Role of lymphadenectomy, adjuvant chemotherapy, and treatment at high-volume centers in patients with resected pancreatic cancer-a distinct view on lymph node yield.

PURPOSE: While the importance of lymphadenectomy is well-established for patients with resectable pancreatic cancer, its direct impact on survival in relation to other predictive factors is still ill-defined. METHODS: The National Cancer Data Base 2006-2015 was queried for patients with resected pancreatic adenocarcinoma (stage IA-IIB). Patients were dichotomized into the following two groups, those with 1-14 resected lymph nodes and those with ≥ 15. Optimal number of resected lymph nodes and the effect of lymphadenectomy on survival were assessed using various statistical modeling techniques. Mediation analysis was performed to differentiate the direct and indirect effect of lymph node resection on survival. RESULTS: A total of 21,912 patients were included; median age was 66 years (IQR 59-73), 48.9% were female. Median number of resected lymph nodes was 15 (IQR 10-22), 10,163 (46.4%) had 1-14 and 11,749 (53.6%) had ≥ 15 lymph nodes retrieved. Lymph node positivity increased by 4.1% per lymph node up to eight examined lymph nodes, and by 0.6% per lymph node above eight. Five-year overall survival was 17.9%. Overall survival was better in the ≥ 15 lymph node group (adjusted HR 0.91, CI 0.88-0.95, p < 0.001). On a continuous scale, survival improved with increasing LNs collected. Patients who underwent adjuvant chemotherapy and were treated at high-volume centers had improved overall survival compared with their counterparts (adjusted HR 0.59, CI 0.57-0.62, p < 0.001; adjusted HR 0.86, CI 0.83-0.89, p < 0.001, respectively). Mediation analysis revealed that lymphadenectomy had only 18% direct effect on improved overall survival, while 82% of its effect were mediated by other factors like treatment at high-volume hospitals and adjuvant chemotherapy. DISCUSSION: While higher number of resected lymph nodes increases lymph node positivity and is associated with better overall survival, most of the observed survival benefit is mediated by chemotherapy and treatment at high-volume centers.

High rate of positive lymph nodes in T1a gallbladder cancer does not translate to decreased survival: a population-based, propensity score adjusted analysis.

BACKGROUND: Current consensus guidelines suggest that gallbladder cancer (GBC) patients with resected T1a disease can be observed while patients with T1b or greater lesions should undergo lymphadenectomy (LNE). The primary aim of this study was to critically explore the impact of LNE in early-stage GBC on overall survival (OS) on a population-based level. METHOD: The 2004-2014 National Cancer Database was reviewed to identify non-metastatic GBC patients with T1a, T1b, or T2 disease and grouped whether a dedicated LNE was performed. OS and relative survival were assessed using Cox proportional hazard regression analyses before and after propensity score adjustments. RESULTS: 4015 patients were included, 246 (6%) had T1a, 654 (16%) T1b, and 3115 (78%) T2 GBC. The rate of positive lymph nodes was 13%, 12%, and 40% for T1a, T1b, and T2 tumors, respectively. Even after propensity score adjustment, no OS benefit was found if LNE was performed for T1a disease (HR:0.63, 95%CI:0.35-1.13) while OS was improved for T1b (HR:0.65, 95%CI:0.49-0.87) and T2 tumors (HR:0.65, 95%CI:0.57-0.73). CONCLUSION: Despite a higher rate of nodal positivity among patients with T1a disease compared to previous reports, there was no impact on survival and current treatment guidelines appear appropriate for the management of T1a disease.

Longitudinal analysis of caloric requirements in critically ill trauma patients: a retrospective cohort study.

PURPOSE: Nutrition is of paramount importance in critically ill trauma patients. However, adequate supply is difficult to achieve, as caloric requirements are unknown. This study investigated caloric requirements over time, based on indirect calorimetry, in critically ill trauma patients. METHODS: Retrospective cohort study at a tertiary trauma center including critically ill trauma patients who underwent indirect calorimetry 2012-2019. Caloric requirements were assessed as resting energy expenditure (REE) during the intensive care unit stay up to 28 days and analyzed in patient-clustered linear regression analysis. RESULTS: A total of 129 patients were included. Median REE per day was 2376 kcal. The caloric intake did not meet REE at any time with a median daily deficit of 1167 kcal. In univariable analysis, ISS was not significantly associated with REE over time (RC 0.03, p = 0.600). Multivariable analysis revealed a significant REE increase (RC 0.62, p < 0.001) and subsequent decrease (RC - 0.03, p < 0.001) over time. Age < 65 years (RC 2.07, p = 0.018), male sex (RC 4.38, p < 0.001), and BMI ≥ 35 kg/m2 (RC 6.94, p < 0.001) were identified as independent predictors for higher REE over time. Severe head trauma was associated with lower REE over time (RC - 2.10, p = 0.030). CONCLUSION: In critically ill trauma patients, caloric requirements significantly increased and subsequently decreased over time. Younger age, male sex and higher BMI were identified as independent predictors for higher caloric requirements, whereas severe head trauma was associated with lower caloric requirements over time. These results support the use of IC and will help to adjust nutritional support in critically ill trauma patients.

Syndromic MEN1 parathyroid adenomas consist of both subclonal nodules and clonally independent tumors.

Primary hyperparathyroidism with parathyroid tumors is a typical manifestation of Multiple Endocrine Neoplasia Type 1 (MEN1) and is historically termed "primary hyperplasia". Whether these tumors represent a multi-glandular clonal disease or hyperplasia has not been robustly proven so far. Loss of Menin protein expression is associated with inactivation of both alleles and a good surrogate for a MEN1 gene mutation. The cyclin-dependent kinase inhibitor 1B (CDKN1B) gene is mutated in MEN4 and encodes for protein p27 whose expression is poorly studied in the syndromic MEN1 setting.Here, we analyzed histomorphology and protein expression of Menin and p27 in parathyroid adenomas of 25 patients of two independent, well-characterized MEN1 cohorts. The pattern of loss of heterozygosity (LOH) was assessed by fluorescence in situ hybridization (FISH) in one MEN1-associated parathyroid adenoma. Further, next-generation sequencing (NGS) was performed on eleven nodules of four MEN1 patients.Morphologically, the majority of MEN1 adenomas consisted of multiple distinct nodules, in which Menin expression was mostly lost and p27 protein expression reduced. FISH analysis revealed that most nodules exhibited MEN1 loss, with or without the loss of centromere 11. NGS demonstrated both subclonal evolution and the existence of clonally unrelated tumors.Syndromic MEN1 parathyroid adenomas therefore consist of multiple clones with subclones, which supports the current concept of the novel WHO classification of parathyroid tumors (2022). p27 expression was lost in a large fraction of MEN1 parathyroids and must therefore be used with caution in suggesting MEN4.

Applicability and Results of Liver Stiffness Measurement and Controlled Attenuation Parameter Using XL Probe for Metabolic-Associated Fatty Liver Disease in Candidates to Bariatric Surgery. A Single-Center Observational Study.

PURPOSE: Patients with morbid obesity are at high risk of liver fibrosis due to metabolic-associated fatty liver disease. Data on liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) by vibration-controlled transient elastography (VCTE, FibroScan®) XL probe for liver fibrosis and steatosis assessment in morbid obesity are needed. MATERIALS AND METHODS: LSM and CAP were measured in candidates to bariatric surgery at a single center during 12 months. In patients who underwent an intraoperative liver biopsy, we compared LSM and CAP with histology findings. Comorbidities, body mass index, type of surgery, and infections after surgery were collected and analyzed. RESULTS: Of the eighty-three patients assessed by XL probe, 49 (59%; female in 63%, BMI 42.6 ± 5.1 kg/m2) had a valid LSM and CAP measurement. LSM was 7.0 ± 3.9 kPa and CAP 329 ± 57 dB/m. In the 14 patients undergoing intraoperative liver biopsy, all had steatosis (severe in 50%), 6 (43%) had NASH (NAS ≥ 5), and 4 (29%) showed significant or bridging fibrosis. LSM accurately discriminated between patients with and without significant or severe fibrosis (AUROC 0.833) and CAP well-identified patients with or without ≥S2 steatosis (AUROC 0.896). Nine of 49 patients (18%) tested positive for significant/severe fibrosis by LSM (cut-off 8.9 kPa). CONCLUSION: Applicability of LSM and CAP by XL probe in patients candidate to bariatric surgery was moderate. However, when technically successful, their reliability to diagnose severe steatosis and fibrosis related to MAFLD was good.