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Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis, with a 5-year survival rate of ≤7% across all stages. Most patients are diagnosed with advanced disease and median overall survival is limited. The limited success of conventional therapies for PDAC is at least partially attributable to its genetic heterogeneity. Extensive genomic efforts have been made to subtype PDAC. The DNA damage repair (DDR) deficiency subtype, also known as unstable genome/DSBR (DNA double-strand break repair) subtype, is one of the most clinically relevant biologic abnormalities in PDAC. Increased PDAC risk was found to be associated with inherited syndromes, which are present in approximately 10% of patients with PDAC. Recent updates to the ASCO and NCCN guidelines recommend risk assessment for all individuals with PDAC, irrespective of personal or family history or ethnicity. Germline BRCA mutations associated with DNA repair dysfunction is one of the best illustrations of actionable biologic subtypes in PDAC. This genetic alteration can indeed be targeted by PARP inhibitors (PARPi). Treatment implications for germline BRCA carriers with PDAC include the use of platinum-based therapy and the validation of PARPi administration as a maintenance strategy in platinum-sensitive patients. In the era of precision medicine, this is the first convincing example of targeting identified germline hereditary mutations in PDAC.Because of the biologic aggressiveness and late presentation of pancreatic ductal adenocarcinoma (PDAC), up to 80% of patients have locally advanced or metastatic disease at presentation. The success of multiagent chemotherapy regimens in the management of metastatic disease has been translated to patients with locally advanced PDAC. Both FOLFIRINOX (fluorouracil/folinic acid/irinotecan/oxaliplatin) and gemcitabine/nab-paclitaxel are used to downstage locally advanced PDAC to render it eligible for resection with curative intent. This paradigm shift has significantly expanded the pool of patients who are eligible for resection with curative intent. However, the generalizability of present studies and the patient selection process are unclear. This article provides an evidence-based review of patient selection considerations and management algorithms, and details our institution's approach to patients with locally advanced PDAC after preoperative chemotherapy.The 21st Century Cures Act (Cures Act), signed into law in 2016, was designed to advance new therapies by modernizing clinical trials, funding research initiatives, and accelerating the development and use of health information technology. To analyze the current issues in cancer care related to the implementation and impact of the Cures Act, NCCN convened a multistakeholder working group. Participants discussed the legislation's impact on the oncology community since enactment and identified the remaining gaps and challenges as experienced by stakeholders. In June 2020, the policy recommendations of the working group were presented at the virtual NCCN Policy Summit Accelerating Advances in Cancer Care Research A Lookback at the 21st Century Cures Act in 2020. The summit consisted of informative discussions and a multistakeholder panel to explore the recommendations and the future of the Cures Act. This article explores identified policy recommendations from the NCCN Working Group and the NCCN Policy Summit, and analyzes opportunities to advance innovative cancer care and patient access to data.
Adrenocortical carcinoma (ACC) is a malignant disorder with rapid evolution and severe prognosis in adults and most produce cortisol and androgen. Estrogen-secreting adrenocortical carcinomas are extremely rare, especially in women, tend to be larger and have worse prognosis compared with other types of ACCs. We report the case of a 58-year-old woman who presented with bilateral breast enlargement and postmenopausal genital bleeding. She presented high estradiol (818 pg/mL - 25 times above upper normal limit for postmenopausal women) and testosterone (158 ng/dL - 2 times above upper normal limit) levels and no suppression of cortisol after overnight 1 mg dexamethasone test (12.5 µg/dL; normal reference value < 1.8 µg/dL). The patient had no clinical features of cortisol excess. MRI showed a 12 cm tumor in the right adrenal. Clinical findings of bilateral breast enlargement and postmenopausal genital bleeding with no signs of hypercortisolism associated with hormonal findings of elevated estradiol and tesd with worse prognosis compared with nonfeminizing ACCs.
Estrogen-secreting adrenocortical carcinomas are exceedingly rare in adults and account for 1-2% of adrenocortical carcinomas. Estrogen-secreting adrenal tumors can be present in females, but are even more rare, we found few cases described in the literature. In women, they present with precocious puberty or postmenopausal bleeding. Feminization in the context of an adrenal tumor is considered almost pathognomonic of malignancy. Feminizing ACCs tend to be larger and with worse prognosis compared with nonfeminizing ACCs.
A 26-year-old Caucasian female with no past medical history or family history of auto-immune disease presented to the emergency department with new onset painless left foot drop. A panel of blood tests revealed blood glucose of 49.9 mmol/L and raised blood ketone levels. The patient was referred to the diabetes team who made a clinical diagnosis of type 1 diabetes (T1DM) and insulin treatment was initiated. MYF-01-37 in vivo Elevated levels of diabetes auto-antibodies were subsequently detected. Nerve conduction studies demonstrated a left common peroneal nerve lesion with conduction block at the fibular head. After 2 weeks of insulin treatment, a significant improvement of her foot drop was observed and after 8 weeks she was walking normally. The most probable cause of her foot drop was acute diabetic mononeuropathy. To our knowledge, there are no similar cases in adult patients reported in the literature. Our case highlights the importance of physicians being aware of atypical presentation of new onset T1DM.
There is an increasing incidence of T1DM with more than half of patients presenting after the age of 20. Diabetic peripheral neuropathy can present both acutely and as a mononeuropathy. Although rare, clinicians should be aware of mononeuropathy as a presenting symptom of T1DM to avoid delay in the treatment initiation. This case highlights an unusual presentation of T1DM and illustrates the importance of the early diagnosis and management of T1DM.
There is an increasing incidence of T1DM with more than half of patients presenting after the age of 20. Diabetic peripheral neuropathy can present both acutely and as a mononeuropathy. Although rare, clinicians should be aware of mononeuropathy as a presenting symptom of T1DM to avoid delay in the treatment initiation. This case highlights an unusual presentation of T1DM and illustrates the importance of the early diagnosis and management of T1DM.