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To determine if minimally invasive right colectomy with intra-corporeal anastomosis improves postoperative recovery compared to extra-corporeal anastomosis.Previous trials have shown that intracorporeal anastomosis improves postoperative recovery; however, it has not yet been evaluated in a setting with optimized perioperative care or with patient-related outcome measures.This was a multicenter, triple-blind, randomized clinical trial at two high-volume colorectal centers with strict adherence to optimized perioperative care pathways. The patients underwent robotic right colectomy with either intracorporeal or extracorporeal anastomosis. The primary outcome was patient-reported postoperative recovery measured using the "Quality of Recovery-15" questionnaire. ClinicalTrials.gov NCT03130166.A total of 89 patients were randomized and analyzed according to the "Intention-to-treat"-principle. We found no statistically significant differences in patient-reported recovery between the groups. Postoperative pain, nausea, time to ambulation, time to first passage of flatus/stool, length of hospital stay, and pathophysiological tests showed no differences either. The duration of time to create the anastomosis was significantly longer with intracorporeal anastomosis (17 vs 13 min, P = 0.003), while all other intraoperative, postoperative, and pathology variables showed no difference.There were no significant differences in postoperative recovery between the two groups.

AIM The aim of this study was to describe the dynamic changes in blood work following individual adjusted dosage of intravenously administered iron(III) isomaltoside in a 4-week period prior to surgery in patients with colorectal cancer. METHODS This was a single-centre, observational cohort study with prospectively collected data, including patients with colorectal cancer receiving preoperative treatment with iron(III) isomaltoside. Blood samples were taken at baseline, 1 week, 2 weeks and 4 weeks after initial treatment. Sixty-two patients were included in the study. RESULTS Sixty-two patients were included for final analysis. The mean increase in haemoglobin was 0.77 g/dl (95% CI 0.52-1.03 g/dl, P 10.31 g/dl) did not show a significant increase (0.66 g/dl, 95% CI -0.29-1.61 g/dl, P = 0.17). The mean of transferrin saturation after 4 weeks was 8% (95% CI 6%-10%, P

Background and aimsAn opioid-sparing postoperative analgesic regimen following laparoscopic hemicolectomy is optimal to promote minimal postoperative pain, early mobilization, and improved quality of recovery. Various regional anesthesia techniques have been tested to improve postoperative pain management after laparoscopic hemicolectomy. In this study, we aimed to assess the effect of administering a preoperative bilateral ultrasound-guided anterior quadratus lumborum nerve block on postoperative opioid consumption after laparoscopic colon cancer surgery.MethodsIn this randomized, controlled, double-blinded trial, 69 patients undergoing laparoscopic hemicolectomy due to colon cancer were randomized to receive an anterior quadratus lumborum block with ropivacaine 0.375% 30 mL on each side or isotonic saline (placebo). The primary outcome measure was total opioid consumption during the first 24 hours postsurgery. The secondary outcome measures were pain scores, accumulated opioid consumption in 6-hour intervals, nausea and vomiting, ability of postoperative ambulation, time to first opioid, orthostatic hypotension or intolerance, postoperative Quality of Recovery-15 scores, surgical complications, length of hospital stay, and adverse events.ResultsThe total opioid consumption in the first 24 hours postsurgery was not significantly reduced in the ropivacaine group compared with the saline group (mean 129 mg (SD 88.4) vs mean 127.2 mg (SD 89.9), p=0.93). In addition, no secondary outcome measures showed any statistically significant intergroup differences.ConclusionThe administration of a preoperative bilateral anterior quadratus lumborum nerve block as part of a multimodal analgesic regimen for laparoscopic hemicolectomy did not significantly reduce opioid consumption 24 hours postsurgery.Trial registration numberNCT03570541.

Previous studies have shown that intracorporeal anastomosis (ICA) in minimally invasive right colectomy may improve postoperative recovery compared with extracorporeal anastomosis (ECA). It has been hypothesized that creating the anastomosis extracorporeally may cause mesenteric traction and compromised intestinal perfusion. The purpose of this study was to investigate the effect of either ICA or ECA on intestinal perfusion.This was a substudy to a multicenter, triple-blind randomized clinical trial comparing ICA with ECA in patients undergoing robotic right colectomy for colonic cancer. Videos from intraoperative Indocyanine Green (ICG) fluorescence imaging were analyzed with quantitative ICG perfusion assessment (q-ICG). q-ICG was performed by extracting perfusion metrics from a time-intensity curve generated from an image analysis software: FA total of 68 patients (33 ICA and 35 ECA) were available for analysis. Demographics were similar between the groups, except for mean arterial blood pressure at the time of ICG infusion, which was significantly lower in the ICA group. We found a significantly steeper slope in the ICA group compared to the ECA group (6.3 vs. 4.7 AU/sec, P = .048). There were no significant differences in FWe found evidence of an improved intestinal perfusion following ICA compared with ECA. This finding may be related to patient outcomes and should be explored further in the future.gov NCT03130166.

AIM Enhanced recovery after surgery programmes in elective colorectal surgery have been developed and implemented widely, but a subgroup of patients may still require longer hospital stays than expected. The aim of this study was to identify and describe factors compromising early postoperative recovery by asking 'why is the patient still in hospital today?' after laparoscopic colorectal cancer surgery within an enhanced recovery after surgery programme. METHOD Patients undergoing elective laparoscopic colorectal cancer resection were evaluated postoperatively with predefined potential reasons for still being in hospital. The primary outcome was 'reason for still being in hospital' on postoperative day 0-4 and secondarily length of stay with a focus on differences between patients with and without a stoma. RESULTS Ninety-six patients having colorectal cancer surgery were included. The median length of stay for the whole group was 3 days (range 1-14). The four dominant causes for patients without a stoma to be in hospital were lack of gastrointestinal function, lack of early mobilization, lack of normal micturition and nausea. Patients with a stoma stayed in hospital due to stoma training, lack of gastrointestinal function, lack of free micturition and a miscellaneous 'others' group. CONCLUSION Delayed gastrointestinal function, insufficient mobilization, poor urinary function and stoma care training have been characterized as dominant compromising factors for postoperative recovery. Together with a focus on frailty, future studies should focus on improving early mobilization, prevention and treatment of postoperative urinary retention and improved stoma care training, in order to minimize delay in postoperative recovery and discharge.

Episodic and ongoing hypoxaemia are well-described after surgery, but, to date, no studies have investigated the occurrence of episodic hypoxaemia following minimally-invasive colorectal surgery performed in an enhanced recovery setting. We aimed to describe the occurrence of postoperative hypoxaemia after minimally-invasive surgery in an enhanced recovery setting, and the association with morphine use, incision site, fluid intake and troponin increase. We performed a prospective observational study of 85 patients undergoing minimally-invasive surgery for colorectal cancer between 25 August 2016 and 17 August 2017. We applied a pulse oximeter with a measurement rate of 1 Hz immediately after surgery either until discharge or until two days after surgery, and recorded the oxygen saturation. We measured troponin I during the first four days after surgery, or until discharge. The median (IQR [range]) length of stay was 3 (2-4 [1-38]) days. Thirty-six percent of patients spent more than 1 h below an oxygen saturation of 90% (4.2% of the day), and with a median (IQR [range]) proportion of 1.3 (0.2-11.1 [0.0-21.4])% of the day spent with an oxygen saturation below 88%. We found no associations between time spent below an oxygen saturation of 88% and morphine use (p = 0.215), fluid intake (p = 0.446), complications (p = 0.808) or extraction site (p = 0.623). Postoperative increases in troponin I were associated both with time spent below an oxygen saturation of 88% (p = 0.026) and hypopnoea episodes (p = 0.003). Even with minimally-invasive surgery and enhanced recovery after surgery, episodic hypoxaemia and hypopnoea episodes are common, but are not associated with morphine use, fluid intake or incision site. Further studies should investigate the relationship between hypoxaemia and troponin increase.

It is assumed that conventional laparoscopy (LAP) and robotic-assisted laparoscopic surgery (RALS) differ in terms of the surgeon's comfort. This study compared muscle workload, work posture and perceived physical exertion of surgeons performing LAP or RALS.Colorectal surgeons with experience in advanced LAP and RALS performed one of each operation. Bipolar surface electromyography (EMG) recordings were made from forearm, shoulder and neck muscles, and expressed relative to EMG maximum (%EMGThe study included 13 surgeons. Surgeons performing LAP showed higher static, median, and peak forearm muscle activity than those undertaking RALS. Muscle activity at peak level was higher during RALS than LAP. Exposure variation analysis demonstrated long-lasting periods of low-level intensity muscle activity in the shoulders for LAP, in the forearms for RALS, and in the neck for both procedures. Postural observations revealed a greater need for a change in work posture when performing LAP compared with RALS. Perceived physical exertion was no different between the surgical modalities.Minimally invasive surgery requires long-term static muscle activity with a high physical workload for surgeons. RALS is less demanding on posture.Se asume que la cirugía laparoscópica (laparoscopic, LAP) y la cirugía laparoscópica asistida por robot (robotic-assisted laparoscopic surgery, RALS) difieren en cuanto a la comodidad del cirujano. En este estudio se comparó la carga de trabajo muscular, la postura de trabajo y el esfuerzo físico percibido por los cirujanos al realizar LAP o RALS. MÉTODOS: Trece cirujanos colorrectales con experiencia en LAP avanzada y RALS realizaron una operación con cada uno de los abordajes. Se registró la electromiografía de superficie bipolar en los músculos del antebrazo, del hombro y del cuello, y se expresó en relación con el EMG máximo (% EMGmax). Se calculó el nivel de actividad muscular estático, mediano y pico, y se realizó un análisis de variación de la exposición. Las observaciones posturales se llevaron a cabo cada diez minutos y se registraron las valoraciones del esfuerzo físico percibido antes y después de la cirugía.La práctica de LAP mostró una mayor actividad muscular estática, mediana y pico del antebrazo en comparación con la práctica de RALS. El hombro izquierdo mostró la mayor actividad muscular en RALS a nivel máximo. El análisis de variación de exposición demostró periodos prolongados de actividad muscular de baja intensidad para LAP en los hombros, para RALS en los antebrazos y para ambos en el cuello. Las observaciones posturales mostraron una mayor necesidad de un cambio en la postura de trabajo al realizar LAP en comparación con RALS. El esfuerzo físico percibido no fue diferente entre ambas modalidades quirúrgicas. CONCLUSIÓN: La cirugía mínimamente invasiva requiere una actividad muscular estática prolongada con una alta carga de trabajo físico para los cirujanos. RALS es menos exigente en el aspecto postural.

Little is known about factors affecting the initiation of adjuvant chemotherapy (AC) after minimally invasive surgery. The aim of this study was to describe the ratio of patients undergoing uncomplicated colorectal cancer surgery in a standardised enhanced recovery after surgery setting receiving AC. Furthermore, the association between post-operative quality of recovery and initiation of AC was investigated.This was a prospective study. Post-operative recovery was measured with the Quality of Recovery-15 questionnaire preoperatively, post-operatively on day 1, at discharge and on post-operative day 30.A total of 115 patients were included between October 2016 and May 2017. Among these, 20 patients were excluded. Hence, 95 patients were followed up as uncomplicated cases. The median length of stay was three days (interquartile range: 2-4). A total of 40 patients were referred for oncological evaluation, but nine patients did not proceed to receive AC. Among the 31 patients starting AC, 48% (n = 15) received AC less-than 4 weeks and 52% (n = 16)4 weeks. No significant difference was seen in post-operative quality of recovery, either when investigating the full cohort or subgroups of patients who initiated AC before and after four weeks.Post-operative recovery may not be the factor limiting patients from receiving adjuvant chemotherapy either before or after post-operative week four.none.The study was approved by the Data Protection Agency (reg. no. REG044-2018).

Background Orthostatic hypotension (OH) and intolerance (OI) are common findings in the early postoperative period after major surgery and may delay early mobilization. The mechanism of impaired orthostatic competence and OI symptoms is not fully understood, and specific data after colorectal surgery with well-defined perioperative care regimens and mobilization protocols are lacking. The aim of this study was to investigate the prevalence, possible risk factors and the impact of OI in patients undergoing elective minimal invasive colorectal cancer resection. Methods A prospective single-centre study with an optimal enhanced recovery program and multimodal analgesic treatment. OI and OH were evaluated using a well-defined mobilization protocol preoperatively and 6 hour and 24 hour postoperatively. Results A total of 100 patients were included in the data analysis. The overall median length of stay was 3 days (1-38). OI was observed in 53% of the patients 6 hour postoperatively and in 24% at 24 hour. OI at 6 hour postoperatively was associated with younger age, lower BMI, and female gender. At 24 hour postoperatively, female gender and ASA class >1 was associated with OI. Opioid consumption and intravenous fluid during the first 24 hour was not associated with OI. Postoperative complications were equally observed between patients with and without OI. Although not statistically significant, patients with OI at 24 hour postoperatively had prolonged LOS (mean 4.0 vs 7.5 days, P = 0.069) compared with patients without OI. Conclusion Postoperative orthostatic intolerance is a common problem during the first 24 hour following laparoscopic colorectal resection and may be followed by delayed recovery.

Identification of lymph nodes and pathological analysis is crucial for the correct staging of colon cancer. Lymph nodes that drain directly from the tumor area are called “sentinel nodes” and are believed to be the first place for metastasis. The purpose of this study was to perform sentinel node mapping in vivo with indocyanine green and ex vivo with methylene blue in order to evaluate if the sentinel lymph nodes can be identified by both techniques. Patients with colon cancer UICC stage I–III were included from two institutions in Denmark from February 2015 to January 2016. In vivo sentinel node mapping with indocyanine green during laparoscopy and ex vivo sentinel node mapping with methylene blue were performed in all patients. Twenty-nine patients were included. The in vivo sentinel node mapping was successful in 19 cases, and ex vivo sentinel node mapping was successful in 13 cases. In seven cases, no sentinel nodes were identified. A total of 51 sentinel nodes were identified, only one of these where identified by both techniques (2.0%). In vivo sentinel node mapping identified 32 sentinel nodes, while 20 sentinel nodes were identified by ex vivo sentinel node mapping. Lymph node metastases were found in 10 patients, and only two had metastases in a sentinel node. Placing a deposit in relation to the tumor by indocyanine green in vivo or of methylene blue ex vivo could only identify sentinel lymph nodes in a small group of patients.

Total mesorectal excision and neoadjuvant radio-chemo-therapy is the standard treatment of locally advanced rectal cancer. In 4-12% of all patients a local recurrence will develop, with more than half located on the lateral pelvic side wall. It is an ongoing controversy, whether malignant lateral pelvic lymph nodes should be considered as regional or distant disease. The role of lateral pelvic lymph node dissection in a Western treatment setting is not clarified, but in this review, we argue that it may reduce the risk of local recurrence in selected patients with locally advanced disease.

A subgroup of patients with benign colonic neoplasia is unsuitable for standard endoscopic treatment modalities. These patients may benefit from a combined endoscopic and laparoscopic surgical (CELS) approach. A CELS procedure may even be an option for some patients with a small malignant lesion where resection of the colon may be associated with an excessively high risk of proced-ure-related morbidity and mortality.All patients considered for a CELS procedure were evaluated at a multidisciplinary team conference. The CELS procedures were performed as laparoscopy-assisted endoscopic mucosal resections or endoscopy-assisted laparoscopic resections.A total of 25 patients were included. Five patients had a malignant and 20 patients had a benign lesion. Two patients with histologically verified malignant lesions pre-operatively had CELS performed due to severe co-morbidity. In one patient with initially benign biopsies, the resected CELS specimen revealed adenocarcinoma. This patient subsequently underwent oncological resection (no residual disease). In the last two cases, the lesions were assessed during CELS and they exhibited endoscopically malignant features. Consequently, both patients underwent immediate oncological segmental colon resection.CELS is a feasible treatment for colonic neoplasia where endoscopic resection alone is not technically possible. In case of severe co-morbidity ruling out segmental resection in patients diagnosed with T1 or T2 colorectal cancer, CELS treatment may be considered.none.This study was assessed by The National Committee on Health Research Ethics (SJ-593), which concluded that the study required no approval from the Committee. The study was approved by the Danish Data Protection Agency (REG-126-2017). .

Early catheter removal is essential to enhance postoperative mobilization and recovery, but may carry a risk of urinary retention. This study aimed to evaluate a standardized regimen for early postoperative catheter removal and re-catheterization in patients undergoing elective laparoscopic colorectal cancer surgery within an optimal ERAS setting. This was a single-center prospective study of patients undergoing elective minimally invasive colorectal resection and postoperative catheter removal within 24 h, with a re-catheterization threshold of 800 ml bladder volume. The primary outcome was postoperative urinary retention rate, and the secondary outcomes were time of catheter removal and length of stay with a special focus on differences between colon and rectal resections. A total of 113 patients were included in the study, and 87 patients were eligible for the final analysis. Rectal resection was performed in 22 of 87 patients, and all operations were performed with minimally invasive technique. The conversion rate was 3.5%, and 30-day mortality was 0%. More than 95% of the patients had their catheter removed within 24 h with no difference between rectal and colonic resections. Postoperative urinary retention was observed in 9% of all patients (rectum 18% vs. colon 6%, p = 0.11). One patient had an indwelling catheter at discharge, but all patients had free voluntary micturition at 30-day follow-up. Median length of stay was 3 days (1–13 days). Catheter removal within 24 h of surgery using a re-catheterization threshold of 800 ml is safe and reduces unnecessary re-catheterizations following minimally invasive colorectal resection.

Background Colorectal cancer (CRC) patients with metastatic disease can become cured if neoadjuvant treatment can enable a resection. The search for predictive biomarkers is often performed on primary tumours tissue. In order to assess the effectiveness of tailored treatment in regard to the primary tumour the differences in the genomic profile needs to be clarified. Methods Fresh-frozen tissue from primary tumours, synchronous liver metastases and adjacent normal liver was collected from 21 patients and analysed by whole-exome sequencing on the Illumina HiSeq 2500 platform. Gene variants designated as ‘damaging’ or ‘potentially damaging’ by Ingenuity software were used for the subsequent comparative analysis. BAM files were used as the input for the analysis of CNAs using NEXUS software. Results Shared mutations between the primary tumours and the synchronous liver metastases varied from 50 to 96%. Mutations in APC, KRAS, NRAS, TP53 or BRAF were concordant between the primary tumours and the metastases. Among the private mutations were well-known driver genes such as PIK3CA and SMAD4. The number of mutations was significantly higher in patients with right- compared to left-sided tumours (102 vs. 66, p = 0.004). Furthermore, right- compared to left-sided tumours had a significantly higher frequency of private mutations (p = 0.023). Similarly, CNAs differed between the primary tumours and the metastases. The difference was mostly comprised of numerical and segmental aberrations. However, novel CNAs were rarely observed in specific CRC-relevant genes. Conclusion The examined primary colorectal tumours and synchronous liver metastases had multiple private mutations, indicating a high degree of inter-tumour heterogeneity in the individual patient. Moreover, the acquirement of novel CNAs from primary tumours to metastases substantiates the need for genomic profiling of metastases in order to tailor metastatic CRC therapies. As for the mutational status of the KRAS, NRAS and BRAF genes, no discordance was observed between the primary tumours and the metastases. Electronic supplementary material The online version of this article (10.1186/s12885-018-4639-4) contains supplementary material, which is available to authorized users.

Summary Background Myocardial injury after non-cardiac surgery (MINS) increases the risk of cardiovascular events and deaths, which anticoagulation therapy could prevent. Dabigatran prevents perioperative venous thromboembolism, but whether this drug can prevent a broader range of vascular complications in patients with MINS is unknown. The MANAGE trial assessed the potential of dabigatran to prevent major vascular complications among such patients. Methods In this international, randomised, placebo-controlled trial, we recruited patients from 84 hospitals in 19 countries. Eligible patients were aged at least 45 years, had undergone non-cardiac surgery, and were within 35 days of MINS. Patients were randomly assigned (1:1) to receive dabigatran 110 mg orally twice daily or matched placebo for a maximum of 2 years or until termination of the trial and, using a partial 2-by-2 factorial design, patients not taking a proton-pump inhibitor were also randomly assigned (1:1) to omeprazole 20 mg once daily, for which results will be reported elsewhere, or matched placebo to measure its effect on major upper gastrointestinal complications. Research personnel randomised patients through a central 24 h computerised randomisation system using block randomisation, stratified by centre. Patients, health-care providers, data collectors, and outcome adjudicators were masked to treatment allocation. The primary efficacy outcome was the occurrence of a major vascular complication, a composite of vascular mortality and non-fatal myocardial infarction, non-haemorrhagic stroke, peripheral arterial thrombosis, amputation, and symptomatic venous thromboembolism. The primary safety outcome was a composite of life-threatening, major, and critical organ bleeding. Analyses were done according to the intention-to-treat principle. This trial is registered with ClinicalTrials.gov, number NCT01661101. Findings Between Jan 10, 2013, and July 17, 2017, we randomly assigned 1754 patients to receive dabigatran (n=877) or placebo (n=877); 556 patients were also randomised in the omeprazole partial factorial component. Study drug was permanently discontinued in 401 (46%) of 877 patients allocated to dabigatran and 380 (43%) of 877 patients allocated to placebo. The composite primary efficacy outcome occurred in fewer patients randomised to dabigatran than placebo (97 [11%] of 877 patients assigned to dabigatran vs 133 [15%] of 877 patients assigned to placebo; hazard ratio [HR] 0·72, 95% CI 0·55–0·93; p=0·0115). The primary safety composite outcome occurred in 29 patients (3%) randomised to dabigatran and 31 patients (4%) randomised to placebo (HR 0·92, 95% CI 0·55–1·53; p=0·76). Interpretation Among patients who had MINS, dabigatran 110 mg twice daily lowered the risk of major vascular complications, with no significant increase in major bleeding. Patients with MINS have a poor prognosis; dabigatran 110 mg twice daily has the potential to help many of the 8 million adults globally who have MINS to reduce their risk of a major vascular complication. Funding Boehringer Ingelheim and Canadian Institutes of Health Research.

Electroporation with calcium (calcium electroporation) can induce ATP depletion-associated cellular death. In the clinical setting, the cytotoxic drug bleomycin is currently used with electroporation (electrochemotherapy) for palliative treatment of tumors. Calcium electroporation offers several advantages over standard treatment options: calcium is inexpensive and may readily be applied without special precautions, as is the case with cytostatic drugs. Therefore, details on the use of calcium electroporation are essential for carrying out clinical trials comparing calcium electroporation and electrochemotherapy.The effects of calcium electroporation and bleomycin electroporation (alone or in combination) were compared in three different cell lines (DC-3F, transformed Chinese hamster lung fibroblast; K-562, human leukemia; and murine Lewis Lung Carcinoma). Furthermore, the effects of electrical pulsing parameters and calcium compound on treatment efficacy were determined.Electroporation with either calcium or bleomycin significantly reduced cell survival (p0.0001), without evidence of a synergistic effect. Cellular death following calcium or bleomycin treatment occurred at similar applied voltages, suggesting that similar parameters should be applied. At equimolar concentrations, calcium chloride and calcium glubionate resulted in comparable decreases in cell viability.Calcium electroporation and bleomycin electroporation significantly reduce cell survival at similar applied voltage parameters. The effect of calcium electroporation is independent of calcium compound.This study strongly supports the use of calcium electroporation as a potential cancer therapy and the results may aid in future clinical trials.

Fibrin sealant for mesh fixation has significant positive effects on early outcome after laparoscopic ventral hernia repair (LVHR) compared with titanium tacks. Whether fibrin sealant fixation also results in better long-term outcome is unknown. We performed a randomized controlled trial including patients with umbilical hernia defects from 1.5 to 5 cm at three Danish hernia centres. We used a 12 cm circular mesh. Participants were randomized to fibrin sealant or titanium tack fixation. Patients were seen in the outpatient clinic at 1 and 12 months follow-up. Forty patients were included of whom 34 were available for intention to treat analysis after 1 year. There were no significant differences in pain, discomfort, fatigue, satisfaction or quality of life between the two groups at the 1-year follow-up. Five patients (26 %) in the fibrin sealant group and one (6 %) in the tack group were diagnosed with a recurrence at the 1-year follow-up (p = 0.182) (overall recurrence rate 17 %). Hernia defects in patients with recurrence were significantly larger than in those without recurrence (median 4.0 vs. 2.8 cm, p = 0.009). Patients with larger hernia defects and fibrin sealant mesh fixation had higher recurrence rates than expected, although the study was not powered for assessment of recurrence. There was no significant difference between groups in any parameters after the 1-year follow-up. The beneficial effects of mesh fixation with fibrin sealant on early outcome warrant further studies on optimization of the surgical technique to prevent recurrence.

Robot-assisted laparoscopy has been reported to be a safe and feasible alternative to traditional laparoscopy. The aim of this study was to compare short-term results in patients with colonic cancer who underwent robot-assisted laparoscopic colonic resection (RC) or laparoscopic colonic resection (LC). The study was a retrospective case control study of all patients with colonic cancer who underwent RC from March 2010 to March 2012 or LC from January 2009 to December 2011 at a tertiary-care university hospital. Data were retrieved from the national chart database and patient journals. Biochemical markers [C-reactive protein (CRP), hemoglobin, white blood cell count, and thrombocyte count] were recorded before surgery and for the first 3 days after surgery. A total of 101 patients underwent RC and 162 patients underwent LC. There were no significant differences in the rate of conversion to open surgery, number of permanent enterostomies, number of intraoperative complications, level of postoperative cellular stress response, number of postoperative complications, length of postoperative hospital stay, or 30-day mortality between the two groups. There was a significantly longer setup time for RC (77.1 vs. 69.7 min, P = 0.000), but surgical time was significantly shorter for RC (165.8 vs. 183.4 min, P = 0.006) and there was no difference in the overall procedure time (254.0 vs. 243.6 min, P = 0.086). We found RC to be a safe and feasible alternative to LC for colonic cancer. We found that for RC surgical time was shorter and overall procedure time was comparable to that for LC; however, these results should be confirmed in future randomized clinical trials.

BACKGROUND: Laparoscopic ventral hernia repair (LVHR) is a well established procedure in the treatment of ventral hernias. It is our clinical experience that patients suffer intense postoperative pain, but this issue and other recovery parameters have not been studied in detail.METHODS: Thirty-five patients with hernias >3 cm prospectively underwent LVHR using "double-crown" titanium tack mesh fixation. Pre- and postoperative pain was measured on a 0-100-mm visual analogue scale (VAS) and health-related quality of life was measured using the Short Form 36 questionnaire (SF-36). Several other recovery parameters were measured systematically in the 6 months follow-up period.RESULTS: We observed no recurrences or severe complications in the follow-up period (n = 31 at day 30 and n = 28 after 6 months). The median in-hospital stay was 2 days (range 0-5). Patients reported significantly more pain during activity than at rest at all times (p < 0.05). The median VAS-pain score during activity vs. at rest at discharge was 60 and 31, respectively. The median VAS-pain score during activity on the day of operation (day 0) was 78; it returned to baseline values at day 30 (p = 0.148) and, after 6 months, it was below the preoperative score (p = 0.01). The scores for general well-being and fatigue returned to baseline values at days 3 and 30, respectively, and at 6 months, they had both significantly improved compared with preoperative values (p = 0.005). The SF-36 scores were significantly worse in three domains at day 30 (p < 0.005). After 6 months, the bodily pain score had increased significantly compared with preoperative values (p < 0.005) and all eight scales were comparable to the Danish reference population scores. Patients resumed normal daily activities after a median of 14 days (range 1-38). Smokers and patients with hard physical demands at work took a significantly longer amount of time to resume work compared with non-smokers (30 vs. 9 days, p < 0.005) and patients with light work demands (29 vs. 9 days, p < 0.05), respectively. VAS-pain scores were strongly correlated to general well-being (r = -0.8, p < 0.001), patient satisfaction (r = -0.67, p < 0.001) and quality of life (r = -0.63, p < 0.001). We found no significant correlation between the number of tacks used (median 59) and postoperative pain.CONCLUSION: LVHR was associated with considerable postoperative pain and fatigue in the first postoperative month, prolonging the time of convalescence and significantly affecting patients' quality of life up to 6 months postoperatively. Mesh fixation with fibrin glue or other non-invasive/degradable products seems promising for reducing pain and it should be investigated in future randomised trials.

Gene transfer to skeletal muscle leads to long-term, stable expression of transferred genes. An exiting development is the use of inducible expression systems. Using the inducible Tet-On system, it has been customary to administer doxycycline in drinking water with added sucrose to ameliorate the bitter taste. During a study aiming at regulating electrotransferred genes through the Tet-On system, we observed excessive drinking behavior among mice. Removal of sugar from the drinking water led to normal drinking behavior and most importantly did not affect the level of gene expression. Based on this study, the practice of adding sucrose to drinking water in doxycycline induction studies should be abandoned.

INTRODUCTION: Incomplete specimens resulting in residual mesorectum in the patient and an increased risk of local recurrence remains a problem. We have introduced transanal-total mesorectal excision (Ta-TME) in our department to potentially overcome this problem due to more direct access to the lower pelvis in patients undergoing TME for rectal cancer and this article presents our initial experience with the new procedure. MATERIALS AND METHODS: Patients with a T1-T3 mid or low rectal cancer eligible for TME or intersphincteric abdominoperineal excision were selected for a combined transanal and transabdominal laparoscopic resection. The primary aim of the study was to evaluate the feasibility and efficacy of the method with a special focus on the quality of the specimen. RESULTS: During a 9-month period, 11 patients were operated with this technique. All procedures resulted in complete or nearly complete specimen. We did, however, find the procedure technically demanding and experienced several complications with three anastomotic leaks (all with preserved intestinal continuity) and a urethral lesion. CONCLUSION: Ta-TME is feasible and might be the answer to obtaining good quality specimens and overcome some of the technical difficulties that can be encountered in the obese narrow male pelvis. The procedure however is technically demanding.

Prognosis for colorectal cancer is dependent on radical surgical intervention. Chemotherapy in patients with advanced disease has improved the survival. A considerable proportion of the patients going through radical surgery will subsequently relapse. Adjuvant chemotherapy is reserved for patients with lymph node metastases, why undetected malignant lymph nodes will result in understaging and exclusion from the possible benefit of adjuvant chemotherapy. With sentinel lymph node mapping it may be possible to detect and resect more malignant lymph node and maybe even avoid extensive resections.

Implementation of robotic technology in surgery is challenging in many ways. The aim of this study was to present the implementation process and results of the first two years of consecutive robot-assisted laparoscopic (RAL) colorectal procedures.The study was a retrospective study of a consecutive, unselected patient population. All outcome parameters were predefined and all patients completed 30-day follow-up. All parameters were reported, including complication rate, reoperation rate and mortality.From April 2010 to April 2012, a total of 223 elective RAL colorectal procedures were performed. The procedures were grouped as follows: left colectomy/sigmoid resection (n = 65), low anterior resection (n = 50), abdominoperineal resection (n = 10), right colectomy (n = 56), rectopexia (n = 21), colectomy (n = 8), palliative procedure (n = 8) and stoma reversal (n = 8). The overall mortality rate was 0.4%; intra- and post-operative complication rates were 5.4% and 16%, respectively; and the reoperation rate was 9%. Conversion to open surgery was necessary in 9% of cases. A positive learning curve was found for low anterior resections with a significant decrease in duration of surgery over the course of the study period.RAL colorectal surgery can be performed as a standard procedure for most colorectal procedures. Appropriate staff education, surgical plan and quality assessment are necessary and we recommend a credentialing system for robotic surgery certification. Future randomized clinical trials should be performed to evaluate the short- and long-term results in these patients.not relevant.not relevant.

The cellular distribution of mRNAS for urokinase-type plasminogen activator (uPA), its specific receptor (uPAR), and its inhibitors (PAI-1 and -2) in mouse skin was analyzed by in situ hybridization after topical application of the tumor promoter phorbol 12-myristate 13-acetate. In the epidermis, strong signals for uPA and PAI-1 mRNA were detected 24 h after treatment in the basal and suprabasal epidermal keratinocytes in areas with pronounced hyperproliferation and increased terminal differentiation, and in some hair follicle keratinocytes. After 48 h, both uPAR and PAI-2 mRNAs were expressed in the epidermal layers from the suprabasal keratinocytes up to the differentiating cells beneath the cornified layer and in hair follicle keratinocytes. Induction of PAI-2 mRNA was detected in epidermis as early as 3 h after treatment and remained stable for up to 7 days. In the dermis, 5 h after application of phorbol 12-myristate 13-acetate to the skin, uPA mRNA was detected in fibroblast-like cells below and around the skin muscle, and PAI-1 mRNA was detected in stromal cells located above the skin muscle. After longer exposure to phorbol 12-myristate 13-acetate, the PAI-1 mRNA-expressing stromal cells were located more superficially, apparently moving toward the epidermal layer. After 9 h, most of the PAI-1 mRNA-positive cells were identified as endothelial cells. Up to 24 h after the application of phorbol 12-myristate 13-acetate, the intensity of the signal for both uPA and PAI-1 increased, followed by a gradual decrease for up to 7 days. These results show that in mouse skin treated with a tumor-promoting phorbol ester, the various components of the plasminogen activation system are expressed by both epithelial and stromal cell types, which in dermis and subcutis are located in different places, depending on the time of exposure to the phorbol ester. Our results suggest that urokinase-mediated extracellular proteolysis has diverse functional roles during the early steps of tumor promotion.

Severe pain is usual after laparoscopic ventral hernia repair (LVHR). Mesh fixation with titanium tacks may play a key role in the development of acute and chronic pain and alternative fixation methods should therefore be investigated. This PhD thesis was based on three studies and aimed too: 1) assess the intensity and impact of postoperative pain by detailed patient-reported description of pain and convalescence after LVHR (Study I), 2) evaluate the feasibility of fibrin sealant (FS) for mesh fixation in an experimental pig model (Study II), and 3) investigate FS vs. tacks for mesh fixation in LVHR in a randomised, double-blinded, clinical controlled study with acute postoperative pain as the primary outcome (Study III). In Study I - a prospective descriptive study - 35 patients were prospectively included and underwent LVHR. Scores of pain, quality of life, convalescence, fatigue, and general well-being were obtained from each patient. Follow-up was six months. Average pain from postoperative day (POD) 0-2 and POD 0-6 measured on a 0-100 mm visual analogue scale (VAS) was 61 and 48, respectively. Pain scores reached preoperative values at POD 30. The incidence of severe chronic pain was 7%. No parameter predicted postoperative pain significantly. Significant correlations were found between pain, and general well-being (rS= -0.8, p0.001), satisfaction (rS= -0.67, pquality of life score (rS= -0.63, p0.001) six months postoperatively. Patients resumed normal daily activity at POD 14. In Study II - a randomised experimental study in pigs - nine pigs were operated laparoscopically with insertion of two different meshes fixed with either FS or tacks. All pigs were euthanized on POD 30. The primary outcome parameter was strength of ingrowth between the mesh and the anterior abdominal wall. A mechanical peel test was performed for each tissue sample. The secondary outcome parameters were grade and strength of adhesions to the mesh, shrinkage and displacement/folding of the mesh and histological parameters. All nine pigs survived without complications until sacrifice. No meshes were displaced from their initial position at autopsy, but in two cases mesh folding was observed. No significant difference in strength of ingrowth was found between different fixation methods or mesh types. Furthermore, no significant difference was found in grade or strength of adhesions or any histological parameters. In Study III - a randomised, controlled, double-blinded, multicenter trial - 40 patients with umbilical hernia defects between 1.5-5 cm, were randomly assigned to receive FS or titanium tacks for mesh fixation in LVHR. Patients, care givers and those assessing the outcomes were blinded to group assignment. The primary outcome was average pain from POD 0-2 (VAS score). Secondary outcome parameters were fatigue, general well-being and time to resume normal daily activity. Follow-up was one month for all. Patients in the FS group reported significantly less pain at POD 0-2 (median VAS 38 (range 6-98) vs. 60 (18-96), p = 0.01). Absolute VAS score difference between groups was 20 mm (95% CI 4-35 mm) at activity, and 19 mm (95% CI 3-34 mm) at rest. Patients in the FS group reported significantly less discomfort from POD 0-2 and POD 0-10, compared with the tack group. No significant difference was found in fatigue score between groups. No significant difference in hospital stay, hernia diameter, or morphine consumption in the post anesthesia care unit was found between groups. Patients in the FS group resumed normal daily activity at POD 7 (1-66) versus POD 18 (1-95) in the tack group (p = 0.03). No recurrences were observed. No adverse events or side effects were observed. No significant differences in predefined complications were found between groups. In conclusion, pain is a significant clinical problem after LVHR with impact on general well-being, quality of life and patient satisfaction. This issue must have first priority in future ventral hernia repair research. It is now documented, that the simple application of fibrin glue instead of titanium tacks for mesh fixation in LVHR of defects5 cm significantly reduced acute pain, discomfort and the period of convalescence. Long-term follow-up will show the value of FS fixation in terms of chronic pain and recurrence. As FS potentially may solve many of the outcome problems associated with LVHR, future studies should include larger hernia defects including large incisional hernias, as the operative technique may be different.

Background The use of tacks for mesh fixation may induce pain after surgery for ventral hernia. The aim of this study was to compare postoperative pain after laparoscopic ventral hernia repair (LVHR) with conventional mesh fixation using titanium tacks versus fibrin sealant (FS). Methods This randomized clinical trial included patients with an umbilical hernia defect ranging from 1·5 to 5 cm at three Danish hernia centres. Participants were assigned randomly to FS or titanium tack fixation. The primary outcome was acute pain, defined as the mean pain score on days 0–2 after surgery, measured on a 0–100-mm visual analogue scale (VAS). Results Forty patients were included, of whom 38 were available for intention-to-treat analysis after 1 month. Patients in the FS group reported less pain than those in the tack group on days 0–2, both at rest (median 19 versus 47 mm; P = 0·025) and during activity (38 versus 60 mm; P = 0·014). The absolute difference in pain score between groups was 19 (95 per cent confidence interval 3 to 34) and 20 (4 to 35) mm at rest and during activity respectively. Patients in the FS group resumed normal daily activity earlier (after median 7 versus 18 days; P = 0·027) and reported significantly less discomfort. No recurrences were observed. Conclusion Mesh fixation with FS in LVHR was associated with less acute postoperative pain, discomfort and a shorter convalescence than tack fixation. Long-term follow-up is needed to show whether the effect of FS fixation persists in terms of chronic pain and recurrence. Registration number: NCT00842842 (http://www.clinicaltrials.gov).

National Danish guidelines for the diagnosis and treatment of Helicobacter pylori (Hp) infection have been approved by the Danish Society for Gastroenterology. All patients with peptic ulcer disease, gastric cancer, and MALT lymphoma should be tested for Hp. We also recommend testing in first degree relatives to patients with gastric cancer, in NSAID-naive patients, who need long-term NSAID therapy, and in patients presenting with dyspepsia and no alarm symptoms. Non-endoscoped patients can be tested with a urea-breath test or a faecal antigen test. Endoscoped patients can be tested with a rapid urease test. Proton pump inhibitor therapy should be stopped at least 1 week prior to Hp testing. All infected patients should be offered Hp eradication therapy. First-line treatment is 7-day triple therapy with a proton pump inhibitor and clarithromycine in combination with metronidazole or amoxicilline. Quadruple therapy for 2 weeks with bismuthsubsalicylate, tetracycline, metronidazole and a proton pump inhibitor is recommended in case of treatment failure. Hp testing should be offered to all patients after eradication therapy but is mandatory in patients with ulcer disease, noninvasive gastric cancer or MALT lymphoma. Testing after eradication should not be done before 4 weeks after treatment has ended.

In development of novel vaccines, attention is drawn to DNA vaccinations. They are heat stable and can be easily produced. Gene electrotransfer is a simple and nonviral means of transferring DNA to cells and tissues and is attracting increasing interest. One very interesting perspective with gene electrotransfer is that choice of tissue can determine the duration of transgene expression. With gene electrotransfer to muscle, long-term expression, that is beyond 1 year, can be obtained, whereas gene electrotransfer to skin gives short-term expression, which is desirable in, for example, DNA vaccinations. Level and duration of transgene expression after gene electrotransfer to skin is essential and here we present data from two independent quantitative studies. Using in vivo bioimaging of a far-red fluorescent molecule, Katushka, allowing for continuous monitoring of local gene expression, compared with measurements of a systemic transgene, that is, serum erythropoietin (EPO) after gene electrotransfer with EPO to skin, we found a significant increase in transgene expression (P< 0.01) with a peak 9 days (Katushka) and 14 days (EPO) after transfection. Duration of expression could be 3-4 weeks, which is a suitable time frame for vaccinations and is applicable, for example, in gene therapy for wound healing or treatment of cancer.

DNA electrotransfer to muscle tissue yields long-term, high levels of gene expression; showing great promise for future gene therapy. We want to characterize the novel far-red fluorescent protein Katushka as a marker for gene expression using time domain fluorescence in vivo imaging. Highly efficient transgenic expression was observed after DNA electrotransfer with 100-fold increase in fluorescent intensity. The fluorescent signal peaked 1 week after transfection and returned to background level within 4 weeks. Katushka expression was not as stable as GFP expression, which was detectable for 8 weeks. Depth and 3D analysis proved that the expression was located in the target muscle. In vivo bio-imaging using the novel Katushka fluorescent protein enables excellent evaluation of the transfection efficacy, and spatial distribution, but lacks long-term stability.

International audience; Gene electrotransfer is gaining momentum as an efficient methodology for nonviral gene transfer. In skeletal muscle, data suggest that electric pulses play two roles: structurally permeabilizing the muscle fibers and electrophoretically supporting the migration of DNA toward or across the permeabilized membrane. To investigate this further, combinations of permeabilizing short high-voltage pulses (HV; hundreds of V/cm) and mainly electrophoretic long low-voltage pulses (LV; tens of V/cm) were investigated in muscle, liver, tumor, and skin in rodent models. The following observations were made: (1) Striking differences between the various tissues were found, likely related to cell size and tissue organization; (2) gene expression is increased, if there was a time interval between the HV pulse and the LV pulse; (3) the HV pulse was required for high electrotransfer to muscle, tumor, and skin, but not to liver; and (4) efficient gene electrotransfer was achieved with HV field strengths below the detectability thresholds for permeabilization; and (5) the lag time interval between the HV and LV pulses decreased sensitivity to the HV pulses, enabling a wider HV amplitude range. In conclusion, HV plus LV pulses represent an efficient and safe option for future clinical trials and we suggest recommendations for gene transfer to various types of tissues.

International audience; Gene transfer by electroporation is gaining momentum now that high-level, long-term expression of transgenes is being obtained. Several different pulse regimens are efficient, yet little information is available about the physiological muscular response to gene electrotransfer. This paper provides a comprehensive evaluation of the physiological and molecular effects on host tissue after DNA electrotransfer. We have tested several pulse regimens with special emphasis on the pulse combination of a short (100 microsec) high-voltage (HV) pulse followed by a long low-voltage (LV) pulse used for DNA electrotransfer, comparing it with 8 HV pulses designed to ensure extensive permeabilization of the muscle membrane. Using both mouse and rat skeletal muscle tissue, we investigated cell permeabilization by the 51Cr-labeled EDTA assay, lactate dehydrogenase release, Na+ and Ca2+ influx, K+ efflux, ATP release, and water content, as well as muscle function both in vivo and ex vivo, Hsp70 induction, and histology. In all these assays, the HVLV pulse combination gave rise to minimal disturbance of cell function, in all cases significantly different from results when using 8 HV pulses. The evaluated parameters were normalized after 1 week. The addition of DNA caused significantly more transmembrane exchange, and this may be due to entrance of the DNA through the membrane. In conclusion, this study comprehensively documents the immediate effects of DNA electrotransfer and shows that only slight cell disturbances occur with the HVLV pulses used for gene transfer. This is highly important, as minimal perturbation of cell physiology is essential for efficient transgene expression.

The aim of this study was to investigate the cholecystectomy rate and rate of gallstone-related complications in patients formerly seen and discharged without operation from the Clinic for Day-Surgery, Glostrup University Hospital, Denmark.From January 2000 to December 2002 a total of 222 patients with gallstones were discharged without operation (lap. cholecystectomy) from the day-surgery clinic. All admittances and surgical procedures in the follow-up period were identified by reading patient files and strategic searches in the National Patient Register in which all operations in Denmark are registered.The median follow-up period was 37 months (range 5-62 months). 25% of patients were operated in the follow-up period (cholecystectomy, n = 54, gallstone ileus, n=1). 13% had gallstone-related complications in the follow-up period. 9 patients had one or more endoscopic retrograde cholangiographies. There was no mortality or serious surgical complications.There is a lack of objective criteria for cholecystectomy in symptomatic cholecystolithiasis. The national guidelines in Denmark advocate cholecystectomy only in patients with socially disabling pain attacks. These guidelines are followed in our department and the strategy seems acceptable and patient-friendly, although the optimal treatment strategy for patients with symptomatic gallstone disease is still unknown.

Background Gene transfer by electroporation (DNA electrotransfer) to muscle results in high level long term transgenic expression, showing great promise for treatment of e.g. protein deficiency syndromes. However little is known about the effects of DNA electrotransfer on muscle fibres. We have therefore investigated transcriptional changes through gene expression profile analyses, morphological changes by histological analysis, and physiological changes by force generation measurements. DNA electrotransfer was obtained using a combination of a short high voltage pulse (HV, 1000 V/cm, 100 μs) followed by a long low voltage pulse (LV, 100 V/cm, 400 ms); a pulse combination optimised for efficient and safe gene transfer. Muscles were transfected with green fluorescent protein (GFP) and excised at 4 hours, 48 hours or 3 weeks after treatment. Results Differentially expressed genes were investigated by microarray analysis, and descriptive statistics were performed to evaluate the effects of 1) electroporation, 2) DNA injection, and 3) time after treatment. The biological significance of the results was assessed by gene annotation and supervised cluster analysis. Generally, electroporation caused down-regulation of structural proteins e.g. sarcospan and catalytic enzymes. Injection of DNA induced down-regulation of intracellular transport proteins e.g. sentrin. The effects on muscle fibres were transient as the expression profiles 3 weeks after treatment were closely related with the control muscles. Most interestingly, no changes in the expression of proteins involved in inflammatory responses or muscle regeneration was detected, indicating limited muscle damage and regeneration. Histological analysis revealed structural changes with loss of cell integrity and striation pattern in some fibres after DNA+HV+LV treatment, while HV+LV pulses alone showed preservation of cell integrity. No difference in the force generation capacity was observed in the muscles 2 weeks after DNA electrotransfer. Conclusion The small and transient changes found in the gene expression profiles are of great importance, as this demonstrates that DNA electrotransfer is safe with minor effects on the muscle host cells. These findings are essential for introducing the DNA electrotransfer to muscle for clinical use. Indeed the HV+LV pulse combination used has been optimised to ensure highly efficient and safe DNA electrotransfer.

Surgical treatment of ventral hernias has changed dramatically over the past decades by the introduction of laparoscopy and prosthetic biomaterials for reinforcement of the abdominal wall. There are many meshes available on the market for laparoscopic ventral hernia repair (LVHR), and new meshes are introduced regularly. Experimental and clinical documentation for safety and efficacy are, however, often not available for the clinician. The choice of mesh may therefore be difficult in clinical practice. We present a review of the current literature regarding safety measures such as adhesions, fistulas, and infections as well as the available data on pain, recurrence, mesh shrinkage, and seroma formation after LVHR.The literature was searched systematically using PubMed/MEDLINE and EMBASE for controlled studies, prospective descriptive series and retrospective case series.The literature clearly points in the direction of very few mesh-related complications after LVHR. Experimental studies and theoretical considerations may argue for using a covered mesh, i.e., a composite mesh, or ePTFE for LVHR in humans, although it is important to stress that there are no human data at the moment to support this. Concerns about using pure polypropylene mesh in the intraperitoneal position may be re-evaluated with the experience of lightweight macropore meshes from open surgery in mind. There is a tendency towards greater shrinkage in ePTFE-based meshes but no differences seems to exist between different mesh materials in other relevant outcome parameters from clinical series.The literature cannot give general recommendations for choice of mesh based on randomized controlled trials. The final choice of mesh for LVHR will therefore typically be based on surgeons' preference and cost while we await further data from randomized controlled clinical trials.

Background: Breakthrough pain (BTP) has not formerly been discussed as such in chronic non-malignant pain patients referred to pain centres and clinics. The purpose of the study was to investigate the prevalence, characteristics and mechanisms of BTP in opioid-treated chronic non-malignant pain patients referred to a pain centre and to assess the short-term effects of pain treatment. Methods: Patients were assessed at referral (T0) and after a treatment period of 3 months (T3) using the visual analogue scale (VAS) of the brief pain inventory (BPI) within somatic nociceptive, neuropathic and/or visceral pain conditions, the mini mental state examination (MMSE) and the hospital anxiety and depression scale (HADS). The main treatment intervention from T0 to T3 was to convert short-acting oral opioids to long-acting oral opioids and to discontinue on demand and parenteral use of opioids. Results: Thirty-three patients were assessed at T0 and 27 at T3. The prevalence of BTP declined significantly from T0 (90%) to T3 (70.4%). Worst, least, average and current pain intensities as well as duration of BTP were significantly reduced from T0 to T3. The majority of BTPs were exacerbation of background pain assumed to be of the same pain mechanisms. High average pain intensity (BPI) was significantly associated with high scores for both anxiety and depression (HADS). Conclusion: BTP in chronic non-malignant pain patients seems to be surprisingly frequent and severe. Stabilizing the opioid regimen seems to reduce pain intensity in general as well as the intensity and duration of BTP. Average pain intensity was associated with anxiety and depression.

A 50-year-old woman had a right hemicoletomy due to a large sessile polyp in the ascending colon, inappropriate for polypectomy. Histopathologic examination of the specimen showed a tubulovillous adenoma with moderate dysplasia and an adjacent 1 x 1 cm submucosal tumor classified as a benign GCT due to the appearance in the light microscope and immunohistochemical analysis. To our knowledge, this is the first reported case of synchronic adenoma and GCT in the colon. To date there is no evidence of any association or disposing factors between GCT in the colon and colonic adenomas or malignancy.

The indication for cholecystectomy in symptomatic, uncomplicated gallstone disease varies in the literature, and there is no international consensus. In Denmark, laparoscopic cholecystectomy is recommended for patients with uncomplicated cholecystolithiasis and socially disabling pain. Postoperative health-related quality of life on this indication is unknown.A prospective consecutive study was conducted. Patients with uncomplicated cholecystolithiasis and socially disabling pain were included and underwent laparoscopic cholecystectomy in the department of day surgery. All patients had uncomplicated gallstone disease. An internationally validated questionnaire, the Gastrointestinal Quality of Life Index (GIQLI), was completed one week before and six weeks after the operation. The questionnaire comprises 32 questions covering five items related to gastrointestinal disease, and each question is rated on a scale of 0 to 4 points. The maximum GIQLI score (GIQLI total) is 128 points (32 x 4 points) and represents the best possible health-related quality of life.75 consecutive patients (62 women) underwent uneventful operations. All patients returned the pre- and postoperative questionnaire. The median age was 42 years (range 18-69), the median body mass index was 26 (19-39) and the median operation time was 56 minutes (24-130). The median GIQLI total scores were 99 (33-127) and 112 (82-128) before and after operation, respectively (P0.001). Scores on all five sub-items were significantly improved as well.Laparoscopic cholecystectomy improves the health-related quality of life six weeks after the operation in patients with socially disabling, uncomplicated cholecystolithiasis.

The aim of this study was to describe the argon beam coagulation (ABC) technique in the palliative treatment of patients with nonresectable carcinoma of the cardia and oesophagus and this treatments needs, complications and tolerance.A retrospective evaluation of 31 patients referred for palliation by ABC over a period of nearly four years (1.1.98-31.8.01).Twenty-two men and nine women, median age 72 years (range 49-91 years), underwent a total of 163 treatments and a median of five treatments per patient (range 1-18). Recanalisation enabling passage of the scope was achieved in 89% of treatments, and most of these patients had dysphagia grade = 2. The median range between reinterventions was 25 days (range 1-175 days). Perforation was seen in three patients and in 1.8% of treatments; procedure related mortality was 1.2%. The median hospital stay for every treatment was two days (range 1-27 days) and the median inpatient stay as a proportion of survival time was 8%. The median survival was 190 days (range 7-612 days) with the 1-year survival 19%.ABC is a well-tolerated, safe and effective treatment in patients with non-resectable cancer of the oesophagus or cardia and offers an acceptable complication rate and number of reinterventions compared with laser and stent placement. The technique is easy and cheap, and requires no further restrictions than conventional monopolar electro coagulation does. Prospective randomised trials comparing the efficacy of the different palliative treatments for patients with oesophagogastric cancer are needed.

The aim of this study was to describe the argon beam coagulation technique in the palliative treatment of patients with non-resectable carcinoma of the cardia and oesophagus and its requirements, complications, and tolerance.31 patients, referred for palliation by ABC in a central hospital over a period of nearly four years (1.1.1998-31.8.2001), were evaluated retrospectively.Twenty-two men and nine women, median age 72 years (range 49-91), underwent a total of 163 treatments and a median of five treatments per patient (range 1-18). Re-canalisation enabling passage of the scope was achieved in 89% of treatments, and most of the patients had dysphagia grade = 2. The median range between reinterventions was 25 days (range 1-175). Perforation was seen in three patients and in 1.8% of treatments procedure-related mortality was 1.2%. The median hospital stay for each treatment was two days (range 1-27) and the median impatient stay as proportion survival time was 8%. The median survival was 190 days (range 7-612) and the one-year survival 19%.ABC is a well tolerated, safe, and effective treatment in patients with non-resectable cancer of the oesophagus or cardia and offers and acceptable complication rate and number of reinterventions compared with laser and stent placement. The technique is easy and inexpensive and requires no further restrictions than conventional monopolar electrocoagulation does.

A recent article published by Schug-Pass et al. [1] highlights a very important problem in laparoscopic ventral hernia repair. The authors studied mesh fixation to the peritoneum using fibrin glue and thereby add further information to the sparse literature in this area. Alternative noninvasive and degradable fixation techniques are highly warranted because of potential complications related to traditional fixation with tacks. The authors performed a biomechanical ‘‘dry-lab’’ test to test strength of ingrowth, and an experimental pig study. In the biomechanical test, a 10 9 15 cm TiMesh light was placed above a prefabricated 4.5-cm defect in a muscle– peritoneum specimen and 2 ml Tissucol was sprayed onto the mesh. Strength of fixation was tested 3 min after glue application and was found to be significantly higher when applied to muscle tissue than to bare peritoneum. In the experimental test, six pigs had a 10 9 15 cm TiMesh light fixed to the nontraumatized peritoneum by spray application of 2 ml Tissucol. After 4 months the pigs were euthanized and mesh migration and adhesions were measured. The authors found incomplete integration/dislocation of the mesh in half of cases (3/6 meshes). Based on these results the authors conclude that glue as a standalone fixation method to the bare peritoneum cannot be recommended. The article correctly states that: ‘‘To date, no randomized clinical trials have investigated intraperitoneal application (of fibrin glue)’’ [1]. However, a few experimental and human studies concerning the safety aspects of the procedure are available. A randomized laparoscopic pig study comparing fibrin glue with tacks for mesh fixation found the glue procedure to be safe with no mesh migrations in 18 meshes (folding was seen in two meshes) [2]. Olmi et al. published a series of 40 patients undergoing laparoscopic ventral hernia repair with glue fixation without recurrences at mean follow-up of 16 months [3] and 60 intraperitoneal onlay mesh (IPOM) procedures for inguinal hernia with no recurrences after 2-year mean follow-up [4]. Recently, Fortelny et al. reported a case of successful paraesophageal hernia repair with mesh fixated with fibrin glue [5]. The amount of glue used may be important for successful repair. In our own study [2] we used 1 ml Tisseel/ 30 cm mesh, and Olmi et al. used 1 ml/50–60 cm mesh [3]. Tisseel/Tissucol is not registered for mesh fixation and, consequently, no minimum dose of glue per mesh area is recommended by the manufacturer to ensure adequate initial fixation. Schug-Pass et al. used 1 ml Tissucol/ 75 cm mesh, which may not have been enough. Which application method should be used: spray or catheter? It is my personal experience that spray application posses some difficulties. The aerosol is nearly invisible and therefore it is actually quite difficult to see when application starts, where the glue ends, and the amount delivered. The initial strength of ingrowth was tested 3 min after application. I am a little critical of this modus operandi. If the aim was to test clinically relevant strength of ingrowth of the initial mesh fixation, 3 min is too early and leaves no chance for the technique. Coagulated Tisseel/Tissucol reaches its maximum strength after 2 h, and 70% strength is achieved after 10 min, a time when most patients are still asleep. J. R. Eriksen (&) Department of Surgical Gastroenterology D, Herlev University Hospital, Copenhagen, Herlev Ringvej 75, 2730 Herlev, Denmark e-mail: jravn@dadlnet.dk

Top of pageAbstract Aim: In vivo electric pulses delivery to muscle for gene transfer (electro gene transfer) can yield long term high levels of gene expression. The method holds great promise for safe and simple gene delivery for gene therapy. A system to regulate the expression of transferred genes is the Tet-On system, which modulates gene expression by administration of doxycycline. The transactivator rtTA induces gene expression in the presence of doxycycline while the repressor tTS inhibits gene expression in the non-induced state. We have optimised the rtTA/tTS system in vivo to minimise DNA use and improve silencing in the non-induced state. Methods: Control of gene expression was investigated by in vivo delivery of three plasmids, one encoding the transactivator (pTet-On), one encoding the repressor (pTet-tTS), and one encoding the green fluorescent protein (GFP) under a Tet-On transactivator (rtTA) responsive promoter (ptetO-GFP). Different amounts of plasmids were co-injected in the tibialis cranialis muscle and followed by transfer into the muscle fibres by electro gene transfer. Results & Conclusion: It was found that 1) the total amount of the injected DNA could be significantly reduced whilst maintaining local expression, 2) the non-induced basal expression of GFP could be significantly reduced by increasing the repressor/activator ratio. When using a mixture of 5 |[mu]|g of ptetO-GFP, 5 |[mu]|g of pTet-On, and 5 |[mu]|g of pTet-tTS transferred into the tibialis cranialis muscle in mice, it was possible both to limit the toxicity related to exposure of high concentrations of DNA in the muscle, improve the control of gene expression as well as reduce the consumption of DNA for experiments. Indeed the use of less DNA may lead to fewer physiological changes happening in the muscle, a particular advantage for physiological studies of the organ.

Ultrasound has a well-established role in the diagnostic assessment of acute abdominal pain where some ultrasonically easily-accessible organs account for several diagnostic possibilities. The objective of the present study was to evaluate whether surgeons without ultrasound experience could perform valid abdominal ultrasound examinations of patients referred with acute abdominal pain.Patients referred with acute abdominal pain had an ultrasound examination by a surgeon in training as well as by an experienced consultant radiologist whose results served as the gold standard. All participating surgeons were without any pre-existing ultrasound experience and received one hour of introduction to abdominal ultrasound.Thirty patients underwent 40 surgeon performed and 30 radiologist performed ultrasound examinations. Regarding gallstone and cholecholecystitis the sensitivity, specificity and kappa-agreement of the surgeon performed ultrasound examination was 1.00 (0.77-1.00), 0.96 (0.79-0.99), 0.94 (0.3-1.00) and 0.40 (0.12-0.77), 0.97 (0.83-0.99), 0.44 (0.00-0.96); respectively. Visualization of the common bile duct was poor having 73% non-diagnostic surgeon-performed ultrasound examinations.Surgeons in training without pre-existing ultrasound experience and only a minimum of formal ultrasound education can perform valid and reliable ultrasound examinations of the gallbladder in patients admitted with acute abdominal pain.