Clinical presentation and in-hospital prognosis of lung cancer patients presenting with suspected and confirmed COVID-19.

We sought to compare the clinical presentation and prognosis of patients with lung cancer and confirmed COVID-19 infection to those with negative RT-PCR SARS-CoV-2 results. We included patients with confirmed lung cancer and suspected COVID-19 who presented to the emergency department. The primary outcome was in-hospital mortality and secondary outcomes included admission to intensive care unit (ICU) or mechanical ventilation. We analyzed the characteristics according to RT-PCR results and primary outcome. We constructed a logistic regression for each RT-PCR result group to find potential predictors of the primary outcome. Among 110 individuals with confirmed lung cancer (65±9 years, 51% male), 38 patients had positive RT-PCR and 72 patients had negative RT-PCR. There was no difference between groups for any clinical characteristic or comorbidities though individuals with confirmed COVID-19 had higher functionality in the ECOG scale. Leucocytes and lymphocytes were lower in individuals with positive tests. The primary outcome occurred in 58 (53%) individuals, 37 (34%) were admitted to the ICU, and 29 (26%) required mechanical ventilation. Although mortality was similar between the two groups, individuals with confirmed COVID-19 were significantly more likely to be admitted to the ICU or receive mechanical ventilation. Only lower lymphocytes and higher CRP were significantly associated with higher mortality. The clinical presentation of COVID-19 in lung cancer is not sufficient to identify higher or lower probability groups among symptomatic individuals, the overall mortality is high irrespective of RT-PCR results, and lymphopenia on admission was associated with the diagnosis and prognosis for COVID-19.

Clinical presentation and in-hospital prognosis of lung cancer patients presenting with suspected and confirmed COVID-19

We sought to compare the clinical presentation and prognosis of patients with lung cancer and confirmed COVID-19 infection to those with negative RT-PCR SARS-CoV-2 results. We included patients with confirmed lung cancer and suspected COVID-19 who presented to the emergency department. The primary outcome was in-hospital mortality and secondary outcomes included admission to intensive care unit (ICU) or mechanical ventilation. We analyzed the characteristics according to RT-PCR results and primary outcome. We constructed a logistic regression for each RT-PCR result group to find potential predictors of the primary outcome. Among 110 individuals with confirmed lung cancer (65±9 years, 51% male), 38 patients had positive RT-PCR and 72 patients had negative RT-PCR. There was no difference between groups for any clinical characteristic or comorbidities though individuals with confirmed COVID-19 had higher functionality in the ECOG scale. Leucocytes and lymphocytes were lower in individuals with positive tests. The primary outcome occurred in 58 (53%) individuals, 37 (34%) were admitted to the ICU, and 29 (26%) required mechanical ventilation. Although mortality was similar between the two groups, individuals with confirmed COVID-19 were significantly more likely to be admitted to the ICU or receive mechanical ventilation. Only lower lymphocytes and higher CRP were significantly associated with higher mortality. The clinical presentation of COVID-19 in lung cancer is not sufficient to identify higher or lower probability groups among symptomatic individuals, the overall mortality is high irrespective of RT-PCR results, and lymphopenia on admission was associated with the diagnosis and prognosis for COVID-19.

Detection of subclinical skin manifestation in patients with psoriasis and psoriatic arthritis by fluorescence optical imaging.

OBJECTIVES: To investigate the frequency of subclinical skin inflammation in both hands by fluorescence optical imaging (FOI) in patients with psoriasis/psoriatic arthritis (Pso/PsA) vs. rheumatoid arthritis (RA) and healthy individuals, and to correlate these findings with cardiovascular (CV) risk factors. PATIENTS AND METHODS: The FOI scans were analyzed retrospectively to detect clinically invisible skin enhancement (0-3 scale) in both hands without relationship to underlying joints or blood vessels. We further characterized the FOI patterns and sorted the scans into groups based on the assumed diagnosis (Pso/PsA, RA, and healthy controls), which was compared with the physician's diagnosis. Furthermore, the associations between CV risk factors and imaging findings were investigated by regression analyses. RESULTS: We included FOI scans of patients with Pso/PsA (n = 80), RA (n = 78), and healthy controls (n = 25). Subclinical skin enhancement on the back of their hands was more common in Pso/PsA (72.5%) than in RA patients (20.5%) and healthy individuals (28.0%) (p < 0.001). Based on the FOI pattern, the majority of patients with Pso/PsA (72.5%), RA (76.9%), and healthy controls (68.0%) were classified correctly using the physician-based diagnosis as reference (overall agreement of 74%, kappa = 0.57). No CV risk factors except body weight (kg) were associated with subclinical skin enhancement (OR 1.04, 95% CI 1.02-1.06; p < 0.001). CONCLUSION: Subclinical subdermal skin inflammation was common in Pso/PsA patients using FOI. Based on the FOI pattern, most patients with Pso/PsA and were classified with the correct diagnosis. We demonstrated an important influence of the body weight on our FOI results. FOI may be a helpful novel tool to study microcirculation in rheumatic diseases with skin involvement.

Transoral robotic surgery (TORS): a new tool for high risk tracheostomy decannulation.

Tracheostomy decannulation has always been considered a procedure with an attendant risk, especially in patients with a reduced upper airway diameter as is commonly observed in the obstructive sleep apnoea (OSA) population. We report on 4 cases where transoral robotic surgery (TORS) helped in the management of long-term cannulated patients. The aims of our paper are: 1. To demonstrate how the otolaryngology team can help identify patients at high risk for decannulation failure; and 2. To demonstrate how TORS may aid in the decannulation process of patients at high risk for failure due to severe tongue base hypertrophy. From our experience, TORS appears to offer an effective option to aid in the decannulation of patients with a severe hypertrophy of the base of tongue and floppy epiglottis.

ESMO consensus guidelines for the management of patients with metastatic colorectal cancer.

Colorectal cancer (CRC) is one of the most common malignancies in Western countries. Over the last 20 years, and the last decade in particular, the clinical outcome for patients with metastatic CRC (mCRC) has improved greatly due not only to an increase in the number of patients being referred for and undergoing surgical resection of their localised metastatic disease but also to a more strategic approach to the delivery of systemic therapy and an expansion in the use of ablative techniques. This reflects the increase in the number of patients that are being managed within a multidisciplinary team environment and specialist cancer centres, and the emergence over the same time period not only of improved imaging techniques but also prognostic and predictive molecular markers. Treatment decisions for patients with mCRC must be evidence-based. Thus, these ESMO consensus guidelines have been developed based on the current available evidence to provide a series of evidence-based recommendations to assist in the treatment and management of patients with mCRC in this rapidly evolving treatment setting.

Bloodstream infection caused by extensively drug-resistant Acinetobacter baumannii in cancer patients: high mortality associated with delayed treatment rather than with the degree of neutropenia.

This study aimed to describe severe infections with extensively drug-resistant Acinetobacter baumannii-calcoaceticus complex (XDR-ABC), as well as to investigate risk factors for mortality, in cancer patients. It was a retrospective study including all patients diagnosed with XDR-ABC bacteraemia during hospitalization in the intensive care unit of a cancer hospital between July 2009 and July 2013. Surveillance cultures were collected weekly during the study period, and clonality was analysed using pulsed field gel electrophoresis (PFGE). We analysed underlying diseases, oncology therapy, neutrophil counts, infection site and management of infection, in terms of their correlation with 30-day mortality. During the study period, 92 patients with XDR-ABC bacteraemia were identified, of whom 35 (38.0%) were patients with haematological malignancy. We identified XDR-ABC strains with four different profile patterns, 91.3% of patients harbouring the predominant PFGE type. Of the 92 patients with XDR-ABC bacteraemia, 66 (71.7%) had central line-associated bloodstream infections; infection occurred during neutropenia in 22 (23.9%); and 58 (63.0%) died before receiving the appropriate therapy. All patients were treated with polymyxin, which was used in combination therapy in 30 of them (32.4%). The 30-day mortality rate was 83.7%. Multivariate analysis revealed that septic shock at diagnosis of XDR-ABC infection was a risk factor for 30-day mortality; protective factors were receiving appropriate therapy and invasive device removal within the first 48 h. Among cancer patients, ineffective management of such infection increases the risk of death, more so than do features such as neutropenia and infection at the tumour site.

Metronomic chemotherapy in the neoadjuvant setting: results of two parallel feasibility trials (TraQme and TAME) in patients with HER2+ and HER2− locally advanced breast cancer

Neoadjuvant chemotherapy has practical and theoretical advantages over adjuvant chemotherapy strategy in breast cancer (BC) management. Moreover, metronomic delivery has a more favorable toxicity profile. The present study examined the feasibility of neoadjuvant metronomic chemotherapy in two cohorts [HER2+ (TraQme) and HER2− (TAME)] of locally advanced BC. Twenty patients were prospectively enrolled (TraQme, n=9; TAME, n=11). Both cohorts received weekly paclitaxel at 100 mg/m2 during 8 weeks followed by weekly doxorubicin at 24 mg/m2 for 9 weeks in combination with oral cyclophosphamide at 100 mg/day (fixed dose). The HER2+ cohort received weekly trastuzumab. The study was interrupted because of safety issues. Thirty-six percent of patients in the TAME cohort and all patients from the TraQme cohort had stage III BC. Of note, 33% from the TraQme cohort and 66% from the TAME cohort displayed hormone receptor positivity in tumor tissue. The pathological complete response rates were 55% and 18% among patients enrolled in the TraQme and TAME cohorts, respectively. Patients in the TraQme cohort had more advanced BC stages at diagnosis, higher-grade pathological classification, and more tumors lacking hormone receptor expression, compared to the TAME cohort. The toxicity profile was also different. Two patients in the TraQme cohort developed pneumonitis, and in the TAME cohort we observed more hematological toxicity and hand-foot syndrome. The neoadjuvant metronomic chemotherapy regimen evaluated in this trial was highly effective in achieving a tumor response, especially in the HER2+ cohort. Pneumonitis was a serious, unexpected adverse event observed in this group. Further larger and randomized trials are warranted to evaluate the association between metronomic chemotherapy and trastuzumab treatment.

Metronomic chemotherapy in the neoadjuvant setting: results of two parallel feasibility trials (TraQme and TAME) in patients with HER2+ and HER2- locally advanced breast cancer.

Neoadjuvant chemotherapy has practical and theoretical advantages over adjuvant chemotherapy strategy in breast cancer (BC) management. Moreover, metronomic delivery has a more favorable toxicity profile. The present study examined the feasibility of neoadjuvant metronomic chemotherapy in two cohorts [HER2+ (TraQme) and HER2- (TAME)] of locally advanced BC. Twenty patients were prospectively enrolled (TraQme, n=9; TAME, n=11). Both cohorts received weekly paclitaxel at 100 mg/m(2) during 8 weeks followed by weekly doxorubicin at 24 mg/m(2) for 9 weeks in combination with oral cyclophosphamide at 100 mg/day (fixed dose). The HER2+ cohort received weekly trastuzumab. The study was interrupted because of safety issues. Thirty-six percent of patients in the TAME cohort and all patients from the TraQme cohort had stage III BC. Of note, 33% from the TraQme cohort and 66% from the TAME cohort displayed hormone receptor positivity in tumor tissue. The pathological complete response rates were 55% and 18% among patients enrolled in the TraQme and TAME cohorts, respectively. Patients in the TraQme cohort had more advanced BC stages at diagnosis, higher-grade pathological classification, and more tumors lacking hormone receptor expression, compared to the TAME cohort. The toxicity profile was also different. Two patients in the TraQme cohort developed pneumonitis, and in the TAME cohort we observed more hematological toxicity and hand-foot syndrome. The neoadjuvant metronomic chemotherapy regimen evaluated in this trial was highly effective in achieving a tumor response, especially in the HER2+ cohort. Pneumonitis was a serious, unexpected adverse event observed in this group. Further larger and randomized trials are warranted to evaluate the association between metronomic chemotherapy and trastuzumab treatment.

Cytokine profile and prognostic significance of high neutrophil-lymphocyte ratio in colorectal cancer.

BACKGROUND: High circulating neutrophil-lymphocyte ratio (NLR) appears to be prognostic in metastatic colorectal cancer (mCRC). We investigated the relationship of NLR with circulating cytokines and molecular alterations. METHODS: We performed retrospective analyses on multiple cohorts of CRC patients (metastatic untreated (n=166), refractory metastatic (n=161), hepatectomy (n=198), stage 2/3 (n=274), and molecularly screened (n=342)). High NLR (ratio of absolute neutrophil-to-lymphocyte counts in peripheral blood) was defined as NLR>5. Plasma cytokines were evaluated using multiplex-bead assays. Kaplan-Meier estimates, non-parametric correlation analysis, and hierarchical cluster analyses were used. RESULTS: High NLR was associated with poor prognosis in mCRC (hazard ratio (HR) 1.73; 95% confidence interval (CI):1.03-2.89; P=0.039) independent of known prognostic factors and molecular alterations (KRAS/NRAS/BRAF/PIK3CA/CIMP). High NLR correlated with increased expression of interleukin 6 (IL-6), IL-8, IL-2Rα, hepatocyte growth factor, macrophage-colony stimulating factor, and vascular epidermal growth factor in exploratory (n=39) and validation (n=166) cohorts. Fourteen additional cytokines correlated with high NLR in the validation cohort. All 20 cytokines fell into three major clusters: inflammatory cytokines, angiogenic cytokines, and epidermal growth factor ligands. In mCRC, composite stratification based on NLR-cytokine score provided enhanced prognostic information (HR 2.09; 95% CI: 1.59-2.76; P<0.001) over and above NLR. CONCLUSIONS: High NLR is an independent poor prognostic marker in CRC and correlates with a distinct cytokine profile related to key biological processes involved in carcinogenesis. A composite NLR-cytokine stratification has enhanced prognostic value in mCRC.

Infection with Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae in cancer patients.

Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-Kp) is an emergent pathogen in healthcare-associated infections (HAIs). The aim of this study was to describe HAIs due to KPC-Kp, as well as identify mortality risk factors in cancer patients. In patients diagnosed with HAIs due to KPC-Kp between January 2009 and July 2013, we evaluated only the first infection episode of each patient, analyzing mortality separately for patients treated for ≥48 h with at least one antimicrobial agent proven to display in vitro activity against KPC-Kp. We evaluated variables related to the malignancy, the severity and characteristics of the HAI, and the antimicrobial therapy. We identified 83 HAIs due to KPC-Kp. The 30-day mortality was 57.8 % for all infections and 72.7 % for bacteremic infections. Of the 83 patients, 60 patients received ≥48 h of appropriate treatment and 44 (53 %) developed bacteremia. Ten patients (12 %) were neutropenic at HAI diagnosis and 33 (39.8 %) had infection at the tumor site. The most common HAI was urinary tract infection, seen in 26 patients (31.3 %), followed by primary bloodstream infection, seen in 24 patients (28.9 %). Forty-four patients (73.3 %) received combination antimicrobial therapy, most often including polymyxin (68.3 %). Risk factors for 30-day mortality are high sequential organ failure assessment (SOFA) score, need for intensive care stay at diagnosis of infection, and acute kidney injury; the removal of invasive devices related to infection and treatment with effective antibiotics for KPC-Kp are protective factors. In cancer patients, high mortality is associated with HAI due to KPC-Kp and mortality risk factors are more often related to acute infection than to the underlying disease.

Association between KRAS mutation and lung metastasis in advanced colorectal cancer.

BACKGROUND: KRAS mutations have been associated with lung metastases at diagnosis of metastatic colorectal cancer (mCRC), but the impact of this mutation on subsequent development of lung metastasis is unknown. We investigated KRAS mutation as a predictor of lung metastasis development. METHODS: We retrospectively evaluated data from patients with mCRC whose tumour was tested for KRAS mutation from 2008 to 2010. The relationships of KRAS mutational status with time-to-lung metastasis (TTLM) and overall survival (OS) were analysed. RESULTS: Of the 494 patients identified, 202 (41%) had tumours with KRAS mutation. KRAS mutations were associated with a shorter TTLM (median 15.2 vs 22.4 months; hazard ratio=1.40; P=0.002) and a two-fold greater odds of developing lung metastases during the disease course in patients with liver-limited mCRC at diagnosis (72 vs 56%, P=0.007). Overall survival did not differ by KRAS status. CONCLUSIONS: Lung metastasis was more likely to develop during the disease course in patients whose tumour had a KRAS mutation than in those whose tumour did not have a KRAS mutation. This finding may have an impact on decision making for surgical resection of metastatic disease.

Serum protein profiling reveals baseline and pharmacodynamic biomarker signatures associated with clinical outcome in mCRC patients treated with chemotherapy ± cediranib.

BACKGROUND: This study evaluated soluble serum proteins as biomarkers to subset patients with metastatic colorectal cancer (mCRC) treated with chemotherapy±cediranib, a vascular endothelial growth factor (VEGF) signalling inhibitor (VEGFi). Exploring biomarkers at pre- and on-treatment may identify patient subgroups showing clinical benefit on cediranib combination. METHODS: Two hundred and seven serum proteins were analysed in 588 mCRC patients at pre- and on-treatment with chemotherapy (FOLFOX/CAPOX)±cediranib 20 mg. Patients were enrolled in the phase III trial HORIZON II. We correlated baseline biomarker signatures and pharmacodynamic (PD) biomarkers with PFS and OS. RESULTS: We identified a baseline signature (BS) of 47 biomarkers that included VEGFA, VEGFD, VEGFR2, VEGFR3 and TIE-2, which defined two distinct subgroups of patients. Patients treated with chemotherapy plus cediranib who had 'high' BS had shorter PFS (HR=1.82, P=0.003) than patients with 'low' BS. This BS did not correlate with PFS of the patients treated with chemotherapy plus placebo. In addition, we identified a profile of 16 PD proteins on treatment associated with PFS (HR=0.58, P<0.001) and OS (HR=0.52, P<0.001) in patients treated with chemotherapy plus cediranib. This PD profile did not correlate with PFS and OS in patients treated with chemotherapy plus placebo. CONCLUSIONS: Serum proteins may represent relevant biomarkers to predict the outcome of patients treated with VEGFi-based therapies. We report a BS and PD biomarkers that may identify mCRC patients showing increased benefit of combining cediranib with chemotherapy. These exploratory findings need to be validated in future prospective studies.

Gastric and endobronchial metastases in a case of lobular breast cancer.

BACKGROUND: Invasive lobular carcinoma (ILC) is the second most common histological type of invasive breast carcinoma, preceded only by infiltrating ductal carcinoma, which has clinical, biological and molecular distinctions. These distinctions imply a different metastatic behavior between the histology of these 2 types of breast cancer. CASE PRESENTATION: We report the case of a 51-year-old woman with breast cancer with ILC histology, diagnosed at an early stage. In the course of her disease, recurrences in the gastric mucosa and endobronchial area occurred. The treatment she received is described herein. CONCLUSION: This is a case of ILC with unusual metastases. The absence of E-cadherin is related to the carcinogenesis of ILC and probably to these patterns of metastasis as well.

Prognostic/predictive value of 207 serum factors in colorectal cancer treated with cediranib and/or chemotherapy.

BACKGROUND: The prognostic and predictive value of multiple serum biomarkers was evaluated using samples from a randomised phase III study (HORIZON II) investigating chemotherapy with or without cediranib in metastatic colorectal cancer (mCRC). METHODS: Baseline levels of 207 protein markers were measured in serum samples from 582 HORIZON II (FOLFOX/XELOX plus cediranib 20 mg (n=330) or placebo (n=252)) patients. Median baseline values of each biomarker were used to categorise patients as high or low. Markers were then assessed for their association with efficacy, defined by progression-free survival (PFS) and overall survival (OS). A generalised boosted regression model identified markers of particular interest. RESULTS: Correlation of protein levels with PFS and OS suggested that multiple factors had a prognostic value, independent of treatment arm, including IL-6, IL-8, C-reactive protein (CRP), ICAM-1 and carcinoembryonic antigen (CEA). Among the angiogenesis regulators, low levels of vascular endothelial growth factor (VEGF), VEGF-D, VEGFR-1, VEGFR-3, NRP1 and Tie-2 correlated with better outcome. CONCLUSION: This large data set generated using serum samples from mCRC patients treated with chemotherapy and VEGF inhibitors, defines baseline characteristics for 207 serum proteins. Multiple prognostic factors were identified that could be disease related or predict which patients derive most benefit from 5-fluorouracil (5-FU)-based chemotherapy, meriting further exploration in prospective studies.

Non-inferiority cancer clinical trials: scope and purposes underlying their design.

BACKGROUND: Non-inferiority clinical trials (NIFCTs) aim to demonstrate that the experimental therapy has advantages over the standard of care, with acceptable loss of efficacy. We evaluated the purposes underlying the selection of a non-inferiority design in oncology and the size of their non-inferiority margins (NIFm's). PATIENTS AND METHODS: All NIFCTs of cancer-directed therapies and supportive care agents published in a 10-year period were eligible. Two investigators extracted the data and independently classified the trials by their purpose to choose a non-inferiority design. RESULTS: Seventy-five were included: 43% received funds from industry, overall survival was the most common primary end point and 73% reported positive results. The most frequent purposes underlying the selection of a non-inferiority design were to test more conveniently administered schedules and/or less toxic treatments. In 13 (17%) trials, a clear purpose was not identified. Among the trials that reported a pre-specified NIFm, the median value was 12.5% (range 4%-25%) for trials with binary primary end points and Hazard Ratio of 1.25 (range 1.10-1.50) for trials that used time-to-event primary outcomes. CONCLUSION: Cancer NIFCT harbor serious methodological and ethical issues. Many use large NIFm and nearly one-fifth did not state a clear purpose for selecting a non-inferiority design.

Prognostic and predictive value of VEGF, sVEGFR-2 and CEA in mCRC studies comparing cediranib, bevacizumab and chemotherapy.

BACKGROUND: The prognostic/predictive value of potential vascular endothelial growth factor (VEGF) signalling biomarkers was evaluated retrospectively using samples from two randomized Phase III studies (HORIZON II and III) investigating cediranib in metastatic colorectal cancer (mCRC). METHODS: Baseline levels of VEGF, soluble VEGF receptor-2 (sVEGFR-2) and carcinoembryonic antigen (CEA) were measured in plasma/serum samples collected from patients participating in HORIZON II (n=860; FOLFOX/XELOX plus cediranib 20 mg (n=502) or placebo (n=358)) and HORIZON III (n=1422; mFOLFOX6 plus cediranib 20 mg (n=709) or bevacizumab (n=713)). Median biomarker baseline levels determined cutoff values for the patient subgroups. RESULTS: Baseline data were available for 88-97% of patients/study (>2000 patients). In both the studies, high baseline VEGF and CEA were associated with worse outcomes for progression-free survival (PFS) and overall survival (OS) independent of treatment (HORIZON II OS: VEGF, hazard ratio (HR)=1.35 (95% confidence interval (CI): 1.12-1.63); CEA, HR=1.63 (1.36-1.96); HORIZON III OS: VEGF, HR=1.32 (1.12-1.54); CEA, HR=1.50 (1.29-1.76)). sVEGFR-2 was not prognostic for PFS/OS. Baseline VEGF and CEA were not predictive for PFS/OS outcome to cediranib treatment; low sVEGFR-2 was associated with a trend towards improved cediranib effect in HORIZON II. CONCLUSION: Baseline VEGF and CEA levels were treatment-independent prognostic biomarkers for PFS and OS in both the studies.

ESMO Consensus Guidelines for management of patients with colon and rectal cancer. a personalized approach to clinical decision making.

Colorectal cancer (CRC) is the most common tumour type in both sexes combined in Western countries. Although screening programmes including the implementation of faecal occult blood test and colonoscopy might be able to reduce mortality by removing precursor lesions and by making diagnosis at an earlier stage, the burden of disease and mortality is still high. Improvement of diagnostic and treatment options increased staging accuracy, functional outcome for early stages as well as survival. Although high quality surgery is still the mainstay of curative treatment, the management of CRC must be a multi-modal approach performed by an experienced multi-disciplinary expert team. Optimal choice of the individual treatment modality according to disease localization and extent, tumour biology and patient factors is able to maintain quality of life, enables long-term survival and even cure in selected patients by a combination of chemotherapy and surgery. Treatment decisions must be based on the available evidence, which has been the basis for this consensus conference-based guideline delivering a clear proposal for diagnostic and treatment measures in each stage of rectal and colon cancer and the individual clinical situations. This ESMO guideline is recommended to be used as the basis for treatment and management decisions.

Oxaliplatin-related thrombocytopenia.

Oxaliplatin is a third generation platinum compound that inhibits DNA synthesis, mainly through intrastrandal cross-links in DNA. Most of the experience with the clinical use of this drug is derived from colorectal cancer but it is also used in other tumor types such as ovary, breast, liver and non-Hodgkin's lymphoma. Thrombocytopenia is a frequent toxicity seen during oxaliplatin treatment, occurring at any grade in up to 70% of patients and leading to delays or even discontinuation of the chemotherapy. Although myelossupression is recognized as the main cause of oxaliplatin-related thrombocytopenia, new mechanisms for this side-effect have emerged, including splenic sequestration of platelets related to oxaliplatin-induced liver damage and immune thrombocytopenia. These new pathophysiology pathways have different clinical presentations and evolution and may need specific therapeutic maneuvers. This article attempts to review this topic and provides useful clinical information for the management of oxaliplatin-related thrombocytopenia.

Efficacy of capecitabine versus 5-fluorouracil in colorectal and gastric cancers: a meta-analysis of individual data from 6171 patients.

BACKGROUND: To compare the effects of oral capecitabine-containing chemotherapy regimens with i.v. 5-fluorouracil (5-FU)-containing chemotherapy regimens on overall survival in patients with gastrointestinal cancers. METHODS: A meta-analysis, based on individual patient data from six randomised non-inferiority trials, was carried out at the request of regulatory authorities to compare the effects of single-agent capecitabine or capecitabine-containing chemotherapy versus matched 5-FU-based regimens in terms of overall survival in patients with stage III colon, metastatic colorectal or advanced gastric cancer. RESULTS: Data from a total of 6171 patients with stage III colon cancer (n = 1987), metastatic colorectal cancer (n = 3868) or advanced gastric cancer (n = 316) were included. A total of 3097 patients were treated with capecitabine-containing chemotherapy and 3074 patients with 5-FU-containing chemotherapy. The unadjusted hazard ratio for overall survival for capecitabine-containing chemotherapy versus 5-FU-containing chemotherapy was 0.94 (95% confidence interval 0.89-1.00; P = 0.0489). CONCLUSIONS: Oral capecitabine is at least equivalent to i.v. 5-FU in terms of overall survival in patients with gastrointestinal cancers. Capecitabine and 5-FU can be used interchangeably in these patient populations.

Fabry's disease and psychosis: causality or coincidence?

A 21-year-old female with Fabry's disease (FD) presented acute psychotic symptoms such as delusions, auditory hallucinations and formal thought disorders. Since the age of 14, she had suffered from various psychiatric symptoms increasing in frequency and intensity. We considered the differential diagnoses of prodromal symptoms of schizophrenia and organic schizophrenia-like disorder. Routine examinations including cognitive testing, electroencephalography and structural magnetic resonance imaging revealed no pathological findings. Additional structural and functional imaging demonstrated a minor CNS involvement of FD, yet without functional limitations. In summary our examination results support the thesis that in the case of our patient a mere coincidence of FD and psychotic symptoms is more likely than a causal connection.