Tumor infiltrating lymphocytes and homologous recombination deficiency are independently associated with improved survival in ovarian carcinoma.

OBJECTIVE: The presence of tumor infiltrating lymphocytes (TIL) and defects in homologous recombination (HR) are each important prognostic factors in ovarian carcinoma (OC). We characterized the association between HR deficiency (HRD) and the presence of TILs in a cohort of OC patients and the relative contribution to overall survival. METHODS: Patients with carcinoma of the ovary, fallopian tube, or peritoneum were prospectively enrolled. Malignant neoplasm and serum samples were collected. Immunohistochemistry for CD3+ T cells and CD68+ tumor associated macrophages (TAMs) was performed on specimens collected at primary surgery. Damaging germline and somatic mutations in genes in the HR-mediated repair (HRR) pathway were identified using BROCA sequencing. HRD was defined as a damaging mutation in one of 12 genes in the HRR pathway or promoter hypermethylation in BRCA1 or RAD51C. RESULTS: Ninety-eight of 250 patients included in the analysis had HRD OC (39.2%). HRD OC were enriched for CD3+ TILs and CD68+ TAMs. High CD3+ TIL was present in 65.3% of HRD OC compared to 43.4% of non-HRD OC (P = 0.001). High CD68+ TAM was present in 66.3% of HRD OC compared to 50.7% of non-HRD OC (P = 0.015). Patients with HRD OC and high CD3+ TILs had the longest median overall survival compared to non-HRD OC with low CD3+ TILs (70.9 vs. 35.8 months, adjusted HR 0.38, 95% CI (0.25-0.59)). CONCLUSIONS: Patients that have both CD3+ TILs and HRD OC are afforded the greatest improvement in overall survival. This finding may have therapeutic implications for OC patients treated with emerging immunotherapies.

Acute kidney injury in allopurinol-induced DRESS syndrome: a case report of concurrent tubulointerstitial nephritis and kidney-limited necrotizing vasculitis
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Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare but potentially fatal adverse drug reaction with variable renal involvement. We report the case of a man who presented with allopurinol-induced DRESS and acute kidney injury (AKI) requiring hemodialysis. Kidney biopsy revealed eosinophilic tubulointerstitial nephritis and necrotizing vasculitis of the intralobular arteries without systemic markers of vasculitis. After cyclophosphamide and glucocorticoids, his symptoms and AKI resolved. To our knowledge, this is the first case of kidney-limited necrotizing vasculitis, questioning whether a biopsy should be routinely performed in patients with DRESS accompanied by severe AKI. It is possible that kidney-limited necrotizing vasculitis is an under-diagnosed manifestation of DRESS syndrome, and in such a setting, early recognition, stopping the offending agent, and use of aggressive immunosuppressive therapy, including cyclophosphamide, may lead to a favorable outcome.
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ß-cell loss and ß-cell apoptosis in human type 2 diabetes are related to islet amyloid deposition.

Amyloid deposition and reduced ß-cell mass are pathological hallmarks of the pancreatic islet in type 2 diabetes; however, whether the extent of amyloid deposition is associated with decreased ß-cell mass is debated. We investigated the possible relationship and, for the first time, determined whether increased islet amyloid and/or decreased ß-cell area quantified on histological sections is correlated with increased ß-cell apoptosis. Formalin-fixed, paraffin-embedded human pancreas sections from subjects with (n = 29) and without (n = 39) diabetes were obtained at autopsy (64 ± 2 and 70 ± 4 islets/subject, respectively). Amyloid and ß cells were visualized by thioflavin S and insulin immunolabeling. Apoptotic ß cells were detected by colabeling for insulin and by TUNEL. Diabetes was associated with increased amyloid deposition, decreased ß-cell area, and increased ß-cell apoptosis, as expected. There was a strong inverse correlation between ß-cell area and amyloid deposition (r = -0.42, P < 0.001). ß-Cell area was selectively reduced in individual amyloid-containing islets from diabetic subjects, compared with control subjects, but amyloid-free islets had ß-cell area equivalent to islets from control subjects. Increased amyloid deposition was associated with ß-cell apoptosis (r = 0.56, P < 0.01). Thus, islet amyloid is associated with decreased ß-cell area and increased ß-cell apoptosis, suggesting that islet amyloid deposition contributes to the decreased ß-cell mass that characterizes type 2 diabetes.

A case of metastatic dysgerminoma treated with two cycles neoadjuvant chemotherapy followed by fertility-sparing minimally invasive surgery.

•Neoadjuvant chemotherapy (NACT) followed by fertility-sparing surgery is a feasible treatment of metastatic dysgerminoma•As few as two cycles of NACT may result in enough of a tumor response for fertility-sparing surgery to be possible.•Tumor lysis syndrome is a possibility when administering chemotherapy to patients with metastatic dysgerminoma.

Heroin Use Is Associated with AA-Type Kidney Amyloidosis in the Pacific Northwest.

BACKGROUND AND OBJECTIVES: AA-type kidney amyloidosis is classically associated with chronic autoimmune or inflammatory disorders. However, some urban centers have reported a high prevalence of injection drug use among patients with kidney AA amyloidosis. Previous reports lack control groups to quantify associations and most predate the opioid epidemic in the United States. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a case-control study of 38 patients with biopsy-confirmed kidney AA amyloidosis and 72 matched control individuals without this condition from two large hospital systems in Seattle, Washington. We ascertained the pattern and duration of heroin use by medical chart review and determined associations using logistic regression. RESULTS: Among case patients, 95% had a prior history of heroin use, 87% had skin abscesses, and 76% and 27% had evidence of muscling and skin popping, respectively. After adjustment for age, race, sex, site, and year of biopsy, any heroin use (past or current) was associated with an estimated 170-times higher risk of kidney AA amyloidosis compared with no heroin use (95% confidence interval, 28 to 1018 times higher; P<0.001). Chronic autoimmune disorders were uncommon among case patients in this study. The median time to ESKD among patients with AA amyloidosis was 2.4 years (interquartile range, 0.5-7.5 years). CONCLUSIONS: Injection heroin use is strongly associated with kidney AA amyloidosis in the Pacific Northwest. Unique aspects of heroin use, in particular geographic regions or frequent associated soft-tissue infections, may be an important cause of this progressive kidney disease.

Metastases from lung adenocarcinoma within a leiomyoma: A case report.

BACKGROUND: Pulmonary adenocarcinoma rarely spreads to the gynecologic tract, and has not been fully reported to metastasize within a leiomyoma. CASE: A 47 year-old woman with recurrent pulmonary adenocarcinoma was incidentally found to have a positron emission tomography (PET) avid pelvic mass at the time of restaging. She was also noted to be anemic, and reported significant vaginal bleeding. She was taken for an uncomplicated hysterectomy. She was unexpectedly found to have adenocarcinoma within a leiomyoma, consistent with metastasis from her primary pulmonary adenocarcinoma. CONCLUSION: We report one of the first cases of pulmonary adenocarcinoma metastatic to a uterine leiomyoma. A personal history of cancer should always be considered in patients presenting with symptomatic leiomyoma.