The role of different adjuvant therapies in locally advanced gastric adenocarcinoma

Complete surgical resection remains the only curative treatment option in locally advanced gastric cancer (GC). Several studies were conducted to prevent local recurrence and to increase the chance of cure. The aim of this study was to summarize our experience in locally advanced GC patients treated with adjuvant chemoradiotherapy (CRT) and to evaluate overall survival (OS), disease-free survival (DFS), toxicity rate and compliance to treatment

Pharmacological therapy features in patient with Hepatocellular carcinoma

In Italia, la maggior parte dei casi di epatocarcinoma (HCC) insorge in pazienti affetti da cirrosi epatica, che presentano un grado variabile di insufficienza epatica. Pertanto, la prognosi dei pazienti con HCC è condizionata non solo dalla estensione della neoplasia, ma anche dalla residua funzione epatica. Scopo della Tesi Analizzare i principali aspetti della terapia farmacologica del paziente affetto da HCC attraverso: 1. Ricerca di predittori clinico-laboratoristici di risposta al Sorafenib in pazienti ambulatoriali con HCC; 2. Indagare se il decorso naturale e la risposta al trattamento anticoagulante della Trombosi non neoplastica del sistema venoso portale (PVT) nei pazienti con cirrosi complicata da HCC differisca da quelli senza HCC; 3. Fornire nuovi aggiornamenti sull’immunoterapia antineoplastica che promette di plasmare il futuro scenario terapeutico dell'HCC mediante una revisione della letteratura. Studio 1: Ha confermato l'efficacia e il profilo di sicurezza di Sorafenib nel trattamento a lungo termine dei pazienti con HCC, evidenziando come il trattamento con Sorafenib può dare un significativo aumento della sopravvivenza, in presenza anche di un soddisfacente profilo di sicurezza, in una rilevante quota di pazienti (22%). Lo studio 2 ha dimostrato che la presenza di HCC attivo non influisce negativamente sul decorso della Trombosi non neoplastica del sistema venoso portale (PVT) e sull'efficacia del trattamento anticoagulante. Pertanto, il paziente con HCC con Trombosi non neoplastica del sistema venoso portale, non presenta condizioni sfavorevoli al trattamento con anticoagulanti, eventualmente permettendo, in caso di risoluzione della trombosi, terapie altrimenti controindicate (TACE) Lo studio 3 conferma come l'immunoterapia per l'HCC sembra essere un campo di indagine molto intenso, suscitando la speranza che nuove opportunità terapeutiche molto efficaci diventino presto disponibili e portino a nuove e più vantaggiose strategie nella gestione dei pazienti con HCC.In Italy, most cases of Hepatocellular carcinoma (HCC) occur in patients with Liver Cirrhosis, who have a variable degree of liver failure. Therefore, the prognosis of patients with HCC is conditioned not only by the extension of tumour, but also by the residual liver function. Purpose of the thesis: Analyze the main features of pharmacological therapy in patient with Hepatocellular carcinoma through: 1. Research of clinical-laboratory predictors of response to Sorafenib treatment in outpatients with HCC; 2. To investigate whether the natural course and response to anticoagulant treatment of non-neoplastic portal vein thrombosis (PVT) in patients with cirrhosis complicated by HCC differs from those without HCC; 3. Provide new updates on antineoplastic immunotherapy that promises to shape the future therapeutic scenario of HCC through a literature review. Study 1: Confirms the efficacy and safety profile of Sorafenib in the long-term treatment of patients with HCC, highlighting how treatment with Sorafenib can give a significant increase in survival, even in the presence of a satisfactory safety profile, in a significant group of patients (22%) Study 2 : Shows that the presence of active HCC does not negatively influence the course of non-neoplastic portal vein thrombosis (PVT) and the efficacy of anticoagulant treatment. Therefore, patient with HCC with non-neoplastic portal vein thrombosis, does not present unfavorable conditions for treatment with anticoagulants, possibly enabling, in case of resolution of thrombosis, contraindicated alternative therapies (TACE) Study 3 Confirms that immunotherapy for HCC appears to be a very intense field of investigation with the hope that new highly effective therapeutic opportunities will soon become available and lead to new and more advantageous strategies in management of patients with HCC

Clinical benefit of adding oxaliplatin to standard neoadjuvant chemoradiotherapy in locally advanced rectal cancer: a meta-analysis : Oxaliplatin in neoadjuvant treatment for rectal cancer

Abstract. Background: To evaluate the treatment tolerance and clinical outcomes in patients aged 70 years and older with locally advanced oropharyngeal cancer treated by definitive intensity-modulated radiation therapy (IMRT). Patients and Methods: We retrospectively analyzed 15 consecutive elderly patients, with histologically-proven squamous cell carcinoma of the oropharynx, staged T3-4 with or without involved lymph nodes at diagnosis, who received definitive sequential IMRT (70 Gy; 2 Gy/fraction). Adult Comorbidity Evaluation-27 (ACE-27) score was calculated and its influence on treatment tolerance and clinical outcomes was analyzed. Results: A total of 15 patients were included with a median age of 77 years (range=70-88 years). At baseline, 8 patients (53.3%) had an ACE-27 score of 1, and the remainder (n=7, 46.7%) had a comorbidity index of 0. All patients completed programmed IMRT treatment, without any reduction of total dose. Oral pain and mucositis were the most common acute side-effects, classified as grade 3 in 6 patients (40%) only. Xerostomia was reported in 13 patients (86.7%), without severe manifestation. There was no hematological toxicity. ACE-27 score was not related to higher severe acute toxicity. No patients experienced grade 3 or more late toxicity. Five-year overall survival and disease-free survival rates were 63.6% (95% confidence interval=32.7-83.3%) and 55% (95% confidence interval=24.4-77.6%), respectively. Comorbidity score did not influence survival outcomes, both overall survival (p=0.46) and disease-free survival (p=0.55). Conclusion: Treatment tolerance, as well as survival outcomes were good in elderly oropharyngeal cancer patients treated with definitive sequential IMRT. Due to age and comorbidity, no dose or volume reduction for IMRT should be considered in this setting of patients. A prospective randomized trial with a large sample size should be conducted to confirm our result

Surgical resection for gastrointestinal stromal tumors (GIST): experience on 25 patients

BACKGROUND: Gastrointestinal stromal tumors (GIST) are infrequent and diagnosis and prognosis could be troublesome. We present short and long term results of surgical resection for GIST at the Department of Surgery, University of Insubria, during a period of 17 years. MATERIALS AND METHODS: All patients' data, tumor characteristics, surgical procedure and survival data were analyzed retrospectively. Tumors were divided in risk classes using the classification proposed by Fletcher, based on tumor size and number of mitosis. RESULTS: Between 1987 and 2004, 25 patients underwent surgical resection for GIST. Stomach was the most common site of localization. Complete resection was achieved in 88% cases, while in 12% radical resection was not possible. The mean tumor size was 9.2 cm (1.2 – 30 cm): <5 cm diameter in 14/25 cases (56%), 5–10 cm in 5/25 (20%) and >10 cm in 6/25 (24%). Mitotic count was <10/50 HPF in 68% (17/25) and >10/50 in 32% (8/25). Using Fletcher's classification, tumors were divided in very low (11/25, 44%), low (4/25, 16%), intermediate (6/25, 24%) and high-risk (4/25, 16%) groups. The 5-year overall survival was 65% and 34% respectively with a statistically significant difference between tumors <5 cm and >10 cm in diameter and between complete and incomplete resection. High-risk tumors had a significantly shorter survival than low or very low risk. CONCLUSION: Our experience confirms that GIST's are uncommon and aggressive cancers. The prognosis is strictly related to tumor size and number of mitosis. Although significant advances on new chemotherapeutic regimes have been made, to date, only radical surgery offers the chance of long-term survival

Injection of colorectal cancer cells in mesenteric and antimesenteric sides of the colon results in different patterns of metastatic diffusion: An experimental study in rats

BACKGROUND: This experimental study was designed to investigate the differences in pattern of local growth and diffusion of colorectal cancer cells injected into either mesenteric (M) or antimesenteric (AM) sides of the colon. METHODS: A total of 1 × 10(6 )colonic adenocarcinoma cells (line DHD/K12-TRb) were injected into the cecal wall of BDIX syngeneic male rats at an M or AM site of the colon. At six weeks after injection, all animals were sacrificed and the presence or absence of tumor in the cecum as well as regional metastasis and peritoneal carcinomatosis were determined. RESULTS: Six weeks after injection, macroscopic tumor growth was observed in 27/37 (72%) animals in group M and 21/32 (65%) in group AM (P = 0.98). In group AM, diffuse peritoneal carcinomatosis was present in 19/21 rats (90.4%) versus 3/27 rats (11%) in group M; this difference was statistically significant (P = 0.025). Regional mesenteric lymph nodes were the only location in which tumor was detected in 23/27 rats (85%) in group M versus 2/21 (9.5%) in group AM; this difference too was statistically significant (P = 0.031) CONCLUSION: The patterns of diffusion of tumors implanted in mesenteric and antimesenteric sites of the colon appear to be different, although the reason for this is not clear

Induction chemotherapy followed by neoadjuvant chemoradiotherapy and surgery in locally advanced rectal cancer: preliminary results of a phase II study

PURPOSE: To report preliminary results of induction chemotherapy (IC) followed by neoadjuvant chemoradiotherapy (CRT) and surgery in locally advanced rectal cancer (LARC) patients.MATERIALS AND METHODS: This is the preliminary evaluation of a phase II study. Patients with histologically proven rectal adenocarcinoma, stage II-III disease, who met the inclusion criteria, received induction FOLFOXIRI (5-FU, leucovorin, oxaliplatin and irinotecan) regimen in combination with targeted agents followed by CRT and surgery. Analysis of the first 8 patients was required to confirm the treatment feasibility before the accrual of 20 additional patients. RESULTS: The first 8 patients were evaluated. The median follow-up time was 23 months. There were no treatment-related deaths. Trimodality strategy was well tolerated with high compliance and a good level of toxicity. There were no evidence of febrile neutropenia and any grade 4 adverse events were recorded. Three patients had pathologic complete response (pCR) and 1 patient had a nearly pCR (ypT1 ypN0). CONCLUSION: Preliminary results are encouraging. FOLFOXIRI regimen plus targeted agents followed by CRT and surgery seems a safe approach. Longer follow-up and higher number of patients are mandatory to confirm such findings

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Regorafenib Combined with Other Systemic Therapies: Exploring Promising Therapeutic Combinations in HCC

: Regorafenib was the first drug to demonstrate a survival benefit as a second-line agent after sorafenib failure in patients with unresectable hepatocellular carcinoma (HCC). Recent studies have shown that its mechanism of action is not only limited to its very broad spectrum of inhibition of angiogenesis, tumor proliferation, spread, and metastasis, but also to its immunomodulatory properties that have favorable effects on the very intricate role that the tumor microenvironment plays in carcinogenesis and tumor growth. In this review, we discuss rationale and evidence supporting regorafenib efficacy in HCC and that led to its approval as a second-line treatment, after sorafenib failure. We also discuss the evidence from clinical practice studies that confirm the results previously achieved in clinical trials. Finally, we analyze the potential role of regorafenib in emerging combined treatment approach with immunotherapy strategies using immune checkpoint blockade and its potential extension to patient categories not included in the registrative study