Stomach size in anorexia nervosa: A new challenge?

BACKGROUND & AIMS: Changes in stomach size may impact eating behaviour. A recent study showed gastric dilatation in restrictive eating disorders using computed tomography scans. This study aimed to describe stomach size in the standing position in women with anorexia nervosa (AN). METHODS: Women treated for AN at our institution were retrospectively included if they had undergone upper gastrointestinal radiography (UGR) after the diagnosis of AN. Two control groups (CG1 and CG2) were included, both comprising female patients: CG1 patients were not obese and underwent UGR for digestive symptoms of other aetiologies, and CG2 comprised obese individuals who had UGR before bariatric surgery. A UGR-based Stomach Size Index (SSI), calculated as the ratio of the length of the stomach to the distance between the upper end of the stomach and the top of the iliac crests, was measured in all three groups. Gastromegaly was defined as SSI >1.00. RESULTS: 45 patients suffering from AN (28 with restrictive and 17 with binge/purge subtype), 10 CG1 and 20 CG2 subjects were included in this study. Stomach Size Index was significantly higher in AN (1.27 ± 0.24) than in CG1 (0.80 ± 0.11) and CG2 (0.68 ± 0.09); p < 0.001, but was not significantly different between patients with the restrictive and binge/purge subtypes. Gastromegaly was present in 82.2% of patients with AN and not present in the control groups. In patients with AN, gastromegaly was present in 12/15 patients without digestive symptoms (80.0%) and in 25/30 patients with digestive complaints (83.3%) at time of UGR (p = 0.99). In the AN group, no significant relationship was found between SSI and body mass index. CONCLUSION: Gastromegaly is frequent in AN and could influence AN recovery. This anatomical modification could partially explain the alterations of gastric motility previously reported in AN.

Assessing the time-to-removal of totally implantable venous access devices comparing valved-versus open-ended catheters in patients treated with chemotherapy.

BACKGROUND: Totally IntraVenous Acess Devices (TIVAD) are used to have long-term bloodstream access. The catheter connected to the subcutaneous chamber may be valved (TIVAD-V) or open-ended (TIVAD-O). Infectious and occlusion complications require the removal of the TIVAD. We compared the two types of catheters (TIVAD-V and TIVAD-O) in terms of time-to-removal and complication rates. METHODS: A retrospective study of 636 patients treated for any malignancy using a TIVAD were included. TIVAD complication was defined as the occurrence of infection or occlusion requiring TIVAD removal. Risk factors of complications and time-to-removal of TIVAD were assessed by a Cox proportional hazard analysis. RESULTS: A total of 55 TIVADs (8.7%) were removed including 47 for infection and eight for occlusion in 54 months. There was no significant difference in the frequency of complications between TIVAD-V and TIVAD-O. There was no significant difference in time-to-removal between TIVAD-V and TIVAD-O (17.0 months, IQR [10.5-25.0] and 18.4 months, IQR [11.5-22.9], p = 0.345, respectively). CONCLUSION: There was no difference between TIVAD with valved and open catheter in terms of complications and time-to-removal in patients treated by chemotherapy.

Characteristics and treatment options of glucagonomas: a national study from the French Group of Endocrine Tumors and ENDOCAN-RENATEN network.

OBJECTIVE: Glucagonoma is a very rare functional pancreatic neuroendocrine tumor (PanNET). We aimed to provide data on the diagnosis, prognosis, and management of patients with glucagonoma. DESIGN AND METHODS: In this retrospective national cohort, we included all patients with glucagonoma, defined by at least 1 major criterion (necrolytic migratory erythema [NME] and/or recent-onset diabetes, and/or weight loss ≥ 5 kg) associated with either glucagonemia > 2 × upper limit of normal or positive glucagon immunostaining. Antisecretory efficacy was defined as partial/complete resolution of glucagonoma symptoms. Antitumor efficacy was assessed according to the time to next treatment (TTNT). RESULTS: Thirty-eight patients were included with median age 58.7 yo, primary PanNET located in the tail (68.4%), synchronous metastases (63.2%). Median Ki-67 index was 3%. Most frequent glucagonoma symptoms at diagnosis were NME (86.8%), weight loss (68.4%), and diabetes (50%). Surgery of the primary PanNET was performed in 76.3% of cases, mainly with curative intent (61.5%). After surgery, complete resolution of NME was seen in 93.8% (n = 15/16). The secretory response rates were 85.7%, 85.7%, 75%, and 60% with surgery of metastases (n = 6/7), chemotherapy (n = 6/7), liver-directed therapy (n = 6/8), and somatostatin analogs (n = 6/10), respectively. All lines combined, longer TTNT was reported with chemotherapy (20.2 months). Median overall survival (OS) was 17.3 years. The Ki-67 index > 3% was associated with shorter OS (hazard ratio 5.27, 95% CI [1.11-24.96], P = .036). CONCLUSION: Patients with glucagonoma had prolonged survival, even in the presence of metastases at diagnosis. Curative-intent surgery should always be considered. Chemotherapy, peptide receptor radionuclide therapy, or liver-directed therapy seems to provide both substantial antitumor and antisecretory efficacies.

Genetic counselling referral practices for patients with pancreatic adenocarcinoma: A French retrospective multicentre observational cohort study (CAPANCOGEN).

BACKGROUND/OBJECTIVES: Genetic counselling (GC) is a key step in the identification of inherited germline mutations. However, the oncogenetic practices are poorly described for pancreatic adenocarcinoma (PA) in Europe. The CAPANCOGEN study aimed to describe the GC referral practices in France and assess the implementation of international guidelines in patients with PA. METHODS: Information about GC referrals with PA was collected in 13 French centres from September 2019 to October 2021. In the 5 largest centres, personal and familial histories of cancers and diseases associated with a higher risk of germline mutations were collected in 460 patients, according to international, American, European and French GC referral guidelines. Univariate and multivariate logistic regression analysis were performed to identify the factors influencing GC referral. RESULTS: Among 833 patients, a total of 100 patients (12%) had an indication of GC according to local multidisciplinary tumour board meetings (MTBM). Among these patients, 41% did not undergo GC. The median time between MTBM and GC was 55 days (IQR: 14.5-112). Among 460 patients with collected personal and familial history, 31.5% were not referred to a GC despite an existing indication. In multivariate logistic regression analysis, suspected CDKN2A (p = 0.032) or BRCA mutation (p < 0.001), familial pancreatic cancer history (p < 0.001) and controlled disease with first-line platinum-based chemotherapy (p < 0.001) increased the referral rate. Conversely, older age (p = 0.002) and a locally advanced PA (p = 0.045) decreased the risk of GC referral. CONCLUSIONS: GC referral is inadequate despite valuable information in patients' medical files.

Prevalence of cannabidiol (CBD) consumption and cancer patients' expectations in one oncology day-hospital: A cross-sectional study and questionnaire validation.

INTRODUCTION: The growing interest of cannabidiol (CBD) in medical care prompted French health authorities to explore the potential of CBD in cancer-related severe symptoms. This study aimed to assess the prevalence of CBD use among cancer patients with potential associated factors and to measure the cancer patient's health literacy (HL) on CBD consumption. METHODS: In a prospective study in oncology day-care hospital including patients from 29 October to 20 December 2021, we collected demographic, biological, and oncological characteristics. Patient CBD HL was measured by the hetero-questionnaire 8-item-CBD HL scale (HLS-8-CBD) whose conception has been validated by a psychometric analysis. RESULTS: Among 363 participants, 20 patients (5.5%) reported CBD use. Factors associated with CBD use were: age <60 years (odd ratio = 7.80[1.36-13.32], p < 10-4 versus ≥60 years), smoking history (OR = 5.53[1.81-16.88], p < 0.01), and no smoking cessation (OR = 5.07[1.66-15.46], p < 0.01). CBD use was also associated with a better CBD total HL score than non-users (p-value = 0.02). CONCLUSION: Identification of factors associated with CBD use and a relatively high patient CBD HL in CBD users showed that CBD use in cancer patients care represented a new concern and should enhance health professionals to consider CBD with its associated drug-related problems.

Beta-blocker exposure and survival outcomes in patients with advanced pancreatic ductal adenocarcinoma: a retrospective cohort study (BETAPANC).

Introduction: Preclinical studies have demonstrated the possible role of beta-adrenergic receptors in pancreatic ductal adenocarcinoma (PDAC) tumor invasion and migration. The current study aimed to explore the possible association between survival outcomes and beta-blocker (BB) exposure in patients with advanced PDAC. Methods: This retrospective single-center study included 182 patients with advanced PDAC. Clinical [age, sex, BMI, cardiovascular condition, presence (SBB) or absence (NSBB) of beta-1 selectivity of BB, exposure duration, and multimorbidity], oncological (stage and anticancer treatment regimen), and biological (renal and liver function) data were collected. The endpoints were overall survival (OS) and progression-free survival (PFS). Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for survival outcomes associated with BB exposure were estimated using Cox regression model and propensity score (PS) methods. Results: Forty-one patients (22.5%) were exposed to BB. A total of 104 patients progressed (57.1%) to PDAC and 139 (76.4%) patients died at the end of follow-up (median, 320 days; IQR, 438.75 days). When compared to the non-exposed group, there was no increase in survival outcomes associated with BB use (OS: HR = 1.38, 95% CI = 0.80-2.39, p = 0.25; PFS: adjusted HR = 0.95, 95% CI = 0.48-1.88, p = 0.88). Similar results were obtained using the PS method. Compared to no BB usage, SBB use was associated with a significant decrease in OS (HR = 1.80, 95% CI = 1.16-2.80, p < 10-2). Conclusion: BB exposure was not associated with improved PDAC survival outcomes. Beta-1-selectivity was not independently associated with any differences.

Cannabidiol-drug interaction in cancer patients: A retrospective study in a real-life setting.

Cannabidiol (CBD) consumption in cancer patients is growing and there is a need to investigate how to detect cannabidiol-drug interactions (CDIs). However, CDIs and the clinical relevance between CBD, anticancer treatment, supportive care and conventional drugs is poorly studied especially in real-life settings. In 1 oncology day-hospital, a cross-sectional study in 363 cancer patients treated with chemotherapy revealed 20 patients (5.5%) who consumed CBD. In this study we aimed to explore the prevalence and clinical relevance of CDIs among these 20 patients. CDI detection used the Food and Drug Administration Drugs.com database and clinical relevance was assessed accordingly. Ninety CDIs with 34 medicines were detected (4.6 CDI/patient). The main clinical risks were central nervous system depression and hepatoxicity. The main CDIs were assessed as moderate and anticancer treatment do not seem to add to the risk. CBD discontinuation appears to be the most consistent management. Future studies should explore the clinical relevance of drug interactions with CBD in cancer patients.

Renal impairment and abnormal liver function tests in pre-therapeutic phenotype-based DPD deficiency screening using uracilemia: a comprehensive population-based study in 1138 patients.

Background: Dihydropyrimidine dehydrogenase (DPD) deficiency screening is a pre-therapeutic standard to prevent severe fluoropyrimidine-related toxicity. Although several screening methods exist, the accuracy of their results remains debatable. In France, the uracilemia measurement is considered the standard in DPD deficiency screening. The objective of this study was to describe the hyperuracilemia (⩾16 ng/mL) rate and investigate the influence of hepatic and renal impairment in uracilemia measurements since the guidelines were implemented. Patients and methods: Using a cohort of 1138 patients screened between 18 October 2018 and 18 October 2021, basic demographic characteristics, date of blood sampling, and potential biological confounders including liver function tests [aspartate aminotransaminase (AST), alanine aminotransaminase (ALT), gamma-glutamyl transferase (γGT), alkaline phosphatase (ALP), and bilirubin] and estimated glomerular filtration rate (eGFR) were collected. The second same-patient uracilemia analysis was also performed. Temporal change was graphically represented while potential confounders were stratified to show linearity when suspected. Results: Hyperuracilemia was diagnosed in 12.7% (n = 150) samples with 6.7%, 5.4%, 0.5%, and 0.08% between 16 and 20 ng/mL, 20 and 50 ng/mL, 50 and 150 ng/mL, and >150 ng/mL, respectively. The median uracilemia concentration was 9.4 ng/mL (range: 1.2 and 172.3 ng/mL) and the monthly hyperuracilemia rate decreased steadily from >30% to around 9%. Older age, normalized AST, γGT, ALP results, bilirubin levels, and decreased eGFR were linearly associated with higher plasma uracil concentrations (all p < 0.001). In the adjusted multivariate linear model, AST, eGFR, and ALP remained associated with uracilemia (p < 0.05). When measured twice in 39 patients, the median uracilemia rate of change was -2.5%, which subsequently changed the diagnosis in nine patients (23.1%). Conclusions: Better respect of pre-analytical conditions may explain the steady decrease in monthly hyperuracilemia rates over the 3 years. Elevated AST, ALP levels, and reduced eGFR could induce a false increase in uracilemia and second uracilemia measurements modified the first DPD deficiency diagnosis in almost 25% of the patients.

The PRSS3P2 and TRY7 deletion copy number variant modifies risk for chronic pancreatitis.

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.

Association of Low Handgrip Strength with Chemotherapy Toxicity in Digestive Cancer Patients: A Comprehensive Observational Cohort Study (FIGHTDIGOTOX).

In the FIGHTDIGO study, digestive cancer patients with dynapenia experienced more chemotherapy-induced neurotoxicities. FIGHTDIGOTOX aimed to evaluate the relationship between pre-therapeutic handgrip strength (HGS) and chemotherapy-induced dose-limiting toxicity (DLT) or all-grade toxicity in digestive cancer patients. HGS measurement was performed with a Jamar dynamometer. Dynapenia was defined according to EWGSOP2 criteria (<27 kg (men); <16 kg (women)). DLT was defined as any toxicity leading to dose reduction, treatment delay, or permanent discontinuation. We also performed an exploratory analysis in patients below the included population's median HGS. A total of 244 patients were included. According to EWGSOP2 criteria, 23 patients had pre-therapeutic dynapenia (9.4%). With our exploratory median-based threshold (34 kg for men; 22 kg for women), 107 patients were dynapenic (43.8%). For each threshold, dynapenia was not an independent predictive factor of overall DLT and neurotoxicity. Dynapenic patients according to EWGSOP2 definition experienced more hand-foot syndrome (p = 0.007). Low HGS according to our exploratory threshold was associated with more all-grade asthenia (p = 0.014), anemia (p = 0.006), and asthenia with DLT (p = 0.029). Pre-therapeutic dynapenia was not a predictive factor for overall DLT and neurotoxicity in digestive cancer patients but could be a predictive factor of chemotherapy-induced anemia and asthenia. There is a need to better define the threshold of dynapenia in cancer patients.

Neoadjuvant chemotherapy for borderline resectable and upfront resectable pancreatic cancer increasing overall survival and disease-free survival?

Background: Pancreatic ductal adenocarcinoma (PDAC) is the most common pancreatic neoplasm. Surgery is the factual curative option, but most patients present with advanced disease. In order to increase resectability, results of neoadjuvant chemotherapy (NAC) on metastatic disease were extrapolated to the neoadjuvant setting by many centers. The aim of our study was to retrospectively evaluate the outcome of patients who underwent upfront surgery (US)-PDAC and borderline (BR)-PDAC, and those resected after NAC to determine prognostic factors that might affect the outcome in these resected patients. Methods: One hundred fifty-one patients between January 2012 and March 2021 in our department were reviewed. Epidemiological characteristics and pre-operative induction treatment were assessed. Pathological reports were analyzed to evaluate the quality of oncological resection (R0/R1). Post-operative mortality and morbidity and survival data were reviewed. Results: One hundred thirteen patients were addressed for US, and 38 were considered BR and referred for surgery after induction chemotherapy. The pancreatic resection R0 was 71.5% and R1 28.5%. pT3 rate was significantly higher in the US than BR (58,4% vs 34,2%, p= 0.005). The mean OS and DFS rates were 29.4 months 15.9 months respectively. There was no difference between OS and DFS of US vs BR patients. N0 patients had significantly longer OS and DFS (p=<0.001). R0 patients had significantly longer OS (p=0.03) and longer DFS (P=0.08). In the multivariate analysis, the presence of postoperative pancreatic fistula, R1 resection, N+ and not access to adjuvant chemotherapy were bad prognostic factors of OS. Conclusions: Our study suggests the benefits of NAC for BR patients in downstaging tumors and rendering them amenable to resection, with same oncological result compared to US.

Impact of Guidelines Regarding Dihydropyrimidine Dehydrogenase (DPD) Deficiency Screening Using Uracil-Based Phenotyping on the Reduction of Severe Side Effect of 5-Fluorouracil-Based Chemotherapy: A Propension Score Analysis.

Dihydropyrimidine dehydrogenase (DPD) deficiency is associated with severe fluoropyrimidines-induced toxicity. As of September 2018, French recommendations call for screening for DPD deficiency by plasma uracil quantification prior to all fluoropyrimidine-based chemotherapy. A dose reduction of fluoropyrimidine is recommended when uracil concentration is equal to or greater than 16 ng/mL. This matched retrospective study assessed the impact of DPD screening on the reduction of severe side effects and on the management of DPD-deficient patients. Using a propensity score, we balanced the factors influencing 5-Fluorouracil (5-FU) toxicity. Then, the severity scores (G3 and G4 severity as well as their frequency) of patients who did not benefit from DPD screening were compared with those of patients who benefited from DPD screening for each treatment cycle (from 1 to 4). Among 349 screened patients, 198 treated patients were included. Among them, 31 (15.7%) had DPD deficiency (median uracilemia 19.8 ng/mL (range: 16.1−172.3)). The median toxicity severity score was higher in the unscreened group for each treatment cycle (0 vs. 1, p < 0.001 at each cycle from 1 to 4) as well as the cumulative score during all courses of treatment (p = 0.028). DPD-deficient patients received a significantly lower dose of 5-FU (p < 0.001). This study suggests that pretherapeutic plasmatic uracil assessment, along with 5-FU dosage adjustment, may be beneficial in reducing 5-FU toxicity in real-life patients.

Pesticides and pancreatic adenocarcinoma: A transversal epidemiological, environmental and mechanistic narrative review.

Pancreatic adenocarcinoma (PA) incidence is rising worldwide, especially in France. The evolution of known risk factors such as tobacco smoking, obesity, type 2 diabetes, chronic pancreatitis, or constitutional mutations is not sufficient to explain this trend. Pesticides are known risk factors in other malignancies. Previous studies have outlined pesticides' influence in PA, such as dichlorodiphenyltrichloroethane as plausible risk factors. The general population is directly or indirectly exposed to pesticides through air, food or water. Some of these chemicals may accumulate in the body all along lifetime and may harm carriers. The toxic mixing effects of these chemicals are not well documented. Several hypotheses have been put forward to explain how pesticides can induce indirect (fatty pancreas, induced diabetes) or direct (oxidative stress, cell damage) carcinogenesis in pancreatic cells through inflammation. A strong corpus exists acknowledging pesticides as a PA risk factor. However, published studies do not provide a sufficient level of evidence to prove causality and current prospective case-control studies are still ongoing.

One-year COVID-19 outcomes on the oncology care patient pathway: Results of a French descriptive, cross-sectional comprehensive study (ONCOCARE-COV).

BACKGROUND: The COVID-19 pandemic led to a widely documented disruption in cancer care pathway. Since a resurgence of the pandemic was expected after the first lockdown in France, the global impact on the cancer care pathway over the year 2020 was investigated. AIMS: This study aimed to describe the changes in the oncology care pathway for cancer screening, diagnosis, assessment, diagnosis annoucement procedure and treatment over a one-year period. MATERIALS & METHODS: The ONCOCARE-COV study was a comprehensive, retrospective, descriptive, and cross-sectional study comparing the years 2019 and 2020. All key indicators along the cancer care pathway assessing the oncological activity over four periods were described. This study was set in a high-volume, public, single tertiary care center divided in two complementary sites (Reims University Hospital and Godinot Cancer Institute, Reims, France) which was located in a high COVID-19 incidence area during both peaks of the outbreak. RESULTS: A total of 26,566 patient's files were active during the year 2020. Breast screening (-19.5%), announcement dedicated consultations (-9.2%), Intravenous and Hyperthermic Intraoperative Intraperitoneal Chemotherapy (HIPECs) (-25%), and oncogeriatric evaluations (-14.8%) were heavily disrupted in regard to 2020 activity. We identified a clear second outbreak wave impact on medical announcement procedures (October, -14.4%), radiotherapy sessions (October, -16%), number of new health record discussed in multidisciplinary tumor board meeting (November, -14.6%) and HIPECs (November, -100%). Moreover, 2020 cancer care activity stagnated compared to 2019. DISCUSSION: The oncological care pathway was heavily disrupted during the first and second peaks of the COVID-19 outbreak. Between lockdowns, we observed a remarkable but non-compensatory recovery as well as a lesser impact from the pandemic resurgence. However, in absence of an increase in activity, a backlog persisted. CONCLUSION: Public health efforts are needed to deal with the consequences of the COVID-19 pandemic on the oncology care pathway.

Impact of the COVID-19 pandemic on disease stage and treatment for patients with pancreatic adenocarcinoma: A French comprehensive multicentre ambispective observational cohort study (CAPANCOVID).

BACKGROUND: The COVID-19 pandemic caused major oncology care pathway disruption. The CAPANCOVID study aimed to evaluate the impact on pancreatic adenocarcinoma (PA) - from diagnosis to treatment - of the reorganisation of the health care system during the first lockdown. METHODS: This multicentre ambispective observational study included 833 patients diagnosed with PA between September 1, 2019 and October 31, 2020 from 13 French centres. Data were compared over three periods defined as before the outbreak of COVID-19, during the first lockdown (March 1 to May 11, 2020) and after lockdown. RESULTS: During the lockdown, mean weekly number of new cases decreased compared with that of pre-pandemic levels (13.2 vs. 10.8, -18.2%; p = 0.63) without rebound in the post-lockdown period (13.2 vs. 12.9, -1.7%; p = 0.97). The number of borderline tumours increased (13.6%-21.7%), whereas the rate of metastatic diseases rate dropped (47.1%-40.3%) (p = 0.046). Time-to-diagnosis and -treatment were not different over periods. Waiting neoadjuvant chemotherapy in resectable tumours was significantly favoured (24.7%-32.6%) compared with upfront surgery (13%-7.8%) (p = 0.013). The use of mFOLFIRINOX preoperative chemotherapy regimen decreased (84.9%-69%; p = 0.044). After lockdown, the number of borderline tumours decreased (21.7%-9.6%) and advanced diseases increased (59.7%-69.8%) (p = 0.046). SARS-CoV-2 infected 39 patients (4.7%) causing 5 deaths (12.8%). CONCLUSION: This cohort study suggests the existence of missing diagnoses and of a shift in disease stage at diagnosis from resectable to advanced diseases with related therapeutic modifications whose prognostic consequences will be known after the planned follow-up. TRIAL REGISTRATION: Clinicaltrials.gov NCT04406571.

Efficacy of treatments for VIPoma: A GTE multicentric series.

BACKGROUND: Vasoactive intestinal peptide-secreting tumor (VIPoma) is a very rare, life-threatening, functioning pancreatic neuroendocrine tumor (pNET). The efficacy of antitumor therapies against functioning symptoms and tumor burden have been poorly described in VIPoma. OBJECTIVE: Describe the impact of treatments on the secretory syndrome, tumor burden and survival in patients with VIPoma. METHODS: We retrospectively reviewed the records of patients with VIPoma treated in seven French expert centers between 1990 and 2016. Diagnostic of VIPoma was reassessed using strict criteria. We evaluated the antisecretory efficacy (>50 % decrease of daily bowel movements), and antitumor efficacy (RECIST 1.1) of all treatments received. RESULTS: Twenty-two patients were included. pNETs were mostly metastatic (77 %) and classified as grade 2 (83 %). Median follow-up was 78.2 months. Surgical excision of nonmetastatic VIPoma effectively controlled the secretory syndrome. Although 4/5 patients had metastatic recurrences, all patients were alive after median post-operative follow-up of 171 months. Among the 87 treatments received for metastatic VIPoma, curative-intent surgery (n = 14), somatostatin analogs alone (n = 11), chemotherapy (n = 23), transarterial liver embolization (TALE) (n = 14), everolimus (n = 10) and sunitinib (n = 7) achieved, respectively, 100 %, 67 %, 83 %, 50 %, 20 % and 100 % antisecretory efficacy. The 5-year OS rate was 63.6 %, with pejorative impact of higher Ki-67 index (P = 0.045) and higher plasma VIP concentration (P = 0.025). CONCLUSIONS: Surgical resection of localized VIPoma is effective but rarely curative. For metastatic VIPoma, curative-intent surgery, chemotherapy and sunitinib are the therapeutic options that best combined antitumor and antisecretory efficacies.

Prognostic Factors and Survival Score for Patients With Anaplastic Thyroid Carcinoma: A Retrospective Study from a Regional Registry.

BACKGROUND/AIM: Anaplastic thyroid carcinoma (ATC) is the least common but most lethal of thyroid cancer, despite various therapeutic options, with limited efficacy. In order to help therapeutic decision-making, the purpose of this study was to develop a new prognostic score providing survival estimates in patients with ATC. PATIENTS AND METHODS: Based on a multivariate analysis of 149 retrospectively analyzed patients diagnosed with ATC from 1968 to 2017 at a referral center, a propensity score was developed. A model was generated providing survival probability at 6 months and median overall survival estimates. RESULTS: The median survival was 96 days. The overall survival rate was 35% at 6 months, 20% at 1 year and 13% at 2 years. Stepwise Cox regression revealed that the most appropriate death prediction model included metastatic spread, tumor size and age class as explanatory variables. This model made it possible to define three categories of patients with different survival profiles. CONCLUSION: Distant metastasis, age and primary tumor size are strong independent factors that affect prognosis in patients with ATC. Using these significant pretreatment factors, we developed a score to predict survival in these patients with poor prognosis.

Simultaneous quantification of seven repurposed COVID-19 drugs remdesivir (plus metabolite GS-441524), chloroquine, hydroxychloroquine, lopinavir, ritonavir, favipiravir and azithromycin by a two-dimensional isotope dilution LC-MS/MS method in human serum.

BACKGROUND: The present COVID-19 pandemic has prompted worldwide repurposing of drugs. The aim of the present work was to develop and validate a two-dimensional isotope-dilution liquid chromatrography tandem mass spectrometry (ID-LC-MS/MS) method for accurate quantification of remdesivir and its active metabolite GS-441524, chloroquine, hydroxychloroquine, lopinavir, ritonavir, favipiravir and azithromycin in serum; drugs that have gained attention for repurposing in the treatment of COVID-19. METHODS: Following protein precipitation, samples were separated with a two-dimensional ultra-high performance liquid chromatography (2D-UHPLC) setup, consisting of an online solid phase extraction (SPE) coupled to an analytical column. For quantification, stable isotope-labelled analogues were used as internal standards for all analytes. The method was validated on the basis of the European Medicines Agency bioanalytical method validation protocol. RESULTS: Detuning of lopinavir and ritonavir allowed simultaneous quantification of all analytes with different concentration ranges and sensitivity with a uniform injection volume of 5 µL. The method provided robust validation results with inaccuracy and imprecision values of ≤ 9.59 % and ≤ 11.1 % for all quality controls. CONCLUSION: The presented method is suitable for accurate and simultaneous quantification of remdesivir, its metabolite GS-441525, chloroquine, hydroxychloroquine, lopinavir, ritonavir, favipiravir and azithromycin in human serum. The quantitative assay may be an efficient tool for the therapeutic drug monitoring of these potential drug candidates in COVID-19 patients in order to increase treatment efficacy and safety.

Dramatic Changes in Oncology Care Pathways During the COVID-19 Pandemic: The French ONCOCARE-COV Study.

The coronavirus disease 2019 (COVID-19) pandemic may have affected cancer management. We aimed to evaluate changes in every oncology care pathway essential step, from screening to treatment, during the pandemic. Monthly oncological activity differences between 2019 and 2020 (screening tests, histopathological analyzes, multidisciplinary tumor board meetings (MTBMs), diagnostic announcement procedures (DAPs), and treatments were calculated in two French areas experiencing different pandemic intensity (Reims and Colmar). COVID-19 has had a dramatic impact in terms of screening (-86% to -100%), diagnosis (-39%), and surgical treatment (-30%). This global decrease in all essential oncology care pathway steps contrasted with the relative stability of chemotherapy (-9%) and radiotherapy use (-16%). Outbreak occurred earlier and with more intensity in Colmar but had a comparable impact in both areas regarding MTMBs and DAPs. The current ONCOCARE-COV study is still in progress and with a longer follow-up to analyze postlockdown situation.