Roland E. Andersson

Appendectomy and protection against ulcerative colitis.

BACKGROUND A history of appendectomy is rare in patients with ulcerative colitis. This suggests a protective effect of appendectomy or that appendicitis and ulcerative colitis are alternative inflammatory responses. We sought to characterize this inverse relation further. METHODS We studied a cohort of 212,963 patients who underwent appendectomy before the age of 50 years between 1964 and 1993 and a cohort of matched controls who were identified from the Swedish Inpatient Register and the nationwide census. The cohort was followed until 1995 for any subsequent diagnosis of ulcerative colitis. RESULTS Patients who underwent appendectomy for appendicitis and mesenteric lymphadenitis had a low risk of ulcerative colitis (for patients with perforated appendicitis, the adjusted hazard ratio was 0.58 [95 percent confidence interval, 0.38 to 0.87]; for those with nonperforated appendicitis it was 0.76 [95 percent confidence interval, 0.65 to 0.90]; and for those with mesenteric lymphadenitis it was 0.57 [95 percent confidence interval, 0.36 to 0.89]). In contrast, patients who underwent appendectomy for nonspecific abdominal pain had the same risk of ulcerative colitis as the controls (adjusted hazard ratio, 1.06; 95 percent confidence interval, 0.74 to 1.52). For the patients who had appendicitis, an inverse relation with the risk of ulcerative colitis was found only for those who underwent surgery before the age of 20 years (P<0.001). CONCLUSIONS Appendectomy for an inflammatory condition (appendicitis or lymphadenitis) but not for nonspecific abdominal pain is associated with a low risk of subsequent ulcerative colitis. This inverse relation is limited to patients who undergo surgery before the age of 20 years.

Nonsurgical Treatment of Appendiceal Abscess or Phlegmon: A Systematic Review and Meta-analysis

Objective:A systematic review of the nonsurgical treatment of patients with appendiceal abscess or phlegmon, with emphasis on the success rate, need for drainage of abscesses, risk of undetected serious disease, and need for interval appendectomy to prevent recurrence. Summary Background Data:Patients with appendiceal abscess or phlegmon are traditionally managed by nonsurgical treatment and interval appendectomy. This practice is controversial with proponents of immediate surgery and others questioning the need for interval appendectomy. Methods:A Medline search identified 61 studies published between January 1964 and December 2005 reporting on the results of nonsurgical treatment of appendiceal abscess or phlegmon. The results were pooled taking the potential clustering on the study-level into account. A meta-analysis of the morbidity after immediate surgery compared with that after nonsurgical treatment was performed. Results:Appendiceal abscess or phlegmon is found in 3.8% (95% confidence interval (CI), 2.6–4.9) of patients with appendicitis. Nonsurgical treatment fails in 7.2% (CI: 4.0–10.5). The need for drainage of an abscess is 19.7% (CI: 11.0–28.3). Immediate surgery is associated with a higher morbidity compared with nonsurgical treatment (odds ratio, 3.3; CI: 1.9–5.6; P < 0.001). After successful nonsurgical treatment, a malignant disease is detected in 1.2% (CI: 0.6–1.7) and an important benign disease in 0.7% (CI: 0.2–11.9) during follow-up. The risk of recurrence is 7.4% (CI: 3.7–11.1). Conclusions:The results of this review of mainly retrospective studies support the practice of nonsurgical treatment without interval appendectomy in patients with appendiceal abscess or phlegmon.

Mortality After Appendectomy in Sweden, 1987–1996

ObjectiveTo study mortality after appendectomy. Summary Background DataThe management of patients with suspected appendicitis remains controversial, with advocates of early surgery as well as of expectant management. Mortality is not known. MethodsThe authors conducted a complete follow-up of deaths within 30 days after all appendectomies in Sweden (population 8.9 million) during the years 1987 to 1996 (n = 117,424) by register linkage. The case fatality rate (CFR) and the standardized mortality ratio (SMR) were analyzed by discharge diagnosis. ResultsThe CFR was 2.44 per 1,000 appendectomies. It was strongly related to age (0.31 per 1,000 appendectomies at 0–9 years of age, decreasing to 0.07 at 20–29 years, and reaching 164 among nonagenarians) and diagnosis at surgery (0.8 per 1,000 appendectomies after nonperforated appendicitis, 5.1 after perforated appendicitis, 1.9 after appendectomies for nonsurgical abdominal pain, and 10.0 for those with other diagnoses). The SMR showed a sevenfold excess rate of deaths after appendectomy compared with the general population. The relation to age was less marked (SMR of 44.4 at 0–9 years, decreasing to 2.4 in patients aged 20–29 years. and reaching 8.1 in nonagenarians). The SMR was doubled after perforation compared with nonperforated appendicitis (6.5 and 3.5, respectively). Nonsurgical abdominal pain and other diagnoses were associated with a high excess rate of deaths (9.1 and 14.9, respectively). The most common causes of deaths were appendicitis, ischemic heart diseases and tumors, followed by gastrointestinal diseases. ConclusionsThe CFR after appendectomy is high in elderly patients. The excess rate of death for patients with nonperforated appendicitis and nonsurgical abdominal pain suggests that the deaths may partly be caused by the surgical trauma. Increased diagnostic efforts rather than urgent appendectomy are therefore warranted among frail patients with an equivocal diagnosis of appendicitis.

Indications for operation in suspected appendicitis and incidence of perforation

Abstract Objective: To clarify poorly understood epidemiological features of appendicitis. Design: Retrospective study of consecutive cases from a defined population and analysis of data from published studies. Setting: County of Jonkoping, Sweden. 3029 patients who underwent operation in 1984-9 and 4717 patients from the county town who underwent operation in 1970-89, all for suspected appendicitis, plus 48 426 cases from six reported studies. Main outcome measures: Incidences specific for age and sex and temporal trends of perforating and non-perforating appendicitis and removal of a normal appendix. Associations between diagnostic accuracy, rate of perforation, and incidences of removal of a normal appendix and of perforating and non-perforating appendicitis. Results: The incidence of appendicitis was 116/100 000 inhabitants. Appendicitis was more common in male patients. The incidence of perforating appendicitis was independent of age, stable overtime, and uninfluenced by the rate of laparotomy, whereas the incidence of non-perforating appendicitis was age dependent, decreasing over time, and related to the diagnostic accuracy and rate of removal of a normal appendix. Conclusions: Perforating and non-perforating appendicitis seem to be separate entities, and appendicitis that resolves spontaneously is common. This may have important implications for managing suspected appendicitis.

The Natural History and Traditional Management of Appendicitis Revisited: Spontaneous Resolution and Predominance of Prehospital Perforations Imply That a Correct Diagnosis is More Important Than an Early Diagnosis

The principle of early exploration on wide indications in order to prevent perforation has been the guiding star for the management of patients with suspected appendicitis for over 100 years, dating back to a time when appendicitis was a significant cause of mortality. Since then there has been a dramatic decrease in mortality due to appendicitis. Emerging evidence calls for a new understanding of the natural history of untreated appendicitis. This motivates a reappraisal of the fundamental principles for the management of patients with suspected appendicitis. Analysis of epidemiologic and clinical studies that elucidate the natural history of appendicitis, i.e. the possibility of spontaneous resolution or the risk of progression to perforation, the determinants of the proportion of perforations and mortality, and the consequence of in-hospital delay. The results presented in a number of studies suggest that spontaneous resolution of appendicitis is common, that perforation can seldom be prevented, that the risk of perforation has been exaggerated and that in-hospital delay is safe. An alternative understanding of the inverse relationship between the proportion of negative explorations and perforation and the increasing proportion of perforation with length of time is presented, mainly explaining these findings by selection due to spontaneous resolution. Evidence suggests that spontaneous resolution of untreated, non-perforated appendicitis is common and that perforation can rarely be prevented and is associated with a lower increase in mortality than was previously thought. This motivates a shift in focus from the prevention of perforation to the early detection and treatment of advanced appendicitis. In order to minimize mortality, morbidity and costs avoidance of negative appendectomies is more important then preventing perforation. In patients with an equivocal diagnosis where advanced appendicitis is deemed less likely a correct diagnosis is more important than a rapid diagnosis. These patients can safely be managed by active observation with an improved diagnostic work-up under observation, which has consistently shown a low proportion of negative appendectomies without an increase in the proportion of perforations or morbidity. A high proportion of perforations can be explained by selection due to undiagnosed resolving appendicitis. The proportion of perforation is therefore a questionable measure of the quality of the management of patients with suspected appendicitis and should be used with caution.

Diagnostic value of disease history, clinical presentation, and inflammatory parameters of appendicitis.

The clinical diagnosis of appendicitis needs to be improved, as up to 40% of explorations for suspected appendicitis are unnecessary. The use of body temperature and laboratory examinations as diagnostic aids in the management of these patients is controversial. The diagnostic power of these variables compared to that of the disease history and clinical findings is not well studied. In this study we prospectively assessed and compared the diagnostic value of 21 elements of the history, clinical findings, body temperature, and laboratory examinations in 496 patients with suspected appendicitis. The diagnostic value of each variable was compared from the area under the receiver operating characteristic (ROC) curve and the likelihood ratios (LR). Logistic regression was used to analyze the diagnostic value of a combination of variables and to analyze independent relations. No single variable had sufficiently high discriminating or predicting power to be used as a true diagnostic test. The inflammatory variables (temperature, leukocyte and differential white blood cell (WBC) counts, C-reactive protein) had discriminating and predicting powers similar to those of the clinical findings (direct and rebound abdominal tenderness and guarding). Anorexia, nausea, and right-sided rectal tenderness had no diagnostic value. The leukocyte and differential WBC counts, C-reactive protein, rebound tenderness, guarding, and gender were independent predictors of appendicitis with a combined ROC area of 0. 93 for appendicitis. This showed that inflammatory variables contain important diagnostic information, especially with advanced appendicitis. They should therefore always be included in the diagnostic workup in patients with suspected appendicitis.

The serum albumin-binding region of streptococcal protein G: a bacterial fusion partner with carrier-related properties.

In this study, we have explored the use of the serum albumin-binding region (BB) from streptococcal protein G (SpG) as a bacterial fusion partner for production of peptide immunogens. The fusion protein BB-M3, containing BB and repeated structures from the Plasmodium falciparum malaria antigen Pf155/RESA, was efficiently purified from Escherichia coli culture supernatants by affinity chromatography using BB as an affinity tag. Rabbits immunized with BB-M3 in Freunds adjuvant produced high levels of antibodies which reacted with both M3 and BB in ELISA and stained intact Pf155/RESA in the membrane of infected erythrocytes. These antibody levels were sustained for more than 30 weeks. BB-M3 also induced antibody responses to M3, BB and intact Pf155/RESA in a number of mouse strains, including several strains which are non-responders to the malaria sequences. In the latter mice, however, BB-M3 only activated BB-specific T cells, suggesting that BB has ability to provide carrier-related T cell help for antibody production. Moreover, the minimal albumin-binding motif of SpG, containing only 46 amino acids, was immunogenic in both B10.BR, B10.D2 and C57BL/6 mice (H-2k, H-2d and H-2b, respectively). These results indicate that BB has both affinity tag and carrier-related properties and suggest that fusion proteins containing BB can be efficient tools for the generation of antibody responses to peptides which are weak immunogens.

Guidelines in the management of obstructing cancer of the left colon: consensus conference of the world society of emergency surgery (WSES) and peritoneum and surgery (PnS) society

BackgroundObstructive left colon carcinoma (OLCC) is a challenging matter in terms of obstruction release as well of oncological issues. Several options are available and no guidelines are established. The paper aims to generate evidenced based recommendations on management of OLCC.MethodsThe PubMed and Cochrane Library databases were queried for publications focusing on OLCC published prior to April 2010. A extensive retrieval, analyses, and grading of the literature was undertaken. The findings of the research were presented and largely discussed among panellist and audience at the Consensus Conference of the World Society of Emergency Surgery (WSES) and Peritoneum and Surgery (PnS) Society held in Bologna July 2010. Comparisons of techniques are presented and final committee recommendation are enounced.ResultsHartmanns procedure should be preferred to loop colostomy (Grade 2B). Hartmanns procedure offers no survival benefit compared to segmental colonic resection with primary anastomosis (Grade 2C+); Hartmanns procedure should be considered in patients with high surgical risk (Grade 2C). Total colectomy and segmental colectomy with intraoperative colonic irrigation are associated with same mortality/morbidity, however total colectomy is associated with higher rates impaired bowel function (Grade 1A). Segmental resection and primary anastomosis either with manual decompression or intraoperative colonic irrigation are associated with same mortality/morbidity rate (Grade 1A). In palliation stent placement is associated with similar mortality/morbidity rates and shorter hospital stay (Grade 2B). Stents as a bridge to surgery seems associated with lower mortality rate, shorter hospital stay, and a lower colostomy formation rate (Grade 1B).ConclusionsLoop colostomy and staged procedure should be adopted in case of dramatic scenario, when neoadjuvant therapy could be expected. Hartmanns procedure should be performed in case of high risk of anastomotic dehiscence. Subtotal and total colectomy should be attempted when cecal perforation or in case of synchronous colonic neoplasm. Primary resection and anastomosis with manual decompression seems the procedure of choice. Colonic stents represent the best option when skills are available. The literature power is relatively poor and the existing RCT are often not sufficiently robust in design thus, among 6 possible treatment modalities, only 2 reached the Grade A.

Appendicitis, mesenteric lymphadenitis, and subsequent risk of ulcerative colitis: cohort studies in Sweden and Denmark

Objective To determine whether the repeatedly observed low risk of ulcerative colitis after appendicectomy is related to the appendicectomy itself or the underlying morbidity, notably appendicitis or mesenteric lymphadenitis. Design Nationwide cohort studies. Setting Sweden and Denmark. Participants 709 353 Swedish (1964-2004) and Danish (1977-2004) patients who had undergone appendicectomy were followed up for subsequent ulcerative colitis. The impact of appendicectomy on risk was also studied in 224 483 people whose parents or siblings had inflammatory bowel disease. Main outcome measures Standardised incidence ratios and rate ratios as measures of relative risk. Results During 11.1 million years of follow-up in the appendicectomy cohort, 1192 patients developed ulcerative colitis (10.8 per 100 000 person years). Appendicectomy without underlying inflammation was not associated with reduced risk (standardised incidence ratio 1.04, 95% confidence interval 0.95 to 1.15). Before the age of 20, however, appendicectomy for appendicitis (0.45, 0.39 to 0.53) or mesenteric lymphadenitis (0.65, 0.46 to 0.90) was associated with significant risk reduction. A similar pattern was seen in those with affected relatives, whose overall risk of ulcerative colitis was clearly higher than the background risk (1404 observed v 446 expected; standardised incidence ratio 3.15, 2.99 to 3.32). In this cohort, appendicectomy without underlying appendicitis did not modify risk (rate ratio 1.04, 0.66 to 1.55, v no appendicectomy), while risk after appendicectomy for appendicitis was halved (0.49, 0.31 to 0.74). Conclusions In individuals with or without a familial predisposition to inflammatory bowel disease, appendicitis and mesenteric lymphadenitis during childhood or adolescence are linked to a significantly reduced risk of ulcerative colitis in adulthood. Appendicectomy itself does not protect against ulcerative colitis.

WSES Jerusalem guidelines for diagnosis and treatment of acute appendicitis

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.