Analytical interference in CA 19-9 immunoassay generates false-positive results in a young woman with a low-grade appendiceal tumor: An educational case report and brief literature review.

CA 19-9 (carbohydrate antigen 19-9) is a tumor marker widely used for the follow-up of patients with pancreatic cancer and other digestive neoplasia. This case report describes a discrepancy between the results of serum CA 19-9 analyses using the Alinity analytical platform (Abbott™) and two other techniques, Kryptor Gold (ThermoFisher Scientific™) and Cobas E411 (Roche™), in the context of a young woman with appendiceal mucocele. In this context, when the serum concentration of CA 19-9 is high, it may raise concerns about potential malignancy or rupture of the mucocele that may lead to tumoral dissemination in the abdominal cavity. In the present case, we observed with Alinity a false elevation in CA 19-9 concentration at 190 kU/L (normal range < 37 kU/L) before appendix resection that continued to increase until reaching 619 kU/L six months after surgery. This situation led to unnecessary additional tests, increased hospitalization time and stress for the patient who also had to interrupt her medically assisted reproduction project. We solved this case using new measurements in CA 19-9 concentration with two other techniques, Kryptor Gold and Cobas E411, and we identified an analytical interference caused by the presence of heterophile antibodies. In all cases, abnormal result initially obtained with Alinity was found below normal range not only with the two other techniques but also with Alinity after a neutralisation step by using Heterophile Blocking Tubes (Scantibodies Laboratory™). Analytical interferences in medical tests can lead to inappropriate medical care. It is an important issue requiring a continuing training of biologists who must be aware of these problems, which are recurring concerns and are not always easy to identify in laboratories of medical biology, in particular when immunoassays are used. This case report also provides an opportunity to do a brief review of the literature and to remind some recommendations and actions to take into consideration in the presence of discrepancies between the clinic and the biology, in particular, one of them is to measure the biological analyte with a different technique. Moreover, the use of Heterophile Blocking Tubes neutralizing specifically the heterophile antibodies may be useful. In all cases, dialogue between clinicians and biologists remains essential.

Pregnancy Outcomes After Bariatric Surgery: Importance of Maternal Ferritin on Birth Weight.

PURPOSE: The risks carried by pregnancy after bariatric surgery (BS) include small-for-gestational age (SGA) newborn and prematurity. However, the underlying mechanisms are not yet fully understood in pregnant women after BS. MATERIAL AND METHODS: This single-center retrospective observational cohort study includes all women with a first and single pregnancy after BS who completed at least one clinical and biological nutritional assessment during pregnancy between 2010 and 2016. The quarterly biological assessment comprised blood count, ferritin, calcium, 25OH vitamin D, parathyroid hormone, fasting glucose, albumin, prealbumin, vitamin A, vitamin B12, folic acid, and zinc. RESULTS: Among 120 pregnancies analysed, two-thirds underwent gastric bypass (Roux-en-Y and one-anastomosis) and one-third a restrictive procedure (adjustable gastric band or sleeve gastrectomy). The median [Q1-Q3] preoperative BMI was 43.8 [41.1-47.7] kg/m2 and the mean age at pregnancy was 32.6 ± 5.3 years. Weight loss and time from surgery to pregnancy were 35.1 ± 15.4 kg and 2.9 [1.3-4.5] years, respectively. Ten women (8%) gave birth prematurely, and 22 newborns (19%) were SGA. Univariate analysis shows that ferritin was significantly higher in mothers with SGA than in those without SGA (35.5 [22.3-69.5] vs. 15 [10-32] ng/ml) at third trimester of pregnancy. Women who received pre-pregnancy nutritional assessment seemed less likely to give birth to a SGA newborn (32% vs. 54%, p = 0.07). CONCLUSION: Iron supplementation should be carefully prescribed and closely monitored during pregnancy in women who have undergone BS.

Prognostic impact of positive microscopic margins (R1 resection) in patients with GIST (gastrointestinal stromal tumours): Results of a multicenter European study.

BACKGROUND: Although several prognostic factors in GIST have been well studied such as tumour size, mitotic rate, or localization, the influence of microscopic margins or R1 resection remains controversial. The aim of this study was to evaluate the influence of R1 resection on the prognosis of GIST in a large multicentre retrospective series of patients. METHODS: From 2001 to 2013, 1413 patients who underwent surgery for any site of GIST were identified from 61 European centers. 1098 patients were included, excluding synchronous metastases, concurrent malignancies, R2 resection or GIST recurrence. Tumour rupture (TR) was reclassified according to the Oslo sarcoma classification. Cox proportional hazards ratio and Kaplan-Meier survival estimates were used to analyse 5-year recurrence-free survival (RFS). RESULTS: Of 1098 patients, 38 (3%) underwent R1 resection with a risk of TR of 11%. The 5-year RFS was 89.6% with a median follow-up of 81 months [range: 31.2-152 months]. On univariate analysis, lower RFS was significantly associated with R1 resection [HR = 2.13; p = 0.04], high risk score according to the modified NIH classification, administration of adjuvant therapy [HR = 2.24; p < 0.001] and intraoperative complications [HR = 2.82; p < 0.001]. Only intraoperative complications [HR = 1.79; p = 0.02] and high risk according to the modified NIH classification including the updated definition of TR [HR = 3.43; p = 0.04] remained significant on multivariate analysis. CONCLUSION: This study shows that positive microscopic margins are not an independent predictive factor for RFS in GIST when taking into account the up-dated classification of TR. R1 resection may be considered a reasonable alternative to avoid major functional sequelae and should not lead to reoperation.

Management of Severe Malnutrition Post-bariatric Surgery Using Artificial Nutrition.

BACKGROUND: Bariatric surgery (BS) results in major and sustained weight loss and improves comorbidities in patients with obesity but can also lead to malnutrition, especially through severe malabsorption and/or surgical complications. Little is known about the efficacy of artificial nutrition (AN) in this setting. METHODS: In this case series, we describe data from consecutive severely malnourished patients after BS (resectional and non-resectional), managed by AN at our hospital unit over a 4-year period. RESULTS: Between January 2018 and June 2022, 18 patients (mean ± SD age 42.2 ± 10.4 years, 94% women) required AN following BS complications. At the time of AN initiation, more than half of the patients (53%) had multiple revisional surgeries (up to four). Mean BMI was 49.7 ± 11.3 kg/m2 before BS and 29.6 ± 9.6 kg/m2 when AN was initiated. Most patients (n=16, 90%) received enteral nutrition. AN management resulted in weight regain (+4.7kg ± 8.0, p=0.034), increased serum albumin (+28%, p=0.02), pre-albumin (+88%, p=0.002), and handgrip strength (+38%, p=0.078). No major AN complication nor death was observed. Median total AN duration was 4.5 months [1-12]. During follow-up, the cumulative duration of hospitalization was 33 days [4-88] with a median of 2.5 hospitalizations [1-8] per patient. CONCLUSION: Malnutrition can occur after any BS procedure, and AN when required in this setting appears safe and effective on nutritional parameters. It is important to recognize the potential risk factors for malnutrition, which include excessive weight loss resulting from surgical complications, eating disorders, multiple revisional BS, and pregnancy.

Serum Versus Fecal Calprotectin Levels in Patients with Severe Obesity Before and 6 Months After Roux-Y-Gastric Bypass: Report of the Prospective Leaky-Gut Study.

INTRODUCTION: Obesity is associated with low-grade inflammation, including intestinal inflammation based on fecal or serum calprotectin (FC-SC) measurement. Roux-en-Y gastric bypass (RYGB) improves obesity-related parameters. However, the association between FC-SC levels and postoperative course and the link with metabolic and inflammatory phenotypes before and after RYGB remains unclear. METHODS: We determined SC levels in 48 patients before (T0) and 6 months after (T6M) RYGB. We then analyzed postoperative changes in FC-SC levels and the relationship with inflammation and metabolic status. RESULTS: Twenty-three patients (48%) had elevated SC levels (˃2.9 µg/mL) at T0 and T6M. Six of 29 patients (20.7%) had elevated FC concentrations (>50 µg/g) at T0 vs. 16 of 17 patients (94.1%) at T6M (p=0.006). At T0, FC levels correlated with BMI (Rho=0.63; p=0.001) and systemic inflammation (CRP: Rho=0.66, p=0.0006; IL-6: Rho=0.48, p=0.03; haptoglobin: Rho=0.75; p= 0.0006). SC tended to be positively associated with triglyceride levels (Rho=0.34; p=0.08), BMI (Rho=0.34; p=0.08), and inflammatory markers (CRP: Rho=0.33; p=0.09; IL-6: Rho=0.36; p=0.06). FC levels were associated with increased jejunal IL-17+CD8+ T-cell densities (Rho:0.90; p=0.0002). FC and SC were correlated together at T0 (Rho=0.83; p<0.001) but not at T6M. At T6M, SC decreased by 53.6%, whereas FC increased by 79.7%. SC and FC were not associated with any of the variables studied at T6M. CONCLUSION: FC is a surrogate marker of systemic and intestinal inflammation and adiposity, whereas SC only tends to correlate with systemic inflammation. At 6 months after RYGB, SC-based systemic inflammation decreased, whereas FC-based intestinal inflammation increased. FC and SC levels follow different trajectories and are unrelated to improvements following bariatric surgery.

Revisional Roux-en-Y Gastric Bypass After Sleeve Gastrectomy for Gastro-esophageal Reflux Disease and or Insufficient Weight-Loss: a Comparative Study.

INTRODUCTION: Sleeve gastrectomy (SG) is a popular surgical weight-loss procedure, but there are increasing reports of revisional Roux-Y-gastric-bypass (R-RYGB) to manage weight-loss failure (WLF) or proton pump inhibitor (PPI)-refractory gastroesophageal reflux disease (GERD) after SG, with little data available in these settings. METHODS: This retrospective study included all consecutive patients undergoing R-RYGB for WLF or RGERD after SG in two bariatric care centers from 2012 to 2018. RESULTS: Of 720 patients, 46 (3.6%) underwent R-RYGB (RGERD, n = 25; 54.4%; WLF, n = 21; 45.6%) within 44.8 ± 27.5 months post-SG. SG had enabled 27% ± 11.6 total weight loss (TWL) in the RGERD group vs. 7.2% ± 12.5% TWL in the WLF group (p < 0.001). At R-RYGB, WLF-group patients had a higher BMI (47.8 ± 8.4 vs. 34.7 ± 6.1 kg/m2; p < 0.001) and a higher number of comorbidities (2.4 ± 1.5 vs 1.5 ± 1.2; p < 0.02) compared to RGERD-group patients, while severe morbidity (Clavien-Dindo ≥ IIIb) was not significantly different between groups (6.5% vs 2.1%, p = 0.6). %TWL was still higher in the RGERD group at 12 months post-R-RYGB (35.6% ± 10.4 vs. 23.8% ± 9.2; p < 0.01) but not after 24 months post-R-RYGB. R-RYGB corrected reflux symptoms in 32 (94%) patients and reduced PPI use in 29 (97%) patients (p < 0.001), with no significant between-group difference. A history of adjustable gastric banding (AGB) (N = 8;17.4%) prior to SG was associated with a similar prevalence of GERD at R-RYGB and a lower %TWL (AGB:13.1 ± 10.2 vs. No AGB:31.6 ± 8.5; p < 0.05) at 3 years post-R-RYGB. CONCLUSION: R-RYGB following SG provides remission of reflux symptoms in 94% of patients and extra weight loss in patients with WLF, except in patients with a history of AGB prior to SG.

Obesity-induced hyperglycemia impairs oral tolerance induction and aggravates food allergy.

Obesity and type 2 diabetes (T2D) have been found to be associated with abnormalities in several organs, including the intestine. These conditions can lead to changes in gut homeostasis, compromising tolerance to luminal antigens and increasing susceptibility to food allergies. The underlying mechanisms for this phenomenon are not yet fully understood. In this study, we investigated changes in the intestinal mucosa of diet-induced obese mice and found that they exhibited increased gut permeability and reduced Treg cells frequency. Upon oral treatment with ovalbumin (OVA), obese mice failed to develop oral tolerance. However, hyperglycemia treatment improved intestinal permeability and oral tolerance induction in mice. Furthermore, we observed that obese mice exhibited a more severe food allergy to OVA, and this allergy was alleviated after treatment with a hypoglycemic drug. Importantly, our findings were translated to obese humans. Individuals with T2D had higher serum IgE levels and downregulated genes related to gut homeostasis. Taken together, our results suggest that obesity-induced hyperglycemia can lead to a failure in oral tolerance and to exacerbation of food allergy. These findings shed light on the mechanisms underlying the relationship among obesity, T2D, and gut mucosal immunity, which could inform the development of new therapeutic approaches.

Precision Bariatric/Metabolic Medicine and Surgery.

Indications and techniques of bariatric surgery (BS) have constantly evolved in recent decades and now face new challenges [...].

Follow-Up, Safety, and Satisfaction with Tele-bariatric Follow-Up Implemented During the COVID-19 French Lockdown: a 2-Year Follow-Up Study.

BACKGROUND: The COVID-19 pandemic was initially responsible for a global restricted access to healthcare resources including the follow-up of at-risk populations such as bariatric patients. We substituted face-to-face bariatric follow-up outpatient clinics (FTFC) with teleclinics (TC) during the lockdown. MATERIAL AND METHODS: We retrospectively reviewed data collected on all patients scheduled for TC during the French lockdown period (March 15 to May 15, 2020) (N = 87). Our aims were to present the patients' outcomes at one and 2 years post-TC implementation and describe patient/practitioner satisfaction. RESULTS: Seven (8%) patients required FTFC, and 80 (92%) underwent TC (study population) for preoperative bariatric assessment (N = 3) and postoperative follow-up (N = 77) after 23.6 ± 29 months following surgery. TC was performed with video and audio (N = 46; 57.5%) or audio alone when video was impossible (N = 34; 42.5%). Sixteen (20%) patients presented at least one complication identified at the first TC and were managed accordingly. There were no readmissions at 30/90 days post-TC. At 1-year after the first TC, overall follow-up rate was 94.9% (TC: 73% vs FTFC: 27%). Patients surveyed on the main advantages of TC over FTFC (N = 46) cited: saving time (97.8%) at a mean 3.9 ± 6.4 h saved per TC, work-advantages (94.3%), and comparable relevance of TC (84.8%). At 2 years post-TC implementation, follow-up rate was 93.5% and satisfaction rate was 80%, with 33% of patients preferring to return to FTFC. CONCLUSIONS: TC is a satisfactory substitute for FTFC, enabling continued bariatric follow-up during and beyond the pandemic setting without compromising patient safety. However, the modest satisfaction outcomes at 2 years highlight a need to discuss follow-up preferences in order to achieve optimal outcomes.

Endoscopy management of sleeve gastrectomy stenosis: what we learned from 202 consecutive patients.

BACKGROUND: Gastric sleeve stenosis (GSS) is described in 1%-4% of patients. OBJECTIVE: To evaluate the role of endoscopy in the management of stenosis after laparoscopic sleeve gastrectomy using a standardized approach according to the characteristic of stenosis. SETTING: Retrospective, observational, single-center study on patients referred from several bariatric surgery departments to an endoscopic referral center. METHODS: We enrolled 202 patients. All patients underwent endoscopy in a fluoroscopy setting, and a systematic classification of the type, site, and length of the GSS was performed. According to the characteristics of the stenosis, patients underwent pneumatic dilatation or placement of a self-expandable metal stent or a lumen-apposed metal stent. Failure of endoscopic treatment was considered an indication for redo surgery, whereas patients with partial or complete response were followed up for 2 years. In the event of a recurrence, a different endoscopic approach was used. RESULTS: We found inflammatory strictures in 4.5% of patients, pure narrowing in 11%, and functional stenosis in 84.5%. Stenosis was in the upper tract of the stomach in 53 patients, whereas medium and distal stenosis was detected in 138 and 11 patients, respectively, and short stenosis in 194 patients. A total of 126 patients underwent pneumatic dilatation, 8 self-expandable metal stent placement, 64 lumen-apposed metal stent positioning, and 36 combined therapy. The overall rate of endoscopy success was 69%. CONCLUSION: GSS should be considered to be a chronic disease, and the endoscopic approach seems to be the most successful treatment, with a prolonged positive outcome of 69%. Characteristics of the stenosis should guide the most suitable endoscopic approach.

French recommendations on the prevention and treatment of osteoporosis secondary to bariatric surgery.

INTRODUCTION: This article presents the initial recommendations of the Groupe de Recherche et d'Information sur les Ostéoporoses (Osteoporosis Research and Information Group [GRIO]) and the Société Française de Rhumatologie (French Rheumatology Society [SFR]) on the prevention and treatment of osteoporosis secondary to bariatric surgery. METHODS: The recommendations were produced by a working group comprising 4 expert rheumatologists, 3 medically qualified nutritionists, 2 obesity surgeons, 1 physical activity specialist, and 1 patient-association representative. RESULTS: The following generally recommended measures apply to all patients with an indication for bariatric surgery or who have already undergone bariatric surgery: normalize calcium and protein intake, attain a 25(OH) vitamin D concentration of between 30 and 60ng/mL; prevent the risk of falls, and introduce a suitable regimen of physical activity. An initial assessment of fracture risk should be routinely performed - ideally before the first bariatric surgery procedure - (i) in the case of RYGB and biliopancreatic diversion, regardless of age, (ii) in patients at high risk of fracture, regardless of age, and (iii) in all menopausal women and all men ≥ 50 years old, regardless of the type of bariatric surgical procedure. The fracture risk assessment is based on a determination of osteoporosis risk factors and bone mineral density measurements. Anti-osteoporosis treatment - zoledronic acid as the first line of treatment - is indicated for menopausal women and men ≥ 50 years old with (i) a history of severe fracture, regardless of T-score, (ii) a history of non-severe fracture and a T-score ≤ -1, and (iii) no history of fracture and a T-score ≤ -2. CONCLUSIONS: There is an increased risk of fracture after bariatric surgery. Clinicians should focus their attention on patients at high fracture risk such as postmenopausal women and men older than 50 years. More research is necessary to direct and support guidelines.

Management of Pathogenic CDH1 Variant Carriers Within the FREGAT Network: A Multicentric Retrospective Study.

OBJECTIVE: To describe the management of pathogenic CDH1 variant carriers (pCDH1vc) within the FREGAT (FRench Eso-GAsTric tumor) network. Primary objective focused on clinical outcomes and pathological findings, Secondary objective was to identify risk factor predicting postoperative morbidity (POM). BACKGROUND: Prophylactic total gastrectomy (PTG) remains the recommended option for gastric cancer risk management in pCDH1vc with, however, endoscopic surveillance as an alternative. METHODS: A retrospective observational multicenter study was carried out between 2003 and 2021. Data were reported as median (interquartile range) or as counts (proportion). Usual tests were used for univariate analysis. Risk factors of overall and severe POM (ie, Clavien-Dindo grade 3 or more) were identified with a binary logistic regression. RESULTS: A total of 99 patients including 14 index cases were reported from 11 centers. Median survival among index cases was 12.0 (7.6-16.4) months with most of them having peritoneal carcinomatosis at diagnosis (71.4%). Among the remaining 85 patients, 77 underwent a PTG [median age=34.6 (23.7-46.2), American Society of Anesthesiologists score 1: 75%] mostly via a minimally invasive approach (51.9%). POM rate was 37.7% including 20.8% of severe POM, with age 40 years and above and low-volume centers as predictors ( P =0.030 and 0.038). After PTG, the cancer rate on specimen was 54.5% (n=42, all pT1a) of which 59.5% had no cancer detected on preoperative endoscopy (n=25). CONCLUSIONS: Among pCDH1vc, index cases carry a dismal prognosis. The risk of cancer among patients undergoing PTG remained high and unpredictable and has to be balanced with the morbidity and functional consequence of PTG.

Assessment of Factors Associated with Morbidity and Textbook Outcomes of Laparoscopic Liver Resection in Obese Patients: A French Nationwide Study.

BACKGROUND: Liver surgeons need to know the expected outcomes of laparoscopic liver resection (LLR) in obese patients. OBJECTIVE: The purpose of the present study is to assess morbidity, mortality and textbook outcomes (TO) after LLR in obese patients. METHODS: This is a French multicenter study of patients undergoing LLR between 1996 and 2018. Obesity was defined by a BMI at or above 30 kg/m 2 . Short-term outcomes and TO were compared between obese (ob) and nonobese (non-ob) patients. Factors associated with severe morbidity and TO were investigated. RESULTS: Of 3,154 patients included, 616 (19.5%) were obese. Ob-group patients had significantly higher American Society of Anesthesiologists (ASA) score and higher incidence of metabolic syndrome and chronic liver disease and were less likely to undergo major hepatectomy. Mortality rates were similar between ob and non-ob groups (0.8 vs 1.1%; p = 0.66). Overall morbidity and hospital stay were significantly increased in the ob group compared with the non-ob group (39.4 vs 34.7%, p = 0.03; and 9.5 vs 8.6 days, p = 0.02), whereas severe 90-day morbidity (at or above Clavien-Dindo grade III) was similar between groups (8% in both groups; p = 0.90). TO rate was significantly lower for the ob group than the non-ob group (58.3 vs 63.7%; p = 0.01). In multivariate analysis, obesity did not emerge as a risk factor for severe 90-day morbidity but was associated with a lower TO rate after LLR (odds ratio = 0.8, 95% CI 0.7-1.0; p = 0.03). CONCLUSIONS: LLR in obese patients is safe and effective with acceptable mortality and morbidity. Obesity had no impact on severe morbidity but was a factor for failing to achieve TO after LLR.

Five-Year Changes in Weight and Diabetes Status After Bariatric Surgery for Craniopharyngioma-Related Hypothalamic Obesity: a Case-Control Study.

PURPOSE: Craniopharyngiomas are tumors located in the hypothalamic region which leads to obesity in about 50% of cases. Long-term efficacy and safety of bariatric surgery are lacking in this peculiar population. The aim of this study is to determine the 5-year weight loss and resolution of type 2 diabetes (T2D) after bariatric surgery in patients operated on craniopharyngioma who had developed hypothalamic obesity. MATERIALS AND METHODS: This is a multicenter french retrospective case-control study. Subjects with craniopharyngioma (n = 23) who underwent sleeve gastrectomy (SG) (n = 9) or Roux-en-Y gastric bypass (RYGB) (n = 14) (median age 35 years [25;43] and BMI 44.2 kg/m2 [40.7; 51.0]; 8/23 with T2D) were individually matched to 2 subjects with common obesity for age, gender, preoperative body mass index, T2D, and type of surgery. RESULTS: TWL% after 1 and 5 years was lower in the craniopharyngioma group than in the control group: 23.1 [15.4; 31.1] (23/23) vs 31.4 [23.9; 35.3] at 1 year (p = 0.008) (46/46) and 17.8 [7.1; 21.9] (23/23) vs 26.2 [18.9; 33.9] at 5 years (p = 0.003) (46/46). After RYGB, TWL% was lower in the craniopharyngioma group compared to the control group (p < 0.001) and comparable after SG both at 1 and 5 years. No difference between the two groups was observed in T2D remission rate and in early and late adverse events. No hormonal deficiency-related acute disease was reported. CONCLUSIONS: Bariatric surgery induced a significant weight loss in the craniopharyngioma group at 1 and 5 years, but less than in common obesity. SG may be more effective than RYGB but this remains to be demonstrated in a larger cohort.