Resection margin involvement after endoscopic excision of malignant colorectal polyps: definition of margin involvement and its impact upon tumour recurrence.

AIMS: Malignant polyps are examined to assess histological features which predict residual tumour in the unresected bowel and guide surgical decision-making. One of the most important of these features is resection margin involvement, although the best definition of margin involvement is unknown. In this study we aimed to investigate three different definitions and determine their impact on clinical outcomes. METHODS AND RESULTS: One hundred and sixty-five malignant polyps removed endoscopically were identified and histological features correlated with either residual tumour in subsequent surgical resections or tumour recurrence following a period of clinical follow-up. Involvement of the polyp margin by cancer was defined in three different ways and outcomes compared. Tumour recurrence was associated with tumour grade, mucinous histology and resection margin involvement. All three definitions of margin involvement separated polyps into clinically significant categories; however, a margin ≤ 1 mm identified 73% of polyps as 'high-risk' compared with 59.1% when involvement was defined as tumour within the zone of coagulation artefact at the polyp base or 50% when tumour was present at the margin. All three 'low-risk' groups had a locoregional recurrence rate < 6.5%. CONCLUSIONS: Definitions of margin involvement for endoscopically removed malignant polyps in the colon and rectum vary between health-care systems, but a 1-mm clearance is widely used in Europe and North America. Our results suggest that a 1-mm margin is unnecessary and should be replaced by a definition based on tumour at the margin or within coagulation artefact at the polyp base.

Is medullary carcinoma of the colon underdiagnosed? An audit of poorly differentiated colorectal carcinomas in a large national health service teaching hospital.

AIMS: Medullary carcinoma is an uncommon colorectal tumour which appears poorly differentiated histologically. Consequently, it may be confused with poorly differentiated adenocarcinoma not otherwise specified (NOS). The principal aim of this study was to review a large series of poorly differentiated colorectal cancers resected at a large National Health Service (NHS) Teaching Hospital to determine how often medullary carcinomas were misclassified . Secondary aims were to investigate how often neuroendocrine differentiation or metastatic tumours were considered in the differential diagnosis, and compare clinico-pathological features between medullary and poorly differentiated adenocarcinoma NOS. METHODS AND RESULTS: Histology slides from 302 colorectal cancer resections originally reported as poorly differentiated adenocarcinoma were reviewed and cases fulfilling World Health Organisation (WHO) criteria for medullary carcinoma identified. The original pathology report was examined for any mention of medullary phenotype, consideration of neuroendocrine differentiation or consideration of metastasis from another site. Clinico-pathological features were compared to poorly differentiated adenocarcinoma NOS. Only one-third of medullary carcinomas were correctly identified between 1997 and 2018. The other two-thirds were reported as poorly differentiated adenocarcinoma NOS. The possibility of an extracolonic origin or neuroendocrine carcinoma was considered in 21 and 27% of reports. Most medullary carcinomas exhibited mismatch repair deficiency, were located in ascending colon and caecum and had a lower rate of vascular channel invasion and lymph node metastasis compared to poorly differentiated adenocarcinoma. CONCLUSIONS: Medullary carcinoma of the colon is often mistaken for poorly differentiated adenocarcinoma NOS and occasionally for neuroendocrine or metastatic carcinoma. Greater familiarity with morphological criteria and use of mismatch repair protein staining should improve diagnosis.

Decreasing formalin concentration improves quality of DNA extracted from formalin-fixed paraffin-embedded tissue specimens without compromising tissue morphology or immunohistochemical staining.

Genomic technologies are increasingly used clinically for both diagnosis and guiding cancer therapy. However, formalin fixation can compromise DNA quality. This study aimed to optimise tissue fixation using normal colon, liver and uterus (n=8 each) by varying neutral buffered formalin (NBF) concentration (1%-5% w/v) and fixation time (24-48 hours). Fixation using 4% NBF improved DNA quality (assessed by qPCR) compared with routine (4% unbuffered formal saline-fixed) specimens (p<0.01). Further improvements were achieved by reducing NBF concentration (p<0.00001), whereas fixation time had no effect (p=0.110). No adverse effects were detected by histopathological or QuPath morphometric analysis. Immunohistochemistry for multicytokeratin and α-smooth muscle actin revealed no changes in staining specificity or intensity in any tissue other than on liver multicytokeratin staining intensity, where the effect of fixation time was more significant (p=0.0004) than NBF concentration (p=0.048). Thus, reducing NBF concentration can maximise DNA quality without compromising tissue morphology or standard histopathological analyses.

High prevalence of irritable bowel syndrome-type symptoms in microscopic colitis: implications for treatment.

BACKGROUND: Patients with microscopic colitis (MC) often present with abdominal pain and diarrhoea, and previous data suggest that there may be overlap between MC and irritable bowel syndrome (IBS). We evaluated the prevalence of IBS-type symptoms in patients with MC, and assess the impact of these symptoms on psychological health and quality of life. METHODS: We conducted a cross-sectional survey of individuals with a histological diagnosis of MC, collecting demographic data, Rome III IBS-type symptoms, and mood, somatization, and quality of life data. RESULTS: In total, 151 (31.6%) of 478 individuals with a new diagnosis of MC completed questionnaires, 52 (34.4%) of whom reported IBS-type symptoms. The commonest histological subtype was collagenous colitis (51.7%, n = 78), followed by lymphocytic colitis (39.1%, n = 59). Individuals with IBS-type symptoms had significantly higher levels of anxiety [Hospital Anxiety and Depression Scale (HADS) anxiety score 8.6 versus 5.1, p < 0.001], depression (HADS depression score 6.2 versus 3.6, p = 0.001), and somatoform-type behaviour (Patient Health Questionnaire 15 score 12.7 versus 8.0, p < 0.001) compared with individuals who did not. Those with IBS-type symptoms scored significantly worse across all domains of the 36-item Short Form questionnaire, except for physical functioning. CONCLUSIONS: More than one third of individuals with MC reported IBS-type symptoms, although whether this is due to ongoing inflammation is unclear. These individuals had higher levels of anxiety, depression, and somatization, and impaired quality of life. Identifying concomitant IBS in individuals with MC may have important implications for management decisions.

Histopathological report of colorectal carcinoma resections: A 5-year audit in Lagos.

BACKGROUND: Complete and accurate pathology reporting of colorectal carcinoma (CRC) resection specimen is critical to clinical management of individual patients. The study aims to audit colorectal cancer histopathology reporting in Lagos between 2011 and 2015 before the adoption of the Society for Gastroenterology and Hepatology in Nigeria pro forma in 2016. MATERIALS AND METHODS: All resected CRC cases were identified from the Histopathology record of our Department and that of a private Laboratory in Lagos over a 5-year from 2011 to 2015. The dataset as contained in the pro forma was extracted from the reports and analysed using SPSS version 16 software. RESULTS: A total of 92 colorectal resections were received during the 5-year period consisting of 90 colonic and 2 rectal tumours. Data inclusiveness on tumour differentiation, extent of primary tumour, total lymph node and lymph node involvement were 96.7%, 91.3%, 83.7% and 92.4%, respectively. Tumour perforation, level of venous involvement and distant metastasis were reported in 73.9%, 21.7% and 96.7% respectively. The circumferential resection margin (CRM) in the 2 rectal tumours had 100% inclusiveness. Tumour node metastasis staging was complete in 87% of cases while Dukes staging was documented in 8.7% of the reports. CONCLUSION: None of the data items was 100% complete except the CRM for rectal carcinoma. Free text reporting results in incomplete data resulting in improper staging, especially the lymph node status. This highlights the need for pro forma reporting to ensure and maintain consistent reporting of important parameters required for proper staging and management of patients with colorectal cancer.

Macroscopic findings, incidence and characteristics of microscopic colitis in a large cohort of patients from the United Kingdom.

OBJECTIVE: Microscopic colitis (MC) is classically associated with normal or near-normal endoscopic appearances. However, non-specific macroscopic findings have been described, the importance of biopsy location for confirming a diagnosis of MC is unclear, and reported incidence data from the United Kingdom are limited. This study was designed to assess macroscopic features, incidence, demographics, and location and positivity of biopsy samples in MC. MATERIALS AND METHODS: Retrospective, cross-sectional study of individuals with newly diagnosed MC. RESULTS: From 2010 to 2015, 540 cases of MC were reported. Macroscopic findings occurred in 16.5% (n = 89) cases, with trends towards increased frequency of ulceration or linear scarring in collagenous colitis (CC). The mean incidence of MC was 11.3 per 100,000 population/year, including 291 (53.9%) with CC (incidence 6.1 per 100,000/year), 203 (37.6%) with lymphocytic colitis (incidence 4.2 per 100,000/year) and 46 (8.5%) with MC, not otherwise specified. Most individuals were female (70.2%). Common features in patients with MC included symptom duration <6 months, weight loss, abdominal pain and use of proton pump inhibitors, statins, or non-steroidal anti-inflammatory drugs. In individuals with right- and left-sided biopsies taken, 98.2% had diagnostic features in both. However, rectal biopsies were only positive in 88.7%. CONCLUSIONS: One in six patients with MC demonstrated distinct macroscopic findings at colonoscopy. Our data confirm a female preponderance in MC, a relatively short symptom duration and use of certain drugs as common features. Both right- and left-sided biopsies were frequently positive, suggesting flexible sigmoidoscopy and biopsy could confirm a diagnosis in certain individuals.

Remote Teaching of Histopathology Using Scanned Slides via Skype Between the United Kingdom and Nigeria.

CONTEXT: -Web-based learning is a major component of distance education. OBJECTIVE: -To explore Web-based applications for pathology teaching in resource-limited sub-Saharan Africa. DESIGN: -The participants were consultant pathologists and trainees drawn from tertiary institutions in Nigeria. They viewed the digital slides via the Leeds virtual pathology Web site, after which, interactive lectures were given via Skype (Skype Communications, Luxembourg City, Luxembourg). Questionnaires were administered via SurveyMonkey (Palo Alto, California) to all participants of 12 sessions between 2014 and 2015. RESULTS: -Nine consultant pathologists and 33 trainees participated in this survey. Of all respondents, 29 (69%) thought it was fairly easy to navigate the system, 11 (26.2%) thought it was easy, whereas 2 (4.8%) felt it was difficult. In addition, 26 respondents (61.9%) found it fairly easy to make a make a diagnosis, 13 (31%) thought it was easy, and 3 (7.1%) noted that it was difficult. Twenty-four respondents (57.1%) had a fairly smooth user experience, 12 (28.6%) experienced occasional crashes, whereas 6 (14.3%) reported a smooth experience. Almost all (41 of 42; 97.6%) respondents felt the pathology teaching was beneficial to their local pathology practice, and all (100%) indicated the need for additional, similar sessions. CONCLUSION: -The beneficial applications of Internet-based lectures make them a viable, cheaper, and cost-effective alternative to face-to-face lectures in our environment.

Establishing a Cancer Research Consortium in Low- and Middle-Income Countries: Challenges Faced and Lessons Learned.

PURPOSE: There is an increasing effort in the global public health community to strengthen research capacity in low- and middle-income countries, but there is no consensus on how best to approach such endeavors. Successful consortia that perform research on HIV/AIDS and other infectious diseases exist, but few papers have been published detailing the challenges faced and lessons learned in setting up and running a successful research consortium. METHODS: Members of the African Research Group for Oncology (ARGO) participated in generating lessons learned regarding the foundation and maintenance of a cancer research consortium in Nigeria. RESULTS: Drawing on our experience of founding ARGO, we describe steps and key factors needed to establish a successful collaborative consortium between researchers from both high- and low-income countries. In addition, we present challenges we encountered in building our consortium, and how we managed those challenges. Although our research group is focused primarily on cancer, many of our lessons learned can be applied more widely in biomedical or public health research in low-income countries. CONCLUSIONS: As the need for cancer care in LMICs continues to grow, the ability to create sustainable, innovative, collaborative research groups will become vital. Assessing the successes and failures that occur in creating and sustaining research consortia in LMICs is important for expansion of research and training capacity in LMICs.

Raman spectroscopy of endoscopic colonic biopsies from patients with ulcerative colitis to identify mucosal inflammation and healing.

Raman spectroscopy was used to differentiate between mucosally healed (or quiescent) and inflamed colon tissue, as assessed endoscopically, in patients with ulcerative colitis. From the analysis of the Raman spectra of 60 biopsy tissue samples, clear differences were identified between the spectra of the quiescent and inflamed tissue. Three carotenoid peaks were found to be approximately twice as intense in the inflamed tissue. Two phospholipid peaks were found to be significantly lower in the inflamed tissue. Using multivariate statistical analysis, we show that these five peaks can be used to discriminate between endoscopically quiescent and inflamed tissue. We also correlated the Raman data with a histological assessment of the tissue. Four of the five peaks were found to be significantly different between the spectra of histologically healed (or quiescent) and histologically inflamed tissue. These findings indicate the ability of Raman spectroscopy to accurately classify colon tissue as either quiescent or inflamed, irrespective of whether an endoscopic or histological grading scheme is followed. We thus demonstrate that Raman spectroscopy could potentially be used as an early diagnosis tool for assessing the presence of mucosal healing or inflammation in patients with ulcerative colitis.

Liver toxicity associated with sofosbuvir, an NS5A inhibitor and ribavirin use.

Hepatitis C virus (HCV) infection is a major cause of end-stage liver disease and hepatocellular carcinoma. There have been rapid advances in HCV treatment with the development of oral direct-acting antivirals (DAAs). Studies have shown sustained virological response rates above 90% with combinations of DAAs, including patients with compensated cirrhosis. Thus far, significant drug toxicity has not been seen with these agents, but there is limited experience of using DAAs in decompensated HCV cirrhosis. This report describes the first experience of serious drug-induced hepatotoxicity with the new DAAs. The mechanism underlying these drug reactions is currently unknown. Few patients with decompensated cirrhosis have been treated with DAAs, so the exact pharmacokinetics in this population have not been characterised. In both cases presented here, patients were taking or had recently taken other drugs. It is possible that an unknown interaction or reaction to the drug combination caused the hepatotoxicity. Although the association with the DAAs is not proven these cases indicate that patients with advanced liver disease need close monitoring while on DAA therapy and if there is a significant unexplained deterioration in liver function the DAAs should be discontinued.

Development and validation of a scoring system to identify patients with microscopic colitis.

BACKGROUND & AIMS: Diarrhea is a common indication for colonoscopy. Biopsies are collected and analyzed from patients with a macroscopically normal colon to exclude microscopic colitis (MC), but the diagnostic yield is low because most patients have functional disease. We developed and validated a diagnostic scoring system to identify patients with MC to reduce the need to collect biopsies from all patients. METHODS: We performed a retrospective study, which analyzed demographic and symptom data from adult patients with chronic diarrhea evaluated by colonoscopy and biopsy at 3 endoscopy centers in Leeds, United Kingdom. To derive the scoring system, we analyzed data from 476 adult patients (mean age, 53.6 years; 63.7% female) examined in 2011. Factors significantly associated with the presence of MC were assigned item scores, and total scores were determined for each patient. To validate the system, we used it to assess data from 460 patients (mean age, 52.9 years; 59.8% female) examined in 2012. The primary aim of the study was to determine the performance of the diagnostic scoring system in identifying patients with MC by using histologic findings as a reference. RESULTS: In the derivation cohort, 85 patients were diagnosed with MC on the basis of histologic analysis. Age ≥50 years, female sex, use of proton pump inhibitors or nonsteroidal anti-inflammatory drugs, weight loss, and absence of abdominal pain were significantly associated with MC. We created a scoring system for diagnosis of MC, with scores ranging from -8 to +38; scores ≥8 were used to identify the presence of MC. This cutoff value identified patients with MC in the validation cohort (74 patients, 16.1%) with 90.5% sensitivity and 45.3% specificity (area under the receiver operating characteristic curve value, 0.76). Because of its ability to exclude MC and therefore avoid the need for routine collection of colonic biopsies, this scoring system reduced the cost of evaluation by >£7000 in the cohort. CONCLUSIONS: We collected data on risk factors for MC to create a scoring system that identifies patients with MC with more than 90% sensitivity. This system can also reduce costs by identifying patients who are unlikely to have MC who do not require biopsy analysis.

Repeat hepatectomy with inferior vena cava re-resection for colorectal liver metastases: case report and review of the literature.

Liver resection in patients with inferior vena cava (IVC) involvement is becoming more common with the adoption of vascular exclusion techniques and replacement of the IVC. Repeat hepatectomy and an aggressive surgical approach can offer satisfactory disease-free survival and a cure in selected patients. We herein describe a case of repeat hepatectomy with en bloc re-do IVC resection and reconstruction with Gore-Tex graft for recurrent colorectal liver disease. The patient had previously undergone non-anatomical right liver resection with IVC partial excision and reconstruction with a porcine pericardial patch. The patient is currently disease-free at 12 months' follow-up. Surgical treatment of liver tumors involving the IVC offers the only hope for prolonged survival. Re-do liver surgery with concomitant re-excision of the IVC is feasible and can be contemplated when macroscopic removal of the tumor is expected. Management of these complex cases by a specialist team with expertise in liver transplantation and vascular techniques is advised.

Fifty-three years of reporting colorectal cancer in Nigerians--a systematic review of the published literature.

AIMS AND OBJECTIVES: This study aimed to perform a systematic review of all the available published data on CRC in Nigerians over a period of 53 years as a proximate indication of the burden of the disease. MATERIALS & METHODS: The data were sourced from PubMed, MEDLINE, EMBASE and Google Scholar search engines as well as direct contact with some authors. All published studies on histologically confirmed CRC in Nigerians constitute the materials. Selected papers were independently reviewed by the authors. RESULTS: Of 35 papers found, 19 met the criteria and a total of 2497 cases reported in these 19 publications constituted the materials utilised for the review. There is increasing incidence as evident by increase in annual frequency increased from 18.2/annum in the early years (1954-1969) to 86.8/annum in the latter years (1991-2007). The average age incidence was 46 years (peak=41-50 age group); 674 (32%) of all the cases were aged below 40 years. The male to female ratio was 1.3:1. Of the 2238 cases in which site was reported, rectum 1349 (60%) was the commonest site followed by caecum 260 (17%). All the cases were adenocarcinomas and 1043 (56%) were well differentiated. Mucinous carcinoma and signet ring type accounted for 309 (17%) and 32 (2%) respectively. Of 1061 cases in which Duke's staging was reported, 622 (59%) presented in stage B disease followed by stage C 266 (25%). CONCLUSIONS: The incidence is of CRC is increasing in Nigeria. The mean age is low and incidence appears to be increasing in younger patients.

A study of indefinite for dysplasia in Barrett's oesophagus: reproducibility of diagnosis, clinical outcomes and predicting progression with AMACR (alpha-methylacyl-CoA-racemase).

AIMS: To assess interobserver variation in the diagnosis of dysplasia in Barrett's oesophagus, especially indefinite dysplasia (IND) using the revised Vienna classification. A secondary aim was to study clinical outcome of IND cases and to evaluate expression of alpha-methyl-CoA racemase (AMACR) as a marker predictive of progression. METHODS AND RESULTS: Cases of Barrett's oesophagus and dysplasia over a 20 year period were assessed. Three experienced histopathologists reviewed 101 cases on set criteria in a blinded fashion. Slides were immunostained for AMACR and evaluated for the presence, extent and location of AMACR expression. Clinical and progression data were collected. Overall agreement for the diagnosis of dysplasia was fair (k = 0.35) but that for IND was poor (k = 0.18). 6 IND cases progressed after a median follow-up of 31.4 months to a higher grade. The sensitivity of AMACR for the detection of abnormality was 22% for IND and specificity 100%. The positive predictive value of AMACR for progression was 0.44 and the negative predictive value was 0.92. CONCLUSION: Fair agreement was achieved for the diagnosis of dysplasia but poor agreement for IND. A proportion of IND cases progress. Re-diagnosis or consensus diagnosis did not predict progression. AMACR shows promise as a marker to indicate IND patients in need of more intensive surveillance.