ABSTRACT
Background: Gynecological cancers of the uterus and cervix are common malignancies in women. The correct management of these tumors involves many figures. Material and methods: Therefore, to respond to these multidisciplinary needs in June 2019 in Azienda Ospedialiero-Universitaria of Modena was born a Diagnostic and Therapeutic Care Pathways (DTCP) with gynaecologists, radiotherapists, medical oncologists, radiologists, nuclear medical doctors, pathologists, anaesthesiologists, a nurse Case Manager and a patients' association representative. A molecular biologist, endocrinologists and nutritionists have already enriched the team after the first year of activity. The group performs weekly collegial discussions of clinical cases and cohort visits, continued in the COVID era. Results: The new diagnoses in the first year of activity were 53 endometrial cancers (EC) and 24 cervical ones (CC). The median age at diagnosis was 51 years between EC patients and 70 years in CC. 87% of EC were endometrioid subtypes, while 65% CC were squamous cell ones. 70% EC patients (pts) were stage (st) I (52% IA and 48% IB), 5,5% st II, 9,4% st III and 11,3% st IV. Immunohistochemical analysis for estrogen and progesterone receptor, p53 and mismatch repair (MMR) proteins were performed on 20 EC. All tumours tested are p53 negative. We found 3 pts who had MMR deficiency, none of them diagnosed with Lynch syndrome at the subsequent genetic counselling. After surgery, 66% pts in st I underwent observation and 34% made radiotherapy (RT). Among st II pts, 1 patient performed RT, one other platinum- based chemotherapy (pCT) and the third did not perform any adjuvant treatment for ECOG. All except one st III pts (67%) underwent pCT with RT. Among st IV one received surgery, pCT and palliative RT, the others (83%) made pCT. Most CC were diagnosed in early st. 9 pts underwent upfront surgery, followed in 2 cases with RT and in 3 with RT and pCT. One patient received neoadjuvant chemo-RT. Radical RT with weekly cisplatin was performed in 9 pts, other 4 pts made RT alone due to advanced age and/or ECOG. One patient started observation for age, ECOG and absence of symptoms. Conclusions: In our experience, DTCP allows the optimization of the diagnostic and therapeutic strategy in EC and CC pts, especially in most complex cases.
ABSTRACT
BACKGROUND: Several independent risk factors have been reported to influence viral shedding following COVID-19 infection, but the influence of host-related molecular factors has not yet been described. We report a case of a cancer patient with Lynch syndrome (hereditary nonpolyposis colorectal cancer, HNPCC) who manifested SARS-CoV-2 PCR (polymerase chain reaction) positivity for at least 54 days after contracting mild COVID-19 illness. We propose that deficient mismatch repair (MMR) may play a role in the prolonged SARS-CoV-2 RNA shedding. CASE PRESENTATION: A patient with Lynch syndrome was under surveillance for metastatic adenocarcinoma after completing palliative chemotherapy in October 2019. Between the period of April 2020 to June 2020, he was admitted multiple times to address several clinical needs mainly related to his underlying malignancy. These included progressive disease observed in the aortocaval lymph nodes leading to recurrent episodes of upper gastrointestinal bleeding, dehydration resulting in acute kidney injury and a short-lived episode of pyrexia. A SARS-CoV-2 PCR of the nasopharyngeal swab (NPS) was positive at his initial admission with mild COVID-19 symptoms. He remained positive on subsequent admissions when tested routinely for SARS-CoV-2 without demonstrating any apparent clinical features of COVID-19 infection. The MMR pathway, a component of DNA damage response (DDR), is impaired in Lynch syndrome due to an inherited genetic mutation. This pathway is also required for viral clearance from the host cells following certain RNA viral infections like influenza virus and other coronaviridae. Here we provide a current understanding of the importance of DDR deficiencies in the clearance of RNA virus and suggest how this may play a similar role in the clearance of COVID-19, as evident in our case that demonstrated persistent positivity. CONCLUSION: The importance of understanding the scientific basis of extended viral shedding during the COVID-19 pandemic is now centre-stage in the establishment of robust track and trace services to allow the recovery and function of societies and economies. This patient with Lynch syndrome recovered from infection but had prolonged viral positivity, which might merit further investigation to better understand the effect of this condition on infection duration and outcome.