Validation of the Appendicitis Inflammatory Response (AIR) score during pregnancy: A nested case-control study.

OBJECTIVES: Appendicitis poses diagnostic challenges. A correct diagnosis is important during pregnancy to avoid unnecessary surgery on the one hand and delayed surgery on the other hand, as both may negatively affect pregnancy outcomes. Clinical scores for risk-stratified management of suspected appendicitis are well established in adults but have not been validated during pregnancy. This nested case-control study evaluated the diagnostic accuracy of the Appendicitis Inflammatory Response (AIR) score and imaging during pregnancy. METHODS: By cross-linking national Swedish health registries from a defined geographical area, we identified a cohort of 154 women who underwent appendectomy for suspected appendicitis during pregnancy and a matched cohort of 232 pregnant women admitted for acute abdominal pain and suspected appendicitis but with a discharge diagnosis of nonspecific abdominal pain (NSAP). All variables were extracted from medical records. The diagnostic value of AIR score and imaging was estimated for patients with a final diagnosis of appendicitis compared with patients with negative appendectomy and NSAP patients. RESULTS: The final diagnoses for the operated patients were uncomplicated and complicated appendicitis in 49.4% and 26.6%, respectively, and negative appendectomy in 24.0%. Nearly half of all the patients underwent diagnostic imaging (41%), mainly by ultrasonography. The sensitivity and specificity of diagnostic imaging were 44.9% (95% CI 32.9%-57.4%) and 42.2% (95% CI 31.9%-53.1%), respectively. The area under the receiver operating characteristic curve of AIR score was 0.88 (95% CI 0.84-0.92) for all appendicitis and 0.90 (95% CI 0.84-0.95) for complicated appendicitis. The sensitivity for complicated appendicitis was 100% at a score of ≥4. The specificity for all appendicitis was 97% at a score of ≥9. CONCLUSIONS: The results of this study suggest that the AIR score may be a suitable diagnostic tool for risk stratification of pregnant women with abdominal pain and suspected appendicitis but further validation among pregnant women is needed.

Female and Male Fertility after Colectomy and Reconstructive Surgery in Inflammatory Bowel Diesase: A National Cohort Study from Sweden.

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 Crohn's 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.

Spontaneous Resolution of Uncomplicated Appendicitis may Explain Increase in Proportion of Complicated Appendicitis During Covid-19 Pandemic: a Systematic Review and Meta-analysis.

BACKGROUND: Reports 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. METHOD: We 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. RESULTS: The 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). CONCLUSION: The 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.

Reoperations and Long-term Survival of Kock's Continent Ileostomy in Patients With IBD: A Population-Based National Cohort Study From Sweden.

BACKGROUND: Kock's continent ileostomy is an option after proctocolectomy for patients not suitable for IPAA 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 IBD and a continent ileostomy were identified. Data on demographics, diagnosis, reoperations, and excisions of the continent ileostomy were obtained. Patients with inconsistent diagnostic coding were classified as IBD-unclassified. MAIN OUTCOME MEASURES: The main outcome measures were 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 IBD-unclassified. After a median follow-up time of 27 (interquartile range, 21-31) years, 191 patients (26%) never had revision surgery. Some 1484 reoperations were performed on 536 patients (74%), and the median number of reoperations was 1 (interquartile range, 0-3) per patient. The continent ileostomy was excised in 77 patients (11%). Reoperation within the first year after reconstruction was associated with a higher rate of revisions (incidence rate ratio, 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 (incidence rate ratio, 2.7; p < 0.001 and HR 2.74; p = 0.013). IBD-unclassified was associated with increased revisions (incidence rate ratio, 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 a register, and no data on quality of life were available were the limitations of this study. CONCLUSION: Continent ileostomy is associated with substantial need for revision surgery, but most patients keep their reconstruction for a long time. See Video Abstract at http://links.lww.com/DCR/C122 . REOPERACIONES Y SUPERVIVENCIA A LARGO PLAZO DE LA ILEOSTOMA CONTINENTE DE KOCK EN PACIENTES CON ENFERMEDAD INFLAMATORIA INTESTINAL UN ESTUDIO DE COHORTE NACIONAL BASADO EN LA POBLACIN DE SUECIA: ANTECEDENTES:La ileostomía continente de Kock es una opción después de la proctocolectomía para los pacientes que no son aptos para la anastomosis ileoanal con reservorio o la anastomosis ileorrectal. La colitis ulcerativa es la indicación más común para la ileostomía continente.OBJETIVO:El objetivo de este estudio fue evaluar el resultado a largo plazo de la ileostomía continente.DISEÑO:Estudio de registro de cohorte retrospectivo.AJUSTES:Los datos se obtuvieron del Registro Nacional de Pacientes de Suecia.PACIENTES:Se identificaron todos los pacientes con enfermedad inflamatoria intestinal e ileostomía continente. Se obtuvieron datos demograficos, diagnóstico, reoperaciones y extirpaciones de la ileostomía continente. Los pacientes con codificación diagnóstica inconsistente se clasificaron como no clasificados con EII.PRINCIPALES MEDIDAS DE RESULTADO:Las principales medidas de resultado fueron el número de reoperaciones, el tiempo hasta las reoperaciones y el tiempo hasta la escisión de la ileostomía continente.RESULTADOS:Identificamos 727 pacientes, 428 (59%) con colitis ulcerativa, 45 (6%) con enfermedad de Crohn y 254 (35%) con EII no clasificada. Después de una mediana de tiempo de seguimiento de 27 (IQR 21-31) años, 191 (26%) pacientes nunca se habían sometido a una cirugía de revisión. Se realizaron 1.484 reintervenciones en 536 (74%) pacientes, la mediana de reintervenciones fue de 1 (RIC 0-3) por paciente. La ileostomía continente se extirpó en 77 (11%) pacientes. La reoperación dentro del primer año después de la reconstrucción se asoció con una mayor tasa de revisiones (IRR 2,90 p < 0,001) y un tiempo más corto hasta la escisión (HR 2,38 p < 0,001). La construcción de la ileostomía continente después del año 2000 se asoció con mayores tasas de revisión y escisión (IRR 2,7 p < 0,001 y HR 2,74 p = 0,013). La EII no clasificada se asoció con un aumento de las revisiones (IRR 1,3 p < 0,001) y la proporción de pacientes con EII no clasificada casi se duplicó desde la década de 1980 (32%) hasta después de 2000 (50%).LIMITACIONES:Diseño retrospectivo, datos de registro. No hay datos disponibles sobre la calidad de vida.CONCLUSIÓN:La ileostomía continente se asocia con una necesidad sustancial de cirugía de revisión, pero la mayoría de los pacientes logran mantener su reconstrucción durante mucho tiempo. Consulte Video Resumen en http://links.lww.com/DCR/C122 . (Traducción-Dr. Yolanda Colorado ).

Impact of COVID-19 on the incidence of CT-diagnosed appendicitis and its complications in the UK and Sweden.

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.

Minor impact on fertility in men with inflammatory bowel disease: A National Cohort Study from Sweden.

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), Crohn's 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.

Esophageal perforations - a population-based nationwide study in Sweden with survival analysis.

BACKGROUND: Esophageal perforation is a rare and life-threatening condition with several treatment options. The aim was to assess the incidence, type of treatment and mortality of esophageal perforations in Sweden and to identify risk factors for 90-day mortality. METHOD: All patients admitted with an esophageal perforation from 2007 to 2017 were identified from the National Patient Register. Mortality was assessed by linkage with the Cause of Death Registry. We analyze the incidence and the impact of age, sex, comorbidities on mortality. RESULTS: 879 patients with esophageal perforation were identified, giving an incidence rate of 1.09 per 100,000 person-years. The median age at diagnosis was 68.8 years and 60% were men. The mortality was 26% at 90 days. Independent risk factors for death within 90 days were age (odds ratio (OR): 6.20; 95% (confidence interval) CI: 2.16-17.79 at 60-74 years and OR: 11.58; 95% CI: 4.04-33.15 at 75 years or older), peripheral vascular disease (OR: 2.92; 95% CI: 1.44-5.92) and underlying malignant disease (OR: 5.91; 95% CI: 3.86-9.03). In patients younger than 45 years, survival was lower among women than among men (at 5 years 73 and 93%, respectively). The cause of death among young women was often drug-related or suicide. CONCLUSIONS: 90-day mortality was 26%, old age, vascular disease and underlying malignant disease were risk factors.

Association of gene and protein expression and genetic polymorphism of CC chemokine ligand 4 in colorectal cancer.

BACKGROUND: Leukocytes, such as T cells and macrophages, play an important role in tumorigenesis. CC chemokine ligand (CCL) 4, which is produced by lymphocytes and macrophages, has been found to be expressed in the mucosa of the gastrointestinal tract and is a potent chemoattractant for various leukocytes. AIM: To examine CCL4 expression and its genetic polymorphism rs10491121 in patients with colorectal cancer (CRC) and evaluate their prognostic significance. METHODS: Luminex technology was used to determine CCL4 Levels in CRC tissue (n = 98), compared with paired normal tissue, and in plasma from patients with CRC (n = 103), compared with healthy controls (n = 97). Included patients had undergone surgical resection for primary colorectal adenocarcinomas between 1996 and 2019 at the Department of Surgery, Ryhov County Hospital, Jönköping, Sweden. Reverse transcription quantitative PCR was used to investigate the CCL4 gene expression in CRC tissue (n = 101). Paired normal tissue and TaqMan single nucleotide polymorphism assays were used for the CCL4 rs10491121 polymorphism in 610 CRC patients and 409 healthy controls. RESULTS: The CCL4 protein and messenger RNA expression levels were higher in CRC tissue than in normal paired tissue (90%, P < 0.001 and 45%, P < 0.05, respectively). CRC tissue from patients with localized disease had 2.8-fold higher protein expression levels than that from patients with disseminated disease. Low CCL4 protein expression levels in CRC tissue were associated with a 30% lower cancer-specific survival rate in patients (P < 0.01). The level of plasma CCL4 was 11% higher in CRC patients than in healthy controls (P < 0.05) and was positively correlated (r = 0.56, P < 0.01) with the CCL4 protein level in CRC tissue. The analysis of CCL4 gene polymorphism rs10491121 showed a difference (P < 0.05) between localized disease and disseminated disease in the right colon, with a dominance of allele A in localized disease. Moreover, the rate of the A allele was higher among CRC patients with mucinous cancer than among those with non-mucinous cancer. CONCLUSION: The present study indicates that the CRC tissue levels of CCL4 and CCL4 gene polymorphism rs10491121, particularly in the right colon, are associated with clinical outcome in CRC patients.

Validation of the Appendicitis Inflammatory Response (AIR) Score.

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 hospital's 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 < 0.001), in patients below age 15 years and in patients with >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 <4 points (Negative Predictive Value 99%, CI 98-100%). Appendicitis is likely at AIR score >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. Trial registration number https://clinicaltrials.gov/ct2/show/NCT00971438.

Cytotoxic T-lymphocyte Antigen-4 (CTLA-4) Gene Polymorphism (rs3087243) Is Related to Risk and Survival in Patients With Colorectal Cancer.

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.

Impaired Fertility in Women With Inflammatory Bowel Disease: A National Cohort Study From Sweden.

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 <0.001] in matched individuals. Fertility was impaired in all IBD subtypes compared with the matched cohort (hazard ratio Crohn's 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.

Incidence of Appendiceal Malignancies in Sweden Between 1970 and 2012.

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 5.8/106 person-years with a peak of 8.4/106 at age 20-30 years, whereafter it plateaued at a somewhat lower level. IR for adenocarcinoma was 3.7/106 person-years, starting at a very low level among the youngest and increasing to 15.4/106 at age 80-89 years. The IR of adenocarcinoma increased from 2.6/106 in 1970-1979 to 5.4/106 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.

Genomic Profiling of Stage II Colorectal Cancer Identifies Candidate Genes Associated with Recurrence-Free Survival, Tumor Location, and Differentiation Grade.

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 in ATM, C11ORF65 was associated with recurrence-free survival. Previous reports regarding the association between BRAF mutation and a higher age at diagnosis, and tumor location in colon were confirmed. APC, BRAF, or KRAS mutation 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.

Genetic polymorphism patterns suggest a genetic driven inflammatory response as pathogenesis in appendicitis.

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.

Genetic Variants of the IL2 Gene Related to Risk and Survival in Patients With Colorectal Cancer.

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.

CT in Differentiating Complicated From Uncomplicated Appendicitis: Presence of Any of 10 CT Features Versus Radiologists' Gestalt Assessment.

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 < 0.001), although the pooled specificity was lower (43% vs 76%; difference, -33% [95% CI, -48% to -17%]; p < 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.

Increased risk of rickets but not fractures during childhood and adolescence following necrotizing enterocolitis among children born preterm in Sweden.

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 <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.

Association study on IL-4, IL-4Rα and IL-13 genetic polymorphisms in Swedish patients with colorectal cancer.

BACKGROUND: Interleukin 4 (IL-4) and interleukin 13 (IL-13) are anti-inflammatory and immunomodulatory cytokines which share a common cellular receptor IL4Rα and are involved in the same signaling pathways. Our purpose was to assess whether genetic variants within IL-4, IL-13 and IL-4Rα 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-4Rα 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.