Two Patient Studies of a Companion Diagnostic Immuno-Positron Emission Tomography (PET) Tracer for Measuring Human CA6 Expression in Cancer for Antibody Drug Conjugate (ADC) Therapy.

An antigen binding fragment (BFab) derived from a tumor-associated mucin 1-sialoglycotope antigen (CA6) targeting antibody (huDS6) was engineered. We synthesized a companion diagnostic positron emission tomography (PET) tracer by radiolabeling BFab with [64Cu] to measure CA6 expression on cancer tissues prior to anti-human CA6 (huDS6-DM4 antibody-drug conjugate) therapy for ovarian and breast cancer patients. After chemotherapy, the ovarian patient received PET scan with 18F-2-fluoro-2-deoxyglucose ([18F]FDG: 10 mCi), followed by [64Cu]-DOTA-BFab ([64Cu]BFab; 5.5 mCi) 1 week later for PET scanning of CA6 expression and subsequent surgery. The breast cancer patient was treated with chemotherapy before primary tumor resection and subsequent [18F]FDG-PET scan. 4 weeks later the patient received of [64Cu]BFab (11.7 mCi) for CA6 PET scan. Whole body [18F]FDG-PET of the breast cancer patient indicated FDG-avid tumor metastases to the liver, bilateral hila and thoracic spine, but no uptake was observed for the ovarian patient. Each patient was also imaged by PET/CT with [64Cu]BFab at 1 and 24 hours after tracer administration. The [64Cu]BFab tracer was well tolerated by both patients without adverse effects, and no significant tracer uptake was observed in both patients. Immunohistochemistry (IHC) data indicated CA6 expressions were weak to intermediate and matched with the [64Cu]BFab-PET signals.

Impact of preoperative chemotherapy on the histological response of patients with peritoneal metastases from colorectal cancer according to peritoneal regression grading score (PRGS) and TRG.

BACKGROUND: This study evaluated the histologic response after preoperative systemic therapy (pST) using the Peritoneal Regression Grading Score (PRGS) and tumor regression grade (TRG) classifications for patients with peritoneal metastases (PM) from colorectal cancer (CRC). METHODS: Twenty-three patients were selected from a prospective database of 196 patients who underwent CRS followed by HIPEC for synchronous PM from CRC. In all study patients, biopsies of the PM obtained before pST (during the first laparoscopy) and after pST (during cytoreductive surgery) were compared. RESULTS: Complete (PRGS 1), Major (PRGS 2), Minor (PRGS 3) and no histological responses (PRGS 4) were obtained in 17,5%, 52% and 13% and 17,5% of patients, respectively. Major (TRG 1-2), partial (TRG3), and no (TRG4-5) histological tumor regression were observed in 61%, 9% and 30% of patients, respectively. Regardless of the classification applied, median OS was significantly higher in patients with a "complete or major" response than in those with a "minor/partial or no" response (54 vs. 26 months, p < 0.05). CONCLUSIONS: The PRGS and TRG can be used in clinical practice to evaluate the histological response after pST. This study demonstrated that a complete histologic response of PM from CRC can be obtained after pST.

Evaluation of a new histological grading system for assessing the response to chemotherapy of peritoneal metastases from colorectal cancer: A mouse model study.

This experimental study evaluated the histological response of peritoneal metastases (PM) from colorectal cancer (CRC) after preoperative systemic chemotherapy (pCT). The results demonstrated that the Peritoneal Regression Grade Score could be used in medical practice. AIM: The aim was to evaluate the histological criteria used by the tumour regression grade (TRG) and Peritoneal Regression Grade Score (PRGS) for determining the response to chemotherapy (CT), in a mouse model of peritoneal metastases (PM) from colorectal cancer (CRC). METHODS: Twenty immunocompetent BALB/c mice were randomized into four groups at day (D) 10 after intraperitoneal (ip) injection with bioluminescent CRC tumour cells (CT26-luc). A histology before treatment group was obtained by sacrifice on D10; the other groups all received one of the following ip treatments over 15 days: 5% glucose (control, G5); 5-fluorouracil (5FU, 0.03 mg/g); or 5FU with oxaliplatin (Ox, 0.006 mg/g). The histological response (HR) was analysed by comparing the histology of PM before and after treatment, using both scores: TRG and PRGS. RESULTS: All mice showed limited PM as visualised by bioluminescence and confirmed at the time of sacrifice in the histology before treatment group. The mean peritoneal carcinomatosis index (PCI) was = 8 [6-10], The rate of complete HR was significantly higher in the Ox-5FU group (83.3%) than 5FU group (0%) and G5 group (0%) (p = 0.016). Fibrosis was present only in CT-treated groups (p = 0.05). PCI, ascites volume and haemorrhagic ascites were significantly higher in the G5 group than CT groups (p < 0.05). CONCLUSIONS: The TRG score can be used in practice when we want to compare the HR between the primary tumour and the PMs. The PRGS is a good measure of HR and is correlated with the efficacy of CT.

Sudden adult death: an autopsy series of 534 cases with gender and control comparison.

The aim of our study was to highlight the epidemiological difference in adult sudden death between males and females. The type of pathologies found in adult victims of sudden death was compared to control cases in order to determine the most significant pathologies involved in sudden death. Among all autopsies performed between 1995 and 2009, 534 adult cases of sudden death and 154 cases who violently died were respectively selected. For each case, a complete autopsy was carried out, including systematic histological examination of all major organs. The sudden death population was composed of 369 males and 165 females. There was no statistical difference regarding age between males and female. Sudden death took place more often at home in women than in men (p < 0.0001). A stressful event was more frequently found in men than in women (p = 0.03). Deaths caused by cardiovascular diseases were more frequent in males than in females, especially Coronary Artery Disease (CAD) (p < 0.0001). Cardiomyopathy was more often the cause of death in women, particularly Arrythmogenic Right Ventricular Cardiomyopathy (ARVC). Cardiac pathologies were found in 45% of the control cases. CAD and ARVC were statistically more frequent in the sudden death group than in the control group. According to our study, profile of sudden death is different between males and females. Those data seem to be important for clinicians involved in prevention programs of sudden death, as they can adapt their screening according to the gender.

[Eosinophilic esophagitis]. / Œsophagite à éosinophiles.

Esophagitis is the first cause of dysphagia and food impaction in a young male adult. Eosinophilic esophagitis is a clinical and pathological entity with involvement limited to the oesophagus. Eosinophilic esophagitis is associated with allergy and atopy. Most common in Caucasians, with 3:1 male predominance. Endoscopic findings are unspecific. Clinical and histological diagnosis has to be confirmed by unresponsiveness to proton pump inhibitor. Recommended first therapeutic approach: topical corticoids.

Pitfalls and mimickers at 64-section helical CT that cause negative appendectomy: an analysis from 1057 appendectomies.

PURPOSE: To determine the rate of negative appendectomy and clarify the causes of negative appendectomy in patients with clinically suspected acute appendicitis who had surgery after 64-section helical computed tomography (CT). MATERIAL AND METHODS: A retrospective analysis of 1057 patients who had appendectomy after 64-section helical CT was performed to determine the rate of negative appendectomy. The 64-section helical CT examinations obtained with submillimeter and isotropic voxels in the patients with negative appendectomy were analyzed by two readers and compared to clinical, operative and histopathological reports, discharge summaries and original radiology reports. RESULTS: The negative appendectomy rate was 1.7% (18/1057). Appendix enlargement (>6 mm) and fat stranding were present in 17 (17/18; 94%) and 6 patients (6/18; 33%), respectively. In 13 patients (13/18; 72%) 64-section helical CT findings were consistent with acute appendicitis. Interpretive errors in original imaging reports were identified in five patients (5/18; 28%). CONCLUSION: The preoperative use of 64-section helical CT results in a very low rate of negative appendectomy. Patients with negative appendectomy have 64-section helical CT findings consistent with a diagnosis of acute appendicitis in the majority of cases. Interpretive errors are less frequent.