Health economic analysis of laparoscopic lavage versus Hartmann's procedure for diverticulitis in the randomized DILALA trial

BACKGROUND: Open surgery with resection and colostomy (Hartmann's procedure) has been the standard treatment for perforated diverticulitis with purulent peritonitis. In recent years laparoscopic lavage has emerged as an alternative, with potential benefits for patients with purulent peritonitis, Hinchey grade III. The aim of this study was to compare laparoscopic lavage and Hartmann's procedure with health economic evaluation within the framework of the DILALA (DIverticulitis – LAparoscopic LAvage versus resection (Hartmann's procedure) for acute diverticulitis with peritonitis) trial. METHODS: Clinical effectiveness and resource use were derived from the DILALA trial and unit costs from Swedish sources. Costs were analysed from the perspective of the healthcare sector. The study period was divided into short‐term analysis (base‐case A), within 12 months, and long‐term analysis (base‐case B), from inclusion in the trial throughout the patient's expected life. RESULTS: The study included 43 patients who underwent laparoscopic lavage and 40 who had Hartmann's procedure in Denmark and Sweden during 2010–2014. In base‐case A, the difference in mean cost per patient between laparoscopic lavage and Hartmann's procedure was €–8983 (95 per cent c.i. –16 232 to –1735). The mean(s.d.) costs per patient in base‐case B were €25 703(27 544) and €45 498(38 928) for laparoscopic lavage and Hartmann's procedure respectively, resulting in a difference of €–19 794 (95 per cent c.i. –34 657 to –4931). The results were robust as demonstrated in sensitivity analyses. CONCLUSION: The significant cost reduction in this study, together with results of safety and efficacy from RCTs, support the routine use of laparoscopic lavage as treatment for complicated diverticulitis with purulent peritonitis

Substrate Effect on the High Temperature Oxidation Behavior of a Pt-modified Aluminide Coating. Part II: Long-term Cyclic-oxidation Tests at 1,050 C

This second part of a two-part study is devoted to the effect of the substrate on the long-term, cyclic-oxidation behavior at 1,050 C of RT22 industrial coating deposited on three Ni-base superalloys (CMSX-4, SCB, and IN792). Cyclicoxidation tests at 1,050 C were performed for up to 58 cycles of 300 h (i.e., 17,400 h of heating at 1,050 C). For such test conditions, interdiffusion between the coating and its substrate plays a larger role in the damage process of the system than during isothermal tests at 900, 1,050, and 1,150 C for 100 h and cyclicoxidation tests at 900 C which were reported in part I [N. Vialas and D. Monceau, Oxidation of Metals 66, 155 (2006)]. The results reported in the present paper show that interdiffusion has an important effect on long-term, cyclic-oxidation resistance, so that clear differences can be observed between different superalloys protected with the same aluminide coating. Net-mass-change (NMC) curves show the better cyclic-oxidation behavior of the RT22/IN792 system whereas uncoated CMSX-4 has the best cyclic-oxidation resistance among the three superalloys studied. The importance of the interactions between the superalloy substrate and its coating is then demonstrated. The effect of the substrate on cyclic-oxidation behavior is related to the extent of oxide scale spalling and to the evolution of microstructural features of the coatings tested. SEM examinations of coating surfaces and cross sections show that spalling on RT22/CMSX-4 and RT22/SCB was favored by the presence of deep voids localized at the coating/oxide interface. Some of these voids can act as nucleation sites for scale spallation. The formation of such interfacial voids was always observed when the b to c0 transformation leads to the formation of a two-phase b/c0 layer in contact with the alumina scale. On the contrary, no voids were observed in RT22/IN792, since this b to c0 transformation occurs gradually by an inward transformation of b leading to the formation of a continuous layer of c0 phase, parallel to the metal/scale interface

Treatment of acute diverticulitis laparoscopic lavage vs. resection (DILALA): study protocol for a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Perforated diverticulitis is a condition associated with substantial morbidity. Recently published reports suggest that laparoscopic lavage has fewer complications and shorter hospital stay. So far no randomised study has published any results.</p> <p>Methods</p> <p>DILALA is a Scandinavian, randomised trial, comparing laparoscopic lavage (LL) to the traditional Hartmann's Procedure (HP). Primary endpoint is the number of re-operations within 12 months. Secondary endpoints consist of mortality, quality of life (QoL), re-admission, health economy assessment and permanent stoma. Patients are included when surgery is required. A laparoscopy is performed and if Hinchey grade III is diagnosed the patient is included and randomised 1:1, to either LL or HP. Patients undergoing LL receive > 3L of saline intraperitoneally, placement of pelvic drain and continued antibiotics. Follow-up is scheduled 6-12 weeks, 6 months and 12 months. A QoL-form is filled out on discharge, 6- and 12 months. Inclusion is set to 80 patients (40+40).</p> <p>Discussion</p> <p>HP is associated with a high rate of complication. Not only does the primary operation entail complications, but also subsequent surgery is associated with a high morbidity. Thus the combined risk of treatment for the patient is high. The aim of the DILALA trial is to evaluate if laparoscopic lavage is a safe, minimally invasive method for patients with perforated diverticulitis Hinchey grade III, resulting in fewer re-operations, decreased morbidity, mortality, costs and increased quality of life.</p> <p>Trial registration</p> <p>British registry (ISRCTN) for clinical trials <a href="http://www.controlled-trials.com/ISRCTN82208287">ISRCTN82208287</a><url>http://www.controlled-trials.com/ISRCTN82208287</url></p

European Society of Coloproctology: guidelines for the management of diverticular disease of the colon

The guideline was developed during several working phases including three voting rounds and one consensus meeting. The two project leads (JKS and EA) appointed by the ESCP guideline committee together with one member of the guideline committee (WB) agreed on the methodology, decided on six themes for working groups (WGs) and drafted a list of research questions. Senior WG members, mostly colorectal surgeons within the ESCP, were invited based on publication records and geographical aspects. Other specialties were included in the WGs where relevant. In addition, one trainee or PhD fellow was invited in each WG. All six WGs revised the research questions if necessary, did a literature search, created evidence tables where feasible, and drafted supporting text to each research question and statement. The text and statement proposals from each WG were arranged as one document by the first and last authors before online voting by all authors in two rounds. For the second voting ESCP national representatives were also invited. More than 90% agreement was considered a consensus. The final phrasing of the statements with < 90% agreement was discussed in a consensus meeting at the ESCP annual meeting in Vienna in September 2019. Thereafter, the first and the last author drafted the final text of the guideline and circulated it for final approval and for a third and final online voting of rephrased statements

Inhibition of dendritic cell migration by transforming growth factor-β1 increases tumor-draining lymph node metastasis

<p>Abstract</p> <p>Background</p> <p>Transforming growth factor (TGF)-β is known to be produced by progressor tumors and to immobilize dendritic cells (DCs) within those tumors. Moreover, although TGF-β1 has been shown to promote tumor progression, there is still no direct, in vivo evidence as to whether TGF-β1 is able to directly induce distant metastasis.</p> <p>Methods</p> <p>To address that issue and investigate the mechanism by which TGF-β1 suppresses DC activity, we subdermally inoculated mouse ears with squamous cell carcinoma cells stably expressing TGF-β1 or empty vector (mock).</p> <p>Results</p> <p>The numbers of DCs within lymph nodes draining the resultant TGF-β1-expressing tumors was significantly lower than within nodes draining tumors not expressing TGF-β1. We then injected fluorescently labeled bone marrow-derived dendritic cells into the tumors, and subsequent analysis confirmed that the tumors were the source of the DCs within the tumor-draining lymph nodes, and that there were significantly fewer immature DCs within the nodes draining TGF-β1-expressing tumors than within nodes draining tumors not expressing TGF-β1. In addition, 14 days after tumor cell inoculation, lymph node metastasis occurred more frequently in mice inoculated with TGF-β1 transfectants than in those inoculated with the mock transfectants.</p> <p>Conclusions</p> <p>These findings provide new evidence that tumor-derived TGF-β1 inhibits migration of DCs from tumors to their draining lymph nodes, and this immunosuppressive effect of TGF-β1 increases the likelihood of metastasis in the affected nodes.</p

Microvessel density as new prognostic marker after radiotherapy in rectal cancer

<p>Abstract</p> <p>Background</p> <p>The extent of angiogenesis is an important prognostic factor for colorectal carcinoma, however, there are few studies concerning changes in angiogenesis with radiotherapy (RTX). Our aim was to investigate changes in tumor angiogenesis influenced by radiotherapy to assess the prognostic value of angiogenesis the microvessel density (MVD) in overall survival after radiotherapy.</p> <p>Methods</p> <p>Tumor specimens were taken from 101 patients resected for rectal cancer. The patients were divided into three groups according to the treatment they received before surgery (not treated, a short course, or long course of RTX). Tumor specimens were paraffin-embedded and immunohistochemistry was performed with primary antibody against CD-34 to count MVD.</p> <p>Results</p> <p>MVD was significantly lower in the group of patients treated with a long course of RTX (p <0.025). The mean MVD for the long RTX group was 134.8; for the short RTX group – 192.5; and for those not treated with RTX – 193.0. There were no significant statistical correlations between MVD and age, sex, grade of tumor differentiation (G) and tumor size (T) in those untreated with RTX. In long RTX group we found a significant prognostic rate for MVD when the density cut off was near 130 with 92.3% sensitivity and 64.7% specificity. When the MVD was lower than a cut off of 130, the survival period significantly increased (p = 0.001), the mortality rate is significantly higher if the MVD is higher than 130 (microvessel/mm²) (1953.047; p = 0.002), if the histological grade is moderate/poor (127.407; p = 0.013), if the tumor is T3/T4 (111.618; p = 0.014), and if the patient is male (17.92; p = 0.034) adjusted by other variable in model.</p> <p>Conclusion</p> <p>Our results show that a long course of radiotherapy significantly decreased angiogenesis in rectal cancer tissue. MVD was found to be a favourable marker for tumor behaviour during RTX and a predictor of overall survival after long course of RTX. Further investigations are now needed to determine the changes in angiogenesis during a shorter course of RTX.</p