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Background: The treatment of advanced cutaneous head and neck cutaneous squamous cell carcinomas (HNcSCC) results in significant morbidity. Recently, immune checkpoint inhibitor treatment has been approved for DNA mismatch repair (MMR) deficient patients in a histology-agnostic manner. This study aims to evaluate the incidence of MMR deficiency in advanced HNcSCC and its association with clinicopathologic factors., Methods: The cohort included 176 consecutive HNcSCC cases treated with curative intent. Immunohistochemistry for MMR proteins (hMLH1, hMSH2, hMSH6, and hPMS2) was performed. Clinicopathological and survival data was collected prospectively., Results: The incidence of MMR protein deficiency was 9.1%. There was no association between age, incidence of metachronous malignancies, clinicopathological factors, or survival outcomes., Conclusion: A higher incidence of MMR deficiency was observed in this cohort of advanced HNcSCC. The lack of association with young age at onset or increased incidence of metachronous malignancies suggests that MMR deficiency is likely to be sporadic in HNcSCC., (© 2020 Wiley Periodicals LLC.)

An unexplained increase in the incidence of oral cavity squamous cell carcinoma (oSCC) has been observed despite decreasing smoking rates, particularly in younger patients. Links to defects in the DNA mismatch repair (MMR) system are well established in early onset colorectal, urothelial and gynaecological malignancies. MMR deficient patients treated with immune checkpoint inhibitors have demonstrated improved response rates. Studies exploring MMR status in head and neck squamous cell carcinoma (HNSCC) demonstrate conflicting results. This study explores the incidence of MMR protein loss and its association with clinicopathological features and outcome in oSCC. Immunohistochemical staining using tissue microarrays to assess the expression of MMR proteins (hMLH1, hMSH2, hMSH6, and hPMS2) was performed on 285 consecutive oSCC cases between 2000 and 2016. Data on smoking, alcohol and metachronous malignancies were retrospectively collected. Proportional hazards regression models were used to compare survival in MMR intact and deficient patients. MMR deficiency was seen in 21 patients (7.4%). MMR deficient tumours were associated with bone invasion (52% vs 32%, p=0.05), higher pT stage (pT4 in 57% vs 35%, p<0.001) and a higher number of metachronous malignancies (p=0.05). MMR deficiency was not associated with younger age at presentation or absence of smoking or alcohol. There was no significant association between MMR status and survival (overall survival hazard ratio 1.36; p=0.32). The incidence of MMR loss in oSCC is low and is not associated with young age at presentation. MMR deficiency in oSCC is associated with an increase in the number of metachronous malignancies and more advanced primary tumours., (Copyright © 2019 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)

Background: Chemotherapy has in some series been linked with increased morbidity after a hepatectomy. Hepatic injuries may result from the treatment with chemotherapy, but can also be secondary to co-morbid diseases. The aim of the present study was to draw correlations between clinical features, treatment with chemotherapy and injury phenotypes and assess the impact of each upon perioperative morbidity., Patients and Methods: Retrospective samples (n= 232) were scored grading steatosis, steatohepatitis and sinusoidal injury (SI). Clinical data were retrieved from medical records. Correlations were drawn between injury, clinical features and perioperative morbidity., Results: Injury rates were 18%, 4% and 19% for steatosis, steatohepatitis and SI, respectively. High-grade steatosis was more common in patients with diabetes [odds ratio (OR) = 3.33, P= 0.01] and patients with a higher weight (OR/kg = 1.04, P= 0.02). Steatohepatitis was increased with metabolic syndrome (OR = 5.88, P= 0.02). Chemotherapy overall demonstrated a trend towards an approximately doubled risk of high-grade steatosis and steatohepatitis although not affecting SI. However, pre-operative chemotherapy was associated with an increased SI (OR = 2.18, P= 0.05). Operative morbidity was not increased with chemotherapy, but was increased with steatosis (OR = 2.38, P= 0.02)., Conclusions: Diabetes and higher weight significantly increased the risk of steatosis, whereas metabolic syndrome significantly increased risk of steatohepatitis. The presence of high-grade steatosis increases perioperative morbidity, not administration of chemotherapy per se., (© 2012 International Hepato-Pancreato-Biliary Association.)