An elevated serum alkaline phosphatase level in hepatic metastases of grade 1 and 2 gastrointestinal neuroendocrine tumors is unusual and of prognostic value.

In our clinical practice we have observed that despite a high hepatic metastatic tumor burden, serum alkaline phosphatase (AP) levels are frequently normal in cases of metastatic neuroendocrine tumor (NET).We retrospectively reviewed the records of patients with grade 1 and 2 NETs with liver metastases but without bone metastases seen at our institution in 2013. In total, 49 patients were included (22 female), with a median age of 60 years (range: 28 to 84 years). The primary tumors were located in the duodenum/pancreas (n = 29), small bowel (n = 17) or colon/rectum (n = 3); 10 cases were grade 1 and 39 grade 2. Hepatic involvement was bulky, with more than 10 lesions in 23 patients and a tumor burden above 10% of the liver volume in 26 patients.Serum AP levels were elevated (≥ upper limit of normal (ULN)) in 16 patients. In multiparametric analysis, elevated serum AP levels were not associated with the primary site, grade, or number or volume of metastases. In multiparametric analysis, progression-free survival was only correlated with grade (p = 0.010) and AP level (p = 0.017).Serum AP levels are frequently normal in liver metastases from NET, even in the event of a major tumor burden, and the serum AP level can be of prognostic value

Comparison of AP values (in X ULN) follows the number of liver metastases (left panel) or tumor burden as a percentage of the total liver volume (right panel).

<p>Bar: median value, dot: mean value.</p

Univariate and multivariate analyses of prognostic factors for progression-free survival.

<p>Univariate and multivariate Cox regressions, with Kaplan-Meier estimations of the median, hazard ratio and p-value according to log-rank tests for progression-free survival. Nbr: number; Obs: observations; ULN: upper limit of normal.</p

Progression-free survival follows the alkaline phosphatase value.

<p>Progression-free survival follows the alkaline phosphatase value.</p

Characteristics of 49 patients with liver metastases from gastrointestinal neuroendocrine tumor grade 1 and 2; AP: Alkaline phosphatase, CGA: Chromogranin A, 5HIAA: Urinary 5 hydroxy-indole acetate acid; ULN: Upper limit of normal; mets: Metastases; D-Pas: Duodeno-pancreas.

<p>P values are given according to the Wilcoxon test for continuous variables and the Chi-squared test for categorical variables.</p

Is Piecemeal Endoscopic Resection Acceptable for Early Colorectal Cancers in Certain Situations? A Single-Center French Study

International audienceBackground & Aims: The use of endoscopic treatment for early colorectal cancer (ECC) is increasing. The European guidelines suggest performing piecemeal endoscopic resection (pmR) for benign lesions and en bloc resection for ECC, especially for patients with favorable lymph node involvement risk evaluations. However, en bloc resections for lesions larger than two centimeters require invasive endoscopic techniques. Our retrospective single-center study aimed to determine the clinical impact of performing pmR for ECC rather than traditional en bloc resection. Methods: A single-center study was performed between January 2012 and September 2017. All ECC patients were included. The main objective was to evaluate the number of patients who potentially underwent unnecessary surgery due to piecemeal resection. The secondary endpoints were as follows: disease-free survival (DFS), defined as the time from pmR to endoscopic failure (local recurrence not treatable by endoscopy), complication rate, number of patients who did not undergo surgery by default, and factors predictive of outcomes and complications. Results: One hundred and forty-six ECC endoscopically treated patients were included. In total, 85 patients were excluded (71 who underwent en bloc resection, 14 with pending follow-up). Data from 61 patients (33 women and 28 men) were analyzed. Two patients underwent potentially unnecessary surgery [3.28% (0.9%-11.2%)]. The DFS rate was 87% (75%-93%) at 6 months and 85% [72%-92%] at 12 months. The median followup time was 16.5 months (12.4-20.9). Three patients (4.9%) had complications. One patient did not undergo surgery by default. A Paris classification of 0-2c (HR=9.3 (2.4-35.9), p<0.001) and Vienna classification of 5 [HR=16.3 (3.3-80.4), p<0.001] were factors associated with poor DFS. Conclusion: Performing pmR in place of en bloc resection for ECC had a limited impact on patients. If the pathology (especially deep margins) is analyzable, careful monitoring could be acceptable in ECC patients who undergo pmR

Celiac Disease After Administration of Immune Checkpoint Inhibitors: A Case Report

International audienceImmune checkpoint inhibitors (ICI) reinvigorate the immune system to recognize and destroy tumor cells. Because of this biological mechanism, patients might develop autoimmune toxicities, notably in the digestive tract (most frequently, hepatitis or colitis). A 70-year-old man with relapsed mesothelioma was treated with nivolumab in 3rd line. He was hospitalized for watery and foul-smelling diarrhea. He underwent gastrointestinal endoscopy, showing duodenitis and villous atrophy and measurement of serum IgA antibodies to tissue transglutaminase (tTG-IgA+), leading to the diagnosis of ICI-induced celiac disease. He was treated with steroids, proton pump inhibitors, and a gluten-free diet. If ICI-induced celiac disease is rare in the literature, increasing reports suggest that celiac disease might represent an underestimated ICI toxicity. This case highlights the necessity of complementary investigation (including tTG-IgA and endoscopic biopsies) in patients with atypical digestive symptoms during immunotherapy

Pancreatology

BACKGROUND: PRSS1 and PRSS2 constitute the only functional copies of a tandemly-arranged five-trypsinogen-gene cluster (i.e., PRSS1, PRSS3P1, PRSS3P2, TRY7 and PRSS2) on chromosome 7q35. Variants in PRSS1 and PRSS2, including missense and copy number variants (CNVs), have been reported to predispose to or protect against chronic pancreatitis (CP). We wondered whether a common trypsinogen pseudogene deletion CNV (that removes two of the three trypsinogen pseudogenes, PRSS3P2 and TRY7) might be associated with CP causation/predisposition. METHODS: We analyzed the common PRSS3P2 and TRY7 deletion CNV in a total of 1536 CP patients and 3506 controls from France, Germany, India and Japan by means of quantitative fluorescent multiplex polymerase chain reaction. RESULTS: We demonstrated that the deletion CNV variant was associated with a protective effect against CP in the French, German and Japanese cohorts whilst a trend toward the same association was noted in the Indian cohort. Meta-analysis under a dominant model yielded a pooled odds ratio (OR) of 0.68 (95% confidence interval (CI) 0.52-0.89; p = 0.005) whereas an allele-based meta-analysis yielded a pooled OR of 0.84 (95% CI 0.77-0.92; p = 0.0001). This protective effect is explicable by reference to the recent finding that the still functional PRSS3P2/TRY7 pseudogene enhancers upregulate pancreatic PRSS2 expression. CONCLUSIONS: The common PRSS3P2 and TRY7 deletion CNV was associated with a reduced risk for CP. This finding provides additional support for the emerging view that dysregulated PRSS2 expression represents a discrete mechanism underlying CP predisposition or protection