A novel likely pathogenic CLCN5 variant in Dent's disease.

BACKGROUND: The majority of cases of Dent's disease are caused by pathogenic variants in the CLCN5 gene, which encodes a voltage-gated chloride ion channel (ClC-5), resulting in proximal tubular dysfunction. We present three members of the same family and one unrelated paediatric patient with the same insertion-deletion CLCN5 variant. The identification of these patients and positive familial segregation led to the re-classification of this variant from one of unknown significance to one of likely pathogenicity. CASE PRESENTATION: A 41 year old male presented with end stage kidney failure, proteinuria and haematuria. Whole genome sequencing identified an insertion-deletion variant in CLCN5, resulting in a missense change (c.1744_1745delinsAA p.(Ala582Lys)). His brother and nephew, who both exhibited renal impairment, haematuria, proteinuria, glycosuria and nephrocalcinosis, were found to have the same variant. In addition, genetic testing of an unrelated paediatric patient who presented with proteinuria and hypercalciuria, demonstrated the same variant. CONCLUSIONS: The identification of this novel variant in four individuals with features of Dent's disease, has led to the re-classification of the variant to one of likely pathogenicity. As a result, our patients and any future patients with the same variant can be offered a likely diagnosis, without the need for kidney biopsy, and their family members can be offered genetic screening.

A rare case of primary retroperitoneal extraovarian granulosa cell tumor.

Extraovarian granulosa cell tumors (GCTs) are rare neoplasms. They arise from the ectopic gonadal tissue along the embryonal route of genital ridge. We present a case of an extraovarian tumor in an elderly female who presented with lump in the abdomen occupying the pelvic region. She was operated and the mass was excised with intact capsule. Histopathology revealed the mass to be an adult granulosa cell tumor. Extraovarian granulosa cell tumors are very rare with only 13 such cases reported in literature to date. The present case is the largest primary retroperitoneal adult granulosa cell tumor reported till date.

A fast, easy and reliable method for hamstrings graft size prediction in anterior cruciate ligament reconstruction.

PURPOSE: The aim of this study is to describe and validate a simple and reliable method to pre-operatively predict the size of the ACL graft in the double strand technique with autologous semitendinosus-gracilis tendons on the same MRI used for ACL rupture diagnosis. METHODS: The study included 92 patients, with a median age of 31 years (IQR 26-41 years), 73/92 (79%) of whom were males. All patients that underwent an ACL reconstruction with doubled ST + GT between 2017 and 2022 were counted in the study. RESULTS: Overall, the median predicted graft diameter from MR imaging was similar to the actual graft diameter with no significant differences (n.s.). Regarding the comparison between predicted and actual graft size, concordance was 78/92 (85%, 95% CI 76-91%), with κ = 0.797 which corresponds to a level of agreement defined as "Strong". Tendon sizes calculated on pre-operative MRI were evaluated both with intra-observer and inter-observer reliability demonstrating a statistically reproducible method. The predicted graft was then compared to the reported one with a statistically significant reliability found. CONCLUSION: This study can help the surgeons to perform a fast pre-operative planning of an ACL reconstruction for graft selection. If the planned graft with ST and GT is smaller than 8 mm, the clinician can decide to switch to a different type of graft or plan a different graft preparing technique and, therefore, reduce the risk of post-operative ligament re-rupture. The method proposed is reliable and reproducible. The major strength of the planning technique proposed is that it relies on data that are already available for the clinician before surgery, without the need of further analysis. LEVEL OF EVIDENCE: IV.

Real-world experience of monoclonal antibodies in mild-to-moderate COVID-19 patients at a tertiary care center.

Background: Neutralizing antibodies cocktail (casirivimab and imdevimab) has received emergency use authorization recommendation by Food and Drug Administration (FDA) and WHO for mild-to-moderate COVID-19 infection in specific high-risk groups. Antibodies cocktail has shown promising results in preventing progression to severe disease, but the real-world experience is still evolving. Herein, we present a retrospective analysis of 22 patients who were administered the antibodies cocktail between August 2021 and March 2022 at our tertiary care center. Methods: We conducted an observational retrospective analysis of clinicoradiological, inflammatory parameters, progression of the disease, and outcome among 22 mild and moderate COVID-19 patients treated with antibodies cocktail. Results: The mean age was 67.7 years (SD ± 18.3) and comprised of 13 males (59%), while 9 were females (40.9%). Nine (40.9%) patients were fully vaccinated with two doses, nine (40.9%) were partially vaccinated with one dose while four patients (18.2%) were unvaccinated, and the rest were unvaccinated. Diabetes and hypertension were the commonest comorbidities; hematological and solid organ malignancies were other comorbidities. Eight patients had radiological opacities consistent with COVID-19 pneumonia and had shown significant regression in four patients after the therapy. None of our patients required supplemental oxygen or progressed to severe acute respiratory distress syndrome. All patients were discharged in a stable condition within 6 days of the therapy. Conclusions: The neutralizing antibodies cocktail has shown encouraging results in our analysis in preventing progression to severe disease in patients with high-risk conditions.

Low genetic confirmation rate in South Indian subjects with a clinical diagnosis of maturity-onset diabetes of the young (MODY) who underwent targeted next-generation sequencing for 13 genes.

PURPOSE: To screen for maturity-onset diabetes of the young (MODY) variants in subjects with an early age of onset and positive family history of diabetes mellitus. METHODS: 60 subjects with onset of diabetes between 3 and 30 years of age and parental history (onset < 35 years) of diabetes were recruited after excluding autoimmune, pancreatic and syndromic forms of diabetes. Detailed pedigree chart and clinical data were recorded. MODY genetic testing (MODY 1-13) was performed and variant classification was done adhering to the ACMG guidelines. RESULTS: Baseline characteristics of subjects were as follows: mean age of onset of diabetes 19.9 ± 7 years, mean duration of diabetes 6.3 ± 6.8 years, BMI 23.3 ± 3 kg/m2 and C-peptide 1.56 ± 1.06 nmol/l. Four out of sixty (6.6%) were positive for variants classifiable as pathogenic/likely pathogenic: one patient with HNF4Ac.691C > T, (p.Arg231Trp), two with HNF 1A c.746C > A(p.Ser249Ter) and c.1340C > T(p.Pro447Leu), and one with ABCC8 c.4544C > T (p.Thr1515Met). MODY 1 and MODY 3 variants were documented in the paediatric age group (< 18 years). CONCLUSION: A genetic diagnosis of MODY could be confirmed in only 6.6% (4/60) of patients clinically classifiable as MODY. This is less than that reported in clinically diagnosed MODY subjects of European descent. Newly published population data and more stringent criteria for assessment of pathogenicity and younger age of onset of type 2 diabetes in Indians could have contributed to the lower genetic confirmation rate. Apart from variants in the classical genes (HNF1A, HNF4A), a likely pathogenic variant in a non-classical gene (ABCC8) was noted in this study.

Sweetness and positivity together aren't a happy ending: Case controlled study amongst severe COVID-19 for impact of diabetes mellitus on survival.

Background: India is the epicenter of diabetes mellitus (DM). The relationship between COVID and DM in age/gender-matched non-diabetics has not been studied yet. The role of DM in predicting the disease severity and outcome in COVID patients might provide new insight for effective management. Methods: We conducted a prospective comparative study at a COVID care center from 25th April-31st May 2021. Among 357 severe-COVID patients screened, all consecutive diabetes (n-113) and age/gender-matched non-diabetes (n-113) patients were recruited. All diabetics and non-diabetics at admission were subjected to high resolution computed tomography (HRCT) chest and inflammatory markers (C-reactive protein (CRP), D-dimer, ferritin, interleukin-6 (IL-6), lactate dehydrogenase (LDH), Neutrophil-Lymphocyte Ratio (NLR)) before starting anti- COVID therapy. Statistical analysis was done using JMP 15·0 ver·3·0·0. Results: The prevalence of DM among the screened population (n-357) was 38·37%. The mean age of the study population was 61y with male preponderance (57%). There was no statistical difference in the HRCT-score or inflammatory markers in the two groups except for higher NLR (p-0·0283) in diabetics. Diabetics had significantly inferior overall survival (OS) (p-0·0251) with a 15d-OS of diabetics vs. non-diabetics being 58·87%, 72·67%, and 30d-OS of diabetics vs. non-diabetics being 46·76%, 64·61%, respectively. The duration of the hospital stay was not statistically different in the two groups (p-0·2). Conclusion: The mortality is significantly higher in severe-COVID patients with DM when compared to age/gender-matched non-diabetics. There was no significant difference in most inflammatory markers/CT at admission between the two groups.

Vitamin D, body mass composition and metabolic risk factors in healthy young Indians.

BACKGROUND: Studies have linked vitamin D to risk factors for cardiovascular disease. Obesity is a potential confounder in these studies. This study examined the relationship of 25 (OH) cholecalciferol (25[OH] D3) with insulin resistance, blood glucose, and lipid profile in lean male adults. METHOD: We enrolled two hundred and thirty four military recruits before beginning of military training. Demographic and anthropometric data were collected from them. The participants underwent body mass composition analysis by dual energy X ray absorptiometry. Fasting samples were collected for measurement of blood glucose, lipid profile, 25(OH) D3, serum parathormone (PTH) and insulin. RESULTS: Vitamin D deficiency and insufficiency was found in 47.7% (107/224) and 31.6% (71/224) of participants, respectively. Using Pearson's correlation coefficient 25(OH) cholecalciferol and fasting blood glucose (FBG) were inversely correlated (p = 0.023). However, similar relation was not found between 25(OH) D3 and total cholesterol, triglycerides, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, homeostatic model assessment of insulin resistance and levels of PTH. On body composition analysis, there was no correlation of 25(OH) cholecalciferol with body mass index or fat mass index. CONCLUSION: This study showed that in lean young male population, 25(OH) cholecalciferol and FBG are inversely correlated but no association of 25(OH) D3 with other cardiometabolic risk factors could be demonstrated.

In vivo high-throughput profiling of CRISPR-Cpf1 activity.

CRISPR from Prevotella and Francisella 1 (Cpf1) is an effector endonuclease of the class 2 CRISPR-Cas (clustered regularly interspaced short palindromic repeats-CRISPR-associated proteins) gene editing system. We developed a method for evaluating Cpf1 activity, based on target sequence composition in mammalian cells, in a high-throughput manner. A library of >11,000 target sequence and guide RNA pairs was delivered into human cells using lentiviral vectors. Subsequent delivery of Cpf1 into this cell library induced insertions and deletions (indels) at the integrated synthetic target sequences, which allowed en masse evaluation of Cpf1 activity by using deep sequencing. With this approach, we determined protospacer-adjacent motif sequences of two Cpf1 nucleases, one from Acidaminococcus sp. BV3L6 (hereafter referred to as AsCpf1) and the other from Lachnospiraceae bacterium ND2006 (hereafter referred to as LbCpf1). We also defined target-sequence-dependent activity profiles of AsCpf1, which enabled the development of a web tool that predicts the indel frequencies for given target sequences (http://big.hanyang.ac.kr/cindel). Both the Cpf1 characterization profile and the in vivo high-throughput evaluation method will greatly facilitate Cpf1-based genome editing.

Efficient Ground-State Cooling of Large Trapped-Ion Chains with an Electromagnetically-Induced-Transparency Tripod Scheme.

We report the electromagnetically-induced-transparency (EIT) cooling of a large trapped ^{171}Yb^{+} ion chain to the quantum ground state. Unlike conventional EIT cooling, we engage a four-level tripod structure and achieve fast sub-Doppler cooling over all motional modes. We observe simultaneous ground-state cooling across the complete transverse mode spectrum of up to 40 ions, occupying a bandwidth of over 3 MHz. The cooling time is observed to be less than 300 µs, independent of the number of ions. Such efficient cooling across the entire spectrum is essential for high-fidelity quantum operations using trapped ion crystals for quantum simulators or quantum computers.

A survey on surgeon practice shows lack of consensus on the management of primary shoulder stiffness.

Shoulder stiffness is a condition of painful restriction in active and passive glenohumeral range of motion, which can arise spontaneously or as consequence of a known cause. Numerous therapeutic approaches are available; however, no consensus has been reached on the best algorithm for successful treatment. The aim of this study was to investigate local practice patterns regarding management of primary shoulder stiffness. Randomized controlled trials reporting results of shoulder stiffness treatment were collected and analyzed prior to study begin. Controversial elements in the treatment of primary shoulder stiffness were identified and a survey was created and administrated to clinicians participating at an annual national congress dedicated to shoulder pathologies and their treatment. 55 completed questionnaires were collected. Physical therapy was recommended by 98% of the interviewed. The use of oral corticosteroids was considered by 58% and injections of corticosteroids by 60%. Injective therapy with local anaesthetics was considered by 56% of the clinicians and acupuncture by 36%. 38% of the interviewed did never treat shoulder stiffness surgically. Various strategies to manage shoulder stiffness have been proposed and high-level evidence has been published. Numerous controversial points and a substantial lack of consensus emerged both from literature reviews and from this survey. The treatment of shoulder stiffness should be tailored to the patient's clinical situation and the stage of its pathology, aiming primarily at identifying risk factors for recurrence, reducing pain, restoring range of motion and function and shortening the duration of symptoms.

A multicentre cohort study of serum and peritoneal biomarkers to predict anastomotic leakage after rectal cancer resection.

AIM: Anastomotic leakage (AL) is one of the most feared complications after rectal resection. This study aimed to assess a combination of biomarkers for early detection of AL after rectal cancer resection. METHOD: This study was an international multicentre prospective cohort study. All patients received a pelvic drain after rectal cancer resection. On the first three postoperative days drain fluid was collected daily and C-reactive protein (CRP) was measured. Matrix metalloproteinase-2 (MMP2), MMP9, glucose, lactate, interleukin 1-beta (IL1ß), IL6, IL10, tumour necrosis factor alpha (TNFα), Escherichia coli, Enterococcus faecalis, lipopolysaccharide-binding protein and amylase were measured in the drain fluid. Prediction models for AL were built for each postoperative day using multivariate penalized logistic regression. Model performance was estimated by the c-index for discrimination. The model with the best performance was visualized with a nomogram and calibration was plotted. RESULTS: A total of 292 patients were analysed; 38 (13.0%) patients suffered from AL, with a median interval to diagnosis of 6.0 (interquartile ratio 4.0-14.8) days. AL occurred less often after partial than after total mesorectal excision (4.9% vs 15.2%, P = 0.035). Of all patients with AL, 26 (68.4%) required reoperation. AL was more often treated by reoperation in patients without a diverting ileostomy (18/20 vs 8/18, P = 0.03). The prediction model for postoperative day 1 included MMP9, TNFα, diverting ileostomy and surgical technique (c-index = 0.71). The prediction model for postoperative day 2 only included CRP (c-index = 0.69). The prediction model for postoperative day 3 included CRP and MMP9 and obtained the best model performance (c-index = 0.78). CONCLUSION: The combination of serum CRP and peritoneal MMP9 may be useful for earlier prediction of AL after rectal cancer resection. In clinical practice, this combination of biomarkers should be interpreted in the clinical context as with any other diagnostic tool.

The effect of vitamin D supplementation on cardiorespiratory fitness and muscle strength in male adults undergoing basic military training.

BACKGROUND: Vitamin D deficiency (VDD) is ubiquitous in the Indian subcontinent. VDD has been shown to impair muscle functions. However, the association of VDD with cardiorespiratory endurance is uncertain. Hence, we enrolled and supplemented vitamin D in military recruits with VDD with an aim to evaluate effect of supplementation on cardiorespiratory endurance and muscle strength. METHOD: We enrolled 90 military recruits with VDD and randomly allotted them to two groups equally. The group I received cholecalciferol granules 60,000 IU every fortnight for twelve weeks (cases), and the group II was observed as control. Muscle strength and cardiorespiratory endurance was assessed with a battery of tests (standing broad jump, bent arm hang test, 20 m shuttle run) at baseline and repeated at the end of training (nineteen weeks). Blood samples were collected for measurement of serum 25(OH)D and parathyroid hormone. RESULTS: In Group I and Group II, there was significant increase in 25(OH) D levels (25.8 ± 7.1 and 17.3 ± 3.5 ng/ml, respectively), and in VO2 max (9.8 ± 8.8 and 12.7 ± 8.6 ml/kg/min, respectively) compared with the baseline values. However, no significant change was observed in muscle strength after supplementation. There was no difference between the groups in VO2 max and muscle strength at baseline and at the end of training. CONCLUSION: Vitamin D supplementation did not improve muscle strength and cardiorespiratory endurance in military recruits with VDD. A significant rise in 25(OH) D was observed even in those not supplemented with vitamin D.

Levels of Mycoplasma genitalium Antimicrobial Resistance Differ by Both Region and Gender in the State of Queensland, Australia: Implications for Treatment Guidelines.

Mycoplasma genitalium is frequently associated with urogenital and rectal infections, with the number of cases of macrolide-resistant and quinolone-resistant M. genitalium infection continuing to increase. In this study, we examined the levels of resistance to these two common antibiotic treatments in geographically distinct locations in Queensland, Australia. Samples were screened for macrolide resistance-associated mutations using a commercially available kit (ResistancePlus MG; SpeeDx), and quinolone resistance-associated mutations were identified by PCR and DNA sequencing. Comparisons between antibiotic resistance mutations and location/gender were performed. The levels of M. genitalium macrolide resistance were high across both locations (62%). Quinolone resistance mutations were found in ∼10% of all samples, with a number of samples harboring mutations conferring resistance to both macrolides and quinolones. Quinolone resistance was higher in southeast Queensland than in north Queensland, and this was consistent in both males and females (P = 0.007). The M. genitalium isolates in rectal swab samples from males harbored high levels of macrolide (75.9%) and quinolone (19%) resistance, with 15.5% harboring resistance to both classes of antibiotics. Overall, the lowest observed level of resistance was to quinolones in females from north Queensland (1.6%). These data highlight the high levels of antibiotic resistance in M. genitalium isolates within Queensland and the challenges faced by sexually transmitted infection clinicians in managing these infections. The data do, however, show that the levels of antibiotic resistance may differ between populations within the same state, which has implications for clinical management and treatment guidelines. These findings also support the need for ongoing antibiotic resistance surveillance and tailored treatment.

Multicentre study of non-surgical management of diverticulitis with abscess formation.

This multicentre retrospective cohort study included 447 patients with Hinchey Ib and II diverticular abscesses, who were treated with antibiotics, with or without percutaneous drainage. Abscesses of 3 and 5 cm in size were at higher risk of short-term treatment failure and emergency surgery respectively. Initial non-surgical treatment of Hinchey Ib and II diverticular abscesses was comparable between patients treated with antibiotics only and those who underwent percutaneous drainage in combination with antibiotics, with regard to short- and long-term outcomes. Most do not need drainage.

Transanal total mesorectal excision: how are we doing so far?

AIM: This subgroup analysis of a prospective multicentre cohort study aims to compare postoperative morbidity between transanal total mesorectal excision (TaTME) and laparoscopic total mesorectal excision (LaTME). METHOD: The study was designed as a subgroup analysis of a prospective multicentre cohort study. Patients undergoing TaTME or LaTME for rectal cancer were selected. All patients were followed up until the first visit to the outpatient clinic after hospital discharge. Postoperative complications were classified according to the Clavien-Dindo classification and the comprehensive complication index (CCI). Propensity score matching was performed. RESULTS: In total, 220 patients were selected from the overall prospective multicentre cohort study. After propensity score matching, 48 patients from each group were compared. The median tumour height for TaTME was 10.0 cm (6.0-10.8) and for LaTME was 9.5 cm (7.0-12.0) (P = 0.459). The duration of surgery and anaesthesia were both significantly longer for TaTME (221 vs 180 min, P < 0.001, and 264 vs 217 min, P < 0.001). TaTME was not converted to laparotomy whilst surgery in five patients undergoing LaTME was converted to laparotomy (0.0% vs 10.4%, P = 0.056). No statistically significant differences were observed for Clavien-Dindo classification, CCI, readmissions, reoperations and mortality. CONCLUSION: The study showed that TaTME is a safe and feasible approach for rectal cancer resection. This new technique obtained similar postoperative morbidity to LaTME.

Non-operative treatment as a strategy for patients with parastomal hernia: a multicentre, retrospective cohort study.

AIM: Parastomal hernia is the most common complication following stoma construction. Surgical treatment is usually chosen over non-operative treatment, but a clear rationale for the choice of management is often lacking. This study aims to investigate the reasons for non-operative treatment, cross-over rates and postoperative complications. METHOD: A multicentre, retrospective cohort study was conducted. Patients diagnosed with a parastomal hernia between January 2007 and December 2012 were included. Data on baseline characteristics, primary surgery and hernias were collected. For non-operative treatment, reasons for this treatment and cross-over rates were evaluated. For all patients undergoing surgery (surgical treatment and cross-overs), complication and recurrence rates were analysed. RESULTS: Of the 80 patients included, 42 (53%) were in the surgical treatment group and 38 (48%) in the non-operative treatment group. Median follow-up was 46 months (interquartile range 24-72). The reasons for non-operative treatment were absence of symptoms in 12 patients (32%), comorbidities in nine (24%) and patient preference in three (7.9%). In 14 patients (37%) reasons were not documented. Eight patients (21%) crossed over from non-operative treatment to surgical treatment, of whom one needed emergency surgery. In 23 patients (55%), parastomal hernia recurred after the original surgical treatment, of whom 21 (91%) underwent additional repair. CONCLUSION: Parastomal hernia repair is associated with high recurrence and additional repair rates. Non-operative treatment has a relatively low cross-over and emergency surgery rate. Given these data, non-operative treatment might be a better choice for patients without complaints or with comorbidities.

Incidence, risk factors and prevention of stoma site incisional hernias: a systematic review and meta-analysis.

AIM: Stoma reversal might lead to a stoma site incisional hernia. Recently, prophylactic mesh reinforcement of the stoma site has gained increased attention, supporting the need for accurate data on the incidence of and risk factors for stoma site incisional hernia and to identify high-risk patients. The aim of this study was to assess incidence, risk factors and prevention of stoma site incisional hernias. METHOD: Embase, MEDLINE, Web of Science, Cochrane and Google Scholar databases were searched. Studies reporting the incidence of stoma site incisional hernia after stoma reversal were included. Study quality was assessed with the Newcastle-Ottawa Scale and Cochrane risk of bias tool. Data on incidence, risk factors and prophylactic mesh reinforcement were extracted. RESULTS: Of 1440 articles found, 33 studies comprising 4679 reversals were included. The overall incidence of incisional hernia was 6.5% [range 0%-38%, median follow-up 27.5 (17.54-36) months]. Eleven studies assessed stoma site incisional hernia as the primary end-point, showing an incidence of 17.7% [range 1.7%-36.1%, median follow-up 28 (15.25-51.70) months]. Body mass index, diabetes and surgery for malignant disease were found to be independent risk factors, as derived from eight studies. Two retrospective comparative cohort studies showed significantly lower rates of stoma site incisional hernia with prophylactic mesh reinforcement compared with nonmesh controls [6.4% vs 36.1% (P = 0.001); 3% vs 19% (P = 0.04)]. CONCLUSION: Stoma site incisional hernia should not be underestimated as a long-term problem. Body mass index, diabetes and malignancy seem to be potential risk factors. Currently, limited data are available on the outcomes of prophylactic mesh reinforcement to prevent stoma site incisional hernia.

Systemic Inflammatory Cytokines Predict the Infectious Complications but Not Prolonged Postoperative Ileus after Colorectal Surgery.

AIM: Postoperative ileus (POI) is common after surgery. Animal studies indicate that the POI mechanism involves an inflammatory response, which is also activated during postoperative complications. This study aimed to determine whether inflammatory biomarkers might facilitate an early detection of prolonged POI (PPOI) or infectious complications. METHODS: Forty-seven adult patients who underwent oncological colorectal surgery were included. They filled out a perioperative diary to report their gastrointestinal symptoms. Blood samples were collected preoperatively, and on postoperative day (POD) 1 and 3. Levels of leucocytes, C-reactive protein (CRP), interleukin (IL)-6, TNF-α, and IL-1ß were analyzed. RESULTS: Patients with PPOI had significantly longer stay in hospital than patients without (13.6 ± 10.5 versus 7.4 ± 3.2 days, p < 0.001); they also had higher levels of IL-6 ratios, leucocytes, and CRP levels, but did not reach significance. Higher levels of postoperative IL-6 and CRP levels (p < 0.05, resp.) were found in patients with infectious complications. The receiver operating characteristic (ROC) analysis found better diagnostic values of IL-6 ratio on both POD 1 and 3 than that of CRP (POD 1: ROC 0.825, p < 0.001). CONCLUSION: Blood levels of inflammatory cytokines cannot predict PPOI after colorectal surgery. Instead, postoperative IL-6 changes may predict the infectious complications with a better diagnostic value than the current leukocytes or CRP tests.

Faecal occult blood testing screening for colorectal cancer and 'missed' interval cancers: are we ignoring the elephant in the room? Results of a multicentre study.

AIM: Biennial faecal occult blood testing (FOBT) is used to screen for colorectal cancer throughout the UK. Interval cancers are tumours that develop in patients between screening rounds who have had a negative FOBT. Through a multicentre study, we compared the demographics of patients with interval cancers, FOBT screen detected cancers and cancers that developed in patients who chose not to participate in the screening programme. METHOD: Five hundred and sixteen colorectal cancers were detected in the screening age group (60-74 years) population in three UK National Health Service hospitals over 2 years. One hundred and twenty seven (25%) were interval cancers, 161 (31%) were screen detected and 228 (44%) were cancers that developed in patients who had declined FOBT. The interval cancer group had a higher incidence of right-sided cancers (38% vs 29% and 24%), a higher proportion of high tumour stages (Dukes C and D) (70% vs 53% and 33%) and a shorter time from diagnosis to death (10 months vs 13 months and 24 months) compared to patients who had declined the FOBT and the FOBT screen detected cancers. Of all the patients studied, those with right-sided interval cancers had the worst outcome. CONCLUSION: A quarter of the colorectal cancers diagnosed in our study were interval cancers. Patients with right-sided interval cancers had the highest proportion of Dukes C and D tumours coupled with the shortest survival time after diagnosis compared with the other groups.