The Percentage of Signet Ring Cells Is Inversely Related to Aggressive Behavior and Poor Prognosis in Mixed-Type Gastric Cancer.

Background and Objectives: Only recently the percentage of signet ring cells (SRCs) in gastric cancer (GC) has been proposed as an independent predictor of survival. High amounts of SRCs have been related to lower recurrence and mortality rates, better prognosis, and favorable clinicopathological features in a poorly cohesive histotype. It is not known what the effect of SRC percentage in mixed-type GC is. We investigate the role of SRCs as a prognostic marker in mixed-histotype GC. Methods: A retrospective analysis was performed through a prospectively maintained database of patients with diagnosed "mixed-type" gastric carcinoma, defined according to 2019 WHO classification. These patients underwent surgery between 1995 and 2016, and their tissue samples were stored in a tissue bank. All slides were analyzed, and patients were divided into three groups according to the percentage of SRCs: "Group 1" (displaying ≤10% of SRCs), "Group 2" (displaying <90% but >10% of SRCs), and "Group 3" (displaying ≥90% of SRCs). We compared clinical and pathological features as well as prognostic factors between the different groups. Results: Among 164 enrolled patients, 68.9% were male and 31.1% were female (p = 0.612). The mean (±SD) age at diagnosis was 71.4 ± 9.6 years. Ninety-eight (59.7%) patients were classified as "Group 1", 66 (40.3%) as "Group 2", and none as "Group 3". Five-year overall survival was remarkably higher in Group 2 (73.8%) in comparison to Group 1 (35.4%), p < 0.001. Mortality risk was three times higher in patients with ≤10% SRC pattern compared to those with >10% [HR 2.70 (95% CI 1.72-4.24)]. After adjusting according to potential confounding factors, SRC percentage was still an independent predictor of survival. Conclusions: The proportion of SRCs is inversely related to aggressive behavior and poor prognosis in mixed-type GCs, highlighting the role of SRC amount as an independent predictor of survival.

Handgrip strength predicts length of hospital stay in an abdominal surgical setting: the role of frailty beyond age.

BACKGROUND: Chronological age per se cannot be considered a prognostic risk factor for outcomes after elective surgery, whereas frailty could be. A simple and easy-to-get marker for frailty, such as handgrip strength (HGS), may support the surgeon in decision for an adequate healthcare plan. AIMS: The aims of this study were to: (1) determine the prevalence of frailty in an abdominal surgery setting independent of age; (2) evaluate the predictive validity of HGS for the length of hospital stay (LOS). METHODS: This is a retrospective study conducted in subjects who underwent abdominal surgical procedures. Only subjects with complete cognitive, functional, nutritional assessments and available measurement of HGS at admission were included. A final cohort of 108 patients were enrolled in the study. RESULTS: Subjects had a mean age of 67.8 ± 15.8 years (age range 19-93 years old) and were mostly men. According to Fried's criteria, 17 (15.7%, 4F/13 M) were fit, 58 (23.7%; 24F/34 M) were pre-frail and 33 (30.6%; 20F/13 M) were frail. As expected, HGS significantly differed between groups having frail lower values as compared with pre-frail and fit persons (fit: 32.99 ± 10.34 kg; pre-frail: 27.49 ± 10.35 kg; frail: 15.96 ± 9.52 kg, p < 0.0001). A final regression analysis showed that HGS was significantly and inversely associated with LOS (p = 0.020) independent of multiple covariates, including age. DISCUSSION: Most of the population undergoing abdominal surgery is pre-frail or frail. The measurement of handgrip strength is simple and inexpensive, and provides prognostic information for surgical outcomes. Muscle strength, as measured by handgrip dynamometry, is a strong predictor of LOS in a surgical setting.

Antimicrobial Prophylaxis Reduces the Rate of Surgical Site Infection in Upper Gastrointestinal Surgery: A Systematic Review.

Surgical site infection occurs with high frequency in gastrointestinal surgery, contributing to the high incidence of morbidity and mortality. The accepted practice worldwide for the prevention of surgical site infection is providing single- or multiple-dose antimicrobial prophylaxis. However, most suitable antibiotic and optimal duration of prophylaxis are still debated. The aim of the systematic review is to assess the efficacy of antimicrobial prophylaxis in controlling surgical site infection rate following esophagogastric surgery. PubMed and Cochrane databases were systematically searched until 31 October 2021, for randomized controlled trials comparing different antimicrobial regimens in prevention surgical site infections. Risk of bias of studies was assessed with standard methods. Overall, eight studies concerning gastric surgery and one study about esophageal surgery met inclusion criteria. No significant differences were detected between single- and multiple-dose antibiotic prophylaxis. Most trials assessed the performance of cephalosporins or inhibitor of bacterial beta-lactamase. Antimicrobial prophylaxis (AMP) is effective in reducing the incidence of surgical site infection. Multiple-dose antimicrobial prophylaxis is not recommended for patients undergoing gastric surgery. Further randomized controlled trials are needed to determine the efficacy and safety of antimicrobial prophylaxis in esophageal cancer patients.

Non-occlusive mesenteric ischemia (NOMI) and prognostic signs at CT: reperfusion or not reperfusion that is the question!

PURPOSE: Non-occlusive mesenteric ischemia (NOMI) is a misdiagnosed and dangerous condition. To our knowledge, a comprehensive evaluation of CT parameters that can predict the outcome of patients suffering from NOMI is still missing. MATERIALS AND METHODS: Contrast-enhanced CT examination of 84 patients with a confirmed diagnosis of NOMI (37 with clinical and laboratory confirmation and 47 biopsy or surgery proven) was retrospectively reviewed by assessing vessels, mesentery, bowel, and peritoneal cavity CT quantitative and dichotomous parameters, and data were analyzed with Fisher's test. Diameter of superior mesenteric artery (SMA), celiac trunk (CT), inferior vena cava (IVC), superior mesenteric vein (SMV), and differences in CT HU (Delta HU) of the bowel wall before and after intravenous contrast media (ICM) administration were correlated to the patients' outcome using ANOVA test. Receiver operating characteristic (ROC) curves were elaborated after a binary logistic regression was performed. RESULTS: Increased number and diameter of vessels, bowel wall thickening, and hypervascularity were more frequent in patients with good prognosis. Conversely, pale mesentery, paper thin, hypovascularity, and aeroportia were more frequent in patients with bad prognosis. A significant correlation between diameters of SMA, CT, IVC, IMA, and SMV and outcome was found at univariate analysis. Also Delta HU resulted to be correlated with the outcome. At multivariate analysis only IVC and Delta HU were significant (p = 0.038 and 0.01) and the combined AUC resulted in 0.806 (CI 0.708-0.903). CONCLUSION: Dichotomous signs of reperfusion and quantitative CT parameters can predict the outcome of patients with NOMI. In particular the combination of IVC diameter and Delta HU of bowel wall allows to predict the prognosis with the highest accuracy.

Robotic versus laparoscopic gastrectomy for gastric cancer: an umbrella review of systematic reviews and meta-analyses.

An umbrella review was performed to summarize literature data and to investigate benefits and harm of robotic gastrectomy (RG) compared to laparoscopic (LG) approach. To overcome the intrinsic limitations of laparoscopy, the robotic approach is claimed to facilitate lymph-node dissection and complex reconstruction after gastrectomy, to assure oncologic safety also in advanced gastric cancer. A literature search was conducted in PubMed, Cochrane and Embase databases for all meta-analyses published up to December 2019. The search strategy was previously published in a protocol. We selected fourteen meta-analyses comparing outcomes between LG and RG with curative intent in patients with diagnosis of resectable gastric cancer. We highlight that RG has a longer operation time, inferior blood loss, reduction in hospital stay and a more rapid recovery of bowel function. In meta-analyses with statistical significance the number of nodes removed in RG is higher than LG and the distal margin of resection is higher. There is no difference in terms of total complication rate, mortality, morbidity, anastomotic leakage, anastomotic stenosis, intestinal obstruction and in conversion rate to open technique. The safety and efficacy of robotic gastrectomy are not clearly supported by strong evidence, suggesting that the outcomes reported for each surgical technique need to be interpreted with caution, in particular for the meta-analyses in which the heterogeneity is large. Certainly, robotic gastrectomy is associated with shorter time to oral intake, lesser intraoperative bleeding and longer operation time with an acceptable level of evidence. On the other hand, the data regarding other outcomes are insufficient as well as non-significant, from an evidence point of view, to draw any robust conclusion.

Clinical evaluation of the Mannheim Prognostic Index in post-operative peritonitis: a prospective cohort study.

Postoperative peritonitis (PoP), despite their relatively low incidence, are associated with high mortality. Such poor outcomes are also related to the high proportion of aged patients, whose intra-abdominal infections are difficult to manage. The study included 84 consecutive patients with PoP. The aim was the validation of the Mannheim Prognostic Index (MPI) in the context of PoP and the assessment of the prognostic impact of age and other clinical factors in a large series from a tertiary center. PoP had an incidence of 3.9% in all the abdominal surgeries in the study period. Surgical control of POP focus was achieved in 90.5% of cases and a complete abdominal clearance in 58.3%. Complication rate was 75% with a mortality of 26.2%. For MPI score, the ROC curve indicated a cut-off value of 29 with a sensitivity of 72.7% and specificity of 67.7% in predicting death. At univariate analysis, factors significantly related to poorer prognosis included advanced age (p 0.001), site of primary surgery (p 0.05), lack of abdominal clearance (p 0.003), generalized peritonitis (p 0.04) and high MPI score (p < 0.001). Age, MPI score and absence of abdominal clearance resulted in independent prognostic factors at multivariate analysis. MPI showed good efficacy in identifying POP patients at high risk of death. The increased risk of mortality related to advanced age should be considered with MPI score in planning the treatment. An aggressive and early diagnostic-therapeutic approach is required to reduce the MPI score and improve the prognosis.

Robotic versus laparoscopic gastrectomy for gastric cancer: protocol for umbrella review of systematic reviews and meta-analyses.

INTRODUCTION: Laparoscopic surgery has been adopted in some parts of the world as an innovative approach to the resection of gastric cancers. However, in the modern era of surgical oncology, to overcome intrinsic limitations of the traditional laparoscopy, the robotic approach is advocated as able to facilitate the lymph node dissection and complex reconstruction after gastrectomy, to assure oncologic safety also in advanced gastric cancer patients. Previous meta-analyses highlighted a lower complication rate as well as bleeding in the robotic approach group when compared with the laparoscopic one. This potential benefit must be balanced against an increased time of intervention. The aim of this umbrella review is to provide a comprehensive overview of the literature for surgeons and policymakers in order to evaluate the potential benefits and harms of robotic gastrectomy (RG) compared with the laparoscopic approach for gastric cancer. METHODS AND ANALYSIS: We will perform a comprehensive search of the PubMed, Cochrane and Embase databases for all articles published up to May 2019 and reference list of relevant publications for systematic review and meta-analyses comparing the outcomes of RG and laparoscopic gastrectomy in patients with gastric cancer. Studies will be selected by two independent reviewers based on prespecified eligibility criteria and the quality will be assessed according to AMSTAR (A MeaSurement Tool to Assess systematic Reviews) checklist. All information will be collected using piloted and standardised data-extraction forms in DistillerSR developed following the Joanna Briggs Institute's recommended extraction items. ETHICS AND DISSEMINATION: This umbrella review will inform clinical and policy decisions regarding the benefits and harms of RG for treating gastric cancer. The results will be disseminated through a peer-reviewed publication, conference presentations and the popular press. Formal ethical approval is not required as primary data will not be collected. PROSPERO REGISTRATION NUMBER: CRD42019139906.

Feasibility of modified docetaxel, oxaliplatin, capecitabine followed by capecitabine as maintenance chemotherapy as first-line therapy for patients with metastatic gastric or gastroesophageal cancer.

The aim of this study was to evaluate the efficacy and safety of modified docetaxel, oxaliplatin, capecitabine (DOC) combination chemotherapy, followed by maintenance capecitabine as first-line therapy for patients with metastatic gastric or gastroesophageal junction (GEJ) cancer. Treatment consisted of docetaxel 35 mg/m (days 1-8), l-OHP 85 mg/m (day 1), and capecitabine 750 mg/m twice daily (days 1-14), every 3 weeks. After six cycles of DOC, patients who did not progress received maintenance treatment with three-weekly capecitabine 1000 mg/m twice daily (days 1-14), until disease progression or unacceptable toxicity. Six-month disease control rate (DCR) was the primary endpoint and overall survival (OS), progression-free survival (PFS) and safety were the secondary endpoints. The Kaplan-Meier method was applied to estimate OS and PFS. Between July 2014 and September 2017, 37 patients with metastatic gastric or GEJ cancer were enrolled at our institution. Upon completion of the DOC regimen, 35 patients (94.5%) received capecitabine as maintenance chemotherapy for a median of 7 cycles (range, 3-14 cycles). The six-month DCR was 83.7% [95% confidence interval (CI), 71.8-95.6%], median PFS was 8.2 months (95% CI, 6.3-9.8 months), and median OS was 14.4 months (95% CI, 11.7-18.6 months). During DOC chemotherapy, the most common grade 3-4 adverse events were neutropenia (29.7%), anemia (10.8%), and diarrhea (10.8%). During maintenance treatment, toxicity was sporadic and mainly of grade 1-2. Modified DOC followed by capecitabine as maintenance chemotherapy seems to be an active and well tolerated first-line treatment strategy for patients with metastatic gastric and GEJ cancer.

Pathological response and outcome after neoadjuvant chemotherapy with DOC (docetaxel, oxaliplatin, capecitabine) or EOF (epirubicin, oxaliplatin, 5-fluorouracil) for clinical T3-T4 non-metastatic gastric cancer.

PURPOSE: In this prospective observational study, we sought to compare the efficacy and safety of docetaxel + oxaliplatin + capecitabine (DOC) with epirubicin + oxaliplatin + 5-fluouracil (EOF) as neoadjuvant chemotherapy (NAC) for clinical T3 or T4 non-metastatic gastric cancer (GC) patients. METHODS: The DOC NAC consisted of docetaxel 35 mg/m2 (days 1-8), oxaliplatin 85 mg/m2 (day 1), and capecitabine 750 mg/m2 twice daily (days 1-14), every 3 weeks. The EOF NAC consisted of intravenous (IV) epirubicin 50 mg/m2 combined with IV oxaliplatin 130 mg/m2 on day 1 and continuous infusion 5-fluouracil 750 mg/m2 on days 1-5, every 3 weeks. After 4 cycles of NAC or upon progression during chemotherapy, patients underwent gastrectomy with standard D2 or D3 lymphadenectomy. Pathological complete response rate per Becker tumor regression grading system was the primary endpoint and the secondary endpoints included progression-free survival (2-yr PFS) and 2-year overall survival (2-yr OS) and tolerability. RESULTS: Overall, we identified 63 patients with T3-4 non-metastatic GC starting either NAC regimen between January 2010 and December 2017 at our Institution: 34 in the DOC group and 29 in EOF group. Thirty patients (88%) in the DOC group and 22 (76%) in the EOF group completed the 4 planned cycles of NAC. Fifty-seven patients received surgery. Results indicated no statistical significant differences between the two groups, and only a trend for some better data in favour of the DOC group. The R0 resection rate was 90.6% and 88.0% for the DOC and EOF cohorts, respectively. The pathological complete response rate was 6.2% in the DOC group and 4.0% in the EOF group. Becker 1-2 pathological response was found in 46.8% of the DOC cohort and 28.0% of the EOF cohort (p = .14). The 2-yr PFS rate was 54.1% for DOC vs. 41.4% for EOF (p = .14) and the 2-yr OS rate was 80.8% for DOC vs. 58.6% for EOF (p = .05). Neutropenia was the most common grade ≥3 toxicity and occurred in 8 (23.5%) patients of the DOC group and 10 (34.4%) patients of the EOF group (p = .33). CONCLUSIONS: These findings seem to confirm the feasibility of NAC for clinically T3 and T4 non-metastatic GC and, despite no statistical significant difference was documented, suggest a trend for better activity and tolerability for the docetaxel-based regimen (DOC) compared to the epirubicin-based combination (EOF).

From digital world to real life: a robotic approach to the esophagogastric junction with a 3D printed model.

BACKGROUND: Three-dimensional (3D) printing may represent a useful tool to provide, in surgery, a good representation of surgical scenario before surgery, particularly in complex cases. Recently, such a technology has been utilized to plan operative interventions in spinal, neuronal, and cardiac surgeries, but few data are available in the literature about their role in the upper gastrointestinal surgery. The feasibility of this technology has been described in a single case of gastroesophageal reflux disease with complex anatomy due to a markedly tortuous descending aorta. METHODS: A 65-year-old Caucasian woman was referred to our Department complaining heartburn and pyrosis. A chest computed tomography evidenced a tortuous thoracic aorta and consequent compression of the esophagus between the vessel and left atrium. A "dysphagia aortica" has been diagnosed. Thus, surgical treatment of anti-reflux surgery with separation of the distal esophagus from the aorta was planned. To define the strict relationship between the esophagus and the mediastinal organs, a life-size 3D printed model of the esophagus including the proximal stomach, the thoracic aorta and diaphragmatic crus, based on the patient's CT scan, was manufactured. RESULTS: The robotic procedure was performed with the da Vinci Surgical System and lasted 175 min. The surgeons had navigational guidance during the procedure since they could consult the 3D electronically superimposed processed images, in a "picture-in-picture" mode, over the surgical field displayed on the monitor as well as on the robotic headset. There was no injury to the surrounding organs and, most importantly, the patient had an uncomplicated postoperative course. CONCLUSIONS: The present clinical report highlights the feasibility, utility and clinical effects of 3D printing technology for preoperative planning and intraoperative guidance in surgery, including the esophagogastric field. However, the lack of published data requires more evidence to assess the effectiveness and safety of this novel surgical-applied printing technology.

Long-term follow up of metastatic melanoma patients treated with Thymosin alpha-1: investigating immune checkpoints synergy.

BACKGROUND: Immune checkpoint blockade antibodies (imAbs), such as the anti Cytotoxic T Lymphocyte Antigen-4 (CTLA-4) ipilimumab (IPI) raised overall survival (OS) in metastatic melanoma (MM). Further, long-term OS is a crucial endpoint in MM. Thymosin alpha-1 (Tα1) with dacarbazine (DTIC) showed activity in a phase II trial and a compassionate use program (EAP). We report on long-term follow-up of patients treated with Tα1 to investigate the preconditioning role of Tα1 in imAbs-treated patients. METHODS: Records of patients with melanoma treated with Tα1 within a phase II trial and EAP program were reviewed comparing median OS among patients that sequentially received anti-CTLA-4 imAb and Tα1. Further, the effect of Tα1 on IPI long-term survivor patients was investigated. RESULTS: Among patients treated with Tα1, 21/61 patients received sequentially even anti CTLA-4 imAbs. Median OS at the data cut-off was 57.8 and 7.4 months in patients treated sequentially with anti-CTLA-4 imAbs or not, respectively. Moreover, pretreatment with Tα1 in all (95) IPI-evaluable patients confirmed a significant increase in long-term OS. CONCLUSION: This is the first report on long-term follow-up of Tα1-treated patients. Moreover, an advantage in OS in patients sequentially treated with Tα1 and IPI was seen that suggests a synergistic effect.

Efficacy and Safety of Regorafenib With 2/1 Schedule for Patients ≥ 75 Years With Metastatic Colorectal Cancer (mCRC) After Failure of 2 Lines of Chemotherapy.

BACKGROUND: In the CORRECT (patients with metastatic COloRectal Cancer treated with REgorafenib or plaCebo after failure of standard Therapy) trial, regorafenib was proven to extend survival of patients with metastatic colorectal cancer (mCRC) that progressed after all available therapies. Grade 3 to 4 toxicity occurred in 54% of patients, and data on the activity and tolerability of regorafenib in elderly patients were scarce. The aim of this study was to evaluate the efficacy and safety of an alternative schedule, 2-week-on treatment and 1 week-off (2/1 schedule), of regorafenib for elderly patients with mCRC. PATIENTS AND METHODS: Patients ≥ 75 years with mCRC who progressed after oxaliplatin- and irinotecan-based chemotherapy received regorafenib on a 2/1 schedule. Potentially frail subjects were identified by G8 screening tool and excluded. The 2-month disease-control rate was the primary endpoint, and the secondary endpoints included safety, progression-free survival (PFS), overall survival (OS), and objective response rate. RESULTS: Between February 2014 and May 2017, 23 patients with mCRC were recruited at our institution. No partial or complete responses were observed, and the stable disease and disease-control rate were 52.2%. The median PFS was 4.8 months (95% confidence interval, 3.8-6.3 months), and the median OS was 8.9 months (95% confidence interval, 6.9-10.6 months). Adverse events were uncommon, and the most frequent grade 3 toxicity adverse events were hand-foot skin reaction (9%) and fatigue (9%). Toxicity-related dose reductions and discontinuations occurred in 5 and 2 patients, respectively. CONCLUSION: Regorafenib administered with a modified 2/1 schedule to patients who were aged ≥ 75 years and non-frail with treatment-refractory mCRC seems to be tolerable and achieve encouraging results in terms of PFS and OS.

Modulation of cutaneous scavenger receptor B1 levels by exogenous stressors impairs "in vitro" wound closure.

Scavenger receptor B1 (SR-B1) is a trans-membrane protein, involved in tissue reverse cholesterol transport. Several studies have demonstrated that SR-B1 is also implicated in other physiological processes, such as bacteria and apoptotic cells recognition and regulation of intracellular tocopherol and carotenoids levels. Among the tissues where it is localized, SR-B1 has been shown to be significantly expressed in human epidermis. Our group has demonstrated that SR-B1 levels are down-regulated in human cultured keratinocytes by environmental stressors, such as cigarette smoke, via cellular redox imbalance. Our present study aimed to investigate whether such down-regulation was confirmed in a 3D skin model and under other environmental challengers such as particulate matter and ozone. We also investigated the association between oxidation-induced SR-B1 modulation and impaired wound closure. The data obtained showed that not only cigarette, but also the other environmental stressors reduced SR-B1 expression in epidermal cutaneous tissues and that this effect might be involved in impaired wound healing.

Potassium Ascorbate with Ribose: Promising Therapeutic Approach for Melanoma Treatment.

While surgery is the definitive treatment for early-stage melanoma, the current therapies against advanced melanoma do not yet provide an effective, long-lasting control of the lesions and a satisfactory impact on patient survival. Thus, research is also focused on novel treatments that could potentiate the current therapies. In the present study, we evaluated the effect of potassium ascorbate with ribose (PAR) treatment on the human melanoma cell line, A375, in 2D and 3D models. In the 2D model, in line with the current literature, the pharmacological treatment with PAR decreased cell proliferation and viability. In addition, an increase in Connexin 43 mRNA and protein was observed. This novel finding was confirmed in PAR-treated melanoma cells cultured in 3D, where an increase in functional gap junctions and a higher spheroid compactness were observed. Moreover, in the 3D model, a remarkable decrease in the size and volume of spheroids was observed, further supporting the treatment efficacy observed in the 2D model. In conclusion, our results suggest that PAR could be used as a safe adjuvant approach in support to conventional therapies for the treatment of melanoma.

Proteomic analysis of 4-hydroxynonenal and nitrotyrosine modified proteins in RTT fibroblasts.

Rett syndrome (RTT) is a pervasive developmental disorder, primarily affecting girls with a prevalence of 1 in every 10,000 births. A clear etiological factor present in more than 90% of classical RTT cases is the mutation of the gene encoding methyl-CpG-binding protein 2 (MECP2). Recent work from our group was able to shown a systemic oxidative stress (OxS) in these patients that correlates with the gravity of the clinical features. Using freshly isolated skin fibroblasts from RTT patients and healthy subjects, we have performed a two-dimensional gel electrophoresis in order to evidence the oxidative modifications of proteins with special focus on the formation of protein adducts with 4-hydroxynonenal (4-HNE PAs)-a major secondary product of lipid peroxidation- and Nitrotyrosine, a marker derived from the biochemical interaction of nitric oxide (NO) or nitric oxide-derived secondary products with reactive oxygen species (ROS). Then, oxidatively modified spots were identified by mass spectrometry, LC-ESI-CID-MS/MS. Our results showed that 15 protein spots presented 4-HNE PAs and/or nitrotyrosine adducts in fibroblasts proteome from RTT patients compared to healthy control cells. Post-translationally modified proteins were related to several functional categories, in particular to cytoskeleton structure and protein folding. In addition, clear upregulated expression of the inducible NO synthase (iNOS) with high nitrite levels were observed in RTT fibroblasts, justifying the increased nitrotyrosine protein modifications. The present work describes not only the proteomic profile in RTT fibroblasts, but also identifies the modified proteins by 4-HNE and nitrotyrosine. Of note, for the first time, it appears that a dysregulation of NO pathway can be associated to RTT pathophysiology. In conclusion, the evidence of a wide range of proteins able to forms adducts with 4-HNE, Nitrotyrosine or with both confirms the possible alteration of several aspects of cellular functions that well correlates to the complex clinical features of RTT patients.

Monoclonal antibodies-based treatment in gastric cancer: current status and future perspectives.

Gastric cancer (GC) is the second leading cause of cancer-related death, and despite having improved treatment modalities over the last decade, for most patients, only modest improvements have been seen in overall survival. Recent progress in understanding the molecular biology of GC and the related signaling pathways offers, from the clinical point of view, promising advances for selected groups of patients. In the past, targeted therapies have significantly impacted the treatment strategy of several common solid tumors such as breast, colorectal, and lung cancers. Unfortunately, translational and clinical research shows fewer encouraging targeted treatments with regards to the GC. To date, only two monoclonal antibodies (mAb), named trastuzumab and ramucirumab, are approved for the treatment of advanced GC, suggesting that in GC, maybe more than in other cancers, effective targeted therapy requires patient selection based on precise predictive molecular biomarkers. The aim of this review is to summarize the available data on the clinical advantages offered by the use of mAbs in the treatment of advanced/metastatic GC. Future perspective is also discussed.

Impaired enzymatic defensive activity, mitochondrial dysfunction and proteasome activation are involved in RTT cell oxidative damage.

A strong correlation between oxidative stress (OS) and Rett syndrome (RTT), a rare neurodevelopmental disorder affecting females in the 95% of the cases, has been well documented although the source of OS and the effect of a redox imbalance in this pathology has not been yet investigated. Using freshly isolated skin fibroblasts from RTT patients and healthy subjects, we have demonstrated in RTT cells high levels of H2O2 and HNE protein adducts. These findings correlated with the constitutive activation of NADPH-oxidase (NOX) and that was prevented by a NOX inhibitor and iron chelator pre-treatment, showing its direct involvement. In parallel, we demonstrated an increase in mitochondrial oxidant production, altered mitochondrial biogenesis and impaired proteasome activity in RTT samples. Further, we found that the key cellular defensive enzymes: glutathione peroxidase, superoxide dismutase and thioredoxin reductases activities were also significantly lower in RTT. Taken all together, our findings suggest that the systemic OS levels in RTT can be a consequence of both: increased endogenous oxidants as well as altered mitochondrial biogenesis with a decreased activity of defensive enzymes that leads to posttranslational oxidant protein modification and a proteasome activity impairment.

Duodenal tumors. Four case reports.

AIM: Reporting our experience in the treatment of duodenal neoplasms. MATERIAL OF STUDY: Management and treatment of four patients presenting a duodenal neoplasm. RESULTS: Three out of four patients died after surgery for dehiscence and/or bleeding. One, who underwent palliative bypass, died after four months from unknown causes. DISCUSSION: Duodenal neoplasms are rare and their diagnosis is difficult and late. In literature, there is no standardized management of this kind of neoplasm; the commonest surgical approaches are pancreaticoduodenectomy, segmental duodenal resection and palliative operations. The surgical choice is based on site and stage, both in Literature than in our experience. Regardless of the surgical decision, the patients have a poor outcome because of an advanced stage at diagnosis. CONCLUSIONS: It can be asserted that duodenal neoplasia offers many diagnostic and therapeutic difficulties. This may be due to its rarity, which does not allow the definition of a standard course of treatment, resulting in the inability to have a unique diagnostic and therapeutic approach. There is often a late diagnosis and the need to perform emergency surgery. Therefore prognosis is greatly aggravated by the high incidence of postoperative complications, in part due to the urgency in which the surgeries are carried out.

Treatment of median incisional hernia. Laparoscopic vs. open surgery: meta-analysis.

In the last ten years we assisted to spreading of laparoscopic approach on the correction of median incisional hernia, although for increased interesting toward mini-invasive techniques than for matching results between lap and open approaches. The aim of our study is the critical analysis of the results of lap and open surgery in the approach of ventral hernia, through the meta-analytical revision of the principal checked prospective trials. There were emerged 7 perspective studies to fit to a meta-analysis with the revision of the literature, with 1165 patients in total. Among the perioperative outcomes the briefer surgical time and a reduction of postoperative hospitalization were observed with the significant statistic data in favor of the lap. Laparoscopy can be considered a valid technical alternative to traditional open surgery in the treatment of ventral incisional hernia. The advantages of mini-invasive approach are the reducing of the surgical time and of the total hospital stay. There were not emerged any significant differences regarding the other surgical end-points or the recurrences of hernias after 1 and 5 years.

The treatment of breast cancer in one day surgery. A four year experience.

The number of short-stay surgery procedures has progressively increased since the concept of short-stay surgery was first introduced. Initially this type of surgery was reserved for patients undergoing inguinal hernia repair, proctological surgery, and various minor procedures. Careful patient selection makes it possible to apply one-day surgery to other surgical specialties including breast cancer surgery. Reducing the length of hospital stay lowers health care costs, and shortens waiting lists. The most important benefits for patients are a more rapid return to work and positive psychological effects. Exclusion criteria for one-day surgery are the lack of home care, excessive distance from place of treatment and the presence of any concomitant pathology that is a contraindication to this type of surgery. We report our experience in oncological surgery of the breast in one-day surgery.