Mutational signature analysis identifies MUTYH deficiency in colorectal cancers and adrenocortical carcinomas.

Germline alterations in DNA repair genes are implicated in cancer predisposition and can result in characteristic mutational signatures. However, specific mutational signatures associated with base excision repair (BER) defects remain to be characterized. Here, by analysing a series of colorectal cancers (CRCs) using exome sequencing, we identified a particular spectrum of somatic mutations characterized by an enrichment of C > A transversions in NpCpA or NpCpT contexts in three tumours from a MUTYH-associated polyposis (MAP) patient and in two cases harbouring pathogenic germline MUTYH mutations. In two series of adrenocortical carcinomas (ACCs), we identified four tumours with a similar signature also presenting germline MUTYH mutations. Taken together, these findings demonstrate that MUTYH inactivation results in a particular mutational signature, which may serve as a useful marker of BER-related genomic instability in new cancer types. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

The Damage Pattern to the Gastrointestinal Tract Depends on the Nature of the Ingested Caustic Agent.

BACKGROUND: The mechanisms of damage to the gastrointestinal tract after caustic ingestion are conditioned by the nature of the ingested agent. Whether the nature of the ingested agent has a direct influence on patient outcomes is unknown. METHODS: From January 2013 to April 2015, 144 patients underwent emergency management for caustic injuries at the Saint Louis Hospital in Paris. There were 51 men (51 %) and the median age was 44 years [39, 48]. The ingested agents were soda-based strong alkali in 85 patients (59 %), strong acids in 36 patients (25 %), and bleach in 23 patients (16 %). Emergency and long-term outcomes were compared according to the nature of the ingested agent. RESULTS: Four patients died (3 %) and 40 patients (28 %) experienced complications. After bleach ingestion, emergency morbidity and mortality were nil, no patient required esophageal reconstruction, and functional outcome was successful in all patients. Acids were more likely to induce transmural gastric (31 vs. 13 %, p =0.042) and duodenal (9 vs. 0 %, p = 0.04) necrosis than strong alkalis, but rates of transmural esophageal necrosis were similar (14 vs. 12 %, p = 0.98). No significant differences were recorded between emergency mortality (9 vs. 1 %, p = 0.15), morbidity (33 vs. 33 %, p = 0.92), the need for esophageal reconstruction (25 vs. 20 %, p = 0.88), and functional success rates (76 vs. 84 %, p = 0.31) after acid and alkali ingestion, respectively. CONCLUSION: Bleach causes mild gastrointestinal injuries, while the ingestion of strong acids and alkalis may result in severe complications and death. Acids cause more severe damage to the stomach but similar damage to the esophagus when compared to alkalis.

Prophylactic lymph node dissection in papillary thyroid carcinoma: is there a place for lateral neck dissection?

BACKGROUND: Cervical lymph node (LN) metastases are common in patients with papillary thyroid carcinoma (PTC), and they have a negative impact on recurrence. The management of preoperatively node-negative (N0) PTC is still controversial. The aim of our study was to describe the results of a prophylactic bilateral lymph node dissection (LND) and to investigate its impact on recurrence. METHODS: From 2003 to 2011, we analyzed 603 consecutive preoperatively N0 PTC patients. For each patient, we reviewed demographics data, tumor characteristics, pattern and risk factors of LN metastasis, and outcome. RESULTS: Lymph node metastases were found in 23 % of patients: 19 % in the central compartment and 8 % in the lateral compartment, including 1 % in the lateral compartment on the opposite side from the tumor. Multivariate analysis showed that hyperthyroidism and extrathyroidal invasion of the tumor were significantly associated with LN metastasis. Further analysis showed that localization of the tumor in the upper third of the thyroid lobe and metastatic LN in the central compartment were independent risk factors for lateral LN metastasis. During the 4.3-year follow-up, 23 recurrences were observed (4 %), including 5 in the central compartment. Recurrence rates were 2 % in the N0 group, 5 % in N1a patients, and 22 % in N1b patients (p < 0.001). CONCLUSIONS: In preoperatively N0 PTC patients, LN metastases are frequent in central and ipsilateral lateral compartments. Prophylactic LND in the central and ipsilateral lateral compartments should therefore be recommended in the presence of PTC to identify high-risk patients.