Occult Breast Cancer Metastasis Presenting as Acute Liver Failure

CASE: A 45 year-old-female with history of clinically stage IA ER/PR/Her-2 Negative moderately differentiated ductal carcinoma of right breast presented with abdominal pain, abdominal distension, jaundice, and scleral icterus three weeks after laparoscopic cholecystectomy due to acute cholecystitis. Intraoperatively her liver was noted to be cirrhotic and an intraoperative biopsy was done. Upon discharge after surgery her total bilirubin remained elevated. On presentation she showed signs of acute liver failure and coagulopathy with a bilirubin of 10.5, INR was elevated to 2.8, and AST/ALT downtrending. Clinically she continued to have increased abdominal pain and distension, jaundice, and scleral icterus. Intraoperative biopsy pathology showed fragments of benign liver cyst with granulomatous inflammation. During her hospital course she continued to display worsening liver function with elevated AST/ALT, total bilirubin, alkaline phosphatase, and INR. Post-surgical complications including bile leak, viral, autoimmune, and granulomatous causes of acute liver failure were excluded. Further evaluation with transjugular hepatic biopsy was done due to limited diagnostic value of previous biopsy, and revealed cirrhosis. Immunohistochemical staining was positive for GATA-3 immunostain and CK-7 stain, revealing adenocarcinoma most consistent with primary breast carcinoma. DISCUSSION: Acute Liver Failure (ALF) is defined as sudden liver dysfunction manifesting as coagulopathy and any degree of encephalopathy in a patient without preexisting cirrhosis with illness lasting less than 26 weeks\u27 duration. As much as 20-40% of ALF is due to unclear causes. Hepatic metastases have been identified in up to 40% of adults with malignant tumors. In the case of breast cancer metastases,the liver is considered to among the common sites of metastasis, along with lungs and bone. However, most metastases present in the form of a discrete mass, and patients do not usually present with liver disease. Isolated liver metastases from breast cancer is rare and only seen in 5-12% of breast cancer patients. Prior studies have shown that isolated liver involvement prognosis improves if patients have hormone positive cancer, normal liver function, good performance status, and have had a long Disease Free Interval (DFI). Resection of liver metastasis is indicated of helical CT or MRI demonstrates well-circumscribed mass that can be excised without further damaging liver function. Diffuse liver metastasis is very rare and difficult to diagnose as they are not identifiable on routine radiologic diagnostic studies. There are multiple case reports of occult metastatic breast cancer in the liver presenting with acute liver failure, in patients with a history of known and treated breast cancer. The majority of these cases are only identified as metastasis from breast cancer primary upon autopsy, as the prognosis for such a presentation of metastatic breast cancer is appalling. In few reported cases, early diagnosis and treatment resulted in some improvement beyond the 18-24 months expected prognosis in metastatic breast cancer. CONCLUSION: Our patient presents a challenging case in which liver function and performance status was poor prior to diagnosis of metastasis. Helical CT also demonstrated a unique presentation of cirrhotic liver with vastly diffuse metastatic lesions, with no circumscribed mass seen. The findings of this case emphasize the unique presentations of metastatic breast cancer in patients who are in remission, necessitating a broader differential diagnosis at time of presentation.https://scholarlycommons.henryford.com/merf2019caserpt/1123/thumbnail.jp

Epidemiological and microbiological investigation of a large increase in vibriosis, northern Europe, 2018

Background Vibriosis cases in Northern European countries and countries bordering the Baltic Sea increased during heatwaves in 2014 and 2018. Aim We describe the epidemiology of vibriosis and the genetic diversity of Vibrio spp. isolates from Norway, Sweden, Denmark, Finland, Poland and Estonia in 2018, a year with an exceptionally warm summer. Methods In a retrospective study, we analysed demographics, geographical distribution, seasonality, causative species and severity of non-travel-related vibriosis cases in 2018. Data sources included surveillance systems, national laboratory notification databases and/or nationwide surveys to public health microbiology laboratories. Moreover, we performed whole genome sequencing and multilocus sequence typing of available isolates from 2014 to 2018 to map their genetic diversity. Results In 2018, we identified 445 non-travel-related vibriosis cases in the study countries, considerably more than the median of 126 cases between 2014 and 2017 (range: 87–272). The main reported mode of transmission was exposure to seawater. We observed a species-specific geographical disparity of vibriosis cases across the Nordic-Baltic region. Severe vibriosis was associated with infections caused by Vibrio vulnificus (adjOR: 17.2; 95% CI: 3.3–90.5) or Vibrio parahaemolyticus (adjOR: 2.1; 95% CI: 1.0–4.5), age ≥ 65 years (65–79 years: adjOR: 3.9; 95% CI: 1.7–8.7; ≥ 80 years: adjOR: 15.5; 95% CI: 4.4–54.3) or acquiring infections during summer (adjOR: 5.1; 95% CI: 2.4–10.9). Although phylogenetic analysis revealed diversity between Vibrio spp. isolates, two V. vulnificus clusters were identified. Conclusion Shared sentinel surveillance for vibriosis during summer may be valuable to monitor this emerging public health issue

À jamais... : Anthologie d'écrits de Français 335 (automne 2013)

http://deepblue.lib.umich.edu/bitstream/2027.42/101963/1/Anthologie_2013_Fall.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/101963/3/Release Deep Blue F13.doc

Mobocertinib in Patients with EGFR Exon 20 Insertion-Positive Non-Small Cell Lung Cancer (MOON): An International Real-World Safety and Efficacy Analysis

EGFR exon 20 (EGFR Ex20) insertion mutations in non-small cell lung cancer (NSCLC) are insensitive to traditional EGFR tyrosine kinase inhibitors (TKIs). Mobocertinib is the only approved TKI specifically designed to target EGFR Ex20. We performed an international, real-world safety and efficacy analysis on patients with EGFR Ex20-positive NSCLC enrolled in a mobocertinib early access program. We explored the mechanisms of resistance by analyzing postprogression biopsies, as well as cross-resistance to amivantamab. Data from 86 patients with a median age of 67 years and a median of two prior lines of treatment were analyzed. Treatment-related adverse events (TRAEs) occurred in 95% of patients. Grade ≥3 TRAEs were reported in 38% of patients and included diarrhea (22%) and rash (8%). In 17% of patients, therapy was permanently discontinued, and two patients died due to TRAEs. Women were seven times more likely to discontinue treatment than men. In the overall cohort, the objective response rate to mobocertinib was 34% (95% CI, 24–45). The response rate in treatment-naïve patients was 27% (95% CI, 8–58). The median progression-free and overall survival was 5 months (95% CI, 3.5–6.5) and 12 months (95% CI, 6.8–17.2), respectively. The intracranial response rate was limited (13%), and one-third of disease progression cases involved the brain. Mobocertinib also showed antitumor activity following EGFR Ex20-specific therapy and vice versa. Potential mechanisms of resistance to mobocertinib included amplifications in MET, PIK3CA, and NRAS. Mobocertinib demonstrated meaningful efficacy in a real-world setting but was associated with considerable gastrointestinal and cutaneous toxicity