Long-term, low-dose tigecycline to treat relapsing bloodstream infection due to KPC-producing Klebsiella pneumoniae after major hepatic surgery

Summary A 68-year-old male underwent a right hepatectomy, resection of the biliary convergence, and a left hepatic jejunostomy for a Klatskin tumour. The postoperative course was complicated by biliary abscesses with relapsing bloodstream infections due to Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae (KPC-Kp). A 2-week course of combination antibiotic therapy failed to provide source control and the bacteraemia relapsed. Success was obtained with a regimen of tigecycline 100mg daily for 2 months, followed by tigecycline 50mg daily for 6 months, then 50mg every 48h for 3 months. No side effects were reported

A Case-Control Comparison of Surgical and Functional Outcomes of Robotic-Assisted Spleen-Preserving Left Side Pancreatectomy versus Pure Laparoscopy

Aim During left-sided spleen-preserving pancreatectomy (SPLP), limitations of laparoscopy may require spleen sacrifice or conversion to maintain patient safety. The objective of our study is to compare surgical and functional outcomes of robot-assisted and pure laparoscopic SPLP in patients with benign or borderline lesions of the body/tail of the pancreas. Patients and methods This was a case-matched study: fifteen patients who had robotic SPLP (R-SPLP) were matched with 15 comparable patients who had pure laparoscopic SPLP (L-SPLP). The peri-operative variables (conversion rate, amount of bleeding, operation time, length of hospital stay, complications, mortality and readmission) as well as the spleen preservation rate were compared between the two groups, The European Organisation for Research and Treatment of Cancer QLQ-C30 (EORTC QLQ-C30) specific questionnaires were used in each arm after at least 1 year of follow up in order to evaluate quality of life (QoL). Results No R-SPLP was converted to conventional laparoscopy, hand-assisted laparoscopy, or open surgery whereas L-SPLP had a conversion rate of 13.3% (p=n.s.); also fistula formation (20% vs. 46%; p=n.s.) was higher in the laparoscopic group although not statistically significant. Mean operative time (220 vs. 279 min; p=0.027) was shorter and the spleen-preserving rate (fail/ success, 0/15 vs. 4/11; p=0.03) of R-SPLP was significantly better compared to L-SPLP. Moreover, length of hospital stay was significantly shorter in the R-SPLP group compared to the L-SPLP group (6.5 vs. 8.8 days; p=0.04). Post-operative high grade surgical complications occurred only in one L-SPLP patient (0% vs. 6.6%; p=n.s.). Quality of life scores were not significantly different between the two groups. Conclusions R-SPLP could provide an increased chance for spleen preservation and faster surgical procedure. Furthermore, fistula formation and conversion rate seem to be lower, reducing the length of the hospital stay. Our case matched study confirmed the potential peri-operative benefits of robotic assistance in this setting, however these benefits did not translate into a better quality of life at least one year post-operatively

Pancreatoduodenectomy without vascular resection in patients with primary resectable adenocarcinoma and unilateral venous contact:A matched case study

Purpose. To investigate the oncological outcome and survival of patients following a conservative approach on the portal- mesenteric axis, in an intraoperative ultrasound-selected group of pancreatoduodenectomy (PD), performed on patients with primary resectable with vascular contact (prVC) pancreatic ductal adenocarcinoma (PDAC). Methods. A consecutive series of patients who underwent PD for PDAC at our tertiary care center, between 2008 and 2017, were reviewed. A total of 156 PDs and 88 total pancreatectomies were performed during the study period, including 35 vascular resections. We identified a group of 40 (25.6%) patients with prVC-PDAC in whom after checking the feasibility with intraoperative ultrasound, we were able to perform PD by separation of the tumor from the portomesenteric axis avoiding vascular resection, without residual macroscopic disease (no vascular resection, nvrPD), and compared this group, using case-matched methodology, with the standard PD (sPD) group of primary resectable without vascular contact- (prwVC-) PDAC. Results. The median follow-up was 28.5 ± 23.2 months in the sPD group and 23.8 ± 20.8 months in the nvrPD group (p = 0 35). Isolated local recurrence rate was 2/40 (5%) in both groups. Additionally, there were no statistical differences in the systemic progression of the disease (42.5% sPD vs. 45% nvrPD, p = 0 82) or local plus synchronous systemic disease rates (2.5% sPD vs. 7.5% nvrPD, p = 0 30). The median survival was 22 months for the sPD group and 23 months for the nvrPD group, p = 0 86. The overall survival was similar in the two groups (1 y: 76.3% sPD vs. 70.0% nvrPD; 3 y: 35.6% vs. 31.6%; and 5 y: 28.5% vs. 25.3%; p = 0 80). Conclusions. PD without vascular resection can be considered safe and oncologically acceptable in selected patients with preoperative diagnosis of prVC-PDAC. The poor prognosis of PDAC is related to the aggressive biology and systemic spread of the tumor, rather than the local control of the disease

Short-term clinical outcomes of robot-assisted intersphincteric resection and low rectal resection with double-stapling technique for cancer: a case-matched study

Background: Intersphincteric resection (ISR) with total mesorectal excision (TME) is an accepted technique for the surgical treatment of very low rectal cancer. Historically it is associated with a higher functional complication rate than the Double Stapling (DS) technique when performed with open or laparoscopic approach. The aim of this study was to compare the surgical, short-term oncologic and functional outcomes of robotic ISR TME (R-ISR-TME) with those of robotic low anterior resection TME with a double stapling technique (R-DS-TME). Methods: Between April 2010 and December 2013, 42 patients underwent robot-assisted rectal resection with TME at our General Surgery Unit, including 10 R-ISR-TME. The outcomes of the R-ISR-TME group were compared with a R-DS-TME group selected using a case-matched methodology. We evaluated the operative, pathological, short-term oncologic results and postoperative sexual, urinary and defecation functions using specific questionnaires. Results: The analyses of the data showed similar results for R-ISR-TME and R-DS-TME regarding the operative, pathological and oncologic results. Focusing on urinary and sexual function, no score values were significantly different at any time between the two groups. The daily frequency of defecation 1 year after surgery was 1.9±0.9 for RISR-TME and 1.8±0.3 for RDS-TME indicating no difference between the two groups. Moreover, there were no significant differences between the two groups in other defecation functions. The mean Wexner score 1 year after surgery was 3.0±1.1 in R-ISR-TME and 2.2±1.0 in R-DS-TME group (p=0.2) and defecation-related quality of life for R-ISR-TME and R-DS-TME was not significantly different (modified fecal incontinence quality of life score: 30.3±19.1 vs 27.5±14.5, respectively; p=0.2). Conclusions: These clinical and functional results suggest that R-ISR-TME could be a good sphincter-preserving surgery for patients with very low rectal cancer. Robotic assistance may overcome some intrinsic limitations of the ISR technique flattening the difference with the DS-TME procedure

A prospective, single-arm study on the use of the da Vinci® Table Motion with the Trumpf TS7000dV operating table

BACKGROUND: The da Vinci® Table Motion (dVTM) comprises a combination of a unique operating table (Trumpf Medical™ TruSystem® 7000dV) capable of isocenter motion connected wirelessly with the da Vinci Xi® robotic platform, thereby enabling patients to be repositioned without removal of instruments and or undocking the robot. MATERIALS AND METHODS: Between May 2015 to October 2015, the first human use of dVTM was carried out in this prospective, single-arm, post-market study in the EU, for which 40 patients from general surgery (GS), urology (U), or gynecology (G) were enrolled prospectively. Primary endpoints of the study were dVTM feasibility, efficacy, and safety. RESULTS:Surgeons from the three specialties obtained targeting success and the required table positioning in all cases. Table movement/repositioning was necessary to gain exposure of the operating field in 106/116 table moves (91.3%), change target in 2/116 table moves (1.7%), achieve hemodynamic relief in 4/116 table moves (3.5%), and improve external access for tumor removal in 4/116 table moves (3.5%). There was a significantly higher use of tilt and tilt plus Trendelenburg in GS group (GS vs. U p = 0.055 and GS vs. G p = 0.054). There were no dVTM safety-related or adverse events. CONCLUSIONS: The dVTM with TruSystem 7000dV operating table in wireless communication with the da Vinci Xi is a perfectly safe and effective synergistic combination, which allows repositioning of the patient whenever needed without imposing any delay in the execution of the operation. Moreover, it is helpful in avoiding extreme positions and enables the anesthesiologist to provide immediate and effective hemodynamic relief to the patient when needed

Robot-assisted surgery for the radical treatment of deep infiltrating endometriosis with colorectal involvement: short- and mid-term surgical and functional outcomes.

Sexual and urinary dysfunctions are complications in radical treatment of deep infiltrating endometriosis (DIE) with colorectal involvement. The aim of this article is to report the preliminary results of our single-institution experience with robotic treatment of DIE, evaluating intraoperative and postoperative surgical outcomes and focusing on the impact of this surgical approach on autonomic functions such as urogenital preservation and sexual well-being. METHODS: From January 2011 through December 2013, a case series of 10 patients underwent robotic radical treatment of DIE with colorectal resection using the da Vinci System. Surgical data were evaluated, together with perioperative urinary and sexual function as assessed by means of self-administered validated questionnaires. RESULTS: None of the patients reported significant postoperative complications. Questionnaires concerning sexual well-being, urinary function, and impact of symptoms on quality of life demonstrated a slight worsening of all parameters 1 month after surgery, while data were comparable to the preoperative period 1 year after surgery. Dyspareunia was the only exception, as it was significantly improved 12 months after surgery. CONCLUSIONS: Robot-assisted surgery seems to be advantageous in highly complicated procedures where extensive dissection and proper anatomy re-establishment is required, as in DIE with colorectal involvement. Our preliminary results show that robot-assisted surgery could be associated with a low risk of complications and provide good preservation of urinary function and sexual well-being

Association between a polymorphic variant in the CDKN2B-AS1/ANRIL gene and pancreatic cancer risk

Genes carrying high-penetrance germline mutations may also be associated with cancer susceptibility through common low-penetrance genetic variants. To increase the knowledge on genetic pancreatic ductal adenocarcinoma (PDAC) aetiology, the common genetic variability of PDAC familial genes was analysed in this study. We conducted a multi-phase study analysing 7,745 single nucleotide polymorphisms (SNPs) from 29 genes reported to harbour a high-penetrance PDAC-associated mutation in at least one published study. To assess the effect of the SNPs on PDAC risk, a total of 14,666 PDAC cases and 221,897 controls across five different studies were analysed. The T allele of the rs1412832 polymorphism, that is situated in the CDKN2B-AS1/ANRIL, showed a genome-wide significant association with increased risk of developing PDAC (OR=1.11, 95%CI=1.07-1.15, P=5.25×10-9 ). CDKN2B-AS1/ANRIL is a long non-coding RNA, situated in 9p21.3, and regulates many target genes, among which CDKN2A (p16) that frequently shows deleterious somatic and germline mutations and deregulation in PDAC. Our results strongly support the role of the genetic variability of the 9p21.3 region in PDAC aetiopathogenesis and highlight the importance of secondary analysis as a tool for discovering new risk loci in complex human diseases. This article is protected by copyright. All rights reserved

Sexual and urinary functions after robot-assisted versus pure laparoscopic total mesorectal excision for rectal cancer

Background Laparoscopic total mesorectal excision (LapTME) is a validated technique for the treatment of rectal cancer. However, the ergonomic limitations of pure laparoscopy could lead to high conversion rates and a high rate of autonomic disorders. For these reasons the robot-assisted TME (RobTME) has been proposed to overcome the limitations of LapTME. The aim of this study is to compare surgical outcomes, medium-term oncologic results, and postoperative autonomic function of LapTME versus RobTME, in a single surgeon experience. Patients and Methods The first 26 LapTME were compared with the first 26 RobTME performed by a single surgeon between January 2009 and May 2013. Perioperative outcomes were prospectively collected and compared. The impact of minimally invasive TME on autonomic function and quality of life (QOL) was analyzed with the ICIQ-FLUTS and the ICIQ-MLUTS (International Consultation on Incontinence–Male/Female Lower Urinary Tract Symptoms) and IIEF (International Index of Erectile Function)/FSFI (Female Sexual Function Index) questionnaires. Pathological aspects and oncological outcomes were also collected. Results Of the 26 LapTME, 22 were anterior resections (ARR), 2 intersphincteric resections (ISR), and 2 abdominoperineal resections (APR), while of the 26 RobTME, 17 were ARR, 5 ISR, and 4 APR. Mean operative time was significantly higher (p<0.001) while conversion rate to hand-assisted or open surgery was significantly lower in the robTME group (p<0.05). There were no significant differences in sexual and urinary scores between the two groups before surgery and at 1 year after surgery. There were no differences in 3 year overall survival, disease free survival, and recurrence rate as well as the other parameters analysed. Conclusion RobTME is a safe and effective technique and the results compare favourably to the results obtained with laparoscopic procedures. It seems a promising alternative to preserve autonomic function and results in a low conversion rate even when used for more high risk procedures such as ISR or APR

Zebrafish Patient-Derived Xenograft Model to Predict Treatment Outcomes of Colorectal Cancer Patients

The use of zebrafish embryos for personalized medicine has become increasingly popular. We present a co-clinical trial aiming to evaluate the use of zPDX (zebrafish Patient-Derived Xenografts) in predicting the response to chemotherapy regimens used for colorectal cancer patients. zPDXs are generated by xenografting tumor tissues in two days post-fertilization zebrafish embryos. zPDXs were exposed to chemotherapy regimens (5-FU, FOLFIRI, FOLFOX, FOLFOXIRI) for 48 h. We used a linear mixed effect model to evaluate the zPDX-specific response to treatments showing for 4/36 zPDXs (11%), a statistically significant reduction of tumor size compared to controls. We used the RECIST criteria to compare the outcome of each patient after chemotherapy with the objective response of its own zPDX model. Of the 36 patients enrolled, 8 metastatic colorectal cancer (mCRC), response rate after first-line therapy, and the zPDX chemosensitivity profile were available. Of eight mCRC patients, five achieved a partial response and three had a stable disease. In 6/8 (75%) we registered a concordance between the response of the patient and the outcomes reported in the corresponding zPDX. Our results provide evidence that the zPDX model can reflect the outcome in mCRC patients, opening a new frontier to personalized medicine

Genetics of longevity. Data from the studies on Sicilian centenarians

The demographic and social changes of the past decades have determined improvements in public health and longevity. So, the number of centenarians is increasing as a worldwide phenomenon. Scientists have focused their attention on centenarians as optimal model to address the biological mechanisms of “successful and unsuccessful ageing”. They are equipped to reach the extreme limits of human life span and, most importantly, to show relatively good health, being able to perform their routine daily life and to escape fatal age-related diseases, such as cardiovascular diseases and cancer. Thus, particular attention has been centered on their genetic background and immune system. In this review, we report our data gathered for over 10 years in Sicilian centenarians. Based on results obtained, we suggest longevity as the result of an optimal performance of immune system and an overexpression of anti-inflammatory sequence variants of immune/inflammatory genes. However, as well known, genetic, epigenetic, stochastic and environmental factors seem to have a crucial role in ageing and longevity. Epigenetics is associated with ageing, as demonstrated in many studies. In particular, ageing is associated with a global loss of methylation state. Thus, the aim of future studies will be to analyze the weight of epigenetic changes in ageing and longevity