Incidences of colorectal adenomas and cancers under colonoscopy surveillance suggest an accelerated "Big Bang" pathway to CRC in three of the four Lynch syndromes.

BACKGROUND: Colorectal cancers (CRCs) in the Lynch syndromes have been assumed to emerge through an accelerated adenoma-carcinoma pathway. In this model adenomas with deficient mismatch repair have an increased probability of acquiring additional cancer driver mutation(s) resulting in more rapid progression to malignancy. If this model was accurate, the success of colonoscopy in preventing CRC would be a function of the intervals between colonoscopies and mean sojourn time of detectable adenomas. Contrary to expectations, colonoscopy did not decrease incidence of CRC in the Lynch syndromes and shorter colonoscopy intervals have not been effective in reducing CRC incidence. The prospective Lynch Syndrome Database (PLSD) was designed to examine these issues in carriers of pathogenic variants of the mis-match repair (path_MMR) genes. MATERIALS AND METHODS: We examined the CRC and colorectal adenoma incidences in 3,574 path_MLH1, path_MSH2, path_MSH6 and path_PMS2 carriers subjected to regular colonoscopy with polypectomy, and considered the results based on sojourn times and stochastic probability paradigms. RESULTS: Most of the path_MMR carriers in each genetic group had no adenomas. There was no association between incidences of CRC and the presence of adenomas. There was no CRC observed in path_PMS2 carriers. CONCLUSIONS: Colonoscopy prevented CRC in path_PMS2 carriers but not in the others. Our findings are consistent with colonoscopy surveillance blocking the adenoma-carcinoma pathway by removing identified adenomas which might otherwise become CRCs. However, in the other carriers most CRCs likely arised from dMMR cells in the crypts that have an increased mutation rate with increased stochastic chaotic probabilities for mutations. Therefore, this mechanism, that may be associated with no or only a short sojourn time of MSI tumours as adenomas, could explain the findings in our previous and current reports.

Dominantly inherited micro-satellite instable cancer - the four Lynch syndromes - an EHTG, PLSD position statement.

The recognition of dominantly inherited micro-satellite instable (MSI) cancers caused by pathogenic variants in one of the four mismatch repair (MMR) genes MSH2, MLH1, MSH6 and PMS2 has modified our understanding of carcinogenesis. Inherited loss of function variants in each of these MMR genes cause four dominantly inherited cancer syndromes with different penetrance and expressivities: the four Lynch syndromes. No person has an "average sex "or a pathogenic variant in an "average Lynch syndrome gene" and results that are not stratified by gene and sex will be valid for no one. Carcinogenesis may be a linear process from increased cellular division to localized cancer to metastasis. In addition, in the Lynch syndromes (LS) we now recognize a dynamic balance between two stochastic processes: MSI producing abnormal cells, and the host's adaptive immune system's ability to remove them. The latter may explain why colonoscopy surveillance does not reduce the incidence of colorectal cancer in LS, while it may improve the prognosis. Most early onset colon, endometrial and ovarian cancers in LS are now cured and most cancer related deaths are after subsequent cancers in other organs. Aspirin reduces the incidence of colorectal and other cancers in LS. Immunotherapy increases the host immune system's capability to destroy MSI cancers. Colonoscopy surveillance, aspirin prevention and immunotherapy represent major steps forward in personalized precision medicine to prevent and cure inherited MSI cancer.

The value of intraoperative dynamic liver function test ICG in predicting postoperative complications in patients undergoing staged hepatectomy: a pilot study.

PURPOSE: To assess the predictive value of intraoperative indocyanine green (ICG) test in patients undergoing staged hepatectomy. METHODS: We analyzed intraoperative ICG measurements of future liver remnant (FLR), preoperative ICG, volumetry, and hepatobiliary scintigraphy in 15 patients undergoing associated liver partition and portal vein ligation for staged hepatectomy (ALPPS). Main endpoints were the correlation of intraoperative ICG values to postoperative complications (Comprehensive Complication Index (CCI®)) at discharge and 90 days after surgery, and to postoperative liver function. RESULTS: Median intraoperative R15 (ICG retention rate at 15 min) correlated significantly with CCI® at discharge (p = 0.05) and with CCI® at 90 days (p = 0.0036). Preoperative ICG, volumetry, and scintigraphy did not correlate to postoperative outcome. ROC curve analysis revealed a cutoff value of 11.4 for the intraoperative R15 to predict major complications (Clavien-Dindo ≥ III) with 100% sensitivity and 63% specificity. No patient with R15 ≤ 11 developed major complications. CONCLUSION: This pilot study suggests that intraoperative ICG clearance determines the functional capacity of the future liver remnant more accurately than preoperative tests. This may further reduce the number of postoperative liver failures, even if it means intraoperative abortion of hepatectomy in individual cases.

Mortality by age, gene and gender in carriers of pathogenic mismatch repair gene variants receiving surveillance for early cancer diagnosis and treatment: a report from the prospective Lynch syndrome database.

Background: The Prospective Lynch Syndrome Database (PLSD) collates information on carriers of pathogenic or likely pathogenic MMR variants (path_MMR) who are receiving medical follow-up, including colonoscopy surveillance, which aims to the achieve early diagnosis and treatment of cancers. Here we use the most recent PLSD cohort that is larger and has wider geographical representation than previous versions, allowing us to present mortality as an outcome, and median ages at cancer diagnoses for the first time. Methods: The PLSD is a prospective observational study without a control group that was designed in 2012 and updated up to October 2022. Data for 8500 carriers of path_MMR variants from 25 countries were included, providing 71,713 years of follow up. Cumulative cancer incidences at 65 years of age were combined with 10-year crude survival following cancer, to derive estimates of mortality up to 75 years of age by organ, gene, and gender. Findings: Gynaecological cancers were more frequent than colorectal cancers in path_MSH2, path_MSH6 and path_PMS2 carriers [cumulative incidence: 53.3%, 49.6% and 23.3% at 75 years, respectively]. Endometrial, colon and ovarian cancer had low mortality [8%, 13% and 15%, respectively] and prostate cancers were frequent in male path_MSH2 carriers [cumulative incidence: 39.7% at 75 years]. Pancreatic, brain, biliary tract and ureter and kidney and urinary bladder cancers were associated with high mortality [83%, 66%, 58%, 27%, and 29%, respectively]. Among path_MMR carriers undergoing colonoscopy surveillance, particularly path_MSH2 carriers, more deaths followed non-colorectal Lynch syndrome cancers than colorectal cancers. Interpretation: In path_MMR carriers undergoing colonoscopy surveillance, non-colorectal Lynch syndrome cancers were associated with more deaths than were colorectal cancers. Reducing deaths from non-colorectal cancers presents a key challenge in contemporary medical care in Lynch syndrome. Funding: We acknowledge funding from the Norwegian Cancer Society, contract 194751-2017.

Current Surgical Concepts in Lynch Syndrome and Familial Adenomatous Polyposis.

Background: Approximately 5% of colorectal cancers (CRCs) are associated with hereditary cancer syndromes. The natural history of these syndromes differs from sporadic cancers, and due to their increased risk of metachronous carcinomas, surgical approaches also differ. This review focuses on the current recommendations for surgical treatment and what evidence has led to these recommendations in the most clinically relevant hereditary CRC syndromes: Lynch syndrome (LS) and (attenuated) familial adenomatous polyposis (FAP). Summary: LS has no common phenotype and is caused by individual germline variants in one of the mismatch repair genes (MLH1, MSH2, MSH6, or PMS2). Because each gene is associated with a different risk of metachronous cancer, guidelines now differentiate between genes in their recommendations for oncology interventions. Classical and attenuated FAP are caused by germline mutations in the APC gene and have a characteristic phenotype. Although correlations exist between phenotype and genotype, the indication for surgery is predominantly based on clinical manifestation rather than specific gene mutations. Key Message: Currently, the recommendation on the two diseases tends to go in opposite directions: while some forms of FAP may require less extensive surgery, in some LS patients, more sophisticated knowledge of metachronous carcinoma risk leads to more extensive surgery.

Colorectal cancer incidences in Lynch syndrome: a comparison of results from the prospective lynch syndrome database and the international mismatch repair consortium.

OBJECTIVE: To compare colorectal cancer (CRC) incidences in carriers of pathogenic variants of the MMR genes in the PLSD and IMRC cohorts, of which only the former included mandatory colonoscopy surveillance for all participants. METHODS: CRC incidences were calculated in an intervention group comprising a cohort of confirmed carriers of pathogenic or likely pathogenic variants in mismatch repair genes (path_MMR) followed prospectively by the Prospective Lynch Syndrome Database (PLSD). All had colonoscopy surveillance, with polypectomy when polyps were identified. Comparison was made with a retrospective cohort reported by the International Mismatch Repair Consortium (IMRC). This comprised confirmed and inferred path_MMR carriers who were first- or second-degree relatives of Lynch syndrome probands. RESULTS: In the PLSD, 8,153 subjects had follow-up colonoscopy surveillance for a total of 67,604 years and 578 carriers had CRC diagnosed. Average cumulative incidences of CRC in path_MLH1 carriers at 70 years of age were 52% in males and 41% in females; for path_MSH2 50% and 39%; for path_MSH6 13% and 17% and for path_PMS2 11% and 8%. In contrast, in the IMRC cohort, corresponding cumulative incidences were 40% and 27%; 34% and 23%; 16% and 8% and 7% and 6%. Comparing just the European carriers in the two series gave similar findings. Numbers in the PLSD series did not allow comparisons of carriers from other continents separately. Cumulative incidences at 25 years were < 1% in all retrospective groups. CONCLUSIONS: Prospectively observed CRC incidences (PLSD) in path_MLH1 and path_MSH2 carriers undergoing colonoscopy surveillance and polypectomy were higher than in the retrospective (IMRC) series, and were not reduced in path_MSH6 carriers. These findings were the opposite to those expected. CRC point incidence before 50 years of age was reduced in path_PMS2 carriers subjected to colonoscopy, but not significantly so.

Kidney Retransplantation after Graft Failure: Variables Influencing Long-Term Survival.

Background: There is an increasing demand for kidney retransplantation. Most studies report inferior outcomes compared to primary transplantation, consequently feeding an ethical dilemma in the context of chronic organ shortage. Objective: To assess variables influencing long-term graft survival after kidney retransplantation. Material and Methods. All patients transplanted at our center between 2000 and 2016 were analyzed retrospectively. Survival was estimated with the Kaplan-Meier method, and risk factors were identified using multiple Cox regression. Results: We performed 1,376 primary kidney transplantations and 222 retransplantations. The rate of retransplantation was 67.8% after the first graft loss, with a comparable 10-year graft survival compared to primary transplantation (67% vs. 64%, p=0.104) but an inferior graft survival thereafter (log-rank p=0.026). Independent risk factors for graft survival in retransplantation were age ≥ 50 years, time on dialysis ≥1 year, previous graft survival <2 years, ≥1 mild comorbidity in the Charlson-Deyo index, active smoking, and life-threatening complications (Clavien-Dindo grade IV) at first transplantation. Conclusion: Graft survival is comparable for first and second kidney transplantation within the first 10 years. Risk factors for poor outcomes after retransplantation are previous graft survival, dialysis time after graft failure, recipient age, comorbidities, and smoking. Patients with transplant failure should have access to retransplantation as early as possible.

Towards a Virtual "Global Academia of Surgeons".

OBJECTIVE: To explore the prospects of academic e-learning by evaluating our long-standing internet-based surgical learning program and to assess the impact of training on the presentation skills of our residents. The eventual goal is to search whether such models could be further developed by the European Surgical Association (ESA). BACKGROUND: E-learning has become a major educational trend particularly during the COVID-19 pandemic. For more than a decade, our academic tertiary center has released weekly video-lectures covering the entire abdominal-surgical curriculum for residents. All lessons were prepared under the supervision of specialized experts and recorded and edited by a professional film team before being released on a dedicated YouTube channel ( https://www.usz.ch/surgical-resident-lectures ). METHODS: To date, our channel includes 120 presentations with more than 619,000 views. We conducted a survey among online users with a medical background and tested the benefits and potential for improvements of local stakeholders to collect individual reviews. RESULTS: A total of 708 users from 106 countries participated in the survey. Continuing medical education (49%), specific questions (38%), and exam preparation (33%) were the main motivations for video viewing. The preferred topics were current guidelines (69%), latest research topics (59%), and complex surgical conditions (52%). Ninety-four percent of our local audience reported a positive learning experience. CONCLUSION: E-learning can improve local academic training and promote the global visibility of strong academic centers. Providing free and unrestricted expertise via social media is a novel and groundbreaking opportunity that fills a global education gap by dissemination of surgical education on an unprecedented scale. Expert associations such as the ESA may adopt similar formats and foster their perception as true beacons of knowledge.

Checkpoint Inhibitor-Induced Colitis-A Clinical Overview of Incidence, Prognostic Implications and Extension of Current Treatment Options.

In recent years, anti-tumor immunotherapies have witnessed a major breakthrough with the emergence of immune checkpoint inhibitors (ICIs). However, the use of ICIs has also brought an era of a certain class of adverse events that differ from those of classical chemotherapies and are more reminiscent of autoimmune diseases. This article focuses exclusively on colitis as an irAE with emphasis on vulnerable patient groups, the prognostic significance of colitis, treatment, and new therapeutic approaches that may be applicable. Colitis itself is associated with a favorable oncological outcome of the underlying disease but is as well the most common irAE leading to discontinuation of therapy. Especially in vulnerable patient groups such as IBD patients and elderly patients, colitis occurs more frequently as a side effect. It is precisely in these two patient groups that side effects more often lead to discontinuation of therapy. Therefore, in addition to the current therapy of colitis through immunosuppression, the focus should also be on new forms of therapy of severe colitis, such as fecal transplantation or ileostomy creation.

Long-term immune-related adverse events after discontinuation of immunotherapy.

Immune checkpoint inhibitors have revolutionized the treatment of various cancers but are notorious for their potential to cause severe side effects. While most side effects occur during ongoing therapy, an increasing number of reports of late onset have emerged. It is also not yet clear how long side effects can last. Resolution is achieved under symptomatic therapy, but the side effects may persist latently. We present a patient case with recurrence of colitis after closure of an ileostomy over 1 year after discontinuation of immune checkpoint inhibitor therapy with nivolumab and ipilimumab. To the best of our knowledge, no other case with severe colitis still lasting after more than a year of suspension of therapy has yet been reported.

Lay abstract Checkpoint inhibitors have revolutionized therapy for suitable cancers. However, they can cause side effects that are reminiscent of autoimmune diseases. While most adverse effects occur during ongoing therapy, there are increasing reports of late-onset adverse effects after discontinuation of therapy and of long-lasting adverse effects after discontinuation of treatment, which may remain latent even if symptom relief could be achieved by immunosuppression. We present a patient case with reappearance of a severe inflammation of the large bowel (colitis) after closure of an ostomy over 1 year after withdrawal of immune checkpoint inhibitor therapy. To the best of our knowledge, no other case with severe colitis still lasting after more than a year of suspension of therapy has yet been reported.

Inequalities in access to minimally invasive general surgery: a comprehensive nationwide analysis across 20 years.

BACKGROUND: Minimally invasive surgery (MIS) has profoundly changed standards of care and lowered perioperative morbidity, but its temporal implementation and factors favoring MIS access remain elusive. We aimed to comprehensibly investigate MIS adoption across different surgical procedures over 20 years, identify predictors for MIS amenability and compare propensity score-matched outcomes among MIS and open surgery. METHODS: Nationwide retrospective analysis of all hospitalizations in Switzerland between 1998 and 2017. Appendectomies (n = 186,929), cholecystectomies (n = 57,788), oncological right (n = 9138) and left hemicolectomies (n = 21,580), rectal resections (n = 13,989) and gastrectomies for carcinoma (n = 6606) were included. Endpoints were assessment of temporal MIS implementation, identification of predictors for MIS access and comparison of propensity score-matched outcomes among MIS and open surgery. RESULTS: The rates of MIS increased for all procedures during the study period (p ≤ 0.001). While half of all appendectomies were performed laparoscopically by 2005, minimally invasive oncological colorectal resections reached 50% only by 2016. Multivariate analyses identified older age (p ≤ 0.02, except gastrectomy), higher comorbidities (p ≤ 0.001, except rectal resections), lack of private insurance (p ≤ 0.01) as well as rural residence (p ≤ 0.01) with impaired access to MIS. Rural residence correlated with low income regions (p ≤ 0.001), which themselves were associated with decreased MIS access. Geographical mapping confirmed strong disparities for rural and low-income areas in MIS access. Matched outcome analyses revealed benefits of MIS for length of stay, decreased surgical site infection rates for MIS appendectomies and cholecystectomies and higher mortality for open cholecystectomies. No consistent morbidity or mortality benefit for MIS compared to open colorectal resections was observed. CONCLUSION: Unequal access to MIS exists in disfavor of older and more comorbid patients and those lacking private insurance, living in rural areas, and having lower income. Efforts should be made to ensure equal MIS access regardless of socioeconomic or geographical factors.

Complete Recovery of Immune Checkpoint Inhibitor-induced Colitis by Diverting Loop Ileostomy.

Checkpoint inhibitor-induced side effects such as diarrhea and colitis occur in up to 30% of patients. We present a case of recurrent episodes of checkpoint inhibitor-induced colitis and subsequent Fournier gangrene that resolved after ileostomy formation. Once the Fournier gangrene and colitis had resolved, the ileostomy was reversed. However, within only 4 days, another serious flare-up of colitis occurred, necessitating emergent re-formation of the ileostomy. Expertise in the management of side effects of immune checkpoint inhibitor therapy is currently limited. Although most side effects are mild to moderate and transient, a minority of patients suffer from life-threatening complications, such as colitis. The creation of an ileostomy might be a valid treatment option in severe or recurrent colitis due to immune checkpoint inhibitor therapy. Intestinal diversion surgery may be useful if conservative treatment has failed, similar to other forms of immune-mediated intestinal inflammation.

Direct intraoperative assessment of total mesorectal excision specimens by expert pathologists in patients with very low rectal cancer prevents unnecessary abdominoperineal resections.

PURPOSE: In patients with low rectal cancer, the intraoperative assessment of sufficient distal resection margins can be challenging. The assessment determines whether reconstruction can be performed or whether permanent colostomy is required. The goal of the present study was to evaluate intraoperative assessment of the total mesorectal excision (TME) specimen during an interruption of the operation. METHODS: The intraoperative strategy of eight patients with low rectal cancer was evaluated. In all cases, intraoperative pathological assessment of the TME specimen by an expert pathologist together with the surgeon was performed. Assessment of the distance of the tumor to the resection margin was measured macroscopically as well as microscopically. RESULTS: All patients underwent neoadjuvant chemoradiation. The tumor was located at an average 4.8 ± 1.4 cm from the anal verge. In all cases, preoperative MRI revealed mrT3 tumors. The intraoperative assessment showed a median distal resection margin of 10 mm (2-15 mm). In six patients, sufficient margins allowed for reconstruction while in two patients APR was needed. In three patients (37.5%), the pathological assessment changed the operative strategy: In one patient APR could be avoided while two patients required APR instead of the anticipated TME. CONCLUSION: The intraoperative assessment of the TME specimen by an expert pathologist together with the surgeon is a valuable tool to avoid unnecessary APR or R1 resections. We therefore suggest routine intraoperative pathological assessment in all operations for borderline low rectal cancers.

Impact of adjuvant chemotherapy on patients with ypT0-2 ypN0 rectal cancer after neoadjuvant chemoradiation: a cohort study from a tertiary referral hospital.

BACKGROUND: To investigate the importance of adjuvant chemotherapy in locally advanced rectal cancer (≥ cT3 or N+) staged ypT0-2 ypN0 on final histological work-up after neoadjuvant chemoradiation and radical resection. METHODS: The clinical course of patients with rectal cancer and ypT0-2 ypN0 stages after neoadjuvant chemoradiation and radical resection was analyzed from 1999 to 2012. Patients were divided into two groups depending on whether adjuvant chemotherapy was administered or not. Overall survival, distant metastases, and local recurrence were compared between both groups. RESULTS: Fifty-four patients with adjuvant (ACT) and 50 patients without adjuvant chemotherapy (NACT) after neoadjuvant chemoradiation followed by radical resection for rectal cancer were included in the analysis. Mean follow-up was 68 ± 33.7 months. One patient without adjuvant chemotherapy and none in the ACT group developed a local recurrence. Five patients in the NACT group and three patients in the ACT group had distant recurrences. Median disease-free survival for all patients was 65.5 ± 34.5 months. Multivariate analysis showed adjuvant chemotherapy to be the most relevant factor for disease-free and overall survival. Patients staged ypT2 ypN0 showed a significantly better disease-free survival after application of adjuvant chemotherapy. Disease-free survival in ypT0-1 ypN0 patients showed no correlation to the administration of adjuvant chemotherapy. CONCLUSION: Administration of adjuvant chemotherapy after neoadjuvant chemoradiation and radical resection in rectal cancer improved disease-free and overall survival of patients with ypT0-2 ypN0 tumor stages in our study. In particular, ypT2 ypN0 patients seem to profit from adjuvant treatment.

Dynamics of Genome Alterations in Crohn's Disease-Associated Colorectal Carcinogenesis.

Purpose: Patients with inflammatory bowel diseases, that is, ulcerative colitis and Crohn's disease (CD), face an increased risk of developing colorectal cancer (CRC). Evidence, mainly from ulcerative colitis, suggests that TP53 mutations represent an initial step in the progression from inflamed colonic epithelium to CRC. However, the pathways involved in the evolution of CRC in patients with CD are poorly characterized.Experimental Design: Here, we analyzed 73 tissue samples from 28 patients with CD-CRC, including precursor lesions, by targeted next-generation sequencing of 563 cancer-related genes and array-based comparative genomic hybridization. The results were compared with 24 sporadic CRCs with similar histomorphology (i.e., mucinous adenocarcinomas), and to The Cancer Genome Atlas data (TCGA).Results: CD-CRCs showed somatic copy-number alterations (SCNAs) similar to sporadic CRCs with one notable exception: the gain of 5p was significantly more prevalent in CD-CRCs. CD-CRCs had a distinct mutation signature: TP53 (76% in CD-CRCs vs. 33% in sporadic mucinous CRCs), KRAS (24% vs. 50%), APC (17% vs. 75%), and SMAD3 (3% vs. 29%). TP53 mutations and SCNAs were early and frequent events in CD progression, while APC, KRAS, and SMAD2/4 mutations occurred later. In four patients with CD-CRC, at least one mutation and/or SCNAs were already present in non-dysplastic colonic mucosa, indicating occult tumor evolution.Conclusions: Molecular profiling of CD-CRCs and precursor lesions revealed an inflammation-associated landscape of genome alterations: 5p gains and TP53 mutations occurred early in tumor development. Detection of these aberrations in precursor lesions may help predicting disease progression and distinguishes CD-associated from sporadic colorectal neoplasia. Clin Cancer Res; 24(20); 4997-5011. ©2018 AACR.

Risk factors for early postoperative complications and length of hospital stay in ileocecal resection and right hemicolectomy for Crohn's disease: a single-center experience.

PURPOSE: To determine risk factors for early postoperative complications and longer hospital stay after ileocecal resection and right hemicolectomy in a single-center cohort of patients with Crohn's disease (CD). METHODS: A retrospective analysis of the prospectively maintained surgical database for patients with CD at our institution was performed. All consecutive patients operated on between January 2010 and December 2016 were included. RESULTS: A total of 305 patients were included. Median length of hospital stay was 7 days (interquartile range, IQR 6-10). Major postoperative complications were observed in 9.5% of patients (n = 29). Anastomotic leak was observed in five patients (1.8% of all patients with anastomosis). The rate of local septic complications was 4.3% (n = 13, anastomotic leak, postoperative abscess, and/or postoperative fistula). In multivariable analysis, independent risk factors for major postoperative complications were bowel perforation (odds ratio (OR) = 12.796, 95% CI = 1.144-143.178); elevated preoperative leucocyte levels (OR = 1.115, 95% CI = 1.013-1.228); and low levels of preoperative albumin (OR = 0.885, 95% CI = 0.827-0.948). The cutoff value for albumin was 32.5 g/L (sensitivity 75.9%, specificity 62.6%). CONCLUSIONS: In this large cohort of patients surgically treated for CD in a tertiary referral center, 9.5% of the patients developed major postoperative complications. Preoperative albumin levels > 32.5 g/L significantly reduce the risk for postoperative complications and shorten the length of hospital stay. In a multidisciplinary concept with adequate preoperative management, surgery can be performed with a low rate of major complications and a very low rate of anastomotic leakage.

Clinical and Histopathologic Features of Colorectal Adenocarcinoma in Crohn's Disease.

GOALS: The aim of this study was to assess the histopathologic characteristics of colorectal carcinomas (CRC) in patients with Crohn's disease (CD). BACKGROUND: A higher frequency of microsatellite instability (MSI) is seen in mucinous compared with nonmucinous CRC which suggests that its pathogenesis involves distinct molecular pathways. Several publications reported a higher percentage of mucinous adenocarcinoma in CD patients with CRC. So far, there has been no investigation of MSI in CD patients with mucinous CRC. STUDY: The medical records of patients who underwent surgery for CRC were reviewed and those with a history of CD identified. The data of histologic classification and MSI status of the tumor were investigated. RESULTS: Fourteen patients with CD-associated CRC were identified (5 female, 9 male) resulting in 20 CRC in total. Histologic investigation revealed 7 adenocarcinomas without a mucinous or signet ring cell component. All other CRCs harbored a mucinous (n=11) and/or signet ring cell (n=6) component. All tumors assessed for MSI were found to be microsatellite stable. CONCLUSIONS: Our data indicate that CRCs with signet ring cell and mucinous components were much more common in patients with CD than in patients with sporadic CRC. This observation suggests that CRC in CD represent an own entity with distinct histopathologic and molecular features. This may implicate potential consequences for diagnosis and therapy of CRC in CD in the future as well as new factors to identify patients with an increased risk for developing CRC in CD.

Amplicon sequencing of colorectal cancer: variant calling in frozen and formalin-fixed samples.

Next generation sequencing (NGS) is an emerging technology becoming relevant for genotyping of clinical samples. Here, we assessed the stability of amplicon sequencing from formalin-fixed paraffin-embedded (FFPE) and paired frozen samples from colorectal cancer metastases with different analysis pipelines. 212 amplicon regions in 48 cancer related genes were sequenced with Illumina MiSeq using DNA isolated from resection specimens from 17 patients with colorectal cancer liver metastases. From ten of these patients, paired fresh frozen and routinely processed FFPE tissue was available for comparative study. Sample quality of FFPE tissues was determined by the amount of amplifiable DNA using qPCR, sequencing libraries were evaluated using Bioanalyzer. Three bioinformatic pipelines were compared for analysis of amplicon sequencing data. Selected hot spot mutations were reviewed using Sanger sequencing. In the sequenced samples from 16 patients, 29 non-synonymous coding mutations were identified in eleven genes. Most frequent were mutations in TP53 (10), APC (7), PIK3CA (3) and KRAS (2). A high concordance of FFPE and paired frozen tissue samples was observed in ten matched samples, revealing 21 identical mutation calls and only two mutations differing. Comparison of these results with two other commonly used variant calling tools, however, showed high discrepancies. Hence, amplicon sequencing can potentially be used to identify hot spot mutations in colorectal cancer metastases in frozen and FFPE tissue. However, remarkable differences exist among results of different variant calling tools, which are not only related to DNA sample quality. Our study highlights the need for standardization and benchmarking of variant calling pipelines, which will be required for translational and clinical applications.

Abdominopelvic actinomycosis in three different locations with invasion of the abdominal wall and ureteric obstruction: An uncommon presentation.

INTRODUCTION: Actinomycosis is a rare chronic infectious disease caused by Gram-positive anaerobic bacteria that normally colonize the bronchial system and gastrointestinal tract in humans. The most common diseases associated with actinomycosis are orocervicofacial, thoracic and abdominal infections involving Actinomyces israelii. Due to its rarity, its various clinical presentations and often-infiltrative characteristics in radiological imaging, it can easily be mistaken for other clinical conditions, including malignancy. PRESENTATION OF CASE: We present an uncommon case of extended abdominopelvic actinomycosis with infiltrative lesions in multiple locations, including an abscess in the abdominal wall and ureteric obstruction, which underwent successful surgical and subsequent long-term antibiotic therapy. DISCUSSION: To our knowledge, such a combination of different sites of manifestation has not yet been reported for actinomycosis in the presence of an IUD. Possible differential diagnoses included diverticulitis with covered perforation, pelvic inflammatory disease, tuberculosis and inflammatory bowel disease. The possibility of a malignant process required radical resection. As in most cases of actinomycosis, diagnosis could not be established with certainty until postoperative pathology investigation. CONCLUSION: A rare actinomyceal infection should be considered in patients with a non-specific pelvic mass and atypical abdominal presentations, especially if a previous history of IUD usage is known.

False teeth in an apple core: Unusual presentation of a colorectal carcinoma.

INTRODUCTION: Ingestion of foreign bodies is common amongst the elderly. Although most foreign bodies pass through the gastrointestinal tract without consequence some cause complications including bowel perforation. PRESENTATION OF CASE: We present a case of denture ingestion that lead to the diagnosis of an unsuspected colorectal cancer. The patient underwent radical surgery to remove the tumor and the ingested denture. The operation and recovery were uneventful. DISCUSSION: Complications from ingested foreign bodies mostly occur at points of anatomical intestinal tapering. However, tumors of the gastro-intestinal tract can also lead to obstructions and other complications. As the incidence of tumors increases with age, this possibility should be considered in the differential diagnosis of unusual situation. CONCLUSION: Although impaction of a foreign body in a gastro-intestinal tumor is very rare, our case suggests close follow-up is prudent in the elderly should a foreign body be ingested.