Intracorporeal Versus Extracorporeal Anastomosis in Robotic Right Colectomy: A Multicenter, Triple-blind, Randomized Clinical Trial.

OBJECTIVE: To determine if minimally invasive right colectomy with intra-corporeal anastomosis improves postoperative recovery compared to extra-corporeal anastomosis. BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: There were no significant differences in postoperative recovery between the two groups.

The effect of intracorporeal versus extracorporeal anastomosis in robotic right colectomy on perianastomotic perfusion: a substudy to a multicenter RCT.

PURPOSE: 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. METHOD: 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: FMAX: maximal fluorescence intensity, TMAX: time until maximal fluorescent signal, T1/2MAX: time until half-maximal fluorescent signal, time ratio (T1/2MAX/TMAX) and slope. RESULTS: A 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 FMAX, TMAX, T1/2MAX, and time ratio. CONCLUSION: We 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. CLINICALTRIALS: gov NCT03130166.

The dynamic effects of preoperative intravenous iron in anaemic patients undergoing surgery for colorectal cancer.

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 < 0.0001) at week 1, 1.5 g/dl (95% CI 1.21-1.80 g/dl, P < 0.0001) at week 2 and 2.13 g/dl (95% CI 1.71-2.55 g/dl, P < 0.0001) at week 4. Patients with severe anaemia (<9.02 g/dl) showed the largest increase in haemoglobin during the treatment course (2.92 g/dl, 95% CI 2.27-3.58 g/dl, P < 0.0001). Patients with mild anaemia (>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 < 0.0001). CONCLUSIONS: After intravenously administered iron, patients with severe anaemia had the most substantial increase in haemoglobin, and the increase was largest after 4 weeks. Patients with mild anaemia did not have an increase in haemoglobin during the treatment course. The vast majority of patients still had iron deficiency at surgery 4 weeks after the initial treatment.

Postoperative Urinary Retention After Laparoscopic Colorectal Resection with Early Catheter Removal: A Prospective Observational Study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Short- and long-term outcomes after colorectal anastomotic leakage is affected by surgical approach at reoperation.

BACKGROUND: Anastomotic leakage is the most serious surgical complication following colorectal resection, and surgical intervention is often required. The purpose of the study was to investigate short- and long-term outcomes after reoperation for anastomotic leakage. METHOD: Patients with a symptomatic anastomotic leakage following a laparoscopic colorectal cancer resection from January 2009 to December 2014 were identified from our local prospective database. Patients were grouped according to the management of anastomotic leaks: local, lap, or open approach. Primary outcomes were length of stay, chance of bowel continuity, and overall mortality. RESULTS: A total of 113 patients were included. The median follow-up time was 40 months (0-82 months). Overall mortality was significantly associated with UICC stage III-VI disease (vs. UICC stage I-II disease) [adj. HR 5.35 (CI 2.32-12.4), p = 0.0001] and minimal invasive reoperation compared with open approach [local: adj. HR 0.12 (CI 0.03-0.52), p = 0.004; lap: adj. HR 0.32 (CI 0.12-0.86), p = 0.024]. Chance of bowel continuity was significantly increased in younger patients below 67 years [adj. OR 6.15 (1.76-21.5), p = 0.004] and following a local procedure [adj. OR 7.45 (1.07-51.8), p = 0.043]. Patients in the open group had significantly longer length of stay and time to initiation of adjuvant chemotherapy compared with those in the lap group. CONCLUSION: Our data confirms that minimal invasive reoperation for anastomotic leakage is a safe and feasible approach associated with short- and long-term advantages and can be chosen in selected cases.

In vivo and ex vivo sentinel node mapping does not identify the same lymph nodes in colon cancer.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Combined laparoscopic and transanal total mesorectal excision for rectal cancer: Initial experience and early results.

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.

No differences in short-term morbidity and mortality after robot-assisted laparoscopic versus laparoscopic resection for colonic cancer: a case-control study of 263 patients.

BACKGROUND: 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). METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Detection of collision metastases.

Cancer is a cause of high morbidity and mortality. It is not uncommon for a patient to have more than one primary tumour. This review summarises the knowledge of collision tumours which are defined as two adjacent neoplasms in the same organ, while a collision metastasis is the rare occurrence of two different primary cancers metastasising to the same anatomical site. Identification of collision metastasis is a diagnostic challenge and relies on histopathological examination. As it might have profound impact on prognosis and treatment decisions, it is important to create awareness among both pathologists and clinicians of this phenomenon.

Preoperative multimodal prehabilitation before elective colorectal cancer surgery in patients with WHO performance status I or II: randomized clinical trial.

BACKGROUND: Multimodal prehabilitation is a promising adjunct to the current surgical treatment pathway for colorectal cancer patients to further improve postoperative outcomes, especially for high-risk patients with low functional capacity. The aim of the present study was to test the effect of prehabilitation on immediate postoperative recovery. METHOD: The study was designed as a RCT with two arms (intervention and control). The intervention consisted of 4 weeks of multimodal prehabilitation, with supervised physical training, nutritional support and medical optimization. The control group received standard of care. A total of 40 patients with colorectal cancer (WHO performance status I or II) undergoing elective surgery with curative intent were included. The primary outcome was postoperative recovery within the first 3 postoperative days, measured by Quality of Recovery-15, a validated questionnaire with a scoring range between 0 and 150 and a minimal clinically relevant difference of 8. RESULTS: In total, 36 patients were analysed with 16 in the intervention group and 20 in the control group. The mean age of the included patients was 79 years. The overall treatment effect associated with the intervention was a 21.9 (95% c.i. 4.5-39.3) higher quality of recovery-15 score during the first 3 postoperative days compared to control, well above the minimal clinically relevant difference. CONCLUSION: Four weeks of multimodal prehabilitation prior to elective curative intended colorectal cancer surgery in patients with WHO performance status I or II was associated with a clinically relevant improvement in postoperative recovery.Registration number: NCT04167436 (http://www.clinicaltrials.gov).

Anterior quadratus lumborum block does not reduce postoperative opioid consumption following laparoscopic hemicolectomy: a randomized, double-blind, controlled trial in an ERAS setting.

BACKGROUND AND AIMS: An 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. METHODS: In 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. RESULTS: The 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. CONCLUSION: The 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 number NCT03570541.

Pain and convalescence following laparoscopic ventral hernia repair.

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, p < 0.001), satisfaction (rS= -0.67, p < quality of life score (rS= -0.63, p < 0.001) 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 defects < 5 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.

Diagnosis and treatment of Helicobacter pylori infection.

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.

Post-operative recovery is not a limiting factor for adjuvant chemotherapy in patients undergoing surgery for colorectal cancer.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Post-operative recovery may not be the factor limiting patients from receiving adjuvant chemotherapy either before or after post-operative week four. FUNDING: none. TRIAL REGISTRATION: The study was approved by the Data Protection Agency (reg. no. REG044-2018).

[Suspicious malignant lateral pelvic lymph nodes in locally advanced rectal cancer].

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.

Combined endoscopic laparoscopic surgical treatment of advanced adenomas and early colon cancer.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. FUNDING: none. TRIAL REGISTRATION: 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). .