Background and Aims Colectomy and reconstruction in patients with inflammatory bowel disease [IBD] may adversely affect fertility, but few population-based studies on this subject are available. Methods Fertility was assessed in 2989 women and 3771 men with IBD and prior colectomy during 1964-2014, identified from the Swedish National Patient Register, and in 35 092 matched individuals. Results Reconstruction with ileoanal pouch anastomosis [IPAA] was as common as ileorectal anastomosis [IRA] in ulcerative colitis [UC] and IBD-unclassified [IBD-U] but rare in Crohns disease [CD]. Compared with the matched reference cohort, women with IBD had lower fertility overall after colectomy (hazard ratio [HR] 0.65, confidence interval [CI] 0.61-0.69), with least impact with leaving the rectum intact [HR 0.79, CI 0.70-0.90]. Compared with colectomy only, fertility in female patients remained unaffected after IRA [HR 0.86, CI 0.63-1.17 for UC, 0.86, CI 0.68-1.08 for IBD-U and 1.07, CI 0.70-1.63 for CD], but was impaired after IPAA, especially in UC [HR 0.67, CI 0.50-0.88], and after completion proctectomy [HR 0.65, CI 0.49-0.85 for UC, 0.68, CI 0.55-0.85 for IBD-U and 0.61, CI 0.38-0.96 for CD]. In men, fertility was marginally reduced following colectomy [HR 0.89, CI 0.85-0.94], regardless of reconstruction. Conclusions Fertility was reduced in women after colectomy for IBD. The least impact was seen when a deviated rectum was left intact. IRA was associated with no further reduction in fertility, whereas proctectomy and IPAA were associated with the strongest impairment. IRA therefore seems to be the preferred reconstruction to preserve fertility in selected female patients. Fertility in men was only moderately reduced after colectomy.

BackgroundReports of an increased proportion of complicated appendicitis during the Covid-19 pandemic suggest a worse outcome due to delay secondary to the restrained access to health care, but may be explained by a concomitant decrease in uncomplicated appendicitis. We analyze the impact of the pandemic on the incidences of complicated and uncomplicated appendicitis.MethodWe did a systematic literature search in the PubMed, Embase and Web Of Science databases on December 21, 2022 with the search terms (appendicitis OR appendectomy) AND ("COVID" OR SARS-Cov2 OR "coronavirus"). Studies reporting the number of complicated and uncomplicated appendicitis during identical calendar periods in 2020 and the pre-pandemic year(s) were included. Reports with indications suggesting a change in how the patients were diagnosed and managed between the two periods were excluded. No protocol was prepared in advance. We did random effects meta-analysis of the change in proportion of complicated appendicitis, expressed as the risk ratio (RR), and of the change in number of patients with complicated and uncomplicated appendicitis during the pandemic compared with pre-pandemic periods, expressed as the incidence ratio (IR). We did separate analyses for studies based on single- and multi-center and regional data, age-categories and prehospital delay.ResultsThe meta-analysis of 100,059 patients in 63 reports from 25 countries shows an increase in the proportion of complicated appendicitis during the pandemic period (RR 1.39, 95% confidence interval (95% CI 1.25, 1.53). This was mainly explained by a decreased incidence of uncomplicated appendicitis (incidence ratio (IR) 0.66, 95% CI 0.59, 0.73). No increase in complicated appendicitis was seen in multi-center and regional reports combined (IR 0.98, 95% CI 0.90, 1.07).ConclusionThe increased proportion of complicated appendicitis during Covid-19 is explained by a decrease in the incidence of uncomplicated appendicitis, whereas the incidence of complicated appendicitis remained stable. This result is more evident in the multi-center and regional based reports. This suggests an increase in spontaneously resolving appendicitis due to the restrained access to health care. This has important principal implications for the management of patients with suspected appendicitis.

Aim To compare the number of appendicitis cases and its complications, during the first months of the COVID-19 pandemic in Sweden and the UK and the corresponding time period in 2019. Method Reports of emergency abdominopelvic CT performed at 56 Swedish hospitals and 38 British hospitals between April and July 2020 and a corresponding control cohort from 2019 were reviewed. Two radiologists and two surgeons blinded to the date of cohorts analyzed all reports for diagnosis of appendicitis, perforation, and abscess. A random selection of cases was chosen for the measurement of inter-rater agreement. Result Both in Sweden (6111) and the UK (5591) fewer, abdominopelvic CT scans were done in 2020 compared to 2019 (6433 and 7223, respectively); p < 0.001. In the UK, the number of appendicitis was 36% lower in April-June 2020 compared to 2019 but not in Sweden. Among the appendicitis cases, there was a higher number of perforations and abscesses in 2020, in Sweden. In the UK, the number of perforations and abscesses were initially lower (April-June 2020) but increased in July 2020. There was a substantial inter-rater agreement for the diagnosis of perforations and abscess formations (K = 0.64 and 0.77). Conclusion In Sweden, the number of appendicitis was not different between 2019 and 2020; however, there was an increase of complications. In the UK, there was a significant decrease of cases in 2020. The prevalence of complications was lower initially but increased in July. These findings suggest variability in delay in diagnosis of appendicitis depending on the country and time frame studied.

Background and Aims Onset of inflammatory bowel disease (IBD) in men is most common during childbearing age, but little is known about the impact on fertility. Previous studies of fertility in men were small, which justifies this large nation-based registry study. Methods Fertility was assessed in a national cohort of men with IBD aged 15-44 years in 1964-2014, identified from the Swedish National Patient Register, and in a reference cohort matched for age and place of residence (ratio 1:5). Information about childbirths was found in the Swedish Multi-Generation Register. Patients with indeterminate colitis or inconsistent IBD coding were classified as IBD-unclassified (IBD-U). Results The cohorts included 29,104 men with IBD and 140,901 matched individuals. IBD patients had a lower fertility rate (number of births per 1000 person years) compared with the matched individuals; 1.28 (SD 1.27) versus 1.35 (SD 1.31; p < 0.001). Fertility was somewhat impaired in all IBD subtypes compared with the matched cohort; ulcerative colitis (UC) (hazard ratio [HR] 0.93, 95% CI 0.91-0.96), Crohns disease (CD) (HR 0.95, 95% CI 0.92-0.98) and IBD-U 0.92, 95% CI 0.89-0.95. The cumulated total parity and the parity progression were also decreased for all IBD subtypes. Within the IBD cohort disease severity, intensity of medical treatment (CD) and bowel surgery (IBD-U) were further associated with impaired fertility. Conclusions This nationwide cohort study shows only slightly impaired fertility in men with IBD.

BACKGROUND: Kock’s continent ileostomy is an option after proctocolectomy for patients not suitable for ileal pouch anal anastomosis or ileorectal anastomosis. Ulcerative colitis is the most common indication for continent ileostomy.

OBJECTIVE: The aim of this study was to evaluate the long-term outcome of continent ileostomy.

DESIGN: Retrospective cohort register study.

SETTINGS: Data were obtained from the Swedish National Patient Registry.

PATIENTS: All patients with inflammatory bowel disease and a continent ileostomy were identified. Data on demographics, diagnosis, reoperations, and excisions of the continent ileostomy was obtained. Patients with inconsistent diagnostic coding were classified as inflammatory bowel disease-unclassified.

MAIN OUTCOME MEASURES: The main outcome measures was number of reoperations, time to reoperations and time to excision of continent ileostomy.

RESULTS: We identified 727 patients, 428 (59%) with ulcerative colitis, 45 (6%) with Crohn’s disease and 254 (35%) with inflammatory bowel disease-unclassified. After a median follow-up time of 27 (IQR, 21-31) years 191 (26%) patients had never had revisional surgery. Some 1,484 reoperations were performed on 536 (74%) patients, the median number of reoperations was 1 (IQR, 0-3) per patient. The continent ileostomy was excised in 77 (11%) patients. Reoperation within the first year after reconstruction was associated with higher rate of revisions (IRR, 2.90 p < 0.001) and shorter time to excision (HR 2.38 p < 0.001). Constructing the continent ileostomy after year 2000 was associated with increased revision and excision rates (IRR, 2.7 p < 0.001 and HR 2.74 p = 0.013). Inflammatory bowel disese-unclassified was associated with increased revisions (IRR, 1.3 p < 0.001) and the proportion of IBD-unclassified patients almost doubled from the 1980s (32%) to after 2000 (50%).

LIMITATIONS: Retrospective design, data from register. No data on quality of life available.

CONCLUSION: Continent ileostomy is associated with substantial need for revisional surgery, but most patients get to keep their reconstruction for a long time. See Video Abstract at https://links.lww.com/DCR/C122.

Bile duct injury (BDI) is a dangerous complication of cholecystectomy, with significant postoperative sequelae for the patient in terms of morbidity, mortality, and long-term quality of life. BDIs have an estimated incidence of 0.4-1.5%, but considering the number of cholecystectomies performed worldwide, mostly by laparoscopy, surgeons must be prepared to manage this surgical challenge. Most BDIs are recognized either during the procedure or in the immediate postoperative period. However, some BDIs may be discovered later during the postoperative period, and this may translate to delayed or inappropriate treatments. Providing a specific diagnosis and a precise description of the BDI will expedite the decision-making process and increase the chance of treatment success. Subsequently, the choice and timing of the appropriate reconstructive strategy have a critical role in long-term prognosis. Currently, a wide spectrum of multidisciplinary interventions with different degrees of invasiveness is indicated for BDI management. These World Society of Emergency Surgery (WSES) guidelines have been produced following an exhaustive review of the current literature and an international expert panel discussion with the aim of providing evidence-based recommendations to facilitate and standardize the detection and management of BDIs during cholecystectomy. In particular, the 2020 WSES guidelines cover the following key aspects: (1) strategies to minimize the risk of BDI during cholecystectomy; (2) BDI rates in general surgery units and review of surgical practice; (3) how to classify, stage, and report BDI once detected; (4) how to manage an intraoperatively detected BDI; (5) indications for antibiotic treatment; (6) indications for clinical, biochemical, and imaging investigations for suspected BDI; and (7) how to manage a postoperatively detected BDI.

Background/Aim: Cytotoxic T-lymphocyte antigen 4 (CTLA-4), transiently expressed on T cells, plays a pivotal role in the negative feedback regulation of T-cell activation and proliferation. The aim of the present study was to examine the influence of CTLA-4 gene polymorphism rs3087243 on CRC susceptibility and long-term survival in Swedish patients with CRC. Patients and Methods: Genotypes of 491 patients and 433 healthy controls were determined, using TaqMan single nucleotide polymorphism (SNP) assays based on polymerase chain reaction. Results: Patients carrying allele A were found to be at a higher risk of CRC and this allele was found to be more common in patients with disseminated disease compared to localized disease in the right colon. Kaplan-Meier analysis of cancer-specific survival showed that carriers of allele A had the highest risk of CRC-related death. Conclusion: The SNP rs3087243 of the CTLA-4 gene was associated with CRC risk and, therefore, it could be a prognostic marker for Swedish patients with CRC.

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Background and Aims: Inflammatory bowel disease [IBD] has been associated with reduced female fertility. We analyse fertility in a national cohort of women with IBD. Methods: Fertility was assessed in women with IBD aged 15-44 years in 1964-2014, identified from the Swedish National Patient Register and a matched cohort [ratio 1:5]. Patients with indeterminate colitis or inconsistent IBD coding were classified as IBD-unclassified [IBD-U]. Results: The cohorts included 27 331 women with IBD and 131 892 matched individuals. The fertility rate in IBD was 1.52 (standard deviation [SD] 1.22) births per 1000 person-years and 1.62 [SD 1.28] [p&lt;0.001] in matched individuals. Fertility was impaired in all IBD subtypes compared with the matched cohort (hazard ratio Crohns disease [CD] 0.88, 95% confidence interval [CI] 0.85-0.91; IBD-U 0.86, 95% CI 0.83-0.89; and ulcerative colitis [UC] 0.96, 95% CI 0.93-0.98). Fertility improved during the study period for the IBD cohort except for CD. Parity progression ratio, the proportion of IBD women progressing from one parity to the next compared with the matched cohort, was decreased at all parity levels for CD and IBD-U, but only for multiparous women in UC. Contraceptive usage was higher in IBD, both before and after the diagnosis. Disease severity, bowel resections, and perianal disease in CD affected fertility negatively. Conclusions: Fertility was impaired mainly in women with CD and IBD-U, and less so in UC. During the study period, fertility improved in women with UC or IBD-U. Some results suggest a role of voluntarily reduced fertility.

Background Patients with suspicion of appendicitis present with a wide range of severity. Score-based risk stratification can optimise the management of these patients. This prospective study validates the Appendicitis Inflammatory Response (AIR) score in patients with suspicion of appendicitis. Method Consecutive patients over the age of five with suspicion of appendicitis presenting at 25 Swedish hospitals emergency departments were prospectively included. The diagnostic properties of the AIR score are estimated. Results Some 3878 patients were included, 821 with uncomplicated and 724 with complicated appendicitis, 1986 with non-specific abdominal pain and 347 with other diagnoses. The score performed better in detecting complicated appendicitis (ROC area 0.89 (95% confidence interval (CI) 0.88-0.90) versus 0.83 (CI 0.82-0.84) for any appendicitis, p &lt; 0.001), in patients below age 15 years and in patients with &gt;47 h duration of symptoms (ROC area 0.93, CI 0.90-0.95 for complicated and 0.87, CI 0.84-0.90 for any appendicitis in both categories). Complicated appendicitis is unlikely at AIR score &lt;4 points (Negative Predictive Value 99%, CI 98-100%). Appendicitis is likely at AIR score &gt;8 points, especially in young patients (positive predictive value (PPV) 96%, CI 90-100%) and men (PPV 89%, CI 84-93%). Conclusions The AIR score has high sensitivity for complicated appendicitis and identifies subgroups with low probability of complicated appendicitis or high probability of appendicitis. The discriminating capacity is high in children and patients with long duration of symptoms. It performs equally well in both sexes. This verifies the AIR score as a valid decision support.

BACKGROUND: With a lifelong perspective, 12% of ulcerative colitis patients will need a colectomy. Further reconstruction via ileo-rectal anastomosis or pouch can be affected by patients' perspective of their quality of life after surgery.

AIM: To assess the function and quality of life after restorative procedures with either ileo-rectal anastomosis or ileal pouch-anal anastomosis in relation to the inflammatory activity on endoscopy and in biopsies.

METHOD: A total of 143 UC patients operated with subtotal colectomy and ileo-rectal anastomosis or pouches between 1992 and 2006 at Linköping University Hospital were invited to participate. Those who completed the validated questionnaires (Öresland score, SF-36, Short Health Scale) were offered an endoscopic evaluation including multiple biopsies. Associations between anorectal function and quality of life with type of restorative procedure and severity of endoscopic and histopathologic grading of inflammation were evaluated.

RESULTS: Some 77 (53.9%) eligible patients completed questionnaires, of these 68 (88.3%) underwent endoscopic evaluation after a median follow-up of 12.5 (range 3.5-19.4) years after restorative procedure. Patients with ileo-rectal anastomosis reported better overall Öresland score: median = 3 (IQR 2-5) for ileo-rectal anastomosis (n = 38) and 10 (IQR 5-15) for pouch patients (n = 39) (p < 0.001). Anorectal function (Öresland score) and endoscopic findings (Baron-Ginsberg score) were positively correlated in pouch patients (tau: 0.28, p = 0.006).

CONCLUSION: Patients operated with ileo-rectal anastomosis reported better continence compared to pouches. Minor differences were noted regarding the quality of life. Ileo-rectal anastomosis is a valid option for properly selected ulcerative colitis patients if strict postoperative endoscopic surveillance is carried out.

Background and aims Acute appendicitis (AA) is among the most common causes of acute abdominal pain. Diagnosis of AA is still challenging and some controversies on its management are still present among different settings and practice patterns worldwide. In July 2015, the World Society of Emergency Surgery (WSES) organized in Jerusalem the first consensus conference on the diagnosis and treatment of AA in adult patients with the intention of producing evidence-based guidelines. An updated consensus conference took place in Nijemegen in June 2019 and the guidelines have now been updated in order to provide evidence-based statements and recommendations in keeping with varying clinical practice: use of clinical scores and imaging in diagnosing AA, indications and timing for surgery, use of non-operative management and antibiotics, laparoscopy and surgical techniques, intra-operative scoring, and peri-operative antibiotic therapy. Methods This executive manuscript summarizes the WSES guidelines for the diagnosis and treatment of AA. Literature search has been updated up to 2019 and statements and recommendations have been developed according to the GRADE methodology. The statements were voted, eventually modified, and finally approved by the participants to the consensus conference and by the board of co-authors, using a Delphi methodology for voting whenever there was controversy on a statement or a recommendation. Several tables highlighting the research topics and questions, search syntaxes, and the statements and the WSES evidence-based recommendations are provided. Finally, two different practical clinical algorithms are provided in the form of a flow chart for both adults and pediatric (&lt; 16 years old) patients. Conclusions The 2020 WSES guidelines on AA aim to provide updated evidence-based statements and recommendations on each of the following topics: (1) diagnosis, (2) non-operative management for uncomplicated AA, (3) timing of appendectomy and in-hospital delay, (4) surgical treatment, (5) intra-operative grading of AA, (6) ,management of perforated AA with phlegmon or abscess, and (7) peri-operative antibiotic therapy.

Purpose The pathogenesis of appendicitis is not well understood. Environmental factors are regarded most important, but epidemiologic findings suggest a role of inflammatory and genetic mechanisms. This study determines the association of single nucleotide polymorphisms (SNPs) of inflammatory genes with appendicitis. Methods As part of a larger prospective study on the diagnostic value of inflammatory variables in appendicitis, the genotype frequency of 28 polymorphisms in 26 inflammatory response genes from the appendicitis and control patients was analyzed in blood samples from 343 patients, 100 with appendicitis, and 243 with non-specific abdominal pain, using TaqMan SNP genotyping assays. Results Associations with appendicitis were found for SNPs IL-13 rs1800925 with odds ratio (OR) 6.02 (95% CI 1.52-23.78) for T/T versus C/C + T/T, for IL-17 rs2275913 with OR 2.38 (CI 1.24-4.57) for A/A vs G/G + GA, for CCL22 rs223888 with OR 0.12 (0.02-0.90), and for A/A vs G/G + GA. Signs of effect modification of age for the association with appendicitis were found for IL-13 rs1800925 and CTLA4 rs3087243. Stratified analysis showed difference in association with severity of disease for IL-17 rs2275913 and CD44 rs187115. Conclusions The association of gene variants on risk of appendicitis and its severity suggest an etiologic role of genetically regulated inflammatory response. This may have implications for understanding the prognosis of untreated appendicitis as a possible self-limiting disorder and for understanding the inverse association of appendicitis with ulcerative colitis.

Background:Identification of high-risk stage II colorectal cancer (CRC) patients, potential candidates for adjuvant chemotherapy, is challenging. Current clinical guidelines rely mainly on histopathological markers with relatively weak prognostic value. This motivates further search for prognostic markers.Methods:This explorative study aimed to identify potential candidate gene mutations to facilitate differentiation between subgroups of patients with CRC stage II. Panel-based massive parallel sequencing was used to genetically characterize tumor tissues from 85 patients radically operated for CRC stage II, of which 12 developed recurrent cancer during follow-up. Genetic data was compared between patients with or without cancer recurrence, between tumors located in colon and in rectum, and for association with tumor differentiation grade.Results:Genetic variation inATM,C11ORF65was associated with recurrence-free survival. Previous reports regarding the association betweenBRAFmutation and a higher age at diagnosis, and tumor location in colon were confirmed.APC,BRAF, orKRASmutation was associated with tumor differentiation grade. Multiple correspondence analyses revealed no obvious clustering of patients with the studied clinical characteristics, indicating that the genetic signatures observed here were unique for each individual.Conclusions:Taken together, we have demonstrated the utility of panel-based massive parallel sequencing to explore the pathogenesis of CRC stage II. We have identified promising candidate gene mutations associated with cancer recurrence, tumor location, and differentiation grade in patients with CRC stage II, which merit further investigation.

Background There is limited knowledge about the epidemiology of the major histological subtypes of appendiceal malignancy: adenocarcinoma and neuroendocrine neoplasm of the appendix (A-NEN). The aims of this national cohort study were to assess the prevalence, incidence and trends of appendiceal malignancies in Sweden. Method All individuals who underwent appendicectomy and all diagnosed with appendiceal malignancy from 1970 to 2012 were identified from the National Patient Register and the Swedish Cancer Registry. Demographic data of the background population were obtained from Statistics Sweden. The incidence rate (IR) and the prevalence of appendiceal malignancy per performed appendicectomy were calculated. Results We identified 3774 patients with appendiceal malignancy. IR of A-NEN was 5.8/10(6)person-years with a peak of 8.4/10(6)at age 20-30 years, whereafter it plateaued at a somewhat lower level. IR for adenocarcinoma was 3.7/10(6)person-years, starting at a very low level among the youngest and increasing to 15.4/10(6)at age 80-89 years. The IR of adenocarcinoma increased from 2.6/10(6)in 1970-1979 to 5.4/10(6)in 2010-2012. The IR of A-NEN was stable during the study period. The prevalence per appendicectomy was low for both types of malignancies among the young but increased with age, most dramatically for adenocarcinoma. There was a trend during the study period towards more extensive surgery. Conclusion Adenocarcinoma is most common and increasing in the elderly, whereas A-NEN affects all ages with a peak in young age. This peak probably reflects removal of occult A-NEN due to the higher appendicectomy frequency in the young.

Background Previous studies indicate a low incidence of appendicitis in third-trimester pregnancy, suggesting a protecting effect of pregnancy. This large population-based cohort study analyzes the association of appendicitis with pregnancy in more detail. The aim of the study was to investigate the incidence of appendicitis and negative appendectomy before, during and after pregnancy. Methods Cross-linking between two Swedish health registries provided data on appendectomy for all women in Sweden giving birth between 1973 and 2013. We analyzed the incidence rates (IR) of perforated and non-perforated appendicitis and negative appendectomy before, during and after pregnancy, and secular trends during the study period. Standardized incidence ratios (SIR) were estimated using age-, sex- and period-specific IR from the background population in Sweden. Results Some 3,888,452 pregnancies resulted in birth during the study period. An appendectomy was registered for 27,575 women in the interval starting one year before and ending two years after pregnancy. The incidence of appendicitis varied substantially during and after pregnancy. SIR for perforated appendicitis was 0.47 (95% CI 0.38-0.59) in the third trimester, 3.89 (2.92-5.18) peripartum, 2.20 (1.89-2.55) in the puerperium and 1.27 (1.19-1.36) in the year postpartum. The pattern was similar for non-perforated appendicitis. Negative appendectomy decreased postpartum. Incidence rate of non-perforated appendicitis and negative appendectomy decreased for both pregnant and non-pregnant women during the study period. Conclusions The findings in this study suggest a protecting effect of pregnancy on the development of appendicitis, which is followed by a rebound effect after birth.

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OBJECTIVE. The purpose of this study is to propose a sensitive CT criterion (the presence of any of 10 CT features) for complicated appendicitis that could be used in the nonoperative management of appendicitis and to compare the diagnostic performance of this sensitive CT criterion with that of gestalt assessment. MATERIALS AND METHODS. This retrospective study, which was conducted in a tertiary teaching hospital, included 100 patients with suspected appendicitis on CT. Complicated appendicitis, defined as gangrenous or perforated appendicitis, was pathologically or surgically confirmed in 32 patients. Six radiologists independently determined the presence of 10 previously reported CT features of complicated appendicitis (contrast enhancement defect of the appendiceal wall, abscess, extraluminal air, intraluminal air, extraluminal appendicolith, intraluminal appendicolith, moderate-to-severe periappendiceal fat stranding, periappendiceal fluid, ileus, and ascites) and rated the likelihood score for complicated appendicitis using gestalt assessment. The sensitivity and specificity of CT for complicated appendicitis were measured by the presence of any of 10 CT features (the any-of-10-features criterion) and by the radiologists gestalt assessment. Pooled sensitivity and specificity were compared using a generalized linear mixed model. RESULTS. The pooled sensitivity of the presence of any of 10 CT features was higher than that of gestalt assessment (92% vs 64%; difference, 28% [95% CI, 10-46%]; p amp;lt; 0.001), although the pooled specificity was lower (43% vs 76%; difference, -33% [95% CI, -48% to -17%]; p amp;lt; 0.001). CONCLUSION. The pooled sensitivity of the presence of any of 10 CT features was higher than that of gestalt assessment, at the cost of lower specificity. For prudent selection of patients who should receive nonoperative treatment of appendicitis, the any-of-10-features criterion may be used to decrease treatment failure associated with a false-negative diagnosis of complication.

Background: Interleukin 2 (IL2) is a significant factor activating T-cell-mediated immune response by stimulation of natural killer cells, T-cells and in development of regulatory T (Treg) cells. Recent studies have that IL2 participates in cancer development by modifying the local immune response. Based on the suggested role of the single nucleotide polymorphisms (SNPs) rs2069762, rs6822844 and rs11938795 of IL2 in the pathogenesis of certain diseases, the relationship of these SNPs with clinicopathological variables and their possible implication for prognosis and disease outcome were evaluated in a cohort of Swedish patients with colorectal cancer (CRC). Materials and Methods: TaqMan SNP genotype assays based on polymerase chain reaction were used for analysis of the IL2 SNPs in 467 patients with CRC and 467 healthy controls. Expression analysis of IL2 in plasma and CRC tissue was also performed. Results: The allelic variants T in rs11938795 and G in rs6822844 were significantly associated with a higher risk of CRC. Kaplan-Meier analysis showed that cancer-specific survival was worse for individuals with C allele for rs2069762 with stage II CRC and with T allele for rs6822844 with stage III CRC. Conclusion: SNPs rs2069762, rs6822844 and rs11938795 of the IL2 gene may be helpful as prognostic biomarkers in the follow-up and management of the patients.

BACKGROUND: The aim was to clarify whether children born preterm with a history of necrotizing enterocolitis (NEC) had an increased risk of rickets, fractures, and/or vitamin D deficiency during childhood and adolescence compared to controls without NEC, matched for gestational age. METHODS: All infants born in Sweden between 1987 and 2009 with a gestational age amp;lt;32 + 0 weeks and a diagnosis of NEC were identified. Totally, 465 children with a history of NEC and 2127 controls were included. International Classification of Diseases codes for all categories of fractures, rickets, vitamin D deficiency, and malnutrition were analyzed. RESULTS: In total, 94 of the 465 children with NEC died within 28 days. Of the 2127 controls, 288 died within 28 days. Among the remaining 371 NEC cases, 39 fracture occasions were identified. The 1839 controls had 204 fracture occasions. There was no significant difference in fractures. Rickets was diagnosed in 11 (3%) of the children with a history of NEC compared to 21 (1%) of the controls (odds ratio 2.65, 95% CI 1.26-5.53, p = 0.007). CONCLUSIONS: This study showed an increased risk of rickets but not fractures during childhood and adolescence in children born preterm and with a history of NEC, compared to matched controls.

Pilonidal disease can be treated by less invasive methods such as simple mechanical cleansing of the sinus and cavity of hairs and granulation tissue eventually supplemented by filling the space with an antiseptic or sclerosing agent like phenol (forbidden in Germany due to its toxicity) or space-holding fibrin glue. Minimal excision or debridement of the sinus and/or cavity through amidline or aseparate paramedial excision can also be performed, leaving the wounds open or closed. These methods are simple and cost-efficient, and associated with low pain, rapid healing, and arapid return to normal activity. Adisadvantage is the higher recurrence rate; however, these methods can be used repeatedly for recurrences. Whereas the evidence for treatment with phenol or fibrine glue is weak, there are numerous reports supporting the safety and efficiency of the minimally invasive surgical methods. Because of the associated low risk for complications and morbidity, these procedures are suitable for first-line treatment in the majority of pilonidal disease patients.

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Background: Interleukin 4 (IL-4) and interleukin 13 (IL-13) are anti-inflammatory and immunomodulatory cytokines which share a common cellular receptor IL4R alpha and are involved in the same signaling pathways. Our purpose was to assess whether genetic variants within IL-4, IL-13 and IL-4R alpha are associated with the risk or clinical outcome of colorectal cancer (CRC). Methods: Three single nucleotide polymorphisms (SNPs) were screened in 466 patients with CRC and 445 healthy controls. The selected SNPs were IL-4 SNP rs2243250, IL-4R alpha SNP rs1801275 and IL-13 SNP rs1800925. Results: We found that the genotype variant T/T in IL-13 gene was associated with a higher risk of CRC. Kaplan Meier analysis showed that the cancer specific survival differed between C/C and CT + TT for IL-4 SNP. Moreover, the carriers of the T allele were associated with the highest risk of CRC death with a hazard ratio (HR) of 1.57, 95% CI 1.06-2.36, p = -.024. The observed effect of the T allele was restricted to stage III patients. Conclusion: Our results indicate IL-13 SNP rs1800925 as a risk factor for CRC and that IL-4 SNP rs2243250 could be a useful prognostic marker in the follow-up and clinical management of patients with CRC especially in stage III disease.

National or international guidelines can help surgeons and anesthesiologists make treatment decisions, but the existence of conflicting recommendations can hinder treatment rather than helping. A case in point is the treatment of pilonidal sinus disease, a chronic subcutaneous infection located in the sacrococcygeal area. Its incidence is rising, reaching almost 100/100,000 inhabitants. Three surgical societies have proposed guidelines for treating the disease, but these guidelines vary greatly in their approach to anesthesia. Who should provide input into guidelines? And how can medical disciplines successfully collaborate? Anesthesiologists must be involved in defining perioperative recommendations not only in patients with pilonidal sinus disease.

Paediatric intestinal failure (IF) is a disease entity characterised by gut insufficiency often related to short bowel syndrome. It is commonly caused by surgical removal of a large section of the small intestine in association with necrotising enterocolitis (NEC), which usually affects premature infants. This study investigated the incidence and risk of IF in preterm infants with or without NEC.

Objective

To analyze associations of maternal, fetal, gestational, and perinatal factors with necrotizing enterocolitis in a matched case-control study based on routinely collected, nationwide register data.

Study design

All infants born in 1987 through 2009 with a diagnosis of necrotizing enterocolitis in any of the Swedish national health care registers were identified. For each case up to 6 controls, matched for birth year and gestational age, were selected. The resulting study population consisted of 720 cases and 3,567 controls. Information on socioeconomic data about the mother, maternal morbidity, pregnancy related diagnoses, perinatal diagnoses of the infant, and procedures in the perinatal period, was obtained for all cases and controls and analyzed with univariable and multivariable logistic regressions for the whole study population as well as for subgroups according to gestational age.

Results

In the study population as a whole, we found independent positive associations with necrotizing enterocolitis for isoimmunization, fetal distress, cesarean section, neonatal bacterial infection including sepsis, erythrocyte transfusion, persistent ductus arteriosus, cardiac malformation, gastrointestinal malformation, and chromosomal abnormality. Negative associations were found for maternal weight, preeclampsia, maternal urinary infection, premature rupture of the membranes, and birthweight. Different patterns of associations were seen in the subgroups of different gestational age.

Conclusion

With some interesting exceptions, especially in negative associations, the results of this large, population based study, are in keeping with earlier studies. Although restrained by the limitations of register data, the findings mirror conceivable pathophysiological processes and underline that NEC is a multifactorial disease.

Background: Interleukin 32 (IL32) is an intracellular pluripotent cytokine produced by epithelial cells, monocytes, T-lymphocytes and natural killer cells and seems to be involved in the pathogenesis of cancer and inflammatory diseases. Our purpose was to assess the role of protein expression and genetic polymorphisms of IL32 in colorectal cancer (CRC) susceptibility. Materials and Methods: To gain insight into clinical significance of IL32 in Swedish patients with CRC, using enzyme-linked immunosorbent assay, we determined whether IL32 protein level is altered in CRC tissue (n=75) compared with paired normal tissue and in plasma from patients with CRC (n=94) compared with controls (n=81). The expression of IL32 protein was confirmed by immunohistochemistry (n=73). We used Luminex technology to investigate protein levels of the cytokines IL6, tumor necrosis factor-a (TNFa) and vascular endothelial growth factor (VEGF) to relate these to IL32 levels in CRC tissue. Three single nucleotide polymorphisms (SNPs) (rs28372698, rs12934561, rs4786370) of the IL32 gene have been proposed as modifiers for different diseases. The present study evaluated the susceptibility of patients possessing these SNPs to CRC. Using TaqMan SNP genotyping assays, these SNPs were screened in Swedish patients with CRC (n=465) and healthy controls (n=331). Results: We found no significant differences in the genotypic frequencies between the patients and healthy controls and no relation to survival for any of the SNPs. However, the SNP rs12934561 was statisticalLY significant associated with older patients. IL32 protein was up-regulated in CRC tissue and related to IL6, TNF alpha, and VEGF, and seems to be modulated by SNP rs28372698. The IL32 protein level in CRC tissue also reflects both disseminated disease and location. Conclusion. Our results suggest that altered IL32 protein concentrations in CRC tissue and genotypic variants of IL32 are related to disseminated CRC.

OBJECTIVES: Ulcerative colitis (UC) is a chronic inflammatory disease usually responding well to anti-inflammatory drugs but many patients will still need colectomy. Appendectomy is associated with a lower risk of later developing UC. We aimed to assess the longitudinal relationship between appendectomy, appendicitis, and disease course in UC patients. METHODS: A national cohort of UC patients with a diagnosis in 1964-2010 was identified from the Swedish National Patient Register that also provided information regarding appendicitis and/or appendectomy before or after the UC diagnosis. The risk for colectomy and UC-related hospital admissions was evaluated. RESULTS: Among 63,711 UC patients, 2,143 had appendectomy and 7,690 underwent colectomy. Appendectomy for appendicitis before 20 years of age and for non-appendicitis at all ages before UC diagnosis was associated with a lower risk of colectomy (hazard ratio (HR) 0.44, 0.27-0.72 and HR 0.62, 0.43-0.90, respectively), and fewer hospital admissions (incidence rate ratio (IRR) 0.68, 95% confidence interval (CI) 0.64-0.73 and IRR 0.54, 0.47-0.63, respectively). Appendectomy for appendicitis after the UC diagnosis was associated with a higher risk of colectomy (HR 1.56, 1.20-2.03), whereas no such association was found for other pathology (HR 1.40, 0.79-2.47). CONCLUSIONS: Appendectomy early in life and before developing UC is associated with a lower risk of colectomy as well as UC-related hospital admissions. Appendectomy for appendicitis after established UC appears associated with a worse disease course, with an increased rate of subsequent colectomy.

AIM To investigate association of circulating inflammatory factors at the time of colorectal cancer (CRC) surgery with survival. METHODS Plasma levels from 174 CRC patients (69 females and 105 men), with median age 70 years (range 29-90), localized in the colon (n = 105) or rectum (n = 69), with stage. (n = 24), stage. (n = 54), stage. (n = 67) and stage. (n = 29) were measured using commercially available Bio-Plex Pro (TM) Human Chemokine Panel 40-Plex, including 40 different chemokines, cytokines and interleukins. The prognostic association of each inflammatory factor was analysed as CRC-specific and total mortality. RESULTS Out of 174 patients, 66 died during the follow-up, 40 because of CRC specific mortality. High tertile levels of 8 factors were significantly associated with increased CRC-specific mortality, of which CCL1, CCL20, CCL24, CX3CL1, IL-4 and TNF-alpha remained significant in a multivariate Cox regression analysis. High tertile levels of 14 factors were associated with increased total mortality, of which CCL1, CCL15, CCL20, CX3CL1, CXCL13, IFN-gamma, IL-2, IL-4 and IL-10 remained significant after adjustment for clinical covariates. For most of the inflammatory factors the association between higher tertile levels and an increased mortality in general appeared two years after surgery. High tertile levels of TNF-alpha and CCL24 were exclusively associated with CRC-specific mortality. The distribution of these factors were not associated with TNM stage with exception for CCL20. CONCLUSION High plasma levels of inflammatory factors are associated with increased risk of mortality among CRC patients and could be potential biomarkers for revealing prognosis.

Background Conventional treatment of pilonidal disease with wide excision is associated with high morbidity. We describe the short- and long-term results and the impact on the health care system of a simple operation performed in the office under local anaesthesia, consisting of minimal excision of pilonidal sinuses with primary suture-the modified Lord-Millar operation (mLM). Methods All patients operated with mLM from February 2008 till November 2012 were prospectively followed for recurrence by telephone interviews and examination of symptomatic patients till July 2015. The outcome is compared with that in all patients operated with conventional wide excision from January 2003 till February 2008. The effects on the health care system of a consistent use of mLM is analysed by comparing the management of all patients with pilonidal disease at three hospitals during 2013 and 2014. Results Some 129 patients underwent conventional surgical treatment, and 113 had the mLM operation. The mLM operation was more often performed under local anaesthesia, was less often admitted to hospital, had fewer post-operative health care visits (2.4 vs. 14.6, p amp;lt; 0.001) and a shorter sick leave (1.0 vs. 34.7 days, p amp;lt; 0.001) indicating faster wound healing. The estimated 5-year recurrence rate was similar (32 vs. 23%, p = 0.091). The cost per operated patient was lower (2231 vs. 6222 EUR, p amp;lt; 0.001). The hospital consistently applying the mLM operation used less resources for pilonidal diseased patients (34,545 vs. 77,421 EUR per 100,000 inhabitants and year). Conclusions The mLM operation is simple, cost-efficient and has low morbidity and good long-term results.

Aim: This study investigated space-time clustering of neonatal necrotising enterocolitis over three decades. Methods: Space-time clustering analyses objects that are grouped by a specific place and time. The Knox test and Kulldorffs scan statistic were used to analyse space-time clusters in 808 children diagnosed with necrotising enterocolitis in a national cohort of 2 389 681 children born between 1987 and 2009 in Sweden. The municipality the mother lived in and the delivery hospital defined closeness in space and the time between when the cases were born - seven, 14 and 21 days - defined closeness in time. Results: The Knox test showed no indication of space-time clustering at the residential level, but clear indications at the hospital level in all the time windows: seven days (p = 0.026), 14 days (p = 0.010) and 21 days (p = 0.004). Significant clustering at the hospital level was found during 1987-1997, but not during 1998-2009. Kulldorffs scan statistic found seven significant clusters at the hospital level. Conclusion: Space-time clustering was found at the hospital but not residential level, suggesting a contagious environmental effect after delivery, but not in the prenatal period. The decrease in clustering over time may reflect improved routines to minimise the risk of contagion between patients receiving neonatal care.

BackgroundThe role of imaging in the diagnosis of appendicitis is controversial. This prospective interventional study and nested randomized trial analysed the impact of implementing a risk stratification algorithm based on the Appendicitis Inflammatory Response (AIR) score, and compared routine imaging with selective imaging after clinical reassessment. MethodPatients presenting with suspicion of appendicitis between September 2009 and January 2012 from age 10years were included at 21 emergency surgical centres and from age 5years at three university paediatric centres. Registration of clinical characteristics, treatments and outcomes started during the baseline period. The AIR score-based algorithm was implemented during the intervention period. Intermediate-risk patients were randomized to routine imaging or selective imaging after clinical reassessment. ResultsThe baseline period included 1152 patients, and the intervention period 2639, of whom 1068 intermediate-risk patients were randomized. In low-risk patients, use of the AIR score-based algorithm resulted in less imaging (192 versus 345 per cent; Pamp;lt;0001), fewer admissions (295 versus 428 per cent; Pamp;lt;0001), and fewer negative explorations (16 versus 32 per cent; P=0030) and operations for non-perforated appendicitis (68 versus 97 per cent; P=0034). Intermediate-risk patients randomized to the imaging and observation groups had the same proportion of negative appendicectomies (64 versus 67 per cent respectively; P=0884), number of admissions, number of perforations and length of hospital stay, but routine imaging was associated with an increased proportion of patients treated for appendicitis (534 versus 463 per cent; P=0020). ConclusionAIR score-based risk classification can safely reduce the use of diagnostic imaging and hospital admissions in patients with suspicion of appendicitis. Registration number: NCT00971438 ( ). Reduces imaging and admissions

BACKGROUND amp; AIMS: Patients with ulcerative colitis (UC) have an increased risk of rectal cancer, therefore reconstruction with an ileal pouch-anal anastomosis (IPAA) generally is preferred to an ileorectal anastomosis (IRA) after subtotal colectomy. Similarly, completion proctectomy is recommended for patients with ileostomy and a diverted rectum, although this approach has been questioned because anti-inflammatory agents might reduce cancer risk. We performed a national cohort study in Sweden to assess the risk of rectal cancer in patients with UC who have an IRA, IPAA, or diverted rectum after subtotal colectomy.

METHODS: We collected data from the Swedish National Patient Register for a cohort of 5886 patients with UC who underwent subtotal colectomy with an IRA, IPAA, or diverted rectum from 1964 through 2010. Patients who developed rectal cancer were identified from the Swedish National Cancer Register. The risk of rectal cancer was compared between this cohort and the general population by standardized incidence ratio analysis.

RESULTS: Rectal cancer occurred in 20 of 1112 patients (1.8%) who received IRA, 1 of 1796 patients (0.06%) who received an IPAA, and 25 of 4358 patients (0.6%) with a diverted rectum. Standardized incidence ratios for rectal cancer were 8.7 in patients with an IRA, 0.4 in patients with an IPAA, and 3.8 in patients with a diverted rectum. Risk factors for rectal cancer were primary sclerosing cholangitis in patients with an IRA (hazard ratio, 6.12), and colonic severe dysplasia or cancer before subtotal colectomy in patients with a diverted rectum (hazard ratio, 3.67).

CONCLUSIONS: In an analysis of the Swedish National Patient Register, we found that the risk for rectal cancer after colectomy in patients with UC is low, in relative and absolute terms, after reconstruction with an IPAA. An IRA and diverted rectum are associated with an increased risk of rectal cancer, compared with the general population, but the absolute risk is low. Patients and their health care providers should consider these findings in making decisions to leave the rectum intact, perform completion proctectomy, or reconstruct the colon with an IRA or IPAA.

Objectives: Ileorectal anastomosis (IRA) affects bowel function, sexual function and reproduction less negatively than ileal pouch anal anastomosis (IPAA), the standard reconstruction after colectomy for ulcerative colitis (UC). In younger UC patients, IRA may have a role postponing pelvic surgery and IPAA. The aim of the present study was to investigate the survival of IPAA secondary to IRA compared to IPAA as primary reconstruction, as this has not previously been studied in UC. Patients and methods: All patients with UC diagnosis between 1960 and 2010 in Sweden were identified from the National Patient Registry. From this cohort, colectomized patients reconstructed with primary IPAA and patients reconstructed with IPAA secondary to IRA were identified. The survival of the IPAA was followed up until pouch failure, defined as pouchectomy and ileostomy or a diverting ileostomy alone. Results: Out of 63,796 patients, 1796 were reconstructed with IPAA, either primarily (n=1720) or secondary to a previous IRA (n=76). There were no demographic differences between the groups, including length of follow-up (median 12.6 (IQR 6.7-16.6) years and 10.0 (IQR 3.5-15.9) years, respectively). Failure of the IPAA occurred in 103 (6.0%) patients with primary and in 6 (8%) patients after secondary IPAA (P=0.38 log-rank). The 10-year pouch survival was 94% (95% CI 93-96) for primary IPAA and 92% (81-97) for secondary. Conclusions: Patients choosing IRA as primary reconstruction do not have an increased risk of failure of a later secondary IPAA in comparison with patients with primary IPAA.

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The DNA repair genes XRCC1 and XRCC6 have been proposed to participate in the pathological process of cancer by modulating the DNA repair capacity. This study evaluated the susceptibility of the single-nucleotide polymorphisms (SNPs) XRCC1 (rs25487, G amp;gt; A) and XRCC6 (rs2267437, C amp;gt; G) to colorectal cancer (CRC) and their association with clinical parameters in Swedish patients with CRC. Using the TaqMan system, these SNPs were screened in 452 patients and 464 controls. No significant difference in genotype distribution was found between the patients and controls, or any significant association with cancer-specific or disease-free survival in patients. However, we showed that the carriers of allele A in XRCC1 (rs25487, G amp;gt; A) were connected with a higher risk of disseminated CRC (Odds Ratio = 1.64; 95% Confidence Interval = 1.12-2.41, p = 0.012).

Introduction Patients treated conservatively for acute diverticulitis (AD) are recommended colonic assessment to rule out an underlying Colorectal cancer (CRC). This has been questioned in patients with a CT diagnosis of uncomplicated AD. We analyzed the frequency of CRC and compared the characteristics of the CRC patients with controls. Method A cohort of patients treated conservatively for AD during 2005-2011 was identified through an administrative database. Patients diagnosed with CRC within 1 year after the index admission and four randomly selected controls were identified. The patients files were reviewed to verify the diagnosis and obtain information about the clinical characteristics and the management. A blinded review was performed of CT examinations. The expected number of CRC was calculated from age, sex, and period-specific incidence data. The characteristics of the CRC patients were compared with the controls in a nested case-control study. Results 890 patients (298 men and 592 women) were treated conservatively for AD. 12 patients were diagnosed with CRC within 1 year, and ten of them in the sigmoid, giving a Standardized Incidence Ratio of 20.0 (95 % CI 10.2-35.7, pamp;lt;0.001) for sigmoidal cancer. All CRC patients were aged over 70 years. The cancer was missed in six CT scans at the primary reading and in five at the blinded review. Conclusion Patients conservatively treated for AD are at high risk for an underlying CRC, especially if older than 70 years, which motivates routine follow-up. A CT diagnosis of uncomplicated AD does not rule out CRC.

BACKGROUND: Phospholipase A2 Group IV C (PLA2G4C) catalyzes the release of certain fatty acids from phospholipids and plays a role in a range of physiological functions, such as remodeling of cell membranes and the production of prostaglandins. Furthermore, it has been proposed that PLA2G4C plays an important role in breast cancer cell chemotaxis. This study aimed to investigate the effect of a single nucleotide polymorphism (SNP) rs1549637 (T>A) of the PLA2G4C gene on the prognosis of colorectal cancer (CRC).

MATERIAL AND METHODS: Whole blood DNA was extracted from 381 patients with CRC and 618 controls, and a TaqMan SNP genotyping assay was used to determine the distribution of the genotypes. Cancer-specific and disease-free survival was analyzed by Kaplan-Meier graphs and by uni- and multivariable Cox regression.

RESULTS: The cancer-specific survival differed between the genotypes (p = 0.019) and the carriers of the A allele were associated with the highest risk of CRC death, with a hazard ratio (HR) of 1.72 [95% confidence interval (CI) 1.17-2.53, p = 0.006] compared with homozygous carriers of the T allele. This increased mortality in the carriers with the allele A was especially marked in stage II with an HR of 3.84 (95% CI 1.51-9.78, p = 0.005).

CONCLUSION: The A allele in PLA2G4C SNP (rs1549637) is associated with a worse prognosis in patients with CRC, especially in stage II disease, and it could be a potential prognostic biomarker in the planning of individual adjuvant therapy in stage II patients.

Acute appendicitis (AA) is among the most common cause of acute abdominal pain. Diagnosis of AA is challenging; a variable combination of clinical signs and symptoms has been used together with laboratory findings in several scoring systems proposed for suggesting the probability of AA and the possible subsequent management pathway. The role of imaging in the diagnosis of AA is still debated, with variable use of US, CT and MRI in different settings worldwide. Up to date, comprehensive clinical guidelines for diagnosis and management of AA have never been issued. In July 2015, during the 3rd World Congress of the WSES, held in Jerusalem (Israel), a panel of experts including an Organizational Committee and Scientific Committee and Scientific Secretariat, participated to a Consensus Conference where eight panelists presented a number of statements developed for each of the eight main questions about diagnosis and management of AA. The statements were then voted, eventually modified and finally approved by the participants to The Consensus Conference and lately by the board of co-authors. The current paper is reporting the definitive Guidelines Statements on each of the following topics: 1) Diagnostic efficiency of clinical scoring systems, 2) Role of Imaging, 3) Non-operative treatment for uncomplicated appendicitis, 4) Timing of appendectomy and in-hospital delay, 5) Surgical treatment 6) Scoring systems for intra-operative grading of appendicitis and their clinical usefulness 7) Non-surgical treatment for complicated appendicitis: abscess or phlegmon 8) Pre-operative and post-operative antibiotics.

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Background

Diagnostic imaging is increasingly used in patients with suspected appendicitis, with increased costs and concerns about exposure to ionising radiation. Indications suggest that routine imaging is associated with a higher detection rate and treatment of potentially resolving appendicitis. The efficiency of routine imaging compared with in-hospital observation and selective imaging is not well studied.

Methods

The proportions of negative appendectomy and treatments for appendicitis are studied in 1068 patients with intermediate suspicion of appendicitis, indicated by an Appendicitis Inflammatory Response (AIR) score sum of five to eight points, randomly allocated by opaque sealed envelopes to early routine diagnostic imaging (Imaging group, n=543) or re-assessment after 4–8 hours inhospital observation followed by selective diagnostic imaging (Observation group, n=525). Some 21 hospitals in Sweden participated in this multicentre study.

Findings

The Imaging and Observation groups had the same proportion of negative appendectomies (6·5% in both, difference 0·03%, CI –3·0%–3·1%, p=0·98) but routine imaging was associated with an increased proportion of patients treated for appendicitis (53·4% vs 46·3%, difference  7·1%, CI 1·0–13·2%, p=0·020). As secondary outcomes, the Imaging group had shorter time to surgery (median 13·7 hours vs 15·5 hours, p<0·01), but no difference in admissions, number of perforations or length of hospital stay.

Interpretation

Patients with suspected appendicitis and equivocal clinical findings do not benefit from early routine diagnostic imaging compared with re-assessment after observation and selective imaging. The latter is associated with fewer operations for non-perforated appendicitis which supports the hypothesis of resolving appendicitis.

Background

The management of patients with suspected appendicitis is highly variable with implications for the rate of diagnostic errors, unnecessary admissions and resource consumption. We hypothesise that a structured management algorithm based on the Appendicitis Inflammatory Response (AIR) score can improve diagnostic accuracy, limit the use of diagnostic imaging, and reduce the number of hospital admissions for patients with suspected appendicitis.

Methods

Prospective interventional multicentre study. Patients at 25 Swedish hospitals over the age of five, presenting with suspected appendicitis at the emergency department were considered for inclusion. After an initial period of routine management and registration of the AIR score parameters (baseline period), an AIR-score-based management algorithm was implemented (intervention period). The study analyses the discriminating capacity and predictive value of the AIR score and the impact of implementing the AIR-score-based algorithm.

Results

In total, 3791 patients were included. Advanced appendicitis is unlikely at an AIR score <5 points (sensitivity 0.96), and appendicitis is likely at an AIR score >8 (specificity 0.98). The implementation of the AIR-score-based algorithm resulted in fewer negative explorations and operations for phlegmonous appendicitis (1.6% vs 3.4%, p=0.019 and 5.5% vs 9.4%, p=0.003, respectively), a reduction in admissions to hospital and use of imaging (29.5% vs 42.8%, p<0.001 and 19.2% vs 34.5%, respectively), and no difference with regard to advanced appendicitis in the low-risk group, and a decrease in the use of diagnostic imaging in the high-risk group (38.5% vs 53.1%, p=0.021).

Conclusions

The AIR score has high discriminating capacity. Implementing an AIR-score-based algorithm increased diagnostic accuracy and lowered the use of diagnostic imaging and in-hospital observation.

The diagnosis of appendicitis is difficult and resource consuming. New inflammatory markers have been proposed for the diagnosis of appendicitis, but their utility in combination with traditional diagnostic variables has not been tested. Our objective is to explore the potential of new inflammatory markers for improving the diagnosis of appendicitis. The diagnostic properties of the six most promising out of 21 new inflammatory markers (interleukin [IL]-6, chemokine ligand [CXCL]-8, chemokine C-C motif ligand [CCL]-2, serum amyloid A [SAA], matrix metalloproteinase [MMP]-9, and myeloperoxidase [MPO]) were compared with traditional diagnostic variables included in the Appendicitis Inflammatory Response (AIR) score (right iliac fossa pain, vomiting, rebound tenderness, guarding, white blood cell [WBC] count, proportion neutrophils, C-reactive protein and body temperature) in 432 patients with suspected appendicitis by uni- and multivariable regression models. Of the new inflammatory variables, SAA, MPO, and MMP9 were the strongest discriminators for all appendicitis (receiver operating characteristics [ROC] 0.71) and SAA was the strongest discriminator for advanced appendicitis (ROC 0.80) compared with defence or rebound tenderness, which were the strongest traditional discriminators for all appendicitis (ROC 0.84) and the WBC count for advanced appendicitis (ROC 0.89). CCL2 was the strongest independent discriminator beside the AIR score variables in a multivariable model. The AIR score had an ROC area of 0.91 and could correctly classify 58.3 % of the patients, with an accuracy of 92.9 %. This was not improved by inclusion of the new inflammatory markers. The conventional diagnostic variables for appendicitis, as combined in the AIR score, is an efficient screening instrument for classifying patients as low-, indeterminate-, or high-risk for appendicitis. The addition of the new inflammatory variables did not improve diagnostic performance further.

BACKGROUND:

Laparoscopic appendicectomy has been proposed as the standard for surgical treatment of acute appendicitis, based on controversial evidence. This study compared outcomes after open and laparoscopic appendicectomy in a national, population-based cohort.

METHODS:

All patients who underwent open or intended laparoscopic appendicectomy in Sweden between 1992 and 2008 were identified from the Swedish National Patient Register. The outcomes were analysed according to intention to treat with multivariable adjustment for confounding factors and survival analytical techniques where appropriate.

RESULTS:

A total of 169 896 patients underwent open (136 754) or intended laparoscopic (33 142) appendicectomy. The rate of intended laparoscopic appendicectomy increased from 3·8 per cent (425 of 11 175) in 1992 to 32·9 per cent (3066 of 9329) in 2008. Laparoscopy was used most frequently in middle-aged patients, women and patients with no co-morbidity. The rate of conversion from laparoscopy to open appendicectomy decreased from 75·3 per cent (320 of 425) in 1992 to 19·7 per cent (603 of 3066) in 2008. Conversion was more frequent in women and those with perforated appendicitis, and the rate increased with age and increasing co-morbidity. After adjustment for co-variables, compared with open appendicectomy, laparoscopy was associated with a shorter length of hospital stay (by 0·06 days), a lower frequency of negative appendicectomy (adjusted odds ratio (OR) 0·59; P < 0·001), wound infection (adjusted OR 0·54; P = 0·004) and wound rupture (adjusted OR 0·44; P = 0·010), but higher rates of intestinal injury (adjusted OR 1·32; P = 0·042), readmission (adjusted OR 1·10; P < 0·001), postoperative abdominal abscess (adjusted OR 1·58; P < 0·001) and urinary infection (adjusted OR 1·39; P = 0·020). Laparoscopy had a lower risk of postoperative small bowel obstruction during the first 2 years after surgery, but not thereafter.

CONCLUSION:

The outcomes of laparoscopic and open appendicectomy showed a complex and contrasting pattern and small differences of limited clinical importance. The choice of surgical method therefore depends on the local situation, the surgeon's experience and the patient's preference.

OBJECTIVE: To investigate temporal, seasonal, and geographic variations in the incidence of necrotizing enterocolitis (NEC) and its relation to early infant survival in the Swedish population and in subgroups based on gestational age, birth weight, and gender. less thanbrgreater than less thanbrgreater thanMETHODS: In the Swedish birth cohort of 1987 through 2009 all children with a diagnosis of NEC were identified in the National Patient Register, the Swedish Medical Birth Register, and the National Cause of Death Register. NEC incidence, early mortality, and seasonality were analyzed with descriptive statistics, Poisson regression, and auto regression. less thanbrgreater than less thanbrgreater thanRESULTS: The overall incidence of NEC was 3.4 in 10 000 live births, higher in boys than in girls (incidence rate ratio 1.22, 95% confidence interval 1.06-1.40, P = .005), with a peak in November and a trough in May, and increased with an average of similar to 5% a year during the study period. In most subgroups, except the most immature, an initial decrease was followed by a steady increase. Seven-day mortality decreased strongly in all subgroups over the entire study period (annual incidence rate ratio 0.96, 95% confidence interval 0.95-0.96, P andlt; .001). This was especially marked in the most premature and low birth weight infants. less thanbrgreater than less thanbrgreater thanCONCLUSIONS: After an initial decrease, the incidence of NEC has increased in Sweden during the last decades. An association with the concurrent dramatically improved early survival seems likely.

Avoiding mortality is the ultimate goal when managing patients with suspected appendicitis. Previous studies have shown high mortality after negative appendectomy. This national cohort study analyzes short- and long-term mortality after appendectomy in relation to appendectomy diagnosis, age, co-morbidity, surgical method, hospital volume, and time period. less thanbrgreater than less thanbrgreater thanA total of 223,543 appendectomy patients treated from 1987 to 2006 were identified from the Swedish National Patient Register and followed up via the Swedish Cause of Death Register. Analysis of mortality was conducted as Standardized Mortality Ratio (SMR) and by Cox multivariate regression. less thanbrgreater than less thanbrgreater thanNegative appendectomy was followed by a higher mortality in the short term (30-day Standardized Mortality Ratio (SMR30d) 8.95, confidence interval (CI) 6.68-12.61) than after perforated appendicitis (SMR30d 6.39, CI 5.44-7.48), and remained increased for up to 5 years (SMR5yr 1.31, CI 1.16-1.47). Non-perforated appendicitis had a lower than expected long-term mortality (SMR5yr 0.72, CI 0.68-0.76). These differences remained after adjustment for covariates. Laparoscopic appendectomy had similar short-term mortality as open appendectomy but lower than expected long-term morality (SMR5yr 0.70, CI 0.62-0.78). Mortality was decreasing during the study period. Hospital volume had no influence on mortality. less thanbrgreater than less thanbrgreater thanNegative appendectomy is associated with excess short- and long-term mortality that remains after adjustment for known confounders, suggesting an association with underlying undetected morbidity. This motivates an improved preoperative diagnosis to avoid the additional trauma from unnecessary surgical interventions, but further studies are needed to investigate the cause of the increased long-term mortality and if this can be prevented by an improved follow-up of patients with negative appendectomy. Laparoscopic and open appendectomy have similar short-term mortality. The lower long-term mortality after non-perforated appendicitis and laparoscopic appendectomy suggest selection of healthier patients for these interventions. This possibility should be taken into account when comparing mortality after open and laparoscopic appendectomy.

Nonsurgical treatment with antibiotics has recently been proposed as the first line of treatment for noncomplicated appendicitis. This has met with considerable interest, illustrated by the number of reviews and meta-analyses, which exceed the number of original reports of the issue. The results in these studies are seriously biased due to inclusion of patients with resolving appendicitis. At a time when we need to reduce inappropriate use of antibiotics in the struggle against the increasing rate of antibiotics resistance, there must be strong requirements of a proven effect and an improved cost-benefit ratio before antibiotics treatment is introduced for a new group of patients. These requirements have not yet been met for nonsurgical treatment with antibiotics for assumed uncomplicated appendicitis. Due to the high rate of spontaneous resolution, a randomized placebo-controlled trial is needed that can compare the efficiency of antibiotics treatment and expectant management in this group of patients. Antibiotics treatment, however, remains indicated for treatment of perforated appendicitis with localized abscess or phlegmone and in selected surgical high-risk patients.