Inflammatory response after transanal total mesorectal excision.

INTRODUCTION: The advantages of transanal total mesorectal excision (taTME) would be a reduction of the hernia rate and surgical trauma. The present study reports data for patients undergoing taTME and compares the post-operative immune response in taTME with those of conven-tional laparoscopic surgery (CLS) and single-port laparo-scopic surgery (SPLS). METHODS: A comparative cohort study in patients with rectal cancer undergoing taTME. C-reactive protein (CRP) and white blood cell count (WBC) were measured pre-operatively and on post-operative days one, two, three and four. RESULTS: A total of 40 patients were included in taTME, 20 patients in CLS and 20 in SPLS. Patients' demographics (except for clinical staging), R0 resection and post-operative complication rates were comparable. The length of abdom-inal incisio-n was significantly lower by taTME than by both SPLS and CLS (p < 0.001). Distant resection margin was shorter in the taTME group (p < 0.01), and the quality of specimen differed between groups (p < 0.01). CRP and WBC increased significantly in each group (p < 0.05), but there was no difference between the groups. CONCLUSIONS: There is no difference in the inflammatory response in patients with rectal cancer undergoing taTME surgery compared with CLS and SPLS. We therefore conclude that the length/presence of abdominal incision does not further reduce the post-operative inflammatory stress response in minimally invasive procedures. The surgical trauma extends beyond the abdominal incision and depends on the intra-abdominal handling of the tissue. FUNDING: none. TRIAL REGISTRATION: ID NCT00157972, ethical approval ID H-1-2011-007, H-15000540.

[Interaction between microbiota and immune system in colorectal cancer].

In vivo- and in vitro research accumulate mounting evidence, that the interaction between the colorectal microbiota and the immune system plays an important role in the development and progression of colorectal cancer and for the treatment outcomes. In future, modulation of the microbiota and immune system will, by all accounts, become important targets for prevention and treatment of colorectal cancer. In this review, we summarise current knowledge on bacterial drivers, biofilm formation, colon cancer sidedness and oncological treatment of colorectal cancer including the use of checkpoint inhibitors.

Bacterial biofilm formation inside colonic crypts may accelerate colorectal carcinogenesis.

BACKGROUND: Research in the field of relation between microbes and colorectal carcinogenesis has gained increasing interest in past years. Recently, link between microbial biofilm and carcinogenesis in colon was demonstrated by several authors indicating that biofilm not only is a key player in carcinogenesis, but also may contribute to the understanding of side-specific colon cancer-right sided colon cancer versus left sided. In this article, we briefly highlight the major findings of the research of biofilm and carcinogenesis and demonstrate our findings of colonic cancer tissue and colonic polyp examined for biofilm. CASE PRESENTATION: Colonic cancer tissue from a patient with a right-sided colon cancer, and an adenoma tubular polyp were examined for biofilm formation by flourescens in situ hybridization. In cancer tissue we found biofilm formation on the surface epithelium but surprisingly also deep into the crypts. No biofilms were found in tubular polyp tissue. CONCLUSIONS: To our knowledge, this is the first-time biofilm formation deep into colonic crypts are demonstrated in a patient with right-sided colon cancer. This may indicate that bacterial biofilm may have a key role in carcinogenesis.

The prognostic value of polycomb group protein B-cell-specific moloney murine leukemia virus insertion site 1 in stage II colon cancer patients.

The aim of this study was to investigate the prognostic value of B-cell-specific moloney murine leukemia virus insertion site 1 (BMI1) protein expression in primary tumors of stage II colon cancer patients. BMI1 protein expression was assessed by immunohistochemistry in a retrospective patient cohort consisting of 144 stage II colon cancer patients. BMI1 expression at the invasive front of the primary tumors correlated with mismatch repair status of the tumors. Furthermore, BMI1 expression at the luminal surface correlated with T-stage, tumor location, and the histological subtypes of the tumors. In a univariate Cox proportional hazard analysis, no statistical significant association between risk of relapse and BMI1 protein expression at the invasive front (HR: 1.12; 95% CI 0.78-1.60; p = 0.53) or at the luminal surface of the tumor (HR: 1.06; 95% CI 0.75-1.48; p = 0.70) was found. Likewise, there was no association between 5-year overall survival and BMI1 expression at the invasive front (HR: 1.12; 95% CI 0.80-1.56; p = 0.46) or at the luminal surface of the tumor (HR: 1.16; 95% CI 0.86-1.60; p = 0.33). In conclusion, BMI1 expression in primary tumors of stage II colon cancer patients could not predict relapse or overall survival of the patients, thus having a limited prognostic value in stage II colon cancer patients.

SOX9 expression predicts relapse of stage II colon cancer patients.

The aim of this study was to investigate if the protein expression of sex-determining region y-box 9 (SOX9) in primary tumors could predict relapse of stage II colon cancer patients. One hundred forty-four patients with stage II primary colon cancer were retrospectively enrolled in the study. SOX9 expression was evaluated by immunohistochemistry, and mismatch repair status was assessed by both immunohistochemistry and promoter hypermethylation assay. High SOX9 expression at the invasive front was significantly associated with lower risk of relapse when including the SOX9 expression as a continuous variable (from low to high expression) in univariate (hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.56-0.94; P = .01) and multivariate Cox proportional hazards analyses (HR, 0.75; 95% CI, 0.58-0.96; P = .02), adjusting for mismatch repair deficiency and histopathologic risk factors. Conversely, low SOX9 expression at the invasive front was significantly associated with high risk of relapse, when including SOX9 expression as a dichotomous variable, in univariate (HR, 2.32; 95% CI, 1.14-4.69; P = .02) and multivariate analyses (HR, 2.32; 95% CI, 1.14-4.69; P = .02), adjusting for histopathologic risk factors and mismatch repair deficiency. In conclusion, high levels of SOX9 of primary stage II colon tumors predict low risk of relapse, whereas low levels of SOX9 predict high risk of relapse. SOX9 may have an important value as a biomarker when evaluating risk of relapse for personalized treatment.

Heart rate variability is reduced during acute uncomplicated diverticulitis.

BACKGROUND: The aim of the present study was to report the trajectory of heart rate variability (HRV) indices during a low-grade acute inflammation and their associations to biomarkers for infection. METHODS: Twelve patients with uncomplicated acute diverticulitis completed this observational study, which composed of 3 sessions of continuous HRV recording from 9 PM to 8 AM during ongoing diverticulitis and at complete remission (baseline). The blood samples were collected at each study session measuring C-reactive protein (CRP) and leukocytes. RESULTS: This study showed that the trajectories of the HRV indices were decreased both in time and frequency domains during acute diverticulitis compared to baseline. In particular, the indices reflecting the balance of sympathetic and parasympathetic activities were affected: standard deviation of normal-to-normal beats (P = .003), low-frequency power (P < .001), and total power (P = .001). These HRV changes indicate alterations in the autonomic nervous system during acute inflammation. All reductions of mean HRV indices had significant (P < .001) correlations to increased CRP correlations to increased CRP levels during diverticulitis suggesting inflammatory involvement in the observed HRV alterations. CONCLUSION: We found substantial HRV depression in relation to acute uncomplicated diverticulitis, and this was associated with the elevated CRP levels.

[C-reactive protein as a tool in the diagnosis of anastomotic leak after colorectal surgery]. / Diagnosticering af anastomoselækage efter kolorektal kirurgi ved brug af C-reaktivt protein.

Anastomotic leak (AL) is one of the most severe complications after colorectal surgery. AL is often diagnosed late when the patient is presenting with septic symptoms. C-reactive protein (CRP) as a tool in the diagnosis of AL has been investigated in several studies. CRP is proven to have a high negative predictive value which allows safe discharge of patients with low CRP measurements on day 3 or 4 after surgery. CRP can assist in the diagnosis of AL but cannot be used as a single parameter.

Rapid eye movement-sleep is reduced in patients with acute uncomplicated diverticulitis-an observational study.

Introduction. Sleep disturbances are commonly found in patients in the postoperative period. Sleep disturbances may give rise to several complications including cardiopulmonary instability, transient cognitive dysfunction and prolonged convalescence. Many factors including host inflammatory responses are believed to cause postoperative sleep disturbances, as inflammatory responses can alter sleep architecture through cytokine-brain interactions. Our aim was to investigate alteration of sleep architecture during acute infection and its relationships to inflammation and clinical symptoms. Materials & Methods. In this observational study, we included patients with acute uncomplicated diverticulitis as a model to investigate the isolated effects of inflammatory responses on sleep. Eleven patients completed the study. Patients were admitted and treated with antibiotics for two nights, during which study endpoints were measured by polysomnography recordings, self-reported discomfort scores and blood samples of cytokines. One month later, the patients, who now were in complete remission, were readmitted and the endpoints were re-measured (the baseline values). Results. Total sleep time was reduced 4% and 7% the first (p = 0.006) and second (p = 0.014) nights of diverticulitis, compared to baseline, respectively. The rapid eye movement sleep was reduced 33% the first night (p = 0.016), compared to baseline. Moreover, plasma IL-6 levels were correlated to non-rapid eye movement sleep, rapid eye movement sleep and fatigue. Conclusion. Total sleep time and rapid eye movement sleep were reduced during nights with active diverticulitis and correlated with markers of inflammation.

[One in five surgeons do not wash hands after visiting a toilet - an ethnographic field study].

INTRODUCTION: Non-compliance with regard to hand hygiene is a major problem in the health-care system especially among surgeons and anaesthetists. The purpose of this study was to examine the hand hygiene routines after toilet visits among participants attending an international surgical congress. METHODS: An observational study was conducted at the American College of Surgeons (ACS) Clinical Congress 2012 and at the American Medical Writers Association (AMWA) Congress 2012 as comparison. The study was performed as an ethnographic field study. A standardized observational matrix was developed for observing whether hand washing (as a surrogate measure of hand hygiene) was performed after toilet visits by observers. Frequencies were compared using Fisher's exact test. RESULTS: A total of 100 persons were observed (80% males). Of the 50 males observed at the ACS meeting, ten males did not use hand hygiene in relation to toilet visits (20%), while only one person at the AMWA meeting out of the 50 observed did not use hand hygiene (2%), p = 0.008. At both congresses only males did not use hand hygiene in relation to toilet visits. CONCLUSION: One in five surgeons did not wash hands after visiting a toilet. Even though the observed surgeons were not observed in an operating theatre or in a setting that required a distinct degree of hand hygiene, it does reveal a worrying behaviour. It is not known whether this was a conscious act, the result of business, or if it was due to lack of knowledge about the effects of hand hygiene on bacterial transmission. FUNDING: not relevant. TRIAL REGISTRATION: This study was neither registered at the National Committee of Health Research nor at Clinical Trials since it did not meet the requirements of registration.

Effect of melatonin on human nighttime endotoxaemia: randomized, double-blinded, cross-over study.

BACKGROUND: Endotoxaemia is widely used as an experimental model to study sepsis under controlled conditions. Nighttime endotoxaemia induces a more pronounced inflammatory stress response compared to daytime. Previously, we have shown that melatonin has antioxidative and anti-inflammatory effects in inflammatory response to daytime endotoxaemia. Herein, we examined the effect of melatonin in response to human nighttime endotoxaemia. PATIENTS AND METHODS: Twelve healthy male volunteers were enrolled in a randomized, placebo-controlled, double-blinded cross-over trial. Subjects were induced by lipopolysaccharide (LPS) endotoxin 0.3 ng/kg body weight intravenously at 24:00. One hour prior to induction of endotoxaemia, an 8-h infusion of melatonin 100 mg or placebo was initiated. Blood samples were drawn before and 2, 4, 6 and 8 h after induction of endotoxaemia and plasma was tested for pro-inflammatory markers (tumor necrosis factor alpha, TNF-α, interleukin-1ß, IL-1ß, interleukin-1, IL-6, and YKL-40), anti-inflammatory markers (interleukin-1 receptor antagonist, IL-1Ra, interleukin-10, IL-10, soluble tumor necrosis factor receptors I and II, sTNF-RI and sTNF-RII), marker for oxidative damage (malondialdehyde (MDA)) and antioxidative enzyme (ascorbic acid (AA) and dehydroascorbic acid (DHA)). RESULTS: Compared to placebo, melatonin did not reduce plasma levels of any of pro- and anti-inflammatory markers and it also failed to influence levels of AA, DHA and MDA. CONCLUSION: Melatonin has no beneficial effect on inflammation and oxidative damage induced by nighttime endotoxaemia in contrast to daytime endotoxaemia.

Pronounced inflammatory response to endotoxaemia during nighttime: a randomised cross-over trial.

BACKGROUND: Circadian variation in bodily functions has been shown to impact health in acute and chronic medical conditions. Little is known about the relationship between circadian rhythm and sepsis in humans. We aimed to investigate circadian variations in the host response in a human endotoxaemia model. DESIGN AND METHODS: A cross-over study, where 12 healthy young men received E. coli endotoxin (lipopolysaccharide, LPS) 0.3 ng/kg at 12 noon and, on another day, at 12 midnight. Blood samples were analysed for pro- and anti-inflammatory cytokines: tumour-necrosis factor (TNF)-alpha, soluble TNF receptors (sTNF-R)-1 and -2, interleukin (IL)-1beta, IL-1 receptor antagonist (IL-1Ra), IL-6, and IL-10 as well as YKL-40 and the oxidative stress markers malondialdehyde (MDA), ascorbic acid (AA) and dehydroascorbic acid (DHA) before and at 2, 4, 6 and 8 hours after LPS administration. RESULTS: The levels of MDA and IL-10 where significantly higher during the day time (P<0.05) whereas levels of TNF-alpha, sTNF-RI, sTNF-RII, IL-1Ra, IL-6, and YKL-40 were higher (P<0.01 for all comparisons) during the night time. No significant differences were seen in the levels of AA and DHA. CONCLUSION: A day-night difference in the acute phase response to endotoxaemia exists in healthy volunteers with a more pronounced inflammatory response during the night time. This circadian difference in the response to endotoxaemia may play an important role in the clinical setting and should be investigated further.

Melatonin suppresses markers of inflammation and oxidative damage in a human daytime endotoxemia model.

PURPOSE: Melatonin used as an exogenous drug has been documented to have potent antioxidant and anti-inflammatory effects in animal model. We aimed to examine the effect of melatonin in an experimental human sepsis model. MATERIALS AND METHODS: Twelve healthy males were enrolled in a randomized, placebo-controlled, double-blinded cross-over trial. They received lipopolysaccharide endotoxin 0.3 ng/kg of body weight intravenously at 12:00. Before endotoxemia, an 8-hour infusion of melatonin (100 mg) or placebo (saline) was initiated. Blood samples were drawn before and at 2, 4, 6, and 8 hours after lipopolysaccharide administration. Proinflammatory (tumor necrosis factor α [TNF-α], interleukin [IL] 1ß, IL-6, and YKL-40), anti-inflammatory markers (IL-1Ra, IL-10, soluble tumor necrosis factor receptor I, and soluble tumor necrosis factor receptor II), a marker for oxidative damage (malondialdehyde), and antioxidants (ascorbic acid and dehydroascorbic acid) were analyzed in plasma. RESULTS: Melatonin significantly reduced proinflammatory markers IL-1ß (P < .01) and YKL-40 (P < .05) but not TNF-α and IL-6. None of the anti-inflammatory markers (IL-1Ra, IL-10, soluble tumor necrosis factor receptor I, and soluble tumor necrosis factor receptor II) were lowered by melatonin. Melatonin reduced the levels of ascorbic acid (P < .05) but not dehydroascorbic acid or malondialdehyde. CONCLUSIONS: Melatonin administration before endotoxemia resulted in reduction of certain markers of inflammation and oxidative stress. Further studies are needed to clarify the role of melatonin in clinical setting.

Circadian variation in the response to experimental endotoxemia and modulatory effects of exogenous melatonin.

Disturbances in circadian rhythms are commonly observed in the development of several medical conditions and may also be involved in the pathophysiology of sepsis. Melatonin, with its antioxidative and anti-inflammatory effects, is known to modulate the response to endotoxemia. In this paper, we investigated the circadian variation with or without melatonin administration in an experimental endotoxemia model based on lipopolysaccharide (LPS). Sixty male Sprague-Dawley rats were assigned to six groups receiving an intraperitoneal injection of either LPS (5 mg/kg), LPS + melatonin (1 mg/kg), or LPS + melatonin (10 mg/kg) at either daytime or nighttime. Superoxide dismutase (SOD) was analyzed in liver samples collected after decapitation. Furthermore, inflammatory plasma markers (cytokines interleukin [IL]-6, IL-10) and oxidative plasma markers (ascorbic acid [AA], dehydroascorbic acid [DHA], and malondialdehyde [MDA]) were analyzed before and 5 h after the onset of endotoxemia. There were significant higher levels of SOD (p < 0.05), IL-6 (p < 0.01), and IL-10 (p < 0.05) during nighttime endotoxemia compared with daytime. At daytime, melatonin 1 and 10 mg reduced the levels of MDA and increased SOD, IL-6, IL-10, and DHA (p < 0.05). At nighttime, melatonin reduced the levels of MDA and increased DHA (p < 0.05). Additionally, 10 mg melatonin resulted in lower levels of AA during daytime (p < 0.05). No dose relationship of melatonin was observed. The results showed that the response induced by experimental endotoxemia was dependent on time of day. Melatonin administration modulated the inflammatory and oxidative stress responses induced by endotoxemia and also resulted in higher levels of antioxidants during daytime. The effect of circadian time on the endotoxemia response and possible modulatory effects of melatonin need further investigations in a human endotoxemia model.

Oral antibiotics for perforated appendicitis is not recommended.

In the majority of surgical departments in Denmark, the postoperative treatment for acute perforated appendicitis comprises three days of intravenous antibiotics. Recently, it has been proposed that such antibiotic regimen should be replaced by orally administered antibiotics. The aim of this paper was to give an overview of studies on acute perforated appendicitis with postoperative oral antibiotics. Five studies were found in a database search covering the 1966-2009 period. There is no evidence to support a conversion of the postoperative antibiotic regimen from intravenous to oral administration in patients with acute perforated appendicitis.

Psychological and physical stress in surgeons operating in a standard or modern operating room.

PURPOSE: There have been no studies examining the effect of optimized ergonomic and technical environment on the psychological and physiological stress of the surgeon. The aim of this study was to examine whether optimized ergonomics and technical aids within a modern operating room (OR) affect psychological and physiological stress in experienced laparoscopic surgeons. METHODS: This was a prospective case-controlled study including 10 experienced surgeons. Surgery was performed in 2 different ORs: a standard room and a modern room (OR1-suite, Karl Storz). The surgeons filled out questionnaires concerning physical and psychological wellbeing before and after surgery and had their heart rate variability registered during surgery. RESULTS: Preoperative to postoperative physical strain and pain measurements revealed a systematical difference with 14 of 15 parameters favoring the modern OR. Two of these parameters reached statistical significance. We did not find any significant differences in the subjective parameters of surgeon satisfaction or the measured heart rate variability parameters. CONCLUSIONS: Physical strain on the surgeon was reduced when performing laparoscopic cholecystectomy in a modern OR compared with a standard room.

Acute complicated diverticulitis managed by laparoscopic lavage.

PURPOSE: The classic surgical treatment of acute complicated sigmoid diverticulitis with peritonitis is often a two-stage operation with colon resection and a temporary stoma. This approach is associated with high mortality and morbidity and the reversal of the stoma is in many cases not performed because of concurrent diseases and age. Recently, several studies have experimented with laparoscopic lavage as a treatment of acute complicated diverticulitis. The aim of this review was to give an overview of the literature for this new approach and to determine the safety compared with Hartmann's procedure for patients with acute complicated sigmoid diverticulitis. METHODS: A PubMed search was performed for publications between 1990 and May 2008. The terms acute, perforated, diverticulitis, lavage, drainage, and laparoscopy were used in combination. The EMBASE and Cochrane databases were also searched. RESULTS: Eight studies met the inclusion criteria and reported 213 patients with acute complicated diverticulitis managed by laparoscopic lavage. None of these studies were randomized. The patients' mean age was 59 years and most patients had Hinchey Grade 3 disease. All patients were treated with antibiotics and laparoscopic lavage. Conversion to laparotomy was made in six (3%) patients and the mean hospital stay was nine days. Ten percent of the patients had complications. During the mean follow-up of 38 months, 38% of the patients underwent elective sigmoid resection with primary anastomosis. CONCLUSION: Primary laparoscopic lavage for complicated diverticulitis may be a promising alternative to more radical surgery in selected patients. Larger studies have to be made before clinical recommendations can be given.

[Gastroduodenal intussusception causing gastric retention]. / Duodenal invagination som årsag til ventrikelretention.

A case of gastroduodenal intussusception caused by a duodenal lipoma is presented. The condition was characterized by severe upper gastrointestinal retention, epigastric pain and weight loss. The mass was diagnosed by CT scan. The diagnosis was confirmed by operation. The patient was treated successfully by manually reducing the intussusception and resection of the lipoma. Histopathology confirmed the mass to be a pedunculated submucosal lipoma. The patient had an uneventful recovery.