Pancreatic ductal adenocarcinoma (PDAC) is highly resistant to chemotherapy. It has been described as requiring elevated autophagy for growth and inhibiting autophagy has been proposed as a treatment strategy. To date, all preclinical reports and clinical trials investigating pharmacological inhibition of autophagy have used chloroquine or hydroxychloroquine, which interfere with lysosomal function and block autophagy at a late stage. Verteporfin is a newly discovered autophagy inhibitor that blocks autophagy at an early stage by inhibiting autophagosome formation. Here we report that PDAC cell lines show variable sensitivity to verteporfin in vitro, suggesting cell-line specific autophagy dependence. Using image-based and molecular analyses, we show that verteporfin inhibits autophagy stimulated by gemcitabine, the current standard treatment for PDAC. Pharmacokinetic and efficacy studies in a BxPC-3 xenograft mouse model demonstrated that verteporfin accumulated in tumors at autophagy-inhibiting levels and inhibited autophagy in vivo, but did not reduce tumor volume or increase survival as a single agent. In combination with gemcitabine verteporfin moderately reduced tumor growth and enhanced survival compared to gemcitabine alone. While our results do not uphold the premise that autophagy inhibition might be widely effective against PDAC as a single-modality treatment, they do support autophagy inhibition as an approach to sensitize PDAC to gemcitabine.

Salivary duct carcinoma is an aggressive malignancy with a high mortality rate, which phenotypically resembles high-grade breast ductal carcinoma. The parotid gland is the most common location. Standard treatment is surgery to the primary tumour together with post-operative radiotherapy. Despite this, there is a high rate of local recurrence, cervical nodal involvement and distant metastasis. Chemotherapy is currently considered only for end-stage, disseminated disease; however, current evidence indicates that chemotherapy used with radiotherapy may result in improved disease control and survival.Human epidermal growth factor receptor-2 is a proto-oncogene which is over-expressed in both breast ductal carcinoma and salivary duct carcinoma. Clinical studies of patients with metastatic breast cancer, using trastuzumab, a monoclonal antibody directed against human epidermal growth factor receptor-2, have shown significant efficacy in tumour response, resulting in improved survival. Such advances in immunohistochemistry, and in targeted immunotherapy for breast ductal carcinoma, should be applied to the treatment of salivary duct carcinoma.

There are diverse ways in which the skin is affected by chronic kidney disease (CKD). Various specific and nonspecific skin abnormalities are observed in patients with CKD. The aim of the study was to document the prevalence of skin diseases that commonly occur in patients with CKD on medical treatment and dialysis. A total of 99 patients with CKD were examined for evidence of skin diseases. Ninety-six had at least one cutaneous abnormality attributable to CKD. The most prevalent finding was xerosis (66.7%), followed by pallor (45.45%), pruritus (43.4%), and cutaneous pigmentation (32.3%). Other cutaneous manifestations included dermatitis (27.27%); Kyrle's disease (17.17%); fungal (8.08%), bacterial (11.1%), and viral (5.05%) infections; purpura (10.1%); gynecomastia (4.04%); and yellow skin (5.05%). The common nail changes were half and half nails (36.36%) and onycholysis (13.13%). CKD is associated with various cutaneous abnormalities caused either by the disease or by treatment, the most common being xerosis and pruritus. The dermatologic complications can significantly impair the quality of life in certain individuals; therefore, earlier diagnosis and treatment is important to improve their quality of life.

IDR-1018 suppresses proinflammatory mediators and cell injurious mechanisms in the developing brain, and postinsult treatment is efficacious in reducing LPS-induced hypoxic-ischemic brain damage. IDR-1018 is effective in the brain when given systemically, confers neuroprotection of both gray and white matter, and lacks significant effects on the brain under normal conditions. Thus, this peptide provides the features of a promising neuroprotective agent in newborns with brain injury.

SUMMARYWe report a case of nodular fasciitis of the breast in a 48-year-old woman who presented with a tender rapidly growing right breast lump. Ultrasound guided fine needle aspiration (FNA) of the solid mass was performed. Cytology was reported as atypical spindle cell neoplasm and the patient was referred to a breast surgeon at a tertiary institution for a definitive diagnosis and further management. Follow-up ultrasound showed partial regression and MRI, mammogram after 2-3 weeks confirmed spontaneous and total resolution of the lesion. Nodular fasciitis of the breast is rarely diagnosed on cytology alone and a histological diagnosis is usually required for a definitive diagnosis. However, in this case, the lesion spontaneously resolved prior to core biopsy or diagnostic open biopsy. The cytological features in conjunction with immunohistochemistry and the clinical history strongly suggest nodular fasciitis, which is further supported by a USP6 FISH positive result. BACKGROUND

Objective To determine the prevalence and study the association of ovarian, uterine, and breast cancers with endometriosis. Methods A cross‐sectional study of all women with a tissue‐proven diagnosis of endometriosis postoperatively in a tertiary care hospital between January 1, 2010, and December 31, 2019, was conducted to determine the prevalence of coexistent malignancy. Patient details were obtained from electronic clinical records. Univariate analysis followed by multivariate analysis was done to find independent risk factors associated with malignancy. Results Out of 800 patients, 104 (13.0%) were found to have coexistent malignancy: ovarian (50, 6.2%); endometrial (33, 4.1%); synchronous ovarian and endometrial (7, 0.9%); and breast (14, 1.8%). Increasing age (odds ratio [OR] 1.13; 95% confidence interval [CI] 1.09–1.16), higher levels of cancer antigen 125 (CA 125) (OR 1.002; 95% CI 1.001–1.005), postmenopausal status (OR 6.2; 95% CI 2.0–19.2), duration of endometriosis over 5 years (OR 4.7; 95% CI 2.5–9.0), and endometriomas larger than 8 cm (area under the curve 0.83) were predictive of coexistent malignancy. Conclusion Endometriosis is associated with an increased risk of ovarian, endometrial, and breast malignancy. Increasing age, postmenopausal status, higher levels of CA 125, larger endometrioma, and long‐standing disease are predictive risk factors.

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Electronic medical records of patients who underwent completion staging between January 2011 and December 2014 for endometrial cancer were reviewed. Two hundred and sixty four women with endometrial cancer were evaluated during this period. Twenty women with carcinoma endometrium, with a mean age of 53 (range 31-67) who were previously inadequately staged, were found to be at risk of extrauterine disease, following histopathological review, consented to undergo completion staging over an average of 57 days (range 30-91) following the initial surgery. Forty-five percent (9/20) had a BMI of more than 30, and 40% (8/20) had metabolic syndrome. The most common indications for the initial surgery were perimenopausal abnormal uterine bleeding and postmenopausal bleeding. Only eight patients had a pre-hysterectomy endometrial sampling/biopsy (40%) of whom, one had a pre-operative diagnosis of carcinoma endometrium. Sixteen (80%) had pathological risk factors for lymph nodal involvement and in the others, besides histological grading, surgicopathological details for risk assessment were unavailable. Adnexae were retained in 11, and uterus was bisected/cored during surgery in three women. Following completion staging, 5/20 (25%) patients were upstaged, 9 (45%) required no adjuvant treatment, 5 required vaginal brachytherapy therapy alone and 5 were advised chemotherapy and radiation. Two patients during the study period of 48 months had disease recurrence, and two women died of disease progression. Complications of surgery included the following: iliac vein injury (1) and bladder injury (1). Patients with incidental diagnosis of endometrial cancer following hysterectomy after clinical and radiological assessment and histopathological review, should be offered completion staging, if at risk for extrauterine disease. Completion staging permits appropriate prognostication of disease and thereby allows tailoring of adjuvant treatment, avoiding risks of overtreatment and undertreatment.