COVID-19 pandemic and its impact on emergency surgery in colorectal cancer: A single centre experience.

INTRODUCTION: The COVID-19 pandemic has led to major changes in the provision of surgical services and also affected patients' health-seeking behaviour. This contributes to delayed presentation of many surgical conditions resulting in poorer outcomes. Colorectal cancer (CRC) patients who present with acute surgical emergencies such as complete bowel obstruction, perforation, bleeding or sepsis often require immediate intervention. This study aimed to assess the impact of COVID-19 pandemic on the proportion of emergency surgery in CRC patients. MATERIALS AND METHODS: This is a retrospective cohort study. All CRC patients who underwent elective and emergency surgery from January until December 2019 (pre-COVID era) and September 2020 until August 2021 (COVID era) were included. Patient demographics, presentation, tumour stage, surgery performed and waiting time for surgery were collected. Data were then compared. RESULTS: Seventy-seven and 76 new cases of CRC underwent surgery before and during COVID-19, respectively. The proportions of emergency surgery before and during COVID-19 are 29% vs 33% (p=0.562). Of those who required emergency surgery, the proportions of patients who required stoma formation are 59% vs 72% (p= 0.351). There was no difference in median waiting time for patients requiring elective surgery (p= 0.668). CONCLUSION: The proportion of emergency surgery for CRC patients is not statistically higher during the pandemic.

Serological testing for Lyme Borreliosis in general practice: A qualitative study among Dutch general practitioners.

Background: Concerns are raised about missed, delayed and inappropriate diagnosis of Lyme Borreliosis. Quantitative descriptive studies have demonstrated non-adherence to the guidelines for testing for Lyme Borreliosis.Objectives: To gain insight into the diagnostic practices that general practitioners apply for Lyme Borreliosis, their motives for ordering tests and how they act upon test results.Methods: A qualitative study among 16 general practitioners using semi-structured interviews and thematic content analysis.Results: Five themes were distinguished: (1) recognising localised Lyme Borreliosis and symptoms of disseminated disease, (2) use of the guideline, (3) serological testing in patients with clinically suspect Lyme Borreliosis, (4) serological testing without clinical suspicion of Lyme Borreliosis, and (5) dealing with the limited accuracy of the serological tests. Whereas the national guideline recommends using serological tests for diagnosing, general practitioners also use them for ruling out disseminated Lyme Borreliosis. Reasons for non-adherence to the guideline for testing were to reassure patients with non-specific symptoms or without symptoms who feared to have Lyme disease, confirmation of localised Lyme Borreliosis and routine work-up in patients with continuing unexplained symptoms. Some general practitioners referred all patients who tested positive to medical specialists, where others struggled with the explanation of the results.Conclusion: Both diagnosis and ruling out of disseminated Lyme Borreliosis can be difficult for general practitioners. General practitioners use serological tests to reassure patients and rule out Lyme Borreliosis, thereby deviating from the national guideline. Interpretation of test results in these cases can be difficult.

Case report: A rare case of extravesical, extraperitoneal metastasis after transuretheral resection of urothelial carcinoma.

Bladder perforation secondary to transurethral resection of bladder tumour (TURBT) increases the risk of tumour cell seeding and eventual extravesical metastasis. Here we presented a case where a patient with localised bladder tumour was initially managed with repeated TURBTs for tumour recurrence. Subsequently he was found to have extravesical pelvic metastasis. This was likely secondary to microperforation of bladder and tumour cell seeding. Microscopic bladder perforation is difficult to diagnose. However patients with confirmed bladder perforation during TURBT would justify systemic radiological cancer surveillance in view of higher risk of metastatic disease.

Case report: persistently seronegative neuroborreliosis in an immunocompromised patient.

BACKGROUND: Infection with Borrelia burgdorferi sensu lato complex (B. b. sl) spirochetes can cause Lyme borreliosis, manifesting as localized infection (e.g. erythema migrans) or disseminated disease (e.g. Lyme neuroborreliosis). Generally, patients with disseminated Lyme borreliosis will produce an antibody response several weeks post-infection. So far, no case of neuroborreliosis has been described with persistently negative serology one month after infection. CASE PRESENTATION: We present a patient with a history of Mantle cell lymphoma and treatment with R-CHOP (rituximab, doxorubicine, vincristine, cyclofosfamide, prednisone), with a meningo-encephalitis, who was treated for a suspected lymphoma relapse. However, no malignant cells or other signs of malignancy were found, and microbial tests did not reveal any clues, including Borrelia serology. He did not recall being bitten by ticks, and a Borrelia PCR on CSF was negative. After spontaneous improvement of symptoms, he was discharged without definite diagnosis. Several weeks later, he was readmitted with a relapse of symptoms of meningo-encephalitis. This time however, a Borrelia PCR on CSF was positive, confirmed by two independent laboratories, and the patient received ceftriaxone upon which he partially recovered. Interestingly, during the diagnostic process of this exceptionally difficult case, a variety of different serological assays for Borrelia antibodies remained negative. Only P41 (flagellin) IgG was detected by blot and the Liaison IgG became equivocal 2 months after initial testing. CONCLUSIONS: To the best of our knowledge this is the first case of neuroborreliosis that is seronegative on repeated sera and multiple test modalities. This unique case demonstrates the difficulty to diagnose neuroborreliosis in severely immunocompromised patients. In this case, a delay in diagnosis was caused by broad differential diagnosis, an absent known history of tick bites, negative serology and the low sensitivity of PCR on CSF. Therefore, awareness of the diagnostic limitations to detect Borrelia infection in this specific patient category is warranted.

A multicentre verification study of the QuantiFERON®-TB Gold Plus assay.

OBJECTIVES: The aim of this verification study was to compare the QuantiFERON®-TB Gold Plus (QFT-Plus) to the QuantiFERON®-TB Gold In Tube (QFT-GIT). The new QFT-Plus test contains an extra antigen tube which, according to the manufacturer additionally elicits a CD8+ T-cell response above the CD4+ T-cell response. We assessed the value of this tube in detecting recent latent tuberculosis infections. METHODS: Between May 2015 and December 2016, 1031 subjects underwent QFT-Plus and QFT-GIT test. Overall agreement between both tests and performance for different test indications and/or immune states was assessed. A difference of >0.6 IU/mL interferon-γ release between the two antigen tubes of the QFT-Plus assay was considered a true difference and used as estimation for CD8+ T-cell response. RESULTS: Analysis of the QuantiFERON tests resulted in an overall agreement between assays of 95%. Subjects considered to be recently exposed to tuberculosis had significantly more often a true difference in interferon-γ release compared to all other subjects (p = 0.029). CONCLUSION: Results of QFT-Plus are highly comparable to QFT-GIT. Although there is an indication that a true difference in interferon-γ release between the antigen tubes is associated with recent latent tuberculosis infection, the QFT-Plus could not be used to exclude recent exposure.

[Dilemma: to test or not to test for Lyme borreliosis in general practice]. / Dilemma: wel of niet testen op lymeziekte in de huisartsenpraktijk?

There is no such thing as a perfect diagnostic test and the value of a test depends on the situation in which the test is being used. Here, we discuss two options for dealing with the diagnostic process for Lyme borreliosis in general practice. One option is to manage, treat or refer according to clinical signs and symptoms, in accordance with Dutch practice guidelines. The other option is to use laboratory tests to guide further patient management (treatment or referral). The choice depends on currently unknown factors, such as the pre-test probability of Lyme disease in patients presenting to general practitioners. Furthermore, clarity is required about how to proceed after a positive or negative test result. The consequences of a false test result will depend on the patient's status, possible alternative diagnoses and treatment options. Both physician and patient should be aware of the shortcomings of diagnostic tests.

The diagnostic accuracy of serological tests for Lyme borreliosis in Europe: a systematic review and meta-analysis.

BACKGROUND: Interpretation of serological assays in Lyme borreliosis requires an understanding of the clinical indications and the limitations of the currently available tests. We therefore systematically reviewed the accuracy of serological tests for the diagnosis of Lyme borreliosis in Europe. METHODS: We searched EMBASE en MEDLINE and contacted experts. Studies evaluating the diagnostic accuracy of serological assays for Lyme borreliosis in Europe were eligible. Study selection and data-extraction were done by two authors independently. We assessed study quality using the QUADAS-2 checklist. We used a hierarchical summary ROC meta-regression method for the meta-analyses. Potential sources of heterogeneity were test-type, commercial or in-house, Ig-type, antigen type and study quality. These were added as covariates to the model, to assess their effect on test accuracy. RESULTS: Seventy-eight studies evaluating an Enzyme-Linked ImmunoSorbent assay (ELISA) or an immunoblot assay against a reference standard of clinical criteria were included. None of the studies had low risk of bias for all QUADAS-2 domains. Sensitivity was highly heterogeneous, with summary estimates: erythema migrans 50% (95% CI 40% to 61%); neuroborreliosis 77% (95% CI 67% to 85%); acrodermatitis chronica atrophicans 97% (95% CI 94% to 99%); unspecified Lyme borreliosis 73% (95% CI 53% to 87%). Specificity was around 95% in studies with healthy controls, but around 80% in cross-sectional studies. Two-tiered algorithms or antibody indices did not outperform single test approaches. CONCLUSIONS: The observed heterogeneity and risk of bias complicate the extrapolation of our results to clinical practice. The usefulness of the serological tests for Lyme disease depends on the pre-test probability and subsequent predictive values in the setting where the tests are being used. Future diagnostic accuracy studies should be prospectively planned cross-sectional studies, done in settings where the test will be used in practice.

Diagnostic yield of repeat sampling with immunoassay, real-time PCR, and toxigenic culture for the detection of toxigenic Clostridium difficile in an epidemic and a non-epidemic setting.

Current international guidelines lack definite conclusions regarding repeat stool sampling for the detection of toxigenic Clostridium difficile. We assessed the value of repeat sampling and compared the diagnostic yield in an epidemic to a non-epidemic setting. Consecutive fecal samples obtained during two time frames were analyzed using direct stool immunoassay toxin testing (enzyme immunoassay [EIA]), direct stool real-time PCR toxin gene testing, and toxigenic culture. Samples collected within 7 days of the initial sample were considered repeat tests. In the epidemic setting 989 patients were analyzed, and in the non-epidemic setting 1,015. In the epidemic setting 204 patients had two or more specimens included for analysis and in the non-epidemic setting 287 patients. In the epidemic setting 136 samples yielded a positive results, either by EIA or toxigenic culture; of these, 108 were positive according to EIA and 123 according to toxigenic culture. In the first test round 98 (90.7%, 95% CI 85.3 to 96.2), 114 (92.7%, 88.1 to 97.3), and 126 (92.6%, 88.3 to 97.0) positives were detected. Subsequent test rounds yielded 10 (9.3%, 3.8 to 14.7), 9 (7.3%, 2.7 to 11.9), and 10 (7.4%, 3.0 to 11.7) extra positives. In the non-epidemic setting EIA, toxigenic culture and PCR detected 33, 66, and 83 positives. The three tests combined 93 detected positives. In the first test round 30 (90.9%, 81.1 to 100.7), 63 (95.5%, 90.4 to 110.5), 76 (91.6%, 85.6 to 97.5), and 87 (93.5%, 88.6 to 98.5) positives were detected. Subsequent test rounds yielded 3 (9.1%, -0.7 to 18.9), 3 (4.5%, -0.5 to 9.6), 7 (8.4%, 2.5 to 14.4), and 6 (6.5%, 1.5 to 11.4) extra positives. In conclusion, repeat testing resulted in 4.5% to 9.3% extra positives. No significant difference between the settings studied could be demonstrated. Repeat sampling and multimodality testing may be chosen in an outbreak situation to detect all cases, effectively controlling nosocomial spread.

A Dutch nationwide evaluation of serological assays for detection of Borrelia antibodies in clinically well-defined patients.

Numerous tests for the detection of antibodies against Borrelia burgdorferi are commercially available. Manufacturer-derived data invariably report a high sensitivity and specificity, but comparative studies demonstrate large differences in clinical practice, especially with regard to specificity. We retrospectively collected data from validation studies for B. burgdorferi antibody assays from 8 laboratories in the Netherlands. The total number of samples was 809. Samples were selected based on clinical and laboratory parameters. We included samples from patients with erythema migrans, acrodermatitis chronicum atrophicans, and neuroborreliosis; cross-reactivity controls; and healthy controls. Data are presented from 10 enzyme-linked immunosorbent assays and 5 immunoblots. For manifestations of B. burgdorferi infection with short disease duration, the positivity rate of the assays varied significantly. In patients with long disease duration, the positivity rate differed only marginally. In cross-reactivity controls, there was significant variation in the reactivity rate. The majority of false-positive reactions are of the IgM isotype.

The most frequent cause of 90-day unplanned hospital readmission following colorectal cancer resection is chemotherapy complications.

AIM: NHS England deems 90-day readmission rates as a marker of quality of care. The causes of readmission have not been previously reported in the UK. The aim of this study was to examine the factors associated with 90-day readmission following colorectal cancer surgery at a hospital trust with a catchment population 1.2 million. METHOD: A retrospective review was performed of all patients undergoing resection for colorectal cancer between January 2012 and December 2013. Unplanned readmission was defined as an emergency admission to the trust for any cause within 90 days of surgery. Readmission analyses were restricted to patients discharged from hospital within 28 days of resection. RESULTS: A total of 570 patients underwent surgery, of whom 522 were discharged within 28 days and are included for readmission analysis. The readmission rate was 24.3% (127 patients with a total of 163 episodes of hospital readmissions) within 90 days following surgery. The most frequent cause for readmission was complications related to adjuvant chemotherapy (18.4%) followed by wound-related complications (14.1%). Most patients presenting with wound-related complications were admitted within 60 days and patients with chemotherapy-related complications after 61 days; 13/127 (10.2%) patients who were readmitted underwent emergency surgery, and one patient died following readmission. Multivariate analysis demonstrated that comorbidity was the only independent risk factor. CONCLUSION: Ninety-day readmissions include a high number of readmissions secondary to chemotherapy-related complications, whereas most surgical-related readmission present within 60 days.

Campylobacter seroconversion rates in selected countries in the European Union.

As a major foodborne pathogen, Campylobacter is frequently isolated from food sources of animal origin. In contrast, human Campylobacter illness is relatively rare, but has a considerable health burden due to acute enteric illness as well as severe sequelae. To study silent transmission, serum antibodies can be used as biomarkers to estimate seroconversion rates, as a proxy for infection pressure. This novel approach to serology shows that infections are much more common than disease, possibly because most infections remain asymptomatic. This study used antibody titres measured in serum samples collected from healthy subjects selected randomly in the general population from several countries in the European Union (EU). Estimates of seroconversion rates to Campylobacter were calculated for seven countries: Romania, Poland, Italy, France, Finland, Denmark and The Netherlands. Results indicate high infection pressures in all these countries, slightly increasing in Eastern EU countries. Of these countries, the differences in rates of notified illnesses are much greater, with low numbers in France and Poland, possibly indicating lower probability of detection due to differences in the notification systems, but in the latter case it cannot be excluded that more frequent exposure confers better protection due to acquired immunity.

Biomarker dynamics: estimating infection rates from serological data.

The marginal distribution of serum antibody titres in a cross-sectional population sample can be expressed as a function of the infection rate, taking into account heterogeneity in peak levels and decay rates. This marginal model allows estimation of incidences, as well as simple tests for homogeneity across age, gender or geographic strata, using likelihood ratio tests. An example is given using Campylobacter serum antibody data. Using a hierarchical dynamic model to analyse data from a follow-up study in patients with symptomatic Campylobacter infection, we show that the serum antibody response consists of a rapid increase to peak levels followed by a slow decline with a geometric mean halftime of 1.4, 0.6 and 0.3 years for IgG, IgM and IgA, respectively. Antibody peak levels and decay rates were highly variable among subjects. Incidence estimates are consistent among different antibody classes (IgG, IgM and IgA). High seroconversion rates indicate that Campylobacter infection is a frequent event, occurring approximately once every year in any adult person, in the Netherlands, supporting the conclusion that a small fraction of infections leads to symptoms severe enough for notification.

Gastroenteritis caused by Campylobacter concisus.

We describe a case of gastroenteritis caused by Campylobacter concisus. The pathogenic potential of C. concisus has yet to be elucidated. Recent studies indicate an association with enteric disease in immunocompromised patients and inflammatory bowel disease in children. Molecular identification methods may be necessary for identifying certain Campylobacter species because of phenotypic similarity.

Large differences between test strategies for the detection of anti-Borrelia antibodies are revealed by comparing eight ELISAs and five immunoblots.

We investigated the influence of assay choice on the results in a two-tier testing algorithm for the detection of anti-Borrelia antibodies. Eighty-nine serum samples from clinically well-defined patients were tested in eight different enzyme-linked immunosorbent assay (ELISA) systems based on whole-cell antigens, whole-cell antigens supplemented with VlsE and assays using exclusively recombinant proteins. A subset of samples was tested in five immunoblots: one whole-cell blot, one whole-cell blot supplemented with VlsE and three recombinant blots. The number of IgM- and/or IgG-positive ELISA results in the group of patients suspected of Borrelia infection ranged from 34 to 59%. The percentage of positives in cross-reactivity controls ranged from 0 to 38%. Comparison of immunoblots yielded large differences in inter-test agreement and showed, at best, a moderate agreement between tests. Remarkably, some immunoblots gave positive results in samples that had been tested negative by all eight ELISAs. The percentage of positive blots following a positive ELISA result depended heavily on the choice of ELISA-immunoblot combination. We conclude that the assays used to detect anti-Borrelia antibodies have widely divergent sensitivity and specificity. The choice of ELISA-immunoblot combination severely influences the number of positive results, making the exchange of test results between laboratories with different methodologies hazardous.

Apical node metastasis independently predicts poor survival in Dukes C colorectal cancer.

AIM: The prognostic significance of apical node metastasis in node-positive colorectal cancer (CRC) is disregarded by the Fourth American Joint Committee on Cancer and the International Union Against Cancer (AJCC/UICC) TNM classification system. The influence of apical node metastases on overall 5-year survival among patients with Dukes stage C CRC was examined. METHOD: Patients who underwent operative resection for CRC between 1999 and 2003 were reviewed. RESULTS: Two-hundred and ninety patients were included in the study, including 203 with Dukes C apical node-negative cancers, 39 with Dukes C apical node-positive cancers and 48 with Dukes D cancers. The respective prevalence of extramural vascular invasion was 35%vs 64%vs 56% (P = 0.0005), T4-stage 24%vs 38%vs 48% (P = 0.013), positive resection margin 16%vs 41%vs 23% (P = 0.001), more than three positive nodes harvested 28%vs 85%vs 52% (P < 0.0001) and poorer tumour differentiation grade 9%vs 21%vs 23% (P = 0.009). Multivariate analyses of all Dukes C cancer patients (n = 242) showed a positive apical node to be a highly significant independent predictor of mortality (hazard ratio 2.281, 95% confidence interval 1.421-3.662, P = 0.0006). Extramural vascular invasion and a positive resection margin were also independent predictors of poor survival. Patients with Dukes C apical node-positive cancers had a significantly poorer overall 5-year survival compared to patients with Dukes C apical node-negative cancers (P < 0.0001) but survival was not significantly different compared to patients with distant metastases at initial presentation (P = 0.504). CONCLUSION: Apical node metastasis appears to be a strong independent, negative prognostic factor of poor survival in Dukes C CRC.

Seroepidemiological studies indicate frequent and repeated exposure to Campylobacter spp. during childhood.

The annual number of episodes of clinical gastroenteritis caused by Campylobacter spp. in The Netherlands is estimated to be 75 000, i.e. once per 200 person life-years. This number is based on extrapolation of culture results from population-based studies. The number of culture-confirmed cases of Campylobacter infection peaks in the first 3 years of life and again between the ages of 20 and 25 years. The seroepidemiology of Campylobacter describes the relationship between age and exposure to Campylobacter and reflects both symptomatic and asymptomatic infections. Using a validated ELISA system, antibodies to Campylobacter were measured in an age-stratified sample (n=456) of the PIENTER serum collection of the Dutch general population. The seroprevalence of Campylobacter IgG antibodies increased with age, reaching almost 100% at age 20 years. Antibody levels steadily increased with age until young adulthood, suggesting repeated exposure to Campylobacter. In conclusion, seroepidemiological data demonstrated repeated exposures to Campylobacter throughout life, most of which do not lead to clinical symptoms. From young adulthood, >95% of the population in The Netherlands had serological evidence for exposure to Campylobacter.

The impact of lymph node yield on Duke's B and C colorectal cancer survival.

AIM: The number of positive lymph nodes retrieved following colorectal cancer (CRC) resection impacts on the staging and further treatment of the disease. We compared 5-year survival by lymph node yield for Duke's B and C patients to assess the impact on prognosis. METHOD: A retrospective methodology was employed to review patients who underwent operative resection for Duke's B or C CRC between 1999 and 2003. RESULTS: A total of 351 patients were included in our analyses. Lymph node yield, N-stage and extramural vascular invasion were independent predictors of overall 5-year survival. A significant difference in 5-year survival by lymph node yield was seen among Duke's B patients (< 9 nodes vs ≥ 9 nodes, 45.2%vs 68.4%; P = 0.0043) and Duke's C patients (< 10 nodes vs ≥ 10 nodes, 25.6%vs 48.8%; P = 0.0099). There was a significant reduction in the relative risk of 2.8% in mortality for each additional node sampled in Duke's B and C patients (RR 0.972, 95% confidence interval 0.949-0.994, P = 0.0102). Duke's B patients who had < 9 lymph node yield and no neoadjuvant/adjuvant treatment had a similar survival to all Duke's C patients (47.8%vs 41.7%, P = 0.5136). CONCLUSION: Lymph node yield independently predicts for survival in patients with Duke's B and C CRC. Duke's B patients with < 9 lymph node yield have no better survival than patients with Duke's C disease. Therefore, prospective randomized studies are required to examine if inadequate lymph node yield could be one of the deciding factors in offering adjuvant therapy among Duke's B cancer patients.

The diagnostic value of digital rectal examination in primary care for palpable rectal tumour.

BACKGROUND: Accurate digital rectal examination (DRE) enables the early diagnosis of palpable rectal tumour. We aimed at evaluating the diagnostic value of DRE performed by general practitioners (GPs), with respect to detecting the presence of a palpable rectal tumour. METHOD: All patients diagnosed to have a palpable rectal tumour via a 14-day cancer referral system between May and December 2006 were identified from the colorectal database. Patients referred by GPs during the same period as having a palpable rectal tumour were also identified by reviewing the 14-day cancer referrals. Sensitivity, specificity, positive and negative predictive value of a DRE in primary care were calculated by using these data. RESULTS: Between May and December 2006, 1069 patients were referred to the University Hospital of North Staffordshire to the 14-day urgent colorectal cancer referral service. Of these, 108 patients were referred as having a 'palpable rectal tumour'. Only 32 of the 108 were found to have a rectal lesion on examination in the hospital. Ten tumours were missed by GPs' DREs. CONCLUSION: Digital rectal examination in primary care for palpable rectal tumour has a sensitivity of 0.762, specificity of 0.917, positive predictive value of 0.296 and negative predictive value of 0.988. It is an inaccurate procedure and a poor predictor for palpable rectal tumour.

[Rhombencephalitis due to Listeria monocytogenes]. / Rombencefalitis door Listeria monocytogenes.

A 37-year-old man presented with acute dizziness, nausea, headache and fever. Later on, he developed diplopia, swallowing difficulties, numbness and ataxia. MRI on day 6 showed hypo-intense, contrast-enhancing lesions on TI-weighted scans in the brainstem and cerebellum. Cerebrospinal fluid (CSF) findings on day 6 included pleiocytosis, a mildly-elevated protein level and mildly-decreased glucose level. CSF and blood cultures were initially negative for both bacteria and viruses. Acute disseminated encephalomyelitis (ADEM) was suspected and dexamethasone therapy was started. On day 26, a blood culture was positive for Listeria monocytogenes. The diagnosis 'Listeria rhombencephalitis' was made and the patient was treated with amoxicillin. This resulted in good recovery. In patients with a subacute onset of progressive cranial nerve dysfunction, ataxia, CSF pleiocytosis, and MRI lesions in the brainstem and cerebellum, Listeria rhombencephalitis should be considered. Early diagnosis and treatment improve the prognosis.