Laparoscopic lavage for Hinchey III perforated diverticulitis: factors for treatment failure in two randomized clinical trials.

BACKGROUND: The Scandinavian Diverticulitis (SCANDIV) trial and the LOLA arm of the LADIES trial randomized patients with Hinchey III perforated diverticulitis to laparoscopic peritoneal lavage or sigmoid resection. The aim of this analysis was to identify risk factors for treatment failure in patients with Hinchey III perforated diverticulitis. METHODS: This was a post hoc analysis of the SCANDIV trial and LOLA arm. Treatment failure was defined as morbidity requiring general anaesthesia (Clavien-Dindo grade IIIb or higher) within 90 days. Age, sex, BMI, ASA fitness grade, smoking status, previous episodes of diverticulitis, previous abdominal surgery, time to surgery, and surgical competence were all tested in univariable and multivariable logistic regression analyses using an interaction variable. RESULTS: The pooled analysis included 222 patients randomized to laparoscopic lavage and primary resection (116 and 106 patients respectively). Univariable analysis found ASA grade to be associated with advanced morbidity in both groups, and the following factors in the laparoscopic lavage group: smoking, corticosteroid use, and BMI. Significant factors for laparoscopic lavage morbidity in multivariable analysis were smoking (OR 7.05, 95 per cent c.i. 2.07 to 23.98; P = 0.002) and corticosteroid use (OR 6.02, 1.54 to 23.51; P = 0.010). CONCLUSION: Active smoking status and corticosteroid use were risk factors for laparoscopic lavage treatment failure (advanced morbidity) in patients with perforated diverticulitis.

Stool dynamics after extrinsic nerve injury during right colectomy with extended D3-mesenterectomy.

INTRODUCTION: To improve oncological outcome in right colon cancer surgery, an extended mesenterectomy (D3) is under evaluation. In this procedure, all tissue anterior and posterior to the superior mesenteric vessels from the middle colic to ileocolic artery origin is removed, causing injury to the superior mesenteric nerve plexus. The aim was to study the effects of this injury on bowel dynamics and quality of life (QoL). METHODS: Patients undergoing right colectomy with conventional D2- and extended D3-mesenterectomy were asked to record stool number and consistency for 60 d after surgery and complete questionnaires regarding QoL and bowel function (BF) before and after recovery from surgery. We compared early postoperative stool dynamics and long-term QoL in the groups and presented graphs depicting the temporal profile of stool numbers and consistency. RESULTS: Thirty-three patients operated with a D3-resection and 12 patients with a D2-resection participated. The results revealed significantly higher stool numbers in the D3-group until day 26, with significantly more loose-watery stools until day 40. The most pronounced difference was found on day 9 (Mean difference in the total number of stools: 2.25 stools/day, p=.004. Mean difference in loose-watery stools/day: 2.81 p<.001). About 25% in the D2- and 69.7% in the D3-group reported having more than three stools/day in the early postoperative phase. There were no differences in long-term QoL and BF between the groups except in stool consistency (p=.039). DISCUSSION/CONCLUSIONS: Denervation following extended D3-mesenterectomy leads to transitory reduced consistency and increased frequency. It does not affect long-term QoL or BF.

Long-term outcome and quality of life after continent ileostomy for ulcerative colitis: A systematic review.

AIM: The continent ileostomy allows evacuation of an ileal reservoir at a time convenient to the patient. It is a surgical option for patients with ulcerative colitis (UC) when a restorative option is not suitable or has not succeeded and the patient does not want a conventional end ileostomy. Continent ileostomy types include the Kock pouch, Barnett continent intestinal reservoir and T-pouch. All of the published evidence on the long-term outcome and quality of life after continent ileostomy for UC was systematically reviewed. METHODS: A systematic review was performed in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies published between 1990 and 2020 were included. A descriptive synthesis was used due to the clinical heterogeneity. RESULTS: The search returned 1655 abstracts and after screening of abstracts and full text review, 19 were included in the final review, involving 1602 patients. Operative mortality is low (0%-3.6%) after all types of continent ileostomy but reoperation rates are high (20.8%-65%) because of valve mechanism failures. Rates of fistulae (0%-25.5%) and stomal stenosis (0%-25%) can be relatively high postoperatively. Quality of life scores improve for most patients undergoing continent ileostomy, especially for patients converted from ileal pouch anal anastomosis. Overall, continent ileostomy retention is high in the long-term. DISCUSSION: In the long-term, patients report high satisfaction and a good quality of life with continent ileostomy, despite high reoperation rates and complications. Newer technologies may reinvigorate interest in the continent ileostomy for this population.

Bowel Motility After Injury to the Superior Mesenteric Plexus During D3 Extended Mesenterectomy.

BACKGROUND: Improvement of lymphadenectomy in right colectomy requires removal of all tissue surrounding the superior mesenteric vessels beneath the pancreatic notch. Short- and long-term bowel motility disorders after D3 extended mesenterectomy with consecutive superior mesenteric plexus transection are studied. METHODS: Patients without pre-existing motility disorders undergoing D3 extended mesenterectomy were examined 3 times using the wireless motility capsule: before, at 3 wk, and 6 mo after surgery. Segmental transit times and contractility were analyzed using mixed effect modeling. Correlation between contractility and transit time was assessed by the Pearson correlation coefficient. RESULTS: Fifteen patients (4 men), with median age 62 y, were included. Mean values for the three consecutive examinations are as follows. Gastric transit time increased from 237 to 402 and 403 min, respectively. Small bowel transit time decreased from 246 to 158 (P < 0.01) and 199 (P = 0.03) min, respectively. Colonic transit time decreased from 1742 to 1450 and 1110 (P = 0.02) min, respectively. Gastric contractions per minute (CPM) varied from 1.73 to 1.05 (P = 0.01) and 2.47 (P < 0.01), respectively. Small bowel CPM decreased from 3.43 to 2.68 and 3.34, respectively. Colonic CPM ranged from 1.59 to 1.45 and 1.91 (P = 0.08), respectively. Correlation between small bowel (SB) transit time and CPM was -0.45 (P = 0.09) preoperatively, and -0.03 (P = 0.91) 6 mo postoperatively. CONCLUSIONS: Extrinsic SB denervation leads to significantly accelerated SB transit, reduced contractility, and disturbed correlation between transit time and contractility early after denervation. Both number of contractions and transit time in the denervated SB show a clear tendency toward normalization at 6 mo.

Determinants of optimal bowel function in ileal pouch-anal anastomosis - physiological differences contributing to pouch function.

BACKGROUND: Variability in functional outcome after ileal-pouch anal anastomosis (IPAA) is to a large extent unexplained. The aim of this study was to perform multiple physiological and biochemical tests including an endoscopic examination with histology on IPAA patients with well and poorly functioning pouches to determine factors, or combinations thereof, contributing to functional outcome. METHODS: All patients with ulcerative colitis undergoing restorative proctocolectomy between 2000 and 2013 (N = 108) were interviewed using a pouch functioning score. The best and worst functioning quartiles were invited to undergo examination with a barostat measuring pouch volume at preset variable distension pressures, and a pouch endoscopy. RESULTS: Forty five of 58 eligible patients agreed to participate. The most significant physiological parameter differing between the well and poorly functioning pouches was pouch volume at first sensation, urge and discomfort (p value <.001). Urge volumes were 213 (CI 171-256) ml for poorly and 352 (CI 305-401) ml for well functioning pouches. Pouchitis episodes were negatively correlated to function. The poorly functioning patients had a higher prevalence of histological signs of inflammation and hand-sewn anastomosis, and a longer remaining rectal cuff, however, nonsignificant. The pouch pressure at sensation thresholds did not differ between the groups. CONCLUSIONS: Pouch volume is the most dominant predictor of pouch function in this study. The present comprehensive study of a multitude of different factors that possibly could be contributing to functional outcome, failed to shed much further light on the functional variability among pouch patients. The pouch physiology remains to a large extent unexplained.

Management of Diverticular Disease in Scandinavia.

Throughout the last century, the incidence of diverticular disease of the colon has increased tremendously in industrialized countries; nevertheless, the management of this condition is still controversial. Although several international guidelines for the management of diverticular disease are based on the same evidence, the recommendations differ greatly, emphasizing the lack of high-quality prospective studies. In Scandinavia, official guidelines for the management of diverticular disease exist only in Denmark. However, the treatment policies are quite similar in all Scandinavian countries. Computed tomography is the first choice for imaging of acute diverticulitis and its complications. Furthermore, the use of antibiotics in uncomplicated diverticulitis is nearly abandoned in Scandinavia, whereas several international guidelines still recommend their use. There is a broad consensus that abscesses secondary to acute diverticulitis can safely be managed with percutaneous drainage, which is in line with international recommendations. The surgical management of perforated diverticulitis with peritonitis is still as controversial in Scandinavia as elsewhere. Common surgical options are laparoscopic peritoneal lavage, primary resection with anastomosis, and primary resection with terminal colostomy (Hartmann's procedure). Elective sigmoid resection in patients with diverticular disease seems to be performed less frequently in Scandinavia than in other European countries; the right indications are a current matter of debate. Symptomatic uncomplicated diverticular disease in the absence of diverticulitis has not gained great attention in Scandinavia.

Correlation between pouch function and sexual function in patients with IPAA.

OBJECTIVE: Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the treatment of choice for ulcerative colitis refractory to medical treatment and familial adenomatous polyposis. The objective of this study was to study the impact of postoperative pouch function on sexual function. Sexual function after IPAA surgery has also been compared to sexual function in the average Norwegian population. MATERIAL AND METHODS: All patients having undergone IPAA from 2000 to June 2013 were identified from the hospital medical record files and sent validated questionnaires regarding their sexual function. Pouch function was scored according to Oresland score through a phone interview. Patients operated on or before June 2012 were asked to answer the same questionnaires twice with an interval of one year to see how stable sexual function is over time. RESULTS: Sixty-eight out of 100 consecutive patients answered the questionnaire regarding both sexual function and pouch function (44 men, 24 women). There was no significant relationship between pouch and sexual function in men (p-value 0.158, corr. coefficient - 0.216). In women there was a significant relationship (p-value - 0.01, corr. coefficient 0.517). There was no significant shift in sexual function during the study period. CONCLUSION: We found no significant correlation between sexual function and pouch function in men. In women, we found a significant correlation between poor pouch function and impaired sexual function. As similar studies have found, sexual function remains good after IPAA surgery. This is an important information for patients and physicians, both to inform patients correctly prior to surgery, and in the postoperative follow-up.

Surgery in the age of biological treatment.

Surgery for IBD is in constant evolution; it does not appear that the introduction of biologicals has had a major effect on the chance of a patient being operated on or not. Pouch surgery had its heydays in the 80s and 90s and has since then become less frequent, but the number of patients undergoing surgery still seem about the same from one year to the other. Likewise, there is no substantial evidence that surgery for Crohn's disease is diminishing. There have been fears that patients on biological treatment have an increased risk of postoperative complications. The issue is not completely settled but it is likely that patients on biological treatment who come to surgery are those who do not benefit from biologicals. Thus, they are compromised in that they have an ongoing inflammation, are in bad nutritional state, and might have several other known risk factors for a complicated postoperative course. These factors and perhaps not the biologicals per se is what surgeons should consider. During the recent years, we have seen several new developments in IBD surgery; the ileorectal anastomosis is being used for ulcerative colitis and laparoscopic surgery usually resulting in a shorter hospital stay, less pain, and better cosmetics. We have also seen the introduction of robotic surgery, single incision minimal invasive surgery, transanal minimal invasive surgery, and other approaches to minimize surgical trauma. Time will show which of these innovations patients will benefit from.

Laparoscopic Lavage vs Primary Resection for Acute Perforated Diverticulitis: The SCANDIV Randomized Clinical Trial.

IMPORTANCE: Perforated colonic diverticulitis usually requires surgical resection, which is associated with significant morbidity. Cohort studies have suggested that laparoscopic lavage may treat perforated diverticulitis with less morbidity than resection procedures. OBJECTIVE: To compare the outcomes from laparoscopic lavage with those for colon resection for perforated diverticulitis. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, randomized clinical superiority trial recruiting participants from 21 centers in Sweden and Norway from February 2010 to June 2014. The last patient follow-up was in December 2014 and final review and verification of the medical records was assessed in March 2015. Patients with suspected perforated diverticulitis, a clinical indication for emergency surgery, and free air on an abdominal computed tomography scan were eligible. Of 509 patients screened, 415 were eligible and 199 were enrolled. INTERVENTIONS: Patients were assigned to undergo laparoscopic peritoneal lavage (n = 101) or colon resection (n = 98) based on a computer-generated, center-stratified block randomization. All patients with fecal peritonitis (15 patients in the laparoscopic peritoneal lavage group vs 13 in the colon resection group) underwent colon resection. Patients with a pathology requiring treatment beyond that necessary for perforated diverticulitis (12 in the laparoscopic lavage group vs 13 in the colon resection group) were also excluded from the protocol operations and treated as required for the pathology encountered. MAIN OUTCOMES AND MEASURES: The primary outcome was severe postoperative complications (Clavien-Dindo score >IIIa) within 90 days. Secondary outcomes included other postoperative complications, reoperations, length of operating time, length of postoperative hospital stay, and quality of life. RESULTS: The primary outcome was observed in 31 of 101 patients (30.7%) in the laparoscopic lavage group and 25 of 96 patients (26.0%) in the colon resection group (difference, 4.7% [95% CI, -7.9% to 17.0%]; P = .53). Mortality at 90 days did not significantly differ between the laparoscopic lavage group (14 patients [13.9%]) and the colon resection group (11 patients [11.5%]; difference, 2.4% [95% CI, -7.2% to 11.9%]; P = .67). The reoperation rate was significantly higher in the laparoscopic lavage group (15 of 74 patients [20.3%]) than in the colon resection group (4 of 70 patients [5.7%]; difference, 14.6% [95% CI, 3.5% to 25.6%]; P = .01) for patients who did not have fecal peritonitis. The length of operating time was significantly shorter in the laparoscopic lavage group; whereas, length of postoperative hospital stay and quality of life did not differ significantly between groups. Four sigmoid carcinomas were missed with laparoscopic lavage. CONCLUSIONS AND RELEVANCE: Among patients with likely perforated diverticulitis and undergoing emergency surgery, the use of laparoscopic lavage vs primary resection did not reduce severe postoperative complications and led to worse outcomes in secondary end points. These findings do not support laparoscopic lavage for treatment of perforated diverticulitis. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01047462.

Evaluation of a Group-based Patient Education Program Promoting Self-management in Adults with Hirschsprung Disease and Anorectal Malformations.

INTRODUCTION: Adults with Hirschsprung disease (HD) and anorectal malformations (ARM) may experience persisting and new somatic and psychosocial problems. Patient education programs (PEPs) may improve self-management in patients with chronic illnesses. The aim of this study was to explore HD and ARM adults' experiences with and evaluation of a group-based PEP. We also looked at factors that might influence the attendance rate. METHOD: Non-intellectually impaired HD and ARM adults were invited to attend a diagnosis specific PEP at a pelvic floor interdisciplinary center. Eight health care professionals lectured. Aspects of the PEP were graded anonymously in a patient reported experience measure (PREM). Ethical approval was obtained. RESULTS: 17% (21/125) of invited adults (10HD, 11ARM) attended four PEPs. 19/21 (90%) PREMs were returned. Participants found meeting peers and sharing experiences especially valuable in addition to improved disease knowledge. Lectures by the pediatric and colorectal surgeons, stoma nurse, and sexologist were rated highest by the participants. The majority reported that the PEP would be helpful in managing everyday life. All participants recommended PEP in adolescence. Factors such as gender and travel distance did not affect attendance rate, but participants were older than non-participants, median 37 versus 24 years (p = 0.01). CONCLUSION: Attendance rates were low among HD and ARM adults invited to a PEP, but participants were overall highly satisfied. Peer support, mutual learning, and increased disease knowledge were seen as invaluable assets of the PEP. A web-based PEP was discouraged, while physical PEPs for both adults and adolescents were encouraged. LEVEL OF EVIDENCE: III.

Reaching adulthood with Hirschsprung's disease: Patient experiences and recommendations for transitional care.

BACKGROUND/PURPOSE: The need for transitional care has gained increased focus in the treatment of patients with congenital colorectal disorders. We aimed to acquire in-depth knowledge about the experiences of adult patients with Hirschsprung's disease (HD) and their suggestions for transitional care. METHODS: Binational study applying gender equal focus group interviews (FGI). RESULTS: Seventeen (9 men) of 52 invited patients with median age 29 (19-43) years participated. Three themes evolved from the FGI. "Scarred body and soul" describes the somatic and psychosocial challenges the patients experienced and "limited health literacy on HD" refers to the patients' lack of HD knowledge. "Absent transition" depicts missing transitional care and the patients' inability to find adult HD specialists. The adult HD patients strongly recommended transitional care from early teens with focus on information about HD and establishment of a peer-to-peer program. They also emphasized the possibility of being referred to a pelvic floor center. CONCLUSIONS: HD negatively influences patients' somatic and psychosocial health in childhood, adolescence and adulthood. Adult HD patients strongly recommend transitional care from early teens and the possibility for referral to a center working with pelvic floor dysfunctions. LEVEL OF EVIDENCE: IV TYPE OF RESEARCH: Clinical.

Laparoscopic Lavage vs Primary Resection for Acute Perforated Diverticulitis: Long-term Outcomes From the Scandinavian Diverticulitis (SCANDIV) Randomized Clinical Trial.

Importance: Perforated colonic diverticulitis usually requires surgical resection, with significant morbidity. Short-term results from randomized clinical trials have indicated that laparoscopic lavage is a feasible alternative to resection. However, it appears that no long-term results are available. Objective: To compare long-term (5-year) outcomes of laparoscopic peritoneal lavage and primary resection as treatments of perforated purulent diverticulitis. Design, Setting, and Participants: This international multicenter randomized clinical trial was conducted in 21 hospitals in Sweden and Norway, which enrolled patients between February 2010 and June 2014. Long-term follow-up was conducted between March 2018 and November 2019. Patients with symptoms of left-sided acute perforated diverticulitis, indicating urgent surgical need and computed tomography-verified free air, were eligible. Those available for trial intervention (Hinchey stages

Key components of successful transition for adolescents born with anorectal malformations-a Nordic focus group study.

OBJECTIVES: Transitional care for adolescents with congenital malformations, such as anorectal malformations (ARM), is described sparsely in the literature and referred to as being inadequate. In order to organize future successful healthcare structures, knowledge of patient-reported important aspects of transition is required. The aim of the study was therefore to explore the needs and expectations of transitional- and adult healthcare among adolescents and adults born with ARM. METHODS: Two tertiary paediatric surgical centres, in collaboration with two tertiary pelvic floor centres, in Sweden and Norway, conducted a qualitative study, involving adolescents and adults born with ARM in focus group discussions regarding transitional care. Discussions were analyzed by qualitative content analysis. Ethical approval was obtained. RESULTS: Sixteen participants (10 women) with a median age of 24 (19-47) years, born with mixed subtypes of ARM were included in gender-divided focus groups. Participants emphasized a need for improved knowledge of ARM, both among patients and adult care providers. Participants identified a need for support with coping strategies regarding challenging social- and intimate situations due to impaired bowel function. Participants pin-pointed well-functioning communication between the patient and the paediatric- and adult care providers as a key factor for a successful transitional process. Further, participants emphasized the importance of easy access to specialized adult healthcare when needed, suggested to be facilitated by appointed patient navigators. CONCLUSION: Adolescents and adults born with ARM identify improved knowledge of ARM, well-functioning communication and easy access to specialized adult care as key components of a successful transition.

uPA and PAI-1 in rectal cancer--relationship to radiotherapy and clinical outcome.

BACKGROUND: It is well known that the fibrinolytic system is of importance in inflammation, wound healing, and fibrosis development. However, it is also important in the process of tumor invasion and metastasis. We have investigated protein levels of urokinase plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) in rectal cancer and effects of radiotherapy, links to clinical outcome, and potential use as prognostic factors. MATERIALS AND METHODS: Ninety-one patients with rectal cancer were studied. Blood samples and biopsies were taken during surgery and assayed with enzyme-linked immunosorbent assay for uPA and PAI-1, and patients were followed prospectively (0-96 mo). RESULTS: Higher levels of uPA (P < 0.0001) and PAI-1 (P < 0.0001) were found in tumor compared with mucosa. Mucosa exposed to radiotherapy had higher levels of uPA (P < 0.0001) and of PAI-1 (P < 0.0001). Irradiated tumor tissue had higher levels of PAI-1 (P < 0.001). PAI-1 in tumor was correlated with T stage (P < 0.001) and N stage (P < 0.01). PAI-1 in plasma was higher in patients with synchronous distant metastases (P < 0.001). Cox regression was used to identify high levels of PAI-1 in tumor as an independent factor related to short disease-free survival (P < 0.01) and the ratio of uPA/PAI-1 to development of metastases (P < 0.01). CONCLUSIONS: There is a relationship between PAI-1 in plasma and rectal cancer metastases. PAI-1 in tumor tissue is correlated to histopathological data and to outcome of rectal cancer. If these findings can be confirmed in larger trials, there will be a possibility to use PAI-1 as a prognostic factor.

Preoperative radiotherapy and extracellular matrix remodeling in rectal mucosa and tumour matrix metalloproteinases and plasminogen components.

BACKGROUND. Preoperative radiotherapy reduces recurrence but increases postoperative morbidity. The aim of this study was to explore the effect of radiotherapy in rectal mucosa and rectal tumour extracellular matrix (ECM) by studying enzymes and growth factors involved in ECM remodeling. MATERIALS AND METHODS. Twenty patients with short-term preoperative radiotherapy and 12 control patients without radiotherapy were studied. Biopsies from rectal mucosa and tumour were collected prior to radiotherapy and at surgery. Tissue MMP-1, -2, -9, TIMP-1, uPA, PAI-1, TGF-beta1 and calprotectin were determined by ELISA. Biopsies from irradiated and non-irradiated peritoneal areas were also analysed. RESULTS. Radiotherapy increased the tissue levels of MMP-2 and PAI-1 in both the rectal mucosa and tumours while calprotectin and uPA showed an increase only in the mucosa after irradiation. The increase of calprotectin was due to an influx of inflammatory cells as revealed by immunohistochemistry. Prior to irradiation, the tumour tissues had increased levels of MMP-1, -2, -9, total TGF-beta1, uPA, PAI-1 and calprotectin compared to mucosa, while TIMP-1 and the active TGF-beta1 fraction showed no statistical difference. CONCLUSIONS. This study indicates a radiation-induced effect on selected ECM remodeling proteases. This reaction may be responsible for early and late morbidity. Interference of this response might reduce these consequences.

The impact of rectal cancer tumor height on recurrence rates and metastatic location: A competing risk analysis of a national database.

BACKGROUND: The impact of rectal cancer tumor height on local recurrence and metastatic spread is unknown. The objective was to evaluate the impact of rectal cancer tumor height from the anal verge on metastatic spread and local recurrence patterns. METHODS: The Norwegian nationwide surgical quality registry was reviewed for curative rectal cancer resections from 1/1/1996-12/15/2006. Cancers were stratified into five height groups: 0-3 cm, >3-5 cm, >5-9 cm, >9-12 cm, 12 cm-HI. Competing risk and proportional hazards models assessed the relationship between tumor height and patterns of metastasis and survival. RESULTS: 6859 patients were analyzed. After median follow-up of 52 months (IQR 20-96), 26.7% (n = 1835) experienced recurrence. With tumors >12 cm, the risk of liver metastases increased (crude HR 1.49, p = 0.03), while lung metastases decreased (crude HR 0.66, p = 0.03), and risk of death decreased (crude HR 0.81, p = 0.001) The cumulative incidence of pelvic recurrence were highest for the low tumors (p = 0.01). Median time to liver metastases was 14months (IQR 7-24), lung metastases 25months (IQR 13-39), pelvic recurrence 19months (IQR10-32), (p < 0.0001). Time to metastases in liver and lungs were significantly associated with tumor height (p < 0.001) CONCLUSION: There are distinct differences in metastatic recurrence patterns and time to recurrence from different anatomic areas of the rectum. In crude analyses, tumor height impacted metastatic spread to the liver and lungs. However, when adjusting for treatment variables, the hazard of metastatic spread to the liver and lungs are limited. Nevertheless, time to metastases in liver and lungs is significantly impacted by tumor height. Venous drainage of the rectal cancer may be a significant contributor of rectal cancer metastatic spread, but further research is warranted.