Metastatic incidence of (PET)CT positive lung hilar and retroperitoneal lymph nodes in esophageal cancer patients

BackgroundExtra-regional lymph node metastases strongly determine treatment options in patients with esophageal cancer. Staging modalities such as (FDG-PET) CT scanning frequently show activity in retroperitoneal and lung hilar lymph nodes. This study evaluated the incidence of histologically confirmed metastases, treatment approach and recurrence patterns in patients with (FDG-PET) CT positivity in these regions.MethodsAll patients with (FDG-PET-) CT positive hilar and/or retroperitoneal lymph nodes at primary staging or restaging discussed at a multidisciplinary tumor board meeting for staging of esophageal cancer between January 2012–December 2017 were included. Biopsies and follow-up were evaluated to determine the presence of metastases and progression rates.ResultsFrom 2012 to 2017, 65 of 857 patients (7.6%) were selected with positive retroperitoneal and/or hilar lymph nodes. A total of 47/65 (72.3%) patients had positive retroperitoneal lymph nodes, which contained metastases in 19 (29.2%). When no biopsy was performed and curative treatment was given (n = 14), 9 patients had progression or locoregional and distant recurrence. Positive hilar lymph nodes were identified in 21 (32.3%) patients; 4 were biopsied and none contained metastases. In these patients no recurrence of disease was seen during follow-up.ConclusionsThe majority of biopsied (PET)CT-positive retroperitoneal lymph nodes at staging contained metastases, while biopsied (PET)CT-positive hilar nodes did not. Histological evaluation of (PET)CT -positive retroperitoneal lymph nodes at staging imaging is recommended, while based on this small series, (PET)CT-positive hilar lymph nodes most likely represent reactive lymphadenopathy.     

Defining the rate of nutritional and metabolic derangements after pancreatic resection

Background and aimsPancreatic resection is associated with pancreatic exocrine insufficiency (PEI) leading to nutritional consequences. The Pancreatic Nutrition Clinic was established to diagnose and manage PEI through standardised nutritional assessment. In this prospective observational study, we aimed to define the rate of PEI, diabetes mellitus and nutritional abnormalities in patients who underwent pancreatic resection.MethodsAll Pancreatic Nutrition Clinic patients were included for analysis. Clinical data were prospectively obtained at initial assessment. Biochemical data included micronutrient levels, faecal elastase-1 and haemoglobin A1c. Bone mineral density and nutritional assessment were undertaken.ResultsNinety-eight patients were included. Fifty-nine per cent (58/98) had undergone a pancreatoduodenectomy. Ninety-three patients had a faecal elastase-1 result, 65% (60/93) of which had a faecal elastase-1 less than 200 μg/g of faeces. Seventy-five patients (76%) of the total population required PERT, and thirty-nine (40%) were classified as malnourished using the patient-generated subjective global assessment tool. Seventy-two per cent (70/97) had a biochemical deficiency of one or more micronutrients. Thirty-eight people (39%) had diabetes mellitus. Of the seventy-eight patients with a bone mineral density scan available for analysis, 29% (23/78) had osteoporosis and 49% (38/78) osteopenia.ConclusionsPancreatic exocrine insufficiency, micronutrient deficiency, bone disease, diabetes mellitus and malnutrition are highly prevalent in patients who have undergone pancreatic resection.     

Burden of pancreatic cancer along with attributable risk factors in China from 1990 to 2019, and projections until 2030

ObjectivesUnderstanding epidemiology trends and patterns of pancreatic cancer in China from 1990 to 2019 and predicting the burden to 2030 will provide foundations for future policies development.MethodsWe collected incidence, mortality, and disability-adjusted life-years (DALYs) data of pancreatic cancer in China from 1990 to 2019 based on the Global Burden of Disease Study 2019. We calculated the estimated annual percentage change (EAPC) to depict the trends of pancreatic cancer burden and predicted the incidence and mortality in the next decade by using a Bayesian age-period-cohort analysis.ResultsThe number of incident cases sharply increased from 26.77 thousand in 1990 to 114.96 thousand in 2019, the age-standardized incidence rate (ASIR) nearly doubled from 3.17 per 100,000 in 1990 to 5.78 per 100,000 in 2019, with an EAPC of 2.32 (95% confidence interval [CI]: 2.12, 2.51). The mortality and DALYs presented a similar pattern with incidence. The dominant risk factor for pancreatic cancer was smoking, but the contribution of high body-mass index increased from 1990 to 2019. We projected that the incident cases and deaths of pancreatic cancer would increase to 218.79 thousand and 222.97 thousand, respectively, in 2030 with around 2 times growth.ConclusionsDuring the past three decades, the incidence, mortality and DALYs of pancreatic cancer gradually increased in China, and the absolute number and rate of pancreatic cancer burden would continue to rise over the next decade. Comprehensive policies and strategies need to be implemented to reduce the incidence and mortality.     

The prognostic role of fatigue,depression and anxiety on postoperative outcomes after pancreatectomy for pancreatic cancer. A prospective observational study (FAT-PRO study)

ObjectivesThis study aims to assess the prevalence of preoperative fatigue, depression and anxiety among patients undergoing pancreatic surgery for pancreatic cancer (PC), and possible relationship with postoperative outcomes.MethodsProspective data from 162 consecutive patients undergoing pancreatectomy for PC at a third-level referral centers for pancreatic surgery were collected. All patients preoperatively completed four questionnaires assessing depression (PHQ-9), anxiety (STAI-Y2), chronic illness fatigue (FACIT-F) and cancer therapy fatigue (FACT-G).ResultsForty patients (25%) where in the first quartile for chronic illness (FACIT-F ≤34) and/or cancer therapy (FACT-G ≤78) fatigue, 26 patients (16%) met the criteria for major depression (PHQ-9 ≥10) and 34 patients (21%) had anxiety symptoms (STAI-Y2 ≥40). Cancer therapy fatigue was significantly associated with higher rates of morbidity (70% vs 49%), major morbidity (Clavien-Dindo ≥3) (28% vs 11%), post-pancreatectomy hemorrhage (18% vs 4%), pulmonary complications (20% vs 9%) and mortality (8% vs null) (all P ≤ 0.01). Major depression was associated with higher rates of post-pancreatectomy hemorrhage and readmission (23% vs 5%). Multivariable logistic regression analysis of preoperative factors confirmed diabetes (OR 2.71, 95%CI 1.01–7.20; P = 0.04), ASA score ≥3 (OR 4.12, 95%CI 1.52–11.21; P < 0.01) and cancer therapy fatigue (OR 2.95, 95%CI 1.01–8.74; P = 0.04) to be independent predictors of major morbidity.ConclusionsHigher levels of fatigue (in particular cancer therapy fatigue) strongly correlates with worse postoperative outcomes.     

miR-6858 plays a key role in the process of melatonin inhibition of the malignant biological behavior of glioma

MicroRNAs (miRNAs), small non-coding RNA molecules with a length of 18–25 nucleotides, have been shown to be involved in mediating various malignant properties of GBM, including growth, invasion and angiogenesis. Here, we investigated whether miRNAs might be involved in mediating the suppression of malignant properties of GBM by melatonin (MEL), an amine hormone secreted by the pineal gland. Sequencing was performed to screen specifically for miRNAs induced by MEL in U87 and an orthotopically xenografted primary GBM cell line, GBM#P3. MiR-6858-5p was the most significantly up-regulated miR in GBM cell lines in response to MEL (~5 × ). Transfection of a mimic of miR-6858-5p into both cell lines led to a decrease in viability of ~ 50% at 72 h, confirming a suppressive role for miR-6858-5p in GBM. In contrast, an inhibitor of miR-6858-5p rescued GBM cells from MEL suppression of proliferation, migration and invasion. Analysis using Targetscan yielded candidate mRNAs targeted by miR-6858-5p, some of which are involved in the SIRT/AKT signaling pathway. In cells transfected with a mimic or an inhibitor of miR-6858-5p, levels of SIRT3 and downstream components of the AKT signaling pathway were suppressed or up-regulated, respectively, both in vitro and in an in vivo orthotopic xenograft model. Our results elucidated a novel molecular mechanism underlying MEL suppression of GBM, highlighting a role for miRNAs, and provide a potential therapeutic strategy for GBM.