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Background We assessed feasibility, short-term oncologic safety, and short-term outcomes in robotic total mesorectal excision (R-TME) for rectal cancer compared with laparoscopic TME. Methods From March 2008 to June 2009, 50 patients with proven middle/lower rectal adenocarcinoma underwent minimally invasive TME; 25 received R-TME. The groups were balanced (R-TME versus L-TME) in terms of age (median 69 versus 62 years; p  = 0.8), disease stage, and body mass index (median 23 versus 26.5 kg/m 2 ; p  = 0.06). There were 37 (74%) anterior resections and 13 (26%) abdominoperineal resections. Twenty-three (46%) patients received preoperative radiochemotherapy. The robot was a four-arm Da Vinci S (Intuitive Surgical, Sunnyvale, CA, USA). Results Median operating time (R-TME versus L-TME) was 240 versus 237 min ( p  = 0.2); first bowel movement was 2 versus 3 days ( p  = 0.5); median hospital stay was 6.5 versus 6 days ( p  = 0.4). Major complications with reoperation were two in R-TME (one anastomotic leakage, one small bowel perforation) and three in L-TME (one colonic ischemia, two anastomotic leakage). Postoperative complications were 16% versus 24% ( p  = 0.5). A median of 18 versus 17 ( p  = 0.7) lymph nodes were retrieved; distal resection margins were disease free in both groups; circumferential margin was involved (<1.0 mm) in one (4%) of L-TME. There were 0 versus 1 (5%) conversions to laparotomy. Conclusions R-TME in rectal cancer is feasible, with short-term oncologic and other outcomes similar to those of L-TME. The greater maneuverability and visibility afforded by the robotic approach are attractive. Future studies should more systematically address advantages and costs of R-TME.

BackgroundDuring the past decade, the concept of complete mesocolic excision (CME) has emerged as a possible strategy to minimize recurrence for right colon cancers. The purpose of this study was to compare robotic versus laparoscopic CME in performing right colectomy for cancer.MethodsPertinent data of all patients who underwent robotic or laparoscopic right colectomy with CME using a Pfannenstiel incision and intracorporeal anastomosis performed between October 2005 and November 2015 were entered in a prospectively maintained database.ResultsA total of 202 patients underwent robotic (n = 101) or laparoscopic (n = 101) right colectomy within the study period. Patient characteristics were equivalent between groups. The robotic group showed a statistically significant reduction in conversion rate (0% vs. 6.9%, p = 0.01) but a longer operative time (279 min vs. 236 min, p < 0.001) compared with the laparoscopic group. There were no other differences in perioperative clinical or pathological outcomes. Five-years overall survival was 77 versus 73 months for the robotic versus laparoscopic groups (p = 0.64). The disease-free survival (DFS) rates were 85% and 83% for the robotic versus laparoscopic groups (p = 0.58). Among UICC stage III patients, there was a slight but not significant difference in 5-year DFS for the robotic group (81 vs. 68 months; p = 0.122).ConclusionsBoth approaches for right colectomy with CME were safe and feasible and resulted in excellent survival. Robotic assistance was beneficial for performing intracorporeal anastomosis and dissection as evidenced by the lower conversion rates. Further robotic experience may shorten the operative time.

BackgroundLaparoscopic right hemicolectomy is a commonly performed procedure. Little is known on how to perform the enterotomy closure after stapled side-to-side intracorporeal anastomosis.MethodA multicentric case-controlled study has been designed to compare different ways to fashion enterotomy closure: double layer versus single layer, sewn versus stapled, and robotic versus laparoscopic approach. Furthermore, additional characteristics including sutures’ materials, interrupted versus running suture and the presence of deep corner suture has been investigated.ResultsWe collected data for 1092 patients who underwent right hemicolectomy at ten centers. We analyzed 176 robotic against 916 laparoscopic anastomosis: no significant differences were found in terms of bleedings (p = 0.455) and anastomotic leak (p = 0.405). We collected data from 126 laparoscopic sewn single-layer versus 641 laparoscopic sewn double-layer anastomosis: a significant reduction was recorded in terms of leaks in double-layer group (p = 0.02). About double-layer characteristics, we found a significant reduction of bleedings (p = 0.008) and leaks (p = 0.017) with a running suture; similarly, a reduction of bleedings (p = 0.001) and leaks (p = 0.005) was observed with the usage of deep corner closure. The presence of a barbed suture thread seemed to significantly reduce both bleedings (p = 0.001) and leaks (p = 0.001). We found no significant differences in terms of bleedings (p = 0.245) and anastomotic leak (p = 0.660) comparing sewn versus stapled anastomosis.ConclusionsFashioning a stapled ileocolic intracorporeal anastomosis, we can recommend the adoption of a double-layer enterotomy closure using a running barbed suture in the first layer. Totally, stapled closure and robotic assistance have to be considered a non-inferior alternative.

We investigated changes in skin microbiome and metabolome linked to wound healing and how these are affected by a formula known to improve re-epithelialization. In a clinical study with 21 subjects, forearm lesions were induced by epidermal laser ablation. The areas were left untreated or treated with the formula. Re-epithelialization was monitored for 18 days. Skin swabs were analyzed for microbiome diversity using 16 S rRNA gene sequence analysis. Selected species analyzed using digital droplet polymerase chain reaction. Metabolomic profiles were analyzed by ultra-high performance liquid chromatography-high-resolution mass spectrometry. Microbiota alpha-diversity (richness and evenness) was markedly reduced by laser ablation and returned to pre-ablation levels on Day 5. Formula application accelerated the re-epithelialization time (RT), which was more efficient for slow healing (RTs of 15–19 days) than quick healing (10–12 day RTs) subjects. The repairing effect was associated with greater microbiota diversity and species-specific growth of commensal bacteria. Levels of several metabolites on untreated skin at the RT and the extent of the impact of the formula were different in slow and quick healers. The formula significantly modified the skin metabolome, whereby metabolites involved in promoting wound healing were increased and metabolites consumed by the commensal bacteria were decreased.

BackgroundThe benefits of aerobic training for the main features of asthma, such as bronchial hyperresponsiveness (BHR) and inflammation, are poorly understood. We investigated the effects of aerobic training on BHR (primary outcome), serum inflammatory cytokines (secondary outcome), clinical control and asthma quality of life (Asthma Quality of Life Questionnaire (AQLQ)) (tertiary outcomes).MethodsFifty-eight patients were randomly assigned to either the control group (CG) or the aerobic training group (TG). Patients in the CG (educational programme+breathing exercises (sham)) and the TG (same as the CG+aerobic training) were followed for 3 months. BHR, serum cytokine, clinical control, AQLQ, induced sputum and fractional exhaled nitric oxide (FeNO) were evaluated before and after the intervention.ResultsAfter 12 weeks, 43 patients (21 CG/22 TG) completed the study and were analysed. The TG improved in BHR by 1 doubling dose (dd) (95% CI 0.3 to 1.7 dd), and they experienced reduced interleukin 6 (IL-6) and monocyte chemoattractant protein 1 (MCP-1) and improved AQLQ and asthma exacerbation (p<0.05). No effects were seen for IL-5, IL-8, IL-10, sputum cellularity, FeNO or Asthma Control Questionnaire 7 (ACQ-7; p>0.05). A within-group difference was found in the ACQ-6 for patients with non-well-controlled asthma and in sputum eosinophil and FeNO in patients in the TG who had worse airway inflammation.ConclusionsAerobic training reduced BHR and serum proinflammatory cytokines and improved quality of life and asthma exacerbation in patients with moderate or severe asthma. These results suggest that adding exercise as an adjunct therapy to pharmacological treatment could improve the main features of asthma.Trial registration numberNCT02033122.

Microsatellite instability (MSI) originates from the systematic accumulation of uncorrected deletion/insertion in repetitive DNA tracts in cancer cells with a deficient mismatch repair system. Among colorectal cancers, the MSI signature identifies hereditary cases arising in patients with germline mutations in hMLH1 , hMSH2 , PMS2 and a fraction of those with hMSH6 mutations, as well as sporadic cancers with epigenetic hMLH1 promoter hypermethylation. Considering the specific pathogenesis, pathological features, natural history and response to 5-fluoro-uracil-based chemotherapy of the MSI cancers, confusion about the genetic markers for MSI recognition seems surprising. In this clinically relevant field, an agreement has not been reached concerning the use of di- or mononucleotide markers for MSI assessment. The Revised Bethesda Guidelines still recommend a panel of markers consisting of mono- and dinucleotides, despite being questioned whether it is congruous to continue to use dinucleotide markers for MSI identification. In any event, no single marker is accurate enough for MSI testing, and an awareness of their pros and cons is required for proper interpretation of results. In recent years, several papers have reported different prevalence of MSI in unrelated series, largely depending on the detection and classification method, suggesting that MSI test interpretation also requires the understanding of the phenomenon rather than simply the crude satisfaction of panel recommendations. Inaccuracies can otherwise lead to under- or overdiagnosis and inaccurate disease classification, which always have a negative impact on the clinical practice of medicine.

The clinical use of cisplatin (cis-diamminedichloroplatinum II) is highly limited by its nephrotoxicity. The precise mechanisms involved in cisplatin-induced mitochondrial dysfunction in kidney have not been completely clarified. Therefore, we investigated in vivo the effects of cisplatin on mitochondrial bioenergetics, redox state, and oxidative stress as well as the occurrence of cell death by apoptosis in cisplatin-treated rat kidney. Adult male Wistar rats weighing 200-220 g were divided into two groups. The control group (n = 8) was treated only with an intraperitoneal (i.p.) injection of saline solution (1 ml per 100 g body weight), and the cisplatin group (n = 8) was given a single injection of cisplatin (10 mg/kg body weight, i.p.). Animals were sacrificed 72 h after the treatment. The cisplatin group presented acute renal failure characterized by increased plasmatic creatinine and urea levels. Mitochondrial dysfunction was evidenced by the decline in membrane electrochemical potential and the substantial decrease in mitochondrial calcium uptake. The mitochondrial antioxidant defense system was depleted, as shown by decreased GSH and NADPH levels, GSH/GSSG ratio, and increased GSSG level. Moreover, cisplatin induced oxidative damage to mitochondrial lipids, including cardiolipin, and oxidation of mitochondrial proteins, as demonstrated by the significant decrease of sulfhydryl protein concentrations and increased levels of carbonylated proteins. Additionally, aconitase activity, which is essential for mitochondrial function, was also found to be lower in the cisplatin group. Renal cell death via apoptosis was evidenced by the increased caspase-3 activity. Results show the central role of mitochondria and the intensification of apoptosis in cisplatin-induced acute renal failure, highlighting a number of steps that might be targeted to minimize cisplatin-induced nephrotoxicity.

Current ocular GvHD (oGvHD) treatments are suboptimal. We investigated the safety and efficacy of long-term continuous treatment with autologous platelet lysate (PL) drops in patients with oGvHD Dry Eye Syndrome (DES) score 2–3 refractory to topical conventional therapy. Ophthalmic evaluation was performed at 6 month intervals. Symptoms were assessed using the Glaucoma Symptom Scale (GSS). Patients were defined 'responders' when showing a reduction at least one grade on National Institutes of Health Eye Score from baseline at the 6 month visit. Thirty-one patients were included, and 16 (51%) completed 36 months of follow-up (range 6.5–72.7). At 6 months all patients were classified as responders: median GSS symptom score decreased from 70 to 41 (33 at 36 months), median GSS function score reduced from 68 to 46 (33 at 36 months) (all P< 0.001). Median Tear Break Up Time improved from 3 to 6 s after 6 months and was maintained over time. All signs improved at 6 and 36 months (clinical and statistical significance). No severe adverse events occurred. Long-term treatment with PL drops is secure and effective for oGvHD and can be an efficient therapy option from initial stages of oGvHD to prevent permanent ocular impairment and improving quality of life.

Nephrotoxicity is the major dose-limiting factor of cisplatin chemotherapy. Reactive oxygen species generated in mitochondria are thought to be the main cause of cellular damage in such injury. The present study examined, in vivo, the protective potential of the hydroxyl radical scavenger dimethylthiourea (DMTU) against cisplatin-induced effects on renal mitochondrial bioenergetics, redox state and oxidative stress. Adult male Wistar rats (200 to 220 g) were divided into four groups of eight animals each. The control group was treated only with an intraperitoneal (i.p.) injection of saline solution (1 ml/100 g body weight). The second group was given only DMTU (500 mg/kg body weight, i.p, followed by 125 mg/Kg, i.p., twice a day until they were killed). The third group was given a single injection of cisplatin (10 mg/kg body weight, i.p.). The fourth group was given DMTU (500 mg/kg body weight, i.p.), just before the cisplatin injection (10 mg/kg body weight, i.p.), followed by injections of DMTU (125 mg/kg body weight, i.p.) twice a day until they were killed. Animals were killed 72 h after the treatment. Besides not presenting any direct effect on mitochondria, DMTU substantially inhibited cisplatin-induced mitochondrial injury and cellular death by apoptosis, suppressing the occurrence of acute renal failure. All the following cisplatin-induced effects were prevented by DMTU: (1) increased plasmatic levels of creatinine and blood urea nitrogen (BUN); (2) decreased ATP content, calcium uptake and electrochemical potential; (3) oxidation of lipids, including cardiolipin; and oxidation of proteins, including sulfhydryl, and aconitase enzyme, as well as accumulation of carbonyl proteins; (4) depletion of the antioxidant defense (NADPH and GSH) and (5) increased activity of the apoptosis executioner caspase-3. Our findings show the important role played by mitochondria and hydroxyl radicals in cisplatin-induced nephrotoxicity, as well as the effectiveness of DMTU in preventing the renal mitochondrial damage caused by cisplatin. These results strongly suggest that protection of mitochondria by hydroxyl radical scavengers may be an interesting approach to prevent the kidney tissue damage caused by cisplatin-chemotherapy.

Background Laparoscopic rectal resection (LRR) is an oncologically safe procedure. The impact of conversion to open surgery on outcomes has not been fully elucidated. The aim of the study is to compare short- and long-term outcomes of converted (CR) and not converted (NCR) patients undergoing LRR. Methods Data were drawn from a prospective database of LRR performed between 1999 and 2008. Statistical analysis employed the chi-squared or Wilcoxon test and Kaplan–Meier estimation. Results Of 173 patients undergoing LRR, 26 (15%) required conversion. No differences in age, gender, American Society of Anesthesiologists (ASA) score, and T and N stages were observed between CR and NCR patients. Conversion was associated with higher body mass index (BMI) (27.3 versus 24.9 kg/m 2 , P < 0.001) and American Joint Committee on Cancer (AJCC) stage IV (26.9% versus 4.8%, P < 0.001), and resulted in longer operative time (342 versus 285 min, P = 0.006) and increased intraoperative complication rate (31% versus 5%, P < 0.001). No differences were observed in postoperative outcome between CR and NCR patients. After a mean follow-up of 46 and 36 months, 5-year disease-free survival was 55.7% in CR group and 79.2% in NCR group ( P = 0.007). After exclusion of stage IV patients from the analysis, 5-year disease-free survival was 71.1% in CR group and 85.3% in NCR group ( P = 0.17), while the overall recurrence rate was 26.3% in CR patients and 11.4% in NCR patients ( P = 0.07). Conclusions Our study suggests that conversion to open surgery does not affect postoperative outcome, but could have a negative impact on long-term overall recurrence rate. LRR should be performed by experienced surgeons in selected patients.