Metastatic carcinoma of the urinary bladder in a 67-year-old female with underlying triple primary cancers

AbstractDue to progressive ageing of our population and increasing cancer incidence rates, more and more patients are presenting with multiple primary cancers. Here we describe a case of metastatic carcinoma involving the urinary bladder with underlying triple primary adenocarcinoma in a female adult.A 67-year-old Taiwanese female presented to our institution in November 1997 with gastric signet ring cell carcinoma, pT2N0M0, status post subtotal gastrectomy. In February 2003 she was diagnosed with left breast invasive lobular carcinoma status post modified radical mastectomy, pT2N2M0. Further examination in January 2005 revealed proximal transverse colon cancer, Dukes' C2, with status post right hemicolectomy. She achieved disease-free status from all three malignancies after surgical resection and adjuvant chemotherapy for breast and colon cancers sequentially. In November 2011, she complained about sudden onset of gross hematuria for several days. Diagnostic cystoscopy showed a mass lesion over her urinary bladder. Cystoscope-assisted biopsy showed metastatic poorly differentiated adenocarcinoma with signet ring appearance. Herein we have discussed the pathologic role in the diagnosis of metastatic tumor involving a patient with multiple primary cancers. We also explored the epidemiologic risk and potential causal mechanism of patients with multiple primary cancers

Ductal Carcinoma In Situ Underestimation of Microcalcifications Only by Stereotactic Vacuum-Assisted Breast Biopsy: A New Predictor of Specimens without Microcalcifications

The mammographic appearance of ductal carcinoma in situ (DCIS) is mostly observed as microcalcifications. Although stereotactic vacuum-assisted breast biopsy (VABB) is a reliable alternative to surgical biopsy for suspicious microcalcifications, underestimation of VABB-proven DCIS is inevitable in clinical practice. We therefore retrospectively analyzed the variables in the prediction of DCIS underestimation manifesting as microcalcifications only proved by stereotactic VABB. In 1147 consecutive VABB on microcalcification-only lesions from 2010 to 2016, patients diagnosed with DCIS were selected to evaluate the underestimation rate. The analyzed variables included clinical characteristics, mammographic features, VABB procedure, and biomarkers. Univariate and multivariate analyses were used, and a p value < 0.05 was considered statistically significant. Of the 131 VABB-proven DCIS, 108 cases were diagnosed with DCIS and 23 were upgraded to invasive ductal carcinoma (IDC) after subsequent surgery. The small extent of microcalcification, grouped microcalcifications distribution, nearly complete microcalcification removal, and non-calcified specimens without DCIS were low for DCIS underestimation. Among them, the results of non-calcified specimens with or without DICS were the only statistically significant variables by multivariate logistic regression. These results indicate that the histology of non-calcified specimens was highly predictive of DCIS underestimation. Specimens without DCIS had a low upgrade rate to IDC

Unexpected epithelial ovarian cancers arising from presumed endometrioma: A 10-year retrospective analysis

Objective: To evaluate the incidence and prognosis of unexpected epithelial ovarian cancers (EOCs) occurring in presumed benign endometrioma. Materials and Methods: Patients who underwent primary surgery at Chang Gung Memorial Hospital between November 2003 and October 2013 were searched with the Systematized Nomenclature of Medicine code followed by chart review. Results: The incidence of unexpected EOCs in presumed ovarian endometrioma was 0.14%, as 11 patients were revealed after reviewing 497 patients of pathology-proven EOCs in the current series. All patients were aged ≥ 40 years; seven (63.6%) had inward mass within ovarian cyst in preoperative images, six had cancer antigen-125 (CA-125) > 200 U/mL, and two with CA-125 > 1500 U/mL. Ten patients underwent laparoscopy initially, including five with ovarian preservation at the beginning. Ten patients subsequently completed concurrent or secondary staging surgery, including four totally with laparoscopy. The histologic subtypes had clear-cell (8/11), endometrioid (1/11), mixed clear-cell and endometrioid (1/11), and low-grade serous adenocarcinoma (1/11). Seven patients had endometriosis-associated ovarian carcinoma (EAOC), while the other four were non-EAOC with no endometriosis component. The only mortality was a patient of non-EAOC in Stage IIIc, whereas the other 10 in Stage I were alive. The overall survival rate was 90.9% (10/11) with follow-up ranging from 23 months to 130 months. Conclusion: Unexpected EOCs occurring in presumed ovarian endometrioma was rare and, if present, the prognosis was good in Stage I disease with laparoscopic management. Combining parameters of patient's age, CA-125 level, and inward solid mass at imaging could help to raise the precautions

Neutrophil elastase inhibitor (MPH-966) improves intestinal mucosal damage and gut microbiota in a mouse model of 5-fluorouracil–induced intestinal mucositis

Background: 5-Fluorouracil (5-FU)-based chemotherapy is first-line chemotherapy for colorectal cancer. However, 5-FU-induced intestinal mucositis (FUIIM) is a common adverse effect that severely impairs drug tolerance and results in poor patient health. Methods: Male C57BL/6 mice were given 5-FU (50 mg/kg/day, i.p.) and treated with MPH-966 (5 and 7.5 mg/kg/day, p.o.) for five days. The body weight loss and the amount of food intake, and histopathological findings were recorded and analyzed. In addition, the neutrophil infiltration, levels of neutrophil serine proteases and pro-inflammatory cytokines, and tight junction proteins expression in intestinal tissues were determined. The ecology of gut microbiota was performed through next-generation sequencing technologies. Results: Neutrophil elastase (NE) overexpression is a key feature in FUIIM. This study showed that treatment with the specific NE inhibitor MPH-966 (7.5 mg/kg/day, p.o.) significantly reversed 5-FU-induced loss in body weight and food intake; reversed villous atrophy; significantly suppressed myeloperoxidase, NE, and proteinase 3 activity; and reduced pro-inflammatory cytokine expression in an FUIIM mouse model. In addition, MPH-966 prevented 5-FU-induced intestinal barrier dysfunction, as indicated by the modulated expression of the tight junction proteins zonula occludin-1 and occludin. MPH-966 also reversed 5-FU-induced changes in gut microbiota diversity and abundances, specifically the Firmicutes-to-Bacteroidetes ratio; Muribaculaceae, Ruminococcaceae, and Eggerthellaceae abundances at the family level; and Candidatus Arthromitus abundance at the genus level. Conclusion: These data indicate that NE inhibitor is a key treatment candidate to alleviate FUIIM by regulating abnormal inflammatory responses, intestinal barrier dysfunction, and gut microbiota imbalance

Low PD-L1 Expression Strongly Correlates with Local Recurrence in Epstein-Barr Virus-Positive Nasopharyngeal Carcinoma after Radiation-Based Therapy

The prognostic value of programmed death-ligand 1 (PD-L1) expression in nasopharyngeal carcinoma (NPC) is controversial, with previous studies showing conflicting results. Most NPCs in endemic areas are Epstein-Barr virus (EBV)-positive. Our aim was to evaluate the clinical significance of PD-L1 expression in EBV-positive NPC. We retrospectively analyzed PD-L1 expression on tumor cells (TCs) and immune cells (ICs) by immunohistochemistry in 208 EBV-positive NPC patients who underwent radiotherapy (203 with concurrent chemotherapy). The percentages of TCs and ICs expressing PD-L1 were evaluated respectively. There was a strong correlation between local recurrence and low PD-L1 expression on ICs (p = 0.0012), TCs (p = 0.013) or both (p = 0.000044), whereas all clinical parameters had no influence on local recurrence. Using multivariate analysis, low PD-L1 expression on ICs was an independent adverse prognostic factor (p = 0.0080; HR = 1.88; 95% CI = 1.18–3.00) for disease-free survival. High PD-L1 expression on both ICs and TCs was an independent favorable prognostic factor (p = 0.022; HR = 0.46; 95% CI = 0.24–0.89) for overall survival. We show for the first time that low PD-L1 expression on ICs and TCs strongly correlates with local recurrence in EBV-positive NPC patients after radiation-based therapy. A simple immunohistochemical study for PD-L1 can identify patients prone to local recurrence, and such patients might benefit from more aggressive treatment in future clinical trials

Dual-Energy Contrast-Enhanced Spectral Mammography: Enhancement Analysis on BI-RADS 4 Non-Mass Microcalcifications in Screened Women.

Mammography screening is a cost-efficient modality with high sensitivity for detecting impalpable cancer with microcalcifications, and results in reduced mortality rates. However, the probability of finding microcalcifications without associated cancerous masses varies. We retrospectively evaluated the diagnosis and cancer probability of the non-mass screened microcalcifications by dual-energy contrast-enhanced spectral mammography (DE-CESM).With ethical approval from our hospital, we enrolled the cases of DE-CESM for analysis under the following inclusion criteria: (1) referrals due to screened BI-RADS 4 microcalcifications; (2) having DE-CESM prior to stereotactic biopsy; (3) no associated mass found by sonography and physical examination; and (4) pathology-based diagnosis using stereotactic vacuum-assisted breast biopsy. We analyzed the added value of post-contrast enhancement on DE-CESM.A total of 94 biopsed lesions were available for analysis in our 87 women, yielding 27 cancers [19 ductal carcinoma in situ (DCIS), and 8 invasive ductal carcinoma (IDC)], 32 pre-malignant and 35 benign lesions. Of these 94 lesions, 33 showed associated enhancement in DE-CESM while the other 61 did not. All 8 IDC (100%) and 16 of 19 DCIS (84.21%) showed enhancement, but the other 3 DCIS (15.79%) did not. Overall sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 88.89%, 86.56%, 72.72%, 95.08% and 87.24%, respectively. The performances of DE-CESM on both amorphous and pleomorphic microcalcifications were satisfactory (AUC 0.8 and 0.92, respectively). The pleomorphous microcalcifications with enhancement showed higher positive predictive value (90.00% vs 46.15%, p = 0.013) and higher cancer probability than the amorphous microcalcifications (46.3% VS 15.1%). The Odds Ratio was 4.85 (95% CI: 1.84-12.82).DE-CESM might provide added value in assessing the non-mass screened breast microcalcification, with enhancement favorable to the diagnosis of cancers or lack of enhancement virtually diagnostic for non-malignant lesions or noninvasive subgroup cancers