Long-term oncological outcomes of endoscopic full-thickness resection after previous incomplete resection of low-risk T1 CRC (LOCAL-study): study protocol of a national prospective cohort study.

BACKGROUND: T1 colorectal cancer (CRC) without histological high-risk factors for lymph node metastasis (LNM) can potentially be cured by endoscopic resection, which is associated with significantly lower morbidity, mortality and costs compared to radical surgery. An important prerequisite for endoscopic resection as definite treatment is the histological confirmation of tumour-free resection margins. Incomplete resection with involved (R1) or indeterminate (Rx) margins is considered a strong risk factor for residual disease and local recurrence. Therefore, international guidelines recommend additional surgery in case of R1/Rx resection, even in absence of high-risk factors for LNM. Endoscopic full-thickness resection (eFTR) is a relatively new technique that allows transmural resection of colorectal lesions. Local scar excision after prior R1/Rx resection of low-risk T1 CRC could offer an attractive minimal invasive strategy to achieve confirmation about radicality of the previous resection or a second attempt for radical resection of residual luminal cancer. However, oncologic safety has not been established and long-term data are lacking. Besides, surveillance varies widely and requires standardization. METHODS/DESIGN: In this nationwide, multicenter, prospective cohort study we aim to assess feasibility and oncological safety of completion eFTR following incomplete resection of low-risk T1 CRC. The primary endpoint is to assess the 2 and 5 year luminal local tumor recurrence rate. Secondary study endpoints are to assess feasibility, percentage of curative eFTR-resections, presence of scar tissue and/or complete scar excision at histopathology, safety of eFTR compared to surgery, 2 and 5 year nodal and/or distant tumor recurrence rate and 5-year disease-specific and overall-survival rate. DISCUSSION: Since the implementation of CRC screening programs, the diagnostic rate of T1 CRC is steadily increasing. A significant proportion is not recognized as cancer before endoscopic resection and is therefore resected through conventional techniques primarily reserved for benign polyps. As such, precise histological assessment is often hampered due to cauterization and fragmentation and frequently leads to treatment dilemmas. This first prospective trial will potentially demonstrate the effectiveness and oncological safety of completion eFTR for patients who have undergone a previous incomplete T1 CRC resection. Hereby, substantial surgical overtreatment may be avoided, leading to treatment optimization and organ preservation. Trial registration Nederlands Trial Register, NL 7879, 16 July 2019 ( https://trialregister.nl/trial/7879 ).

Low Incidence of Advanced Neoplasia in Serrated Polyposis Syndrome After (Sub)total Colectomy: Results of a 5-Year International Prospective Cohort Study.

INTRODUCTION: Serrated polyposis syndrome (SPS) is accompanied by a substantially increased colorectal cancer (CRC) risk. To prevent or treat CRC in patients with a very high polyp burden, (sub)total colectomy with ileorectal or ileosigmoidal anastomosis is regularly performed. The CRC risk after (sub)total colectomy might be decreased, but evidence is lacking. We aimed to assess the yield of endoscopic surveillance in patients with SPS who underwent (sub)total colectomy. METHODS: For this post hoc analysis, we used prospectively collected data from a large international prospective cohort study. We included patients diagnosed with SPS (World Health Organization type I and/or III) who underwent (sub)total colectomy. Primary endpoint was the cumulative 5-year incidence of CRC and advanced neoplasia (AN). RESULTS: Forty-eight patients (mean age 61 [±7.8]; 52% men) were included and followed up for a median of 4.7 years (interquartile range 4.7-5.1). None of the patients developed CRC during follow-up. Five patients developed AN, corresponding to a cumulative 5-year AN incidence of 13% (95% confidence interval 1.2-23). In 4 patients, AN was diagnosed at the first surveillance endoscopy after study inclusion, and in 1 patient, AN was detected during subsequent rounds of surveillance. The risk of AN was similar for patients with ileorectal and ileosigmoidal anastomosis (logrank P = 0.83). DISCUSSION: (Sub)total colectomy mitigates much of the excess risk of CRC in patients with SPS. Advanced neoplasms are mainly detected at the first endoscopy after (sub)total colectomy. Based on these results, after the first surveillance, intervals might be extended beyond the currently recommended 1-2 years.

Clinical risk factors of colorectal cancer in patients with serrated polyposis syndrome: a multicentre cohort analysis.

OBJECTIVE: Serrated polyposis syndrome (SPS) is accompanied by an increased risk of colorectal cancer (CRC). Patients fulfilling the clinical criteria, as defined by the WHO, have a wide variation in CRC risk. We aimed to assess risk factors for CRC in a large cohort of patients with SPS and to evaluate the risk of CRC during surveillance. DESIGN: In this retrospective cohort analysis, all patients with SPS from seven centres in the Netherlands and two in the UK were enrolled. WHO criteria were used to diagnose SPS. Patients who only fulfilled WHO criterion-2, with IBD and/or a known hereditary CRC syndrome were excluded. RESULTS: In total, 434 patients with SPS were included for analysis; 127 (29.3%) were diagnosed with CRC. In a per-patient analysis ≥1 serrated polyp (SP) with dysplasia (OR 2.07; 95% CI 1.28 to 3.33), ≥1 advanced adenoma (OR 2.30; 95% CI 1.47 to 3.67) and the fulfilment of both WHO criteria 1 and 3 (OR 1.60; 95% CI 1.04 to 2.51) were associated with CRC, while a history of smoking was inversely associated with CRC (OR 0.36; 95% CI 0.23 to 0.56). Overall, 260 patients underwent surveillance after clearing of all relevant lesions, during which two patients were diagnosed with CRC, corresponding to 1.9 events/1000 person-years surveillance (95% CI 0.3 to 6.4). CONCLUSION: The presence of SPs containing dysplasia, advanced adenomas and/or combined WHO criteria 1 and 3 phenotype is associated with CRC in patients with SPS. Patients with a history of smoking show a lower risk of CRC, possibly due to a different pathogenesis of disease. The risk of developing CRC during surveillance is lower than previously reported in literature, which may reflect a more mature multicentre cohort with less selection bias.

A squamous cell carcinoma in a young woman with Lynch syndrome.

Lynch syndrome (LS) is an autosomal-dominant inherited disorder characterized by a predisposition to colorectal cancer and extracolonic cancers (particularly endometrium, ovary, stomach, small bowel, hepatobiliary tract, pancreas, urothelial tract, brain, and skin). Muir-Torre syndrome (MTS) is considered a phenotypical variant of LS, where patients develop sebaceous neoplasms and keratoacanthomas. Currently, only few studies and case reports suggest an association between LS and other skin cancers, such as Bowens' disease, melanoma and squamous cell carcinoma (SCC). In this case-report we describe the case of a 33-year-old woman with LS and a proven MSH2 germline mutation, presenting with a SCC on the right cheek. Immunohistochemistry lacked MSH2 and MSH6 protein staining. The tumor showed a discordance between immunohistochemistry and micro-satellite instability status, for which a clear explanation cannot be provided yet. To conclude whether this pattern is indicative for SCC occurring in LS patients, further analyses of other LS patients presenting with SCC should be carried out. Our patient's young age and skin type (Fitzpatrick phototype VI) suggest a possible link between LS and cutaneous SCC.

Troponin T in the first 24 hours after the administration of chemotherapy and the detection of myocardial damage in children.

Early detection of damage to cardiac myocytes after cardiotoxic chemotherapy in paediatric patients may allow timely preventive measures to be taken. We investigated the diagnostic value of cardiac troponin T (cTnT) after the administration of cardiotoxic chemotherapy. In 38 children, cTnT levels were measured at three time points during the first 24 h after 58 cardiotoxic chemotherapy cycles (163 samples). An abnormal cTnT level, defined as a cTnT>0.010 ng/ml, was measured in only six samples from 3 patients. After completion of chemotherapy, 7 out of the 38 patients had left ventricular dysfunction (LV dysfunction). Only 1 of these 7 patients had an elevated cTnT level. 2 other patients with elevated cTnT levels did not develop LV dysfunction until 2 and 7 months after the cTnT measurement. Our data show that the measurement of cTnT within 24 h after administration of chemotherapy does not have a high sensitivity for the identification of patients with subsequent subclinical cardiotoxicity.

Catastrophic antiphospholipid syndrome mimicking a malignant pancreatic tumour--a case report.

The catastrophic antiphospholipid syndrome is characterised by rapid onset thromboses, often resistant to conventional anticoagulant treatment, and resulting in life threatening multiple organ dysfunction. The diagnosis of catastrophic antiphospholipid syndrome may be difficult, predominantly due to its frequently atypical presentation. We report a case of a 35-year-old female who presented with a pancreatic tumour and extensive thromboses. Following a storm of ischemic events due to thrombotic occlusions in spite of therapeutic heparin dose, the suspicion of catastrophic antiphospholipid syndrome emerged. The patient was successfully treated with anticoagulants, immunoglobulins, plasmapheresis and rituximab. The present report shows that the use of the diluted Russell's viper venom time can be helpful in providing additional information on the lupus anticoagulants antibody status, allowing careful monitoring of lupus anticoagulants conversion and hence response to therapy.