVID-19 epidemic and the 60-day outcomes of the hospitalized COVID-19 patients according to the respiratory strategy adopted given the limited available resources. PATIENTS AND METHODS: All COVID-19 patients (26/02/2020-18/04/2020) in the Rimini Province of Italy were included in this population-based cohort study. The hospitalized patients were classified according to the maximum level of respiratory support: oxygen supplementation (Oxygen group), non-invasive ventilation (NIV-only group), invasive mechanical ventilation (IMV-only group), and IMV after an NIV trial (IMV-after-NIV group). Sixty-day mortality risk was estimated with a Cox proportional hazard analysis adjusted by age, sex, and administration of steroids, canakinumab, and tocilizumab. RESULTS: We identified a total of 1,424 symptomatic patients: 520 (36.5%) were hospitalized, while 904 (63.5%) were treated at home with no 60-day deaths. Based on the respiratory support, 408 (78.5%) were assigned to the Oxygen group, 46 (8.8%) to the NIV-only group, 25 (4.8%) to the IMV-after-NIV group, and 41 (7.9%) to the IMV-only group. There was no significant difference in the PaO2/FiO2 at IMV inception in the IMV-after-NIV and IMV-only groups (p=0.9). Overall 60-day mortality was 24.2% (Oxygen: 23.0%; NIV-only: 19.6%; IMV-after-NIV: 32.0%; IMV-only: 36.6%; p=0.165). Compared with the Oxygen group, the adjusted 60-day mortality risk significantly increased in the IMV-after-NIV (HR 2.776; p=0.024) and IMV-only groups (HR 2.966; p=0.001). CONCLUSION: This study provided a population-based estimate of the impact of the COVID-19 outbreak in a severely affected Italian province. A similar 60-day mortality risk was found for patients undergoing immediate IMV and those intubated after an NIV trial with favorable outcomes after prolonged IMV.

E.R.A.S. pathway in colorectal surgery in elderly: Our experience: A retrospective cohort study.

AIM: Numerous geriatric patients develop colorectal disease. Elderly patients are often considered high-risk surgical candidates. Enhanced recovery after surgery (E.R.A.S.) has been proven to be beneficial for patients. The aim of the study was to evaluate the results of an ERAS protocol in older patients that underwent colorectal surgery compared to younger patients. METHOD: In the period between January 2010 to December 2015 a total of 589 patients underwent elective colorectal surgical interventions treated within the E.R.A.S pathway: 211 patients younger than 65 years, 175 patients aged from 66 years to 75 years, and 203 patients older than 75 years. End point of interest were postoperative complications, 90-day mortality, length of hospital stay and readmission within 30 days. RESULTS: Significant differences between the three groups were observed for comorbidities (p:0.001); in particular older patients had significantly more diabetes, renal, cardiac, and respiratory diseases, ASA (p < 0.001), presence of malignancy (p < 0.001). However there were not differences between the groups in surgical procedures (p = 0.095), operative time (p = 0.823), anastomotic leakage (p = 0.960), hospital stay (p = 0.081), readmission rate (p = 0.904), 90-days mortality (p = 0.183) and morbidity (p = 0.973) in accordance with Clavien-Dindo classification. Multivariate logistic regression analysis showed that advanced age in E.R.A.S. pathway is not a predictive factor of morbidity, readmission within 30 days and 90-day mortality. CONCLUSION: There was no significant difference in morbidity, 90-day mortality, length of stay or readmission rate in patients aged over 75 years compared with younger patients. Old age does not represent a contraindication to the implementation of the E.R.A.S protocol in patients that underwent colorectal surgery. WHAT DOES THIS PAPER ADD TO THE EXISTING LITERATURE?: In the literature there are not many studies that address the impact of older age in the treatment of colorectal disease in an ERAS program. The aging of the population raises new questions in the management of the colorectal surgery in the elderly. ERAS pathway has been proven to be beneficial for patients, which results in a reduction of postoperative morbidity. Compared to what is reported in the literature this study confirms that ERAS program in colorectal surgery can be applied in older patients with no significant difference in morbidity, 90-day mortality, length of stay or readmission rate compared with younger.

A comparison of femorocrural bypasses performed with modified heparin-bonded expanded polytetrafluorethylene grafts and those with great saphenous vein grafts to treat critical limb ischemia.

BACKGROUND: The purpose of this study was to evaluate our results involving femorocrural bypasses by comparing heparin-bonded expanded polytetrafluoroethylene (HePTFE) graft (Propaten) modified with handmade distal compliant HePTFE cuffs (mHePTFE graft) to great saphenous vein (GSV) graft. METHODS: A retrospective study involving 74 femorocrural bypasses performed from January 2010 to May 2013 at a single institution was carried out. The indication for revascularization was critical limb ischemia (Rutherford stages 4-6. Forty-one femorocrural bypasses were created in 37 patients with unavailable GSVs using modified ringed HePTFE grafts with a handmade distal radial stretch HePTFE cuff to reduce the mismatch compliance between the graft and the artery wall. Thirty-three femorocrural bypasses were created using a reversed GSV graft. The results were analyzed in terms of primary graft patency, limb salvage, and patient survival using univariate (Kaplan-Meier curves and log-rank test) and multivariate (Cox regression) analyses. RESULTS: The 2 groups were statistically comparable for main risk factors, Rutherford stage, and target artery for distal anastomoses. The run-off anatomy did not significantly differ between the prosthetic and the vein bypass group. The cumulative 30-day operative mortality rate was 2.9%. At 1, 2, and 3 years, the 2 groups were equivalent in primary graft patency (the mHePTFE group: 84%, 80%, and 70%, respectively; the GSV group: 84%,71%, and 71%, respectively; P = 0.93) and were also equivalent in terms of limb salvage (the mHePTFE group: 87%, 87%, and 76%, respectively; the GSV group: 84%, 75%, and 75%, respectively; P = 0.78) and patient survival (the mHePTFE group: 87%, 75%, and 75%, respectively; the GSV group: 87%, 73%, and 65%, respectively; P = 0.86). At Cox regression analysis, only postoperative treatment with warfarin therapy compared with double antiplatelet therapy was independently associated with poorer primary patency (P = 0.003; 95% confidence interval, 1.80-18.00; hazard ratio, 5.7). CONCLUSIONS: In this retrospective study regarding femorocrural bypasses, the mHePTFE grafts had 1-, 2-, and 3-year primary patency and limb salvage results which were not significantly different from those in the GSV grafts. Additional randomized data and larger studies are needed to confirm these results.

Evaluation of the bacterial microflora of the conjunctival sac of healthy dogs and dogs with atopic dermatitis.

The aim of this case-control study was to evaluate and compare the bacterial microflora from the conjunctival sac of dogs with atopic dermatitis and healthy dogs. Twenty-one atopic dogs without clinical and/or cytopathological signs of bacterial blepharoconjunctivitis and 21 breed-matched healthy dogs were enrolled. Under topical anaesthesia, the inferior conjunctival sac of one eye was scraped twice. Material was collected with a Kimura spatula, spread over a slide and stained with a Diff Quick(®) -type stain (Medion Diagnostics GmbH, Düdingen, Switzerland) for cytological examination. An area of 0.5 cm(2) was examined at ×1000 magnification, and the types and numbers of cells and bacteria were recorded. A bacterial swab was collected and inoculated into culture media for the growth of aerobic bacteria. Before sampling, each atopic dog was evaluated for severity of cutaneous lesions, pruritus and conjunctival inflammation. Significant differences were observed between atopic and healthy dogs for the presence of bacteria on cytology (P = 0.015), keratinized (P = 0.001) and nonkeratinized epithelial cells (P = 0.013), eosinophils (P = 0.019) and lymphocytes (P = 0.008). Bacteria were recovered from 12 atopic dogs and three healthy dogs (P = 0.004). Staphylococcus pseudintermedius was the most commonly isolated species in atopic dogs (seven of 12). In atopic dogs, no significant relation was found between conjunctival bacterial colonization (on cytology and culture) and the severity of any of the clinical parameters. This study suggests differences in conjunctival bacterial colonization and cytological features between atopic and healthy dogs.

Second non-breast primary cancer following adjuvant therapy for early breast cancer: a report from the International Breast Cancer Study Group.

The incidence of second non-breast primary cancer following adjuvant treatment was evaluated using data from patients enrolled from 1978 to 1999 in four International Breast Cancer Study Group (IBCSG) trials. The occurrence of these tumours as sites of the first failure was assessed separately for two treatment comparisons: toremifene versus tamoxifen for 5 years in 1035 patients in IBCSG Trials 12-93 and 14-93 with a median follow-up of 8 years and endocrine therapy (toremifene or tamoxifen) versus chemo-endocrine therapy (CMF or AC plus toremifene or tamoxifen) in 1731 patients from IBCSG Trials III, VII and 12-93, with a combined median follow-up of 14 years. No significant differences in second non-breast primary tumours were observed in either comparison. In particular, the incidences of second primary uterine tumours with toremifene and tamoxifen were similar and no significant increase of secondary leukaemias was observed with chemo-endocrine therapy compared with endocrine therapy.

Liver transplantations with donors aged 60 years and above: the low liver damage strategy.

According to transplant registries, grafts from elderly donors have lower survival rates. During 1999-2005, we evaluated the outcomes of 89 patients who received a liver from a donor aged > or = 60 years and managed with the low liver-damage strategy (LLDS), based on the preoperative donor liver biopsy and the shortest possible ischemia time (group D > or = 60-LLDS). Group D > or = 60-LLDS was compared with 198 matched recipients, whose grafts were not managed with this strategy (89 donors < 60 years, group D < 60-no-LLDS and 89 donors aged > or =60 years, group D > or = 60-no-LLDS). In the donors proposed from the age group of > or =60 years, the number of donors rejected decreased during the study period and the LLDS was found to be responsible for this in a significant manner (47% vs. 60%, respectively P < 0.01). Among the recipients transplanted, the clinical features (age, gender, viral infection, child and model for end-stage liver disease score) were comparable among groups, but group D > or = 60-LLDS had a lower mean ischemia time: 415 +/- 106 min vs. 465 +/- 111 (D < 60-no-LLDS), P < 0.05 and vs. 476 +/- 94 (D > or = 60-no-LLDS), P < 0.05. After a median follow-up of 3 years, the 1- and 3-year graft survival rates of group D > or = 60-LLDS (84% and 76%) were comparable with group D < 60-no-LLDS (89% and 76%) and were significantly higher than group D > or = 60-no-LLDS (71% and 54%), P < 0.005. In conclusion, the LLDS optimized the use of livers from elderly donors.

Sublingual immunotherapy for large local reactions caused by honeybee sting: a double-blind, placebo-controlled trial.

BACKGROUND: Sublingual immunotherapy (SLIT) proved effective and safe in respiratory allergy, and thus its use in hymenoptera allergy can be hypothesized. OBJECTIVE: We sought to assess, in a proof-of-concept study, whether SLIT might potentially be beneficial in hymenoptera allergy. The sting challenge in large local reactions (LLRs) was used to test this hypothesis. METHODS: We performed a randomized, double-blind, placebo-controlled study involving patients with LLRs who were monosensitized to honeybee. After the baseline sting challenge, they were randomized to either SLIT or placebo for 6 months. The treatment (Anallergo, Florence, Italy) involved a 6-week build-up period, followed by maintenance with 525 microg of venom monthly. The sting challenge was repeated after 6 months. RESULTS: Thirty patients (18 male patients; mean age, 44.5 years) were enrolled, and 26 completed the study, with 1 dropout in the active group and 3 dropouts in the placebo group. In the active group the median of the peak maximal diameter of the LLRs decreased from 20.5 to 8.5 cm (P = .014), whereas no change was seen in the placebo group (23.0 vs 20.5 cm, P = not significant). The diameter was reduced more than 50% in 57% of patients. One case of generalized urticaria occurred in a placebo-treated patient at sting challenge. No adverse event caused by SLIT was reported. CONCLUSION: Honeybee SLIT significantly reduced the extent of LLRs, and its safety profile was good. Although LLRs are not an indication for immunotherapy, this proof-of-concept study suggests that SLIT in hymenoptera allergy deserves further investigation. Trials involving systemic reactions and dose-ranging studies are needed.

Anemia during adjuvant non-taxane chemotherapy for early breast cancer: Incidence and risk factors from two trials of the International Breast Cancer Study Group.

UNLABELLED: GOAL OF THE WORK: Anemia is a common side effect of chemotherapy. Limited information exists about its incidence and risk factors. The objective of this study was to evaluate the incidence of anemia and risk factors for anemia occurrence in patients with early breast cancer who received adjuvant chemotherapy. MATERIALS AND METHODS: We evaluated risk factors for anemia in pre- and post/perimenopausal patients with lymph node-positive early breast cancer treated with adjuvant chemotherapy in two randomized trials. All patients received four cycles of doxorubicin and cyclophosphamide (AC) followed by three cycles of cyclophosphamide, methotrexate, fluorouracil (CMF). Anemia incidence was related to baseline risk factors. Multivariable analysis used logistic and Cox regression. MAIN RESULTS: Among the 2,215 available patients, anemia was recorded in 11% during adjuvant chemotherapy. Grade 2 and 3 anemia occurred in 4 and 1% of patients, respectively. Pretreatment hemoglobin and white blood cells (WBC) were significant predictors of anemia. Adjusted odds ratios (logistic regression) comparing highest versus lowest quartiles were 0.18 (P < 0.0001) for hemoglobin and 0.52 (P = 0.0045) for WBC. Age, surgery type, platelets, body mass index, and length of time from surgery to chemotherapy were not significant predictors. Cox regression results looking at time to anemia were similar. CONCLUSIONS: Moderate or severe anemia is rare among patients treated with AC followed by CMF. Low baseline hemoglobin and WBC are associated with a higher risk of anemia.

Risk of cancer of the prostate and of the kidney parenchyma following bladder cancer.

AIMS AND BACKGROUND: A registry-based cohort study of male patients with bladder cancer was conducted to determine the relative risk of second primary cancer of the prostate and kidney, the uni-/multivariate differences in relative risk according to patient characteristics, the cumulative risk by duration of the follow-up, and the prevalence:incidence ratio of prostate and kidney cancer cases detected in the first 6 months after the diagnosis of bladder cancer. METHODS: The complete case records of all male patients (n = 2025) diagnosed with bladder cancer between 1986 and 2002 were extracted from the database of the Romagna Cancer Registry: 1539 patients were eligible for analysis of the incidence of following prostate and kidney cancers, of the relative risk and the standardized incidence ratio specific for the time interval of follow-up. RESULTS: A total of 108 prostate cancer cases and 23 kidney cancer cases were observed during the follow-up. The relative risk of second primary cancer of the prostate and kidney was respectively 3.52 (95% CI, 2.89-4.25) and 3.90 (95% CI, 2.47-5.85). The absolute excess risk was 11.8 x 1000 for prostate cancer and 2.5 x 1000 for kidney cancer. The number of prevalent cases of prostate and kidney cancer detected was approximately 10 times greater than the expected number based on incidence rates from the general population. During the follow-up, incidence of prostate cancer stabilized at a level that was 3- to 4-fold greater than that expected. Despite fluctuations, a decrease was also observed for incidence of kidney cancer. CONCLUSIONS: In summary, our study showed the relatively constant high incidence of prostate and kidney cancers in bladder cancer patients over time. The possibility of subsequent cancer implies that an appropriate long surveillance is required. The pertinence depends on the duration of the follow-up as well as the degree of surveillance.

Quality of life assessment of randomized controlled trials.

AIMS AND BACKGROUND: According to the USA Food and Drug Administration, quality of life (QOL) and/or survival are a priority for new anticancer drug approval. This study was performed to review approaches to QOL in randomized controlled clinical trials (RCCTs) and to survey the use of such measures in trials. MATERIAL AND METHODS: A literature survey was carried out using the Medline/Medscape, Embase, Cochrane Library, and Ovid databases. Included in the survey were all publications in the set period (from 1966 to June 2005) with "quality of life" in the title or in the abstract in the field of "randomized, controlled clinical trials". Each trial was evaluated according to the level of importance of QOL as a measure of outcome (primary, important and secondary) and was analyzed using the quality scoring system reported by Nicolucci et al. with some items regarding QOL. RESULTS: Four hundred and five RCCT articles in the oncology setting were found. Fifty-six of the 405 (13.8%) publications had QOL as primary end point. The overall quality score of these trials ranged from 40% to 100%, with a median overall score of 80%. The overall score was correlated with the year of publication (P = 0.007), the type of journal (P = 0.05), the presence of a biostatistician among the authors (P = 0.001), and the number of participating institutions (P = 0.009). CONCLUSIONS: More attention to QOL in all components of RCCTs (design, choice of instruments, data management and processing) is required from both clinicians and statisticians.

Ocular toxicity during adjuvant chemoendocrine therapy for early breast cancer: results from International Breast Cancer Study Group trials.

BACKGROUND: Others have reported ocular toxicity after adjuvant chemoendocrine therapy, but this study looked at ocular toxicity in similarly treated patients from large randomized clinical trials. METHODS: Information was retrieved on incidence and timing of ocular toxicity from the International Breast Cancer Study Group (IBCSG) database of 4948 eligible patients randomized to receive tamoxifen or toremifene alone or in combination with chemotherapy (either concurrently or sequentially). Case reports of patients with ocular toxicity were evaluated to determine whether ocular toxicity occurred during chemotherapy and/or hormonal therapy. Additional information was obtained from participating institutions for patients in whom ocular toxicity occurred after chemotherapy but during administration of tamoxifen or toremifene. RESULTS: Ocular toxicity was reported in 538 of 4948 (10.9%) patients during adjuvant treatment, mainly during chemotherapy. Forty-five of 4948 (0.9%) patients had ocular toxicity during hormone therapy alone, but only 30 (0.6%) patients had ocular toxicity reported either without receiving any chemotherapy or beyond 3 months after completing chemotherapy and, thus, possibly related to tamoxifen or toremifene. In 3 cases, retinal alterations, without typical aspects of tamoxifen toxicity, were reported; 4 patients had cataract (2 bilateral), 12 impaired visual acuity, 10 ocular irritation, 1 optical neuritis, and the rest had other symptoms. CONCLUSION: Ocular toxicity during adjuvant therapy is a common side effect mainly represented by irritative symptoms due to chemotherapy. By contrast, ocular toxicity during hormonal therapy is rare and does not appear to justify a regular program of ocular examination. However, patients should be informed of this rare side effect so that they may seek prompt ophthalmic evaluation for ocular complaints.

Carboplatin and gemcitabine in the palliative treatment of stage IV non-small cell lung cancer: definitive results of a phase II trial.

BACKGROUND: Cisplatin-containing regimens represent the gold standard in the treatment of advanced non-small cell lung cancer, but carboplatin is often preferred for its better toxic profile when palliation is the aim of the treatment. The synergistic effect and tolerability of carboplatin-gemcitabine combination are well known. In this phase II trial, we evaluated the activity and safety of a schedule with carboplatin and gemcitabine, defined in our previous phase I trial. METHODS: Thirty-seven patients with measurable stage IV non-small cell lung cancer were treated with carboplatin, AUC 4.5 mg/ml/min on day 1, and gemcitabine, 800 mg/m2 on days 1 and 8, every 21 days. All patients were treated until disease progression or intractable toxicity and were evaluated before each course of chemotherapy for toxicity and after every 3 courses for response. RESULTS: After a median follow-up of over 10 months, complete response, partial response, and stabilization of the disease were observed in 3 (8.1%), 9 (24.3%), and 15 patients (40.5%), respectively. Median time to progression was 7 months. At this writing, 27 patients have died, with a median survival of 10 months, and 29 (78.3%), 16 (43.2%), and 11 (29.7%) patients are alive after 6, 12, and 15 months of follow-up, respectively. Toxicity was mild, and mainly hematological, with a significant correlation with the number of courses of chemotherapy (P = 0.0003). CONCLUSIONS: Our results are comparable with those reported in the literature and confirm the good activity and tolerability of the carboplatin-gemcitabine combination. Up to 4 courses of chemotherapy with carboplatin and gemcitabine may represent an interesting option in the palliative treatment of non-small cell lung cancer.

Rapid progression of advanced "hormone-resistant" prostate cancer during palliative treatment with progestins for cancer cachexia.

We report three patients with advanced "hormone-resistant" prostate cancer, each of whom had rapid progression of the disease during treatment with megestrol acetate for cancer cachexia. All patients had been previously treated with total androgenic deprivation. With progression of the disease, megestrol acetate was given to palliate the cancer-related wasting syndrome. No other antineoplastic drugs were contemporaneously given, and no concomitant condition that could favor the progression of the disease was present. The worsening observed while receiving megestrol acetate, and the atypical withdrawal syndrome occurring after the treatment was stopped, seem to suggest a promoting role of megestrol acetate in advanced "hormone-resistant" prostate cancer. The risk of rapid disease progression overwhelming the anti-cachectic palliative effect should be kept in mind when progestins are administered as a palliative treatment of cancer cachexia in patients with advanced "hormone-resistant" prostate cancer.

Adjuvant chemotherapy in gastric cancer: a meta-analysis of randomized trials and a comparison with previous meta-analyses.

AIMS AND BACKGROUND: Up to now adjuvant chemotherapy after curative resection for gastric cancer (GC) has been considered an experimental approach. The results of existing phase III randomized trials comparing chemotherapy with control after surgery are controversial. Three meta-analyses have been published in recent years. It is likely that each of them presents a theoretical bias, mainly as regards the inclusion criteria of the trials. In this article we re-examine this potential bias, highlighting the differences between the present and past meta-analyses on adjuvant chemotherapy for GC. METHODS: Only randomized controlled clinical trials comparing systemic adjuvant chemotherapy with control after radical resection of GC were eligible. Total mortality was assessed as outcome measure of the treatment effect and a pooled odds ratio was calculated using the Peto-Mantel-Haenszel method. RESULTS: After the selection process 17 papers (18 comparisons) proved eligible for inclusion in the meta-analysis with a total of 3118 patients, of whom 1546 randomized to the treatment arms and 1572 to the control arms; 762 and 871 deaths occurred in the treatment and control arms, respectively. Statistical analysis suggests an absence of significant heterogeneity between the trials and a significant advantage in survival for adjuvant chemotherapy (pooled odds ratio, 0.72, 95% Cl, 0.62-0.84). CONCLUSIONS: Our meta-analysis would seem to indicate that adjuvant chemotherapy results in a significant survival advantage in patients with GC. However, this observation undoubtedly requires confirmation in large randomized controlled trials including cisplatin before adjuvant chemotherapy after curative resection for GC can be proposed for use in clinical practice.

Staging of breast cancer: new recommended standard procedure.

BACKGROUND: Staging procedures used to detect metastatic breast cancer at the time of diagnosis are bone scan (BS), chest X-ray (CXR), liver ultrasonography (LUS) and laboratory parameters (LP). These procedures are expensive and not all patients need them. We aimed to identify groups of patients with different risks for metastatic disease. METHODS: We reviewed data from 1,218 consecutive cases of breast cancer. Pathological and biological parameters and instrumental procedures performed at the time of diagnosis and during 6 months of follow-up were recorded. True positive and negative, false positive and negative cases were evaluated. All cases were grouped on the basis of tumour size, nodal involvement, biological characteristics, menopausal status and age. RESULTS: We observed 46 (3.8%) true positive cases with metastatic disease at the time of diagnosis. Documentation relating to BS, CXR and LUS was available for 1,193, 1,206 and 1,206 patients, respectively, with 37 (3.1%), 8 (0.7%) and 10 (0.8%) true positive tests. Logistic regression analysis showed significant odds ratio estimates for pT status and nodal status, thus highlighting the role of these morphological data. These findings suggest that breast cancer patients can be divided into two subgroups: first group pT1-3N0-1. with < or = 3 involved nodes, and second group pT1-3N1 with > or = 4 involved nodes, pT4 and pN2 (metastases detection rate 1.46 and 10.68%, respectively). In the former group the appropriate procedures of staging would only be laboratory parameters, whereas in the latter group BS, CXR, LUS, LP and tumour markers CEA and CA 15.3 would.be necessary. CONCLUSIONS: The standard staging procedures to detect metastatic disease at breast cancer diagnosis require modification. On the basis of the literature data and our findings, the full staging procedure is appropriate in the second group of patients.

Bolus fluorouracil and leucovorin with oxaliplatin as first-line treatment in metastatic colorectal cancer.

PURPOSE: A phase II trial investigated the activity and toxicity of a bolus administration schedule of oxaliplatin, fluorouracil (5-FU), and leucovorin (LV) therapy in patients with untreated advanced colorectal cancer. PATIENTS AND METHODS: Forty-five patients in this multicenter, open, nonrandomized study received oxaliplatin 130 mg/m(2) on the first day of each course and 5-FU and LV 350 mg/m(2) and 20 mg/m(2), respectively, as a daily bolus for 5 days, every 21 days, for a maximum of six courses. RESULTS: Partial responses occurred in 18 patients, giving an intent-to-treat response rate of 40.0%. Median time to response was 12.7 weeks; median duration of response was 18.4 weeks. Median progression-free survival was 5.9 months; median survival was 14 months. The independent prognostic factors for improved overall survival were good performance status and negative carcino-embryonic antigen blood level. Incidences of adverse effects were reduced after the 5-FU dose was reduced to 300 mg/m(2). Reversible neurologic toxicity occurred in 44.4% of patients. CONCLUSION: Bolus administration of oxaliplatin, 5-FU, and LV as first-line therapy for untreated advanced colorectal cancer is efficacious and safe. In addition to a more favorable safety profile, the 300 mg/m(2) dosage offered improved dose-intensity compared with the initial dosage.