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Capecitabine is an oral 5-fluorouracil prodrug with antimetabolite activity commonly used in advanced colorectal and breast cancer. It presents with a generally good toxicity profile and most of the adverse events can be managed effectively. Enterocolitis is a rare, under-reported, but potentially fatal adverse event associated with capecitabine use. To the best of our knowledge, there are 21 cases of capecitabine-related enterocolitis reported in the literature. We herein present a narrative literature review of enteritis/colitis cases associated with capecitabine use, with highlight to the most common clinical presentation, common imaging and microscopic findings and management approach. We furthermore present a case of severe capecitabine-related enteritis.

Anti-programmed cell death protein 1 immunotherapy has been incorporated in the treatment algorithm of triple-negative breast cancer (TNBC). However, clinical trial results for patients with hormone receptor (HR)-positive disease appear less compelling. HR-positive tumors exhibit lower levels of programmed death-ligand 1 expression in comparison with their triple-negative counterparts. Moreover, signaling through estrogen receptor alters the immune microenvironment, rendering such tumors immunologically "cold." To explain differential responses to immune checkpoint blockade, this review interrogates differences between HR-positive and TNBC. Starting from distinct genomic features, we further present disparities concerning the tumor microenvironment and finally, we summarize early-phase clinical trial results on promising novel immunotherapy combinations.

Cluster of differentiation 24 (CD24) is a small, highly glycosylated cell adhesion protein that is normally expressed by immune as well as epithelial, neural, and muscle cells. Tumor CD24 expression has been linked with alterations in several oncogenic signaling pathways. In addition, the CD24/Siglec-10 interaction has been implicated in tumor immune evasion, inhibiting macrophage-mediated phagocytosis as well as natural killer (NK) cell cytotoxicity. CD24 blockade has shown promising results in preclinical studies. Although there are limited data on efficacy, monoclonal antibodies against CD24 have demonstrated clinical safety and tolerability in two clinical trials. Other treatment modalities evaluated in the preclinical setting include antibody–drug conjugates and chimeric antigen receptor (CAR) T cell therapy. In this review, we summarize current evidence and future perspectives on CD24 as a potential target for cancer immunotherapy.

Background Accumulating evidence suggests a beneficial effect of tumor necrosis factor-alpha (TNF-α) inhibitors on the outcomes of COVID-19 disease, which, however, is not validated by all studies. We aimed to perform a systematic review and meta-analysis of existing reports to investigate the impact of anti-TNF treatments on the clinical outcomes of COVID-19 patients. Methods A systematic search at PubMed and SCOPUS databases using specific keywords was performed. All reports of COVID-19 outcomes for patients receiving anti-TNF therapy by September-2021 were included. Pooled effect measures were calculated using a random-effects model. The Newcastle Ottawa Scale for observational studies was used to assess bias. Studies that were not eligible for meta-analysis were described qualitatively. Results In total, 84 studies were included in the systematic review, and 31 were included in the meta-analysis. Patients receiving anti-TNF treatment, compared to non-anti-TNF, among confirmed COVID-19 cases had a lower probability of hospitalisation (25 studies, pooled OR=0.34, 95%CI:0.30–0.38, I2=0) and severe disease defined as intensive care unit admission or death (eight studies, pooled OR=0.38, 95%CI: 0.27–0.55, I2=0). After adjustment for validated predictors of adverse disease outcomes, patients receiving anti-TNF treatment, compared to non-anti-TNF, among confirmed COVID-19 cases preserved a lower probability of hospitalisation (eight studies, pooled OR=0.53, 95%CI:0.42–0.67, I2=0) and severe disease (two studies, pooled OR=0.63, 95%CI: 0.41–0.96, I2=0). No difference was found for the risk for hospitalisation due to COVID-19 in populations without COVID-19 for patients receiving anti-TNF treatment compared to non-anti-TNF (three studies, 5,994,958 participants, pooled Risk Ratio=0.97, 95%CI: 0.68–1.39, I2=20) adjusted for age, sex and comorbidities. Conclusion TNF-α inhibitors are associated lower probability of hospitalisation and severe COVID-19 when compared to any other treatment for an underlying inflammatory disease.

Spread through air spaces (STAS) was included as a novel pattern of invasion in lung adenocarcinoma by the World Health Organization in 2015. Since then, multiple studies have investigated the association of STAS with clinicopathological and molecular features and its implication in the prognosis of early stage lung cancer patients undergoing different surgery types. The aim of this comprehensive review is to present current data on the role of STAS and its perspective in lung adenocarcinoma management. © 2020 Elsevier B.V.

Introduction: Programmed death 1/programmed death ligand 1 (PD-L1) axis inhibitors have been proven effective, especially in patients with tumors expressing PD-L1. Their clinical efficacy in patients with EGFR-activating mutations is still unclear, whereas KRAS mutations seem to be associated with good response. Methods: We used multiplexed quantitative immunofluorescence to investigate PD-L1 expression and to characterize tumor infiltrating lymphocyte (TIL) populations and their activation status in more than 150 NSCLC patients with known mutation status. Results: PD-L1 expression was significantly lower in EGFR-mutant compared to KRAS-mutant, and EGFR/KRAS wild-type (WT) tumors. KRAS mutant tumors were more inflamed with higher CD4+, CD8+ and CD20+ TILs. Subgroup analysis by TIL activation status revealed that EGFR mutants had a high frequency of inactive TILs even though lymphocytes were present in the tumor microenvironment. In contrast, in KRAS mutants, when TILs were present they were almost always active. Additionally, we found differences between EGFR mutation sites in CD8+ expression and the TIL activation profile. Finally, activated EGFR correlated with increased PD-L1 expression in EGFR mutants but not in EGFR WT, whereas TIL activation was associated with higher PD-L1 only in EGFR/KRAS WT. Conclusions: Our findings show the unique immune profile of EGFR-mutant tumors. The high frequency of inactive TILs could explain the low immunotherapy response rates in these patients, whereas PD-L1 as a predictive biomarker may reflect the constitutive oncogenic signaling rather than immune signaling, which would be associated with high PD-L1 levels and TILs activation. © 2018 International Association for the Study of Lung Cancer

Background Talactoferrin alfa is an oral dendritic cell (DC)-mediated immunotherapy (DCMI). We tested whether talactoferrin was superior to placebo in advanced non-small-cell lung cancer (NSCLC). Patients and methods An FORTIS-M trial was an international, multicenter, randomized, double-blind comparison of talactoferrin (1.5g p.o. BID) versus placebo BID, in patients with stage IIIB/IV NSCLC whose disease had failed two or more prior regimens. Treatment was administered for a maximum of five 14-week cycles. The primary efficacy end point was overall survival (OS); secondary end points included 6- and 12-month survival, progression-free survival (PFS), and disease control rate (DCR). Results Seven hundred and forty-two patients were randomly assigned (2:1) to talactoferrin (497) or placebo (245). The median OS in the intent-to-treat (ITT) population was 7.66 months in the placebo arm and 7.49 months in the talactoferrin arm [hazard ratio (HR), 1.04; 95% CI, 0.873–1.24; P = 0.6602]. The 6-month survival rates were 59.9% (95% CI, 53.4% to 65.8%) and 55.7% (95% CI, 51.1% to 59.9%), respectively. The 12-month survival rates were 32.2% (95% CI, 26.3% to 38.2%) and 30.9% (95% CI, 26.8% to 35%), respectively. The median PFS rates were 1.64 months and 1.68 months, respectively (HR, 0.99; 95% CI, 0.835–1.16; P = 0.8073). The DCRs were 38.4 and 37.6%, respectively [stratified odds ratio (OR), 0.96; 95% CI, 0.698–1.33; P = 0.8336]. The safety profiles were comparable between arms. Conclusions There was no improvement in efficacy with talactoferrin alfa in patients with advanced NSCLC whose disease had failed two or more previous regimens.

Introduction: The M component and TNM stage groupings for malignant pleural mesothelioma (MPM) have been empirical. The International Association for the Study of Lung Cancer developed a multinational database to propose evidence-based revisions for the eighth edition of the TNM classification of MPM. Methods: Data from 29 centers were submitted either electronically or by transfer of existing institutional databases. The M component as it currently stands was validated by confirming sufficient discrimination (by Kaplan-Meier analysis) with respect to overall survival (OS) between the clinical MO (cM0) and cM1 categories. Candidate stage groups were developed by using a recursive partitioning and amalgamation algorithm applied to all cM0 cases. Results: Of 3519 submitted cases, 2414 were analyzable and 84 were cM1 cases. Median OS for cM1 cases was 9.7 months versus 13.4 months (p = 0.0013) for the locally advanced (T4 or N3) cM0 cases, supporting inclusion of only cM1 in the stage IV group. Exploratory analyses suggest a possible difference in OS for single- versus multiple-site cM1 cases. A recursive partitioning and amalgamation generated survival tree on the OS outcomes restricted to cM0 cases with the newly proposed (eighth edition) T and N components indicates that optimal stage groupings for the eighth edition will be as follows: stage IA (T1N0), stage IB (T2-3N0), stage II (T1-2N1), stage IIIA (T3N1), stage IIIB (T1-3N2 or any T4), and stage IV (any M1). Conclusions: This first evidence-based revision of the TNM classification for MPM leads to substantial changes in the T and N components and the stage groupings. (C) 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

For nearly 40 years, there was no generally accepted staging system for malignant pleural mesothelioma. In 1994, members of the International Mesothelioma Interest Group, in collaboration with the International Association for the Study of Lung Cancer, proposed a TNM staging system based on analyses of outcomes in retrospective surgical series and small clinical trials. Subsequently accepted by the American Joint Commission on Cancer and the Union for International Cancer Control for the sixth editions of their staging manuals, this system has since been the international staging standard. However, it has significant limitations, particularly with respect to clinical staging and to the categories for lymph node staging. Here we provide an overview of the development of the International Association for the Study of Lung Cancer malignant pleural mesothelioma staging database, which was designed to address these limitations through the development of a large international data set. Analyses of this database, described in papers linked to this overview, are being used to inform revisions in the eighth editions of the American Joint Commission on Cancer and Union for International Cancer Control staging systems. ispartof: Journal of Thoracic Oncology vol:11 issue:12 pages:2082-2088 ispartof: location:United States status: published

Background: Persistent air leak following pulmonary lobectomy can be very difficult to treat and results in prolonged hospitalization. We aimed to evaluate the efficacy of a new method of postoperative air leak management using intrapleurally infused fresh frozen plasma via the chest tube. Material/Methods: Between June 2008 and June 2014, we retrospectively reviewed 98 consecutive patients who underwent lobectomy for lung cancer and postoperatively developed persistent air leak treated with intrapleural instillation of fresh frozen plasma. Results: The study identified 89 men and 9 women, with a median age of 65.5 years (range 48–77 years), with persistent postoperative air leak. Intrapleural infusion of fresh frozen plasma was successful in stopping air leaks in 90 patients (92%) within 24 hours, and in 96 patients (98%) within 48 hours, following resumption of the procedure. In the remaining 2, air leak ceased at 14 and 19 days. Conclusions: Intrapleural infusion of fresh frozen plasma is a safe, inexpensive, and remarkably effective method for treatment of persistent air leak following lobectomy for lung cancer. © Med Sci Monit, 2016.

Introduction: The current T component for malignant pleural mesothelioma (MPM) has been predominantly informed by surgical data sets and consensus. The International Association for the Study of Lung Cancer undertook revision of the seventh edition of the staging system for MPM with the goal of developing recommendations for the eighth edition. Methods: Data elements including detailed T descriptors were developed by consensus. Tumor thickness at three pleural levels was also recorded. An electronic data capture system was established to facilitate data submission. Results: A total of 3519 cases were submitted to the database. Of those eligible for T-component analysis, 509 cases had only clinical staging, 836 cases had only surgical staging, and 642 cases had both available. Survival was examined for T categories according to the current seventh edition staging system. There was clear separation between all clinically staged categories except T1a versus T1b (hazard ratio = 0.99, p = 0.95) and T3 versus T4 (hazard ratio = 1.22, p = 0.09), although the numbers of T4 cases were small. Pathological staging failed to demonstrate a survival difference between adjacent categories with the exception of T3 versus T4. Performance improved with collapse of T1a and T1b into a single T1 category; no current descriptors were shifted or eliminated. Tumor thickness and nodular or rindlike morphology were significantly associated with survival. Conclusions: A recommendation to collapse both clinical and pathological T1a and T1b into a T1 classification will be made for the eighth edition staging system. Simple measurement of pleural thickness has prognostic significance and should be examined further with a view to incorporation into future staging. (C) 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Introduction Basal cell carcinomas (BCCs) are the most common skin cancers in the Caucasian population. BCCs are in the majority of cases adequately managed with surgical excision, however a small subset of these tumours exhibit resistance to conventional therapies and progress to become locally advanced or even metastatic. Although Hedgehog inhibitors have been successfully used during the last few years in the treatment of locally advanced or metastatic BCCs, resistance to treatment remains an issue. Until this point, no biomarkers or clinical markers of drug resistance for Hedgehog inhibitors have been identified. Methods and results We report two patients, a female patient with Gorlin syndrome and a male patient with locally advanced BCC, which received treatment with the Hedgehog inhibitor Vismodegib. These patients responded adequately to treatment and they both developed Hedgehog inhibitor-induced alopecia as an adverse event. However, after 2.5 and 1.5 years of treatment, respectively, the patients exhibited progressive disease that was accompanied by reversal of the Hedgehog inhibitor-induced alopecia, although still under treatment with Vismodegib. Conclusion Although alopecia is a well-known adverse event associated with the administration of Hh inhibitors, data associated with the appearance and/or clinical severity of alopecia and the treatment efficacy of Hedgehog inhibitors are limited. The Hedgehog pathway plays an important role in the normal cycling of the hair follicles in adults and, therefore, the pathomechanism of Hedgehog inhibitor-induced alopecia is considered unique for this drug class. Based on the fact that Hh inhibitor resistance is associated with partial reactivation of the Hh pathway, it would not be illogical to suggest that reversal of Hh inhibitor-induced alopecia in patients under treatment with Hh inhibitors could serve as a clinical marker of drug resistance. However, this observation, as reported in this paper, is only limited in two patients and therefore more information is needed in order to assess its actual clinical importance.

BACKGROUND: This trial was designed to compare the efficacy and toxicity of sequential versus alternating administration of cisplatin/etoposide and topotecan in patients with previously untreated extensive-stage smallcell lung cancer (SCLC). PATIENTS AND METHODS: Two hundred eighty-four chemotherapy-naive patients were randomized between the sequential therapy arm (n = 142; 4 cycles of cisplatin 75 mg/m2 intravenously [I.V.] on day 1 with etoposide 100 mg/m2 per day I.V. on days 1-3 followed by 4 cycles of topotecan 1.5 mg/m2 per day I.V. on days 1-5) and the alternating arm (n = 142; same doses of cisplatin/etoposide on cycles 1, 3, 5, and 7 and topotecan on cycles 2, 4, 6, and 8). Treatment cycles for both regimens were administered every 3 weeks. RESULTS: At this preliminary analysis, no statistically significant difference in the overall response rate, duration of response, time to disease progression, or median survival was observed between the 2 arms. A total of 756 cycles of the sequential therapy and 830 cycles of the alternating therapy were administered, with a median numbers of 6 and 7 cycles per patient, respectively. Topotecan was administered in 85 patients on the sequential arm and 132 patients on the alternating arm. Dose reductions for toxicity were similar in both arms. Grade 3/4 toxicities in the sequential and alternating arms, respectively, included neutropenia (51% and 52%; P = NS), anemia (12% and 11%; P = NS), febrile neutropenia (7% and 9%; P = NS), thrombocytopenia (19% and 20%; P = NS), and asthenia (8% and 2%; P = 0.02). There were 4 toxicity-related deaths in the sequential arm versus 3 in the alternating arm. CONCLUSION: Our preliminary conclusion is that the sequential and alternating regimens resulted in comparable activity and tolerability in previously untreated patients with extensive-stage SCLC.

Background Cancer chemotherapy in humans based on metal complexes started at the clinical level in the late 1970s with the use of cisplatin, which forms intra-strand cross-links with DNA. Methods Two new platinum complexes of cis-geometry with the amino acids inosine (ino) and l-alanine (ala), Pt(ino)2Cl2 and cis-[Pt(NH3)2(ala)](NO3), respectively, were synthesized and pure samples were obtained by means of flash chromatography. These complexes were tested on benzo(a)pyrene-induced tumours in Wistar rats to detect their antitumour and toxic effects. Results There was a statistically significant prolongation of the mean survival time of the animals in the two groups tested (272 ± 18 days and 246 ± 26 days, respectively) compared to the control group (195 ± 22 days) (P

Aim: This study was designed to examine the prognostic significance of the coexpression of three genes (bax, bcl-2 and p53) which play a critical role in the apoptotic mechanisms in patients with squamous cell laryngeal carcinoma. 1–3 Materials and Methods: The immunohistochemical expression of bcl-2, bax and p53 genes was retrospectively examined in 38 patients with squamous cell laryngeal carcinoma and in five controls (necrotomic tissue). Tissue specimens were obtained both during the diagnostic biopsy and at the time of surgery. Clinicopathological and survival data were correlated with the staining results. Results: Bcl-2 protein expression ( P =0.0472), stage ( P =0.0087) and lymph-node involvement ( P =0.0488) were found to be independent prognostic factors. Increased bcl-2 protein expression correlated with a better 5-year survival ( P =0.0472). Patients who were bcl-2(−)/p53(−) ( n =25) or bax(+)/bcl-2(−) ( n =13) had a significantly worse overall survival ( P =0.0305 and P =0.0482, respectively). Similarly, patients who were bax(+)/bcl-2(−)/p53(−) ( n =11) also had a worse 5-year survival compared with the rest of the group ( P =0.0088). Changes that were noticed in bax and p53 protein expression from the time of biopsy until the time of surgery did not correlate with a significant increase in the overall survival. Conclusions: The expression of bcl-2 gene appears to be an independent prognostic factor for patients with laryngeal carcinoma. The coexpression of the genes studied can be used to determine aggressive clinical phenotypes.

Background and Objectives: Various techniques are used for the identification of the sentinel node (SLN). We prospectively compare the efficacy of SLN biopsy and the number of SLNs identified, by injecting methylene blue (MB) alone in the subareolar area (SA) or peritumorally (PT) in patients with early stage breast cancer Methods: Patients were randomized in two groups (SA or PT injection). A linear regression model was used to estimate the effect of various parameters on the identification rate and on the number of SLNs retrieved. Results: At least one SLN was identified in 61 of 66 (92.4%) procedures in the SA group and in 57 of 60 (95%) procedures in the PT group (P = 0.55). The mean number of SLNs removed with the SA injection method was 1.64 ± 0.6 nodes compared with 2.23 ± 0.7 nodes identified with the PT injection (range: 1-4, P < 0.001). The injection site was the only factor affecting the number of SLNs retrieved. Conclusion: The use of MB alone is an efficient method for identification of the SLN. The PT injection route yields a higher number of SLNs than the SA route, comparable with the number of SLNs retrieved, when combined tracing agents and multiple injection sites are used. © 2011 Wiley-Liss, Inc.

Breast angiosarcomas that are not related to previous radiotherapy are very rare. Surgical resection is the primary treatment for these tumors, but there is no general agreement on the extent of surgery. The role of multimodality adjuvant treatment also remains controversial. The aim of this study was to summarize the available data from the largest published series of patients in terms of management and outcome. We also sought to identify prognostic factors influencing patient survival. We have included studies presenting detailed data on multimodality therapy and survival of patients with breast angiosarcoma. Ten studies presenting data on 280 patients were included in the review. Seventyfive percent of patients underwent a total mastectomy and 25% had breast-conserving treatment (BCT). In 42% of patients, an axillary node dissection was combined with mastectomy or BCT. Thirty-six percent of patients received chemotherapy and 35% were treated with radiotherapy in an adjuvant or neoadjuvant setting. Survival varied significantly according to tumor size and grade. Adjuvant multimodality therapy may improve the outcome in selected patients with breast angiosarcoma. Tumor size, grade, and margin status are the most important prognostic factors for survival. © 2011 Springer.

Objective: To examine if wound aetiology has an effect on the pain-relieving properties of an ibuprofen-releasing foam dressing, which was previously shown to reduce pain inwounds of various aetiologies, compared with local best practice (LBP). Method: This was a secondary analysis of data from a multicentre, randomised, parallel group trial of patients with painful exuding wounds of various aetiologies. Wound aetiology was determinedatenrolment. Of 853 patients enrolled into the trial, 688 belonged to a wound aetiology subgroup that included > 25 patients and were included in the analysis reported here. Patients were randomised to a dressing containing 112.5mg of ibuprofen (ibuprofen foam) or to LBP for 5 days. Patients recorded pain relief and pain intensity daily. The main endpoint was the proportion of patients who, from day 1 to day 5, reported a summed pain reliefscore > 50% of the total maximum pain relief score (TOTPARD5>50%) and the corresponding number needed to treat (NNT) for each wound aetiology subgroup. Further analyses included the proportion of patients who, on a daily basis, reported pain relief > 50% of the maximum daily pain relief, the proportion of patients who, on day 5,experienced a reduction in pain intensity of > 50% of the maximum score (PIDD5>50%), and if PIDD5>50% was related to baseline pain intensity. Results: Patients were categorised by thefollowing five wound types: arterial, venous, and mixed arterial-venous leg ulcers, vasculitis and traumatic ulcers. The ibuprofenfoam dressing was associated with significantlygreater pain relief than LBP in all different wound aetiology subgroups, whether chronic or traumatic (acute). Overall, TOTPAR D5>50% was 55% in the ibuprofen foam group and 24% in the LBP group (p < 0.0001; NNT, 3.2). The pain intensity evaluations revealed similar results in favour ofibuprofen foam compared with LBP. No correlation was observed between PIDD5>50 and initial pain intensity. Conclusion: In this study, the ibuprofenfoam dressing was shown to consistently relievewound painin exuding wounds of various aetiologies, irrespective of basal painintensity.The data suggest that local pain reliefby an ibuprofenfoam dressing is possible in themost common, painful, exuding, chronic and acute/traumatic wounds and so is a safer alternative to systemic pain treatment. Conflict of interest: Of the ten authors involved inthe preparation of this manuscript, seven declare that theyhave no conflicts of interest. One is a member of the Wound AdvisoryForum for Coloplast A/S, Denmark. Two are employees of Coloplast A/S, Denmark.

Despite advances in research and treatment modalities, colorectal cancer still accounts for around half a million deaths yearly worldwide. Traditional and even newer pharmaceutical therapeutic regimens are limited in terms of tolerance, efficacy and cross-resistance. Additional non-cross resistant therapies with non-overlapping toxicities are needed to improve the outcome for patients with colorectal cancer. Cancer vaccines, designed to activate immune effectors (T-cells and antibodies) to prevent recurrence or treat advanced cancers, have now demonstrated clinical benefit in prostate cancer and lymphoma. Because immune effector infiltration into colon tumours is associated with improved clinical outcome, vaccines intended to activate immune responses against colon cancer have generated significant interest. This review discusses data supportive of the immune responsiveness of colorectal cancer, as well as the current status of colon cancer vaccines under development including those based on whole tumour cells or lysates, peptide or protein antigens, anti-idiotype antibodies, viral vectors, and dendritic cells. We also discuss challenges to colon cancer vaccine development, such as tumour associated mechanisms for immune evasion, and how future strategies may address these challenges.

The pulmonary toxicity induced by novel antineoplastic agents has not been well characterized because of the simultaneous or sequential use of drugs and of a multimodality therapeutic approach. Diagnosis is based on exclusion of other factors that can cause respiratory failure in cancer patients including pneumonia, cardiogenic pulmonary edema, diffuse alveolar hemorrhage, and lymphangitic carcinomatosis. These conditions are not easily differentiated based on clinical presentation and radiographic findings, not even on lung biopsy specimens. Nonspecific interstitial pneumonitis, bronchiolitis obliterans with organizing pneumonia, eosinophilic pneumonia, pulmonary fibrosis, and diffused alveolar damage are the most common pathological patterns, but they are nonspecific for anticancer therapy-induced pulmonary toxicity. Clinicians should be aware of potential pulmonary toxicity as a complication in the treatment of cancer and focus on its early detection or prediction.

Background: Despite the advent of combination chemotherapy regimens achieved within the last decade, long term survival of patients with unresectable metastatic disease from colorectal cancer remains poor. Thermal ablation procedures, including radiofrequency ablation (RFA), are considered feasible options in treating unresectable hepatic tumors either primary (hepatocellular carcinoma) or metastatic, the latter mainly arising from colorectal cancer. Percutaneous access is the least invasive RFA procedure. Methods & Results: A MEDLINE review unfolded a significant clinical heterogeneity among published series reporting on percutaneous RFA in hepatic metastatic disease from colorectal cancer, regarding study population, optimal time and treatment schemes pre- and post-RFA intervention. Notwithstanding, percutaneous RFA survival figures were consistently better than front line chemotherapy. Furthermore, a pooled analysis of larger series demonstrated a clear benefit in overall survival (HR 0.51, 95% CI 0.44 to 0.58). Conclusion: Albeit optimal indications are still pending, percutaneous RFA should nonetheless be considered a viable option in patients with unresectable metastatic disease, as it may prolong survival rates achieved with standard chemotherapy. © 2009 Bentham Science Publishers Ltd.

Non-small cell lung cancer (NSCLC) in young patients is uncommon and is thought to constitute a distinct oncological entity with characteristic clinicopathological patterns. Since the reported data are scant and discordant, the presentation, management and outcome data of NSCLC patients aged under 45 years of age were analyzed and compared with those of patients over 45 years old. Prognostic factors for risk classification were also evaluated.The data were abstracted from the Hellenic Cooperative Oncology Group (HeCOG) cancer registry database. The presentation, management and outcome data of patients with histologically confirmed NSCLC, managed from 1989 until 2004 in HeCOG participating centers, were retrospectively analyzed. The clinicopathological characteristics of patients agedandthan 45 years old were compared and evaluated for prognostic significance regarding outcome.The data for NSCLC patients (1906), of whom 115 were aged45, were retrieved. In comparative analysis, the young patients were more frequently asymptomatic at diagnosis, while older patients presented significantly higher rates of thoracic pain, cough and fatigue (p0.01). The young patients were more commonly diagnosed with adenocarcinoma and less frequently with squamous cancer than patients aged over 45. Although the stage distribution was distinct, with older patients presenting higher rates of stage IV disease (21.9% vs. 12.2%), the rates of early lung cancer (stages I-IIIa) were similar. The overall survival (OS) was not significantly different (median OS 12 vs. 11.5 months, p=0.277). Among patients who underwent first-line palliative chemotherapy, young individuals had a significantly shorter time to progression: 4.3 vs. 5.8 months (p=0.0049). Univariate and multivariate regression analyses established the prognostic usefulness of the performance status, disease stage and disease-free interval for the risk of death, both in the total number of patients (1906) and in young patients (115).This large retrospective series failed to present strong evidence that NSCLC among young individuals constitutes a distinct clinicopathological entity with differing biological behavior, since the same clinicopathological prognostic factors were valid in both age groups. Molecular phenotypic studies are needed to shed light on this controversial subject.

Breast cancer patients are known to be at increased risk for developing other chronic diseases including cardiovascular disease. Studies by different investigators have shown a correlation between increased dietary fat or hypercholesterolemia and the occurrence of breast cancer. Since previous studies on lipoprotein subfractions in this type of cancer have been inconsistent, we evaluated the lipids and lipoprotein subfraction levels in postmenopausal patients with breast cancer in an attempt to identify the risk for the development of cardiovascular disease. The study included 132 patients, 56 of which were suffering from breast cancer, 32 from pancreatic and 44 age-matched controls. Total cholesterol (TC), triglycerides and lipoprotein fractions as well as TC/High density lipoprotein (HDL) and HDL2/HDL3 ratios were estimated by standard laboratory techniques. An increase in triglycerides and a decrease in HDL-cholesterol, especially in the HDL2 subfraction, were observed in patients with breast cancer as compared to the controls (P < 0.05). The maximum changes in TC, and HDL concentrations were observed in patients with advanced disease. Analysis of indexes of atherosclerosis (TC/HDL, and HDL2/HDL3 ratios) demonstrated that breast cancer patients had significantly higher TC/HDL ratio (6.44 ± 1.24) compared with controls (3.43 ± 0.57, p = 0.001), and patients with pancreatic cancer (3.79 ± 0.15, p = 0.027). The results have demonstrated an unfavourable lipid profile in untreated breast cancer patients with high atherosclerosis indexes. This observation is of great importance, considering the potential use of endocrine therapy that could result in further deterioration of lipid indexes. We propose the evaluation and monitoring of lipid profile prior and after the induction of hormonal therapy in breast cancer patients, as a routine in clinical setting. (Mol Cell Biochem 268: 19–24, 2005)

Cancer chemotherapy in humans based on metal complexes started at the clinical level in the late 1970s with the use of cisplatin, which forms intra-strand cross-links with DNA.Two new platinum complexes of cis-geometry with the amino acids inosine (ino) and l-alanine (ala), Pt(ino)2Cl2 and cis-[Pt(NH3)2(ala)](NO3), respectively, were synthesized and pure samples were obtained by means of flash chromatography. These complexes were tested on benzo(a)pyrene-induced tumours in Wistar rats to detect their antitumour and toxic effects.There was a statistically significant prolongation of the mean survival time of the animals in the two groups tested (272 +/- 18 days and 246 +/- 26 days, respectively) compared to the control group (195 +/- 22 days) (P0.001). Toxic effects included a decrease in leucocyte cell count, mild haemolysis, mild haematuria, mild hepatotoxicity, elevated body temperature and hair loss. All of these effects were reversible after drug discontinuation.The two new platinum complexes described here appear to have an effective antitumour activity without severe toxicity when tested on Wistar rats.

Adrenal responsiveness to ACTH stimulation (1 mg, i.m.) was assessed by measuring cortisol (Cort) and 17-hydroxyprogesterone (17OHP) at 0, 30, 60, and 90 minutes and progesterone (P), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA-S), delta 4-androstenedione (delta 4A), and testosterone (T) at 0, 60, and 90 minutes post-ACTH in 30 women with polycystic ovary syndrome (PCO). The results were compared with those from 12 normally menstruating women. Three distinct patterns of responses of the adrenal steroids were observed in PCO patients, while cortisol response was similar to that of normal controls: (a) normal responders (n = 9, 30% of PCO patients), in whom a delta max response similar to that of normals was observed, although basal delta 4A and T levels were found to be elevated; (b) 21-OH dysfunction group (n = 6, 16.6%), in whom delta max 17OHP levels and delta max 17OHP to delta max Cort ratio were significantly higher than those of normals and the other PCO groups, indicating a dysfunction at the 21-hydroxylase level; (c) adrenarchal type of response group (n = 16, 53%), in whom statistically significant (P less than .0001) hyperresponsiveness of DHEA and, in 11 of them, of delta 4A, with high delta max delta 4A to delta max DHEA to delta max Cort ratios were found, indicative of a selective overproduction of the steroids during steroidogenesis. Moreover, the significantly higher delta max delta 4A to delta max 17OHP ratio found in group c is a further indication of increased 17,20-lyase efficiency, as is encountered during adrenarche.(ABSTRACT TRUNCATED AT 250 WORDS)