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Aim: To characterize syndrome of acute liver failure (ALF) from metastatic breast cancer to promote premortem diagnosis. Up to now, only 25 % of the reported 32 cases of this syndrome were diagnosed premortem. Methods: Cases identified by computerized literature review and review of files maintained by senior investigator. Results: Among 32 cases, average age at presentation was 47.9 ± 9.9 years. Common signs include jaundice, hepatomegaly, shifting dullness, and bilateral leg edema. Mean serum level of AST was 296.4 ± 204.0 U/L, ALT, 183.2 ± 198.9 U/L; alkaline phosphatase, 641.5 ± 610.1; and total bilirubin, 8.6 ± 8.3 mg/dL. Twenty-seven patients (84 %) have known prior breast cancer (mean diagnosis = 4.1 + 4.8 years earlier). Abdominal ultrasound findings ( N = 10) include hepatomegaly in three cases, heterogeneous/multifocal hepatic lesions in three, ascites in three, and other in two. Abdominal CT findings ( N = 16) include heterogeneous/multifocal hepatic lesions in six cases, ascites in five, hepatomegaly in three, cirrhosis in three, fatty liver in two, other in two. Hepatic metastases may not be suspected when abdominal CT shows no hepatic lesions. The diagnosis is made postmortem in 24 cases and antemortem in eight, with a statistically significant trend of increasing premortem diagnosis since 2000 (0 % before 2000 vs. 50 % after 2000; p = .001, 95 %-ORCI ≥ 2.86, Fisher's exact test). A new case of ALF from breast cancer is reported with notable features: abdominal CT revealed no discrete hepatic lesions despite widespread hepatic metastases demonstrated by liver biopsy; hepatic metastases occurred 21 years after original breast primary; and original diagnosis of lobular breast cancer in primary lesion was corrected to mixed ductal and lobular carcinoma, based on immunohistochemistry, performed 21 years afterward. Conclusions: This review characterizes the clinical presentation and natural history of this syndrome to promote liver biopsy for premortem diagnosis and appropriate therapy. [ABSTRACT FROM AUTHOR]

Background: KIM-1 staining is upregulated in proximal tubule-derived renal cell carcinoma (RCC) including clear renal cell carcinoma and papillary renal cell carcinoma, but not in chromophobe RCC (distal tubular tumor). This study was designed to prospectively examine urine KIM-1 level before and 1 month after removal of renal tumors. Patients and design: A total of 19 patients were eventually enrolled in the study based on pre-operative imaging studies. Pre-operative and follow-up (1 month) urine KIM-1 levels were measured. The urine KIM-1 levels (uKIM-1) were then normalized to urine creatinine levels (uCr). Renal tumors were also stained for KIM-1 using immunohistochemical techniques. Results: The KIM-1-negative staining group included 7 cases, and the KIM-1-positive group consisted of 12 cases. The percentage of KIM-1-positive staining RCC cells ranged from 10 to 100 %, and the staining intensity ranged from 1+ to 3+. In both groups, serum creatinine levels were both significantly elevated after nephrectomy. In the KIM-1-negative group, uKIM-1/uCr remained at a similar level before (0.37 ± 0.1 ng/mg Cr) and after nephrectomy (0.32 ± 0.01 ng/mg Cr). However, in the KIM-1-positive group, elevated uKIM-1/uCr at 1.20 ± 0.31 ng/mg Cr was significantly reduced to 0.36 ± 0.1 ng/mg Cr, which was similar to the pre-operative uKIM-1/uCr (0.37 ± 0.1 ng/mg Cr) in the KIM-1-negative group. Conclusion: Our small but prospective study showed significant reduction in uKIM-1/uCr after nephrectomy in the KIM-1 positive group, suggesting that urine KIM-1 may serve as a surrogate biomarker for kidney cancer and a non-invasive pre-operative measure to evaluate the malignant potential of renal masses. [ABSTRACT FROM AUTHOR]

Background. To determine the optimal timing and analytic method of 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography (PET) imaging during fractionated radiotherapy (RT) to predict tumor control. Methods. Ten head neck squamous cell carcinoma xengrafts derived from the UT-14-SCC cell line were irradiated with 50Gy at 2Gy per day over 5 weeks. Dynamic PET scans were acquired over 70 minutes at baseline (week 0) and weekly for seven weeks. PET data were analyzed using standard uptake value (SUV), retention index (RI), sensitivity factor (SF), and kinetic index (Ki). Results. Four xenografts had local failure (LF) and 6 had local control. Eighty scans from week 0 to week 7 were analyzed. RI and SF after 10Gy appeared to be the optimal predictors for LF. In contrast, SUV and Ki during RT were not significant predictors for LF. Conclusion. RI and SF of PET obtained after the first week of fractionated RT were the optimal methods and timing to predict tumor control. [ABSTRACT FROM AUTHOR]

Summary: Morphologic examination still forms the main diagnostic tool in the differential diagnosis of molar pregnancies. However, the criteria are subjective and show considerable interobserver variability among pathologists. Once a diagnosis of molar pregnancy is made, DNA ploidy studies help to differentiate a triploid partial mole from diploid complete mole (CM). However, with earlier diagnosis and therapeutic evacuation of molar pregnancies, the differentiation of molar pregnancies from early nonmolar placentation is becoming increasingly difficult. The p57KIP2 gene (CDKN1C) is strongly paternally imprinted and expressed from the maternal allele. Because CM lacks a maternal genome, p57KIP2 immunostaining is correspondingly absent, whereas hydropic abortuses and partial mole show positive staining. We compared the use of p57KIP2 staining in the differential diagnosis of 68 morphologically challenging cases of early first-trimester hydropic placentas. Diagnosis based on p57KIP2 staining was compared with the original diagnosis based on morphology and DNA ploidy analysis. Concordant results were obtained in 65 of 68 cases studied. In 2 of 3 cases with a discordant diagnosis, microsatellite DNA genotyping analysis agreed with the results of p57KIP2 staining, confirming that positive p57KIP2 staining is a highly sensitive and specific marker for excluding CM in this setting. In addition, p57KIP2 staining has the advantage of differentiating hydropic abortuses from CMs, a distinction not made by ploidy analysis. p57KIP2 staining can be used in concert with ploidy studies to refine the diagnosis of early molar pregnancies. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the metabolic information provided by 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) during the early response of head-and-neck squamous cell carcinoma (HNSCC) xenografts to radiotherapy (RT). Methods and Materials: Low-passage HNSCC cells (UT14) were injected into the rear flanks of female nu/nu mice to generate xenografts. After tumors grew to 400–500 mm3, they were treated with either 15 Gy in one fraction (n = 18) or sham RT (n = 12). At various time points after treatment, tumors were assessed with 2-h dynamic FDG-PET and immediately harvested for direct histological correlation. Different analytical parameters were used to process the dynamic PET data: kinetic index (Ki), standard uptake value (SUV), sensitivity factor (SF), and retention index (RI). Tumor growth was assessed using the specific growth rate (SGR) and correlated with PET parameters using the Pearson correlation coefficient (r). Receiver operating characteristic (ROC) and the area under the ROC curve (AUC) were used to test PET parameters for their ability to predict for radiation necrosis and radiation change. Results: Tumor growth was arrested for the first 20 days after RT and recovered thereafter. Histologically, radiation change was observed in the peripheral regions of tumors between days 7 and 23 after RT, and radiation necrosis were observed in the central regions of tumors between days 7 and 40. Ki provided the best correlation with SGR (r = 0.51) and was the optimal parameter to predict for early radiation necrosis (AUC = 0.804, p = 0.07). SUV30 min was the strongest predictor for late radiation necrosis (AUC = 0.959, p = 0.004). Both RI30–60min and SF12–70 min were very accurate in predicting for radiation change (AUC = 0.891 and 0.875, p = 0.009 and 0.01, respectively). Conclusions: Dynamic FDG-PET analysis (such as Ki or SF) may provide informative assessment of early radiation necrosis or radiation change of HNSCC xenografts after RT. [Copyright &y& Elsevier]

Collagenous colitis (CC) is associated with non-bloody, watery diarrhea, which is pathophysiologically reasonable because normal colonic absorption (or excretion) of water and electrolytes can be blocked by the abnormally thick collagen layer in CC. However, CC has also been associated with six previous cases of protein-losing enteropathy (PLE), with no pathophysiologic explanation. The colon does not normally absorb (or excrete) amino acids/proteins, which is primarily the function of the small bowel. Collagenous duodenitis (CD) has not been associated with PLE. This work reports a novel case of CD (and CC) associated with PLE; a pathophysiologically reasonable mechanism for CD causing PLE (by the thick collagen layer of CD blocking normal intestinal amino acid absorption); and a novel association of PLE with severe COVID-19 infection (attributed to relative immunosuppression from hypoproteinemia, hypoalbuminemia, hypogammaglobulinemia, and malnutrition from PLE). [ABSTRACT FROM AUTHOR]

Purpose: To determine the prognostic significance of neuroendocrine differentiation (NED) in Gleason score 8–10 prostate cancer treated with primary radiotherapy (RT). Methods and Materials: Chromogranin A (CgA) staining was performed and overseen by a single pathologist on core biopsies from 176 patients from the William Beaumont prostate cancer database. A total of 143 had evaluable biopsy material. Staining was quantified as 0%, <1%, 1–10%, or >10% of tumor cells. Patients received external beam RT alone or together with high-dose-rate brachytherapy. Cox regression and Kaplan-Meier estimates determined if the presence/frequency of neuroendocrine cells correlated with clinical endpoints. Results: Median follow-up was 5.5 years. Forty patients (28%) had at least focal positive CgA staining (<1% n = 21, 1–10% n = 11, >10% n = 8). No significant differences existed between patients with or without staining in terms of age, pretreatment prostate-specific antigen, tumor stage, hormone therapy administration, % biopsy core involvement, mean Gleason score, or RT dose/modality. CgA staining concentration independently predicted for biochemical and clinical failure, distant metastases (DM), and cause-specific survival (CSS). For patients with <1% vs. >1% staining, 10-year DM rates were 13.4% vs. 55.3%, respectively (p = 0.001), and CSS was 91.7% vs. 58.9% (p < 0.001). As a continuous variable, increasing CgA staining concentration predicted for inferior rates of DM, CSS, biochemical control, and any clinical failure. No differences in outcomes were appreciated for patients with 0% vs. <1% NED. Conclusions: For Gleason score 8–10 prostate cancer, >1% NED is associated with inferior clinical outcomes for patients treated with radiotherapy. This relates most directly to an increase in distant disease failure. [ABSTRACT FROM AUTHOR]