Alpha-fetoprotein (AFP) is the most widely used biomarker for hepatocellular carcinoma (HCC) prognosis. However, AFP is not useful in establishing a prognosis for patients with a tumor in the early stages. hPG80 (circulating progastrin) is a tumor promoting peptide present in the blood of patients with various cancers, including HCC. In this study, we evaluated the prognostic value of plasma hPG80 in patients with HCC, alone or in combination with AFP. A total of 168 HCC patients were tested prospectively for hPG80 and analyzed retrospectively. The prognostic impact of hPG80 and AFP levels on patient survival was assessed using Kaplan-Meier curves and log-rank tests. hPG80 was detected in 84% of HCC patients. There was no correlation between hPG80 and AFP levels in the training and validation cohorts. Both cohorts showed higher sensitivity of hPG80 compared to AFP, especially at early stages. Patients with high hPG80 (hPG80+) levels (optimal cutoff value 4.5 pM) had significantly lower median overall survival (OS) compared to patients with low hPG80 (hPG80−) levels (12.4 months versus not reached respectively, p < 0.0001). Further stratification by combining hPG80 and AFP levels (cutoff 100 ng/mL) improved prognosis in particular for those patients with low AFP level (hPG80−/AFP+ and hPG80−/AFP−, 13.4 months versus not reached respectively, p < 0.0001 and hPG80+/AFP+ and hPG80+/AFP−, 5.7 versus 26 months respectively, p < 0.0001). This was corroborated when analyses were performed using the BCLC staging especially at early stages. Our findings show that hPG80 could serve as a new prognostic biomarker in HCC. Used in combination with AFP, it improves the stratification of the patients in good and poor prognosis, especially for those patients with negative AFP and early-stage HCC.

Background: Nab-paclitaxel/gemcitabine (AG) and FOLFIRINOX (FFX) are promising drugs in metastatic pancreatic cancer (MPC). This study evaluated a new first-line sequential treatment (AG followed by FFX) in MPC that might overcome resistance to primary therapy and delay tumor progression. Patients and methods: Patients with histologically/cytologically confirmed MPC were included in a multicentric trial receiving AG (day 1, 8 and 15) followed by FFX (day 29 and 43). In phase Ib, three dose-levels were tested for maximum tolerated dose (MTD) and recommended phase II dose. In phase II, the main outcome was the objective response rate (ORR) and secondarily safety, progression-free survival (PFS) and overall survival (OS). Results: In phase Ib, we included 33 patients (31 assessable) of median age 61.0 years (range 42-75 years) and represented by 54.8% males. Five dose-limiting toxicities were reported without any death. The main grade 3/4 toxicities were neutropenia with spontaneous resolution (35.5%/32.3%), venous thromboembolism (grade 3: 22.6%) and thrombopenia (grade 3: 29.0%), while the MTD was not reached. In phase II, we included 58 patients of median age 60 years (range 34-72 years), 50% males and with Eastern Cooperative Oncology Group stage score 0 and 1 of 37.9% and 62.1%, respectively. They received a median of 4 (1-9) cycles in 8.5 months (0.5-19.8 months). The ORR was 64.9% [95% confidence interval (CI) 51.1% to 77.1%], and neurotoxicity was remarkably low. The main grade 3-4 toxicities were venous thromboembolism, thrombopenia, neutropenia/febrile neutropenia, nausea, diarrhea, weight loss and asthenia without any death. Tumor response was complete in 3.5% and partial in 61.4%, while disease was stable in 19.3% and progressive in 15.8% of patients. The median PFS was 10.5 months (95% CI 6.0-12.5 months) and median OS was 15.1 months (95% CI 10.6-20.1 months). Conclusion: Sequential AG and FFX showed acceptable toxicity as first-line treatment with no limiting neurotoxicity, while high response rate and survival justify randomized trials.

Question: A 49-yearold woman attended our unit with progressive abdominal pain that progressively worsened over a period of several months, accompanied by chronic diarrhea with 3-4 stools per day, without rectal bleeding. She had no personal or family history of digestive disease and she had travelled to Vietnam and to India 3 and 10 years ago, respectively. Blood testing revealed moderate biological inflammatory syndrome (C-reactive protein levels ranging from 10 to 15 mg/L). Bacterologic stool examinations, Clostridium difficile testing and parasitological stool examinations were all negative for 3 days in a row. A first ileocolonoscopy was carried out and revealed diffuse involvement of the right and the transverse colon, with multiple ulcers surrounded by sections of healthy mucosa, which was compatible with Crohn's disease (Figure A). Pathologic analysis of the colonic mucosa found ulcerations, neutrophil infiltrates with features of cryptitis, and distortion of the crypts. However, no epithelial or gigantocellular granulomas were observed. Magnetic resonance enterography revealed parietal thickening in the ascending colon, with several nodes of the ileocecal pedicle, and no ileal involvement (Figure B). In light of the possibility of Crohn's disease, corticosteroid therapy was initiated, and it led to a clinical response. Thereafter, the patient developed corticodependency that required the administration of a combination therapy comprising azathioprine and infliximab. The infliximab was optimized at week 10 (10 mg/kg) and then administered every 4 weeks (3 infusions). Despite optimization of the infliximab therapy (therapeutic trough levels [6 mg/mL], no antiinfliximab antibody), clinical remission was not achieved. A second ileocolonoscopy was performed, which provided the same findings as the first colonoscopy. Because there was a clear risk of a primary failure, we decided to switch to vedolizumab. This treatment also failed; however, despite optimization (300 mg every 4 weeks). We consequently introduced ustekinumab (6 mg/kg and then 90 mg every 8 weeks), but corticosteroid therapy was required to induce clinical and biological (C-reactive protein <1 mg/L vs 17 mg/L) responses. The patient then became corticoresistant. After experiencing failures with these treatments and prior to inclusion in a clinical research protocol (filgotinib), she underwent a complete endoscopic checkup. The ileocolonoscopy revealed moderate pancolitis with multiple millimetric ulcerations, without ileal involvement. New biopsies were performed (Figure C). What missed diagnosis was finally revealed by this new pathologic examination? Look on page 1484 for the answer and see the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI.