Comparison of four surgical approaches for rectal prolapse: multicentre randomized clinical trial.

BACKGROUND: Several different procedures have been described for surgical treatment of rectal prolapse and consensus on the optimal approach has not been reached. The Swedish Rectal Prolapse Trial was performed with the aim to compare the outcomes after the most common surgical approaches to rectal prolapse. METHOD: A multicentre randomized trial was conducted from 2000 to 2009. Patients were randomized between a perineal or an abdominal approach for correction of rectal prolapse (randomization A) if eligible for any procedures. Patients considered unsuitable for random allocation were only included in randomizations B or C. Patients in randomization B (perineal group) were randomized to Delorme's or Altemeier's procedures and those in randomization C (abdominal group) to suture rectopexy or resection rectopexy. Primary outcomes were bowel function and quality of life, measured using Wexner incontinence score and RAND-36, and secondary outcomes were complications and recurrence at 3 years. RESULTS: During the study period, 134 patients were randomized: 18 in randomization A group, 80 in randomization B group and 54 in randomization C group; of these, 122 patients underwent surgery. Mean follow-up was 2.6 years. Improvements in Wexner and RAND-36 scores were seen but with no significant difference between the groups. Health change scores were significantly improved from baseline up to 1 year after surgery (P < 0.001). At 3 years, recurrence rates were two of seven patients for abdominal versus five of eight patients for perineal approach (P = 0.315), 18 of 31 patients (58 per cent) for Delorme's versus 15 of 30 patients (50 per cent) for Altemeier's (P = 0.611) and four of 19 patients (21 per cent) for suture rectopexy versus two of 21 patients (10 per cent) for resection rectopexy (P = 0.398). There were no significant differences regarding postoperative complications. CONCLUSION: For all procedures, significant improvements from baseline in health change scores were noted after surgery. Recurrence rates were higher than previously reported. Registration number: NCT04893642 (http://www.clinicaltrials.gov).

Robotic vs laparoscopic rectal tumour surgery: a cohort study.

AIM: The aim of this study was to compare robotic and laparoscopic rectal surgery in terms of perioperative data, short-term outcome and compliance to the Enhanced Recovery After Surgery (ERAS) protocol. METHOD: In this cohort study, 224 patients scheduled for rectal resection for cancer or adenoma between January 2011 and January 2017 were evaluated. In the first time period (12 January 2011 to 23 April 2014), 47 (46%) of 102 patients had laparoscopic surgery. In the second time period (24 April 2014 to 30 January 2017), 72 (59%) of 122 patients had robotic surgery. Perioperative data and short-term outcome were collected from the ERAS database and patient charts. Data obtained from laparoscopic and robotic surgery in the two time periods studied were compared. Primary outcome was hospital length of stay (LOS) and secondary outcomes were compliance to the ERAS protocol, difference in postoperative complications and conversion to open surgery. RESULTS: Compliance to the ERAS protocol was 81.1% in the robotic group and 83.4% in the laparoscopic group (P = 0.890). Robotic surgery was associated with shorter median LOS (3 days vs 7 days, P < 0.001), lower conversion rate (11.1% vs 34.0%, P = 0.002), lower rate of postoperative complications (25% vs 49%, P < 0.01) and longer duration of surgery (5.8 h vs 4.5 h, P < 0.001). The differences remained after multivariate analysis. CONCLUSION: Robotic surgery was associated with shorter LOS, lower conversion rates and fewer postoperative complications compared with laparoscopic surgery. Robotic surgery may add benefits to the ERAS protocol.

The impact of perioperative fluid therapy on short-term outcomes and 5-year survival among patients undergoing colorectal cancer surgery - A prospective cohort study within an ERAS protocol.

BACKGROUND: Restricted perioperative fluid therapy is one of several interventions in the enhanced recovery after surgery (ERAS) protocol, designed to reduce morbidity and hospital stay after surgery. The impact of this single intervention on short and long term outcome after colorectal surgery is unknown. PATIENTS AND METHODS: This cohort study includes all consecutive patients operated with abdominal resection of colorectal cancer 2002-2007 at Ersta Hospital, Stockholm, Sweden. All patients were treated within an ERAS protocol and registered in the ERAS-database. Compliance to interventions in the ERAS protocol was analysed. The impact of a restrictive perioperative fluid therapy (≤3000 ml on the day of surgery) protocol on short-term outcomes as well as 5-year survival was assessed with multivariable analysis adjusted for confounding factors. RESULTS: Nine hundred and eleven patients were included. Patients receiving ≤3000 ml of intravenous fluids on the day of surgery had a lower risk of complications OR 0.44 (95% C I 0.28-0.71), symptoms delaying discharge OR 0.47(95% C I 0.32-0.70) and shorter length of stay compared with patients receiving >3000 ml. In cox regression analysis, the risk of cancer specific death was reduced with 55% HR 0.45(95% C I 0.25-0.81) for patients receiving ≤ 3000 ml compared with patients receiving >3000 ml. CONCLUSION: A restrictive compared with a non-restrictive perioperative fluid therapy on the day of surgery may be associated with lower short-term complication rates, faster recovery, shorter length of stay and improved 5-year survival.

Elevated thioredoxin after angioplasty in peripheral arterial disease.

OBJECTIVE: Oxidative stress and inflammation in the vessel wall may play important roles in the development of restenosis after angioplasty. Reactive oxygen species have been suggested to mediate the proliferative phenotype in smooth muscle cells. The role of the redox-active proteins, thioredoxin and glutaredoxin, after angioplasty in patients with peripheral arterial disease has never been assessed before. Circulating thioredoxin impairs the chemotactic response to local sites of inflammation and administration of human recombinant Trx has been shown to attenuate ischemic reperfusion injury. METHODS AND RESULTS: Patients with peripheral arterial disease undergoing angioplasty were included in this observational study. Plasma levels of thioredoxin and glutaredoxin were analysed before and 1, 4 and 24 h, and 1 week after angioplasty. Plasma levels of thioredoxin were significantly elevated 4 h after angioplasty [2.3 ng/ml (0.5-14), p=0.02] and returned to baseline within 24 h [1.1 ng/ml (0.5-3.1), p=0.02]. There may also exist an association between patients with elevated levels of thioredoxin after angioplasty and decreased rate of restenosis at follow-up angiography after 6 months. There were no changes in plasma levels of glutaredoxin after angioplasty. CONCLUSION: These findings provide a new insight to the role of thioredoxin in the complex process of vascular injury and restenosis in patients with peripheral arterial disease, suggesting thioredoxin both as a marker of oxidative stress and as a therapeutic agent.

Truncated thioredoxin (Trx80) induces production of interleukin-12 and enhances CD14 expression in human monocytes.

Human thioredoxin (Trx) is the major 12-kd cellular disulfide-reductase that on secretion acts as a cocytokine with several interleukins. Truncated Trx with the 80 N-terminal residues (Trx80), also present in plasma, was by itself a mitogenic cytokine for human peripheral blood mononuclear cells (PBMC). This study investigated which cells in PBMC are targets of recombinant Trx80. Purified human CD14(+) monocytes, but not B or T cells, in a synthetic medium were activated to differentiation by Trx80 as measured by flow cytometry of surface antigens because exposure to 100 nM Trx80 increased expression of CD14, CD40, CD54, and CD86. Proliferation of the monocytes was increased in a dose-dependent manner by Trx80 in concentrations ranging from 10 nM to 1 microM. Trx or interleukin (IL) 2 did not induce proliferation or expression of surface antigens on monocytes. Trx80 alone induced secretion of IL-12 from CD40(+) monocytes in the PBMC cultures and this effect was enhanced by IL-2. Trx80 and IL-2 together were strongly synergistic to induce secretion of interferon-gamma in PBMC cultures. The results showed that Trx80 is a potent cytokine for normal human monocytes and directs the immune system in favor of a Th1 response via IL-12 production.

Truncated thioredoxin is a mitogenic cytokine for resting human peripheral blood mononuclear cells and is present in human plasma.

Human thioredoxin (Trx) catalyzes intracellular disulfide reductions but has also co-cytokine activity with interleukins after leaderless secretion. A recombinant truncated form of thioredoxin with the 80 N-terminal residues (Trx80) was purified to homogeneity. We discovered that Trx80 by itself is a potent mitogenic cytokine stimulating growth of resting human peripheral blood mononuclear cells. No effect was seen by Trx, but Trx80 at 50-100 nm induced cell proliferation of human peripheral blood mononuclear cells in serum-free synthetic medium, measured as [(3)H]thymidine incorporation after 72 h, with a maximum effect being comparable with that of 5 units/ml of interleukin-2. Trx80 lacked redox activity, but CD spectra suggested a secondary structure similar to Trx. Reduced Trx80 had an M(r) of 25,000, indicating that it is a dimer in solution. We also developed two different sandwich enzyme-linked immunosorbent assays that distinguish between full-length Trx and Trx80 and determined plasma levels of Trx and Trx80 in blood donors. The levels of Trx80 varied from 2 to 175 ng/ml; in comparison levels of Trx varied from 16 to 55 ng/ml without correlation to Trx80. In conclusion, the naturally occurring Trx80 is a novel mitogenic cytokine for normal resting human blood mononuclear cells.

Thioredoxin, a redox enzyme released in infection and inflammation, is a unique chemoattractant for neutrophils, monocytes, and T cells.

Thioredoxin (Trx) is a ubiquitous intracellular protein disulfide oxidoreductase with a CXXC active site that can be released by various cell types upon activation. We show here that Trx is chemotactic for monocytes, polymorphonuclear leukocytes, and T lymphocytes, both in vitro in the standard micro Boyden chamber migration assay and in vivo in the mouse air pouch model. The potency of the chemotactic action of Trx for all leukocyte populations is in the nanomolar range, comparable with that of known chemokines. However, Trx does not increase intracellular Ca2+ and its activity is not inhibited by pertussis toxin. Thus, the chemotactic action of Trx differs from that of known chemokines in that it is G protein independent. Mutation of the active site cysteines resulted in loss of chemotactic activity, suggesting that the latter is mediated by the enzyme activity of Trx. Trx also accounted for part of the chemotactic activity released by human T lymphotropic virus (HTLV)-1-infected cells, which was inhibited by incubation with anti-Trx antibody. Since Trx production is induced by oxidants, it represents a link between oxidative stress and inflammation that is of particular interest because circulating Trx levels are elevated in inflammatory diseases and HIV infection.

Thioredoxin expression and localization in human cell lines: detection of full-length and truncated species.

Thioredoxin (Trx) is an intracellular multifunctional 12-kDa protein with a reduction/oxidation (redox) active disulfide constitutively expressed by most cells of the human body. Trx can also be released by cells such as lymphocytes upon activation or oxidative stress exposure and exert a cocytokine and cytoprotective activity. In addition, a truncated 10-kDa form of Trx has been reported. In order to better understand the function of full-length and truncated Trx, we have produced, for the first time, specific monoclonal antibodies, which can discriminate between the two forms. Using these novel antibodies, designated alpha Trx1 to alpha Trx4, a panel of cell lines derived from human B and T lymphocytes, monocytes, granulocytes, and melanomas was analyzed by immunochemical techniques. The cellular distribution differed between the two forms. All lines contained full-length Trx, also located to a minor extent on the cell surface. One exception was the melanoma cell line FM28.4, which did not show any Trx expression. Truncated Trx was present in most cells in minimal amounts only, whereas the monocytic cell lines THP-1 and U-937 expressed high amounts on the cell surface, as shown by flow cytometric analysis of living cells and confocal laser-scanning microscopy. The biological importance and function of the short versus long forms of Trx as detected by the antibodies are discussed.