Collision of ductal adenocarcinoma and neuroendocrine tumor of the pancreas: a case report and review of the literature

Background: Simultaneous occurrence of exocrine and neuroendocrine tumors of the pancreas is very infrequent. We report a patient with an endocrine tumor in the pancreatic-duodenal area and extensive exocrine carcinoma involving the whole pancreas. Case presentation: A 69-year-old woman was hospitalized in May 2016 for epigastric pain and weight loss. Her past medical history revealed an undefined main pancreatic duct dilation that was subsequently confirmed at CT scan (23 mm) and endoscopic ultrasound. There was no evidence of pancreatic masses, but the cephalic portion of the main pancreatic duct presented hypoechoic nodules. A diagnosis of the main-duct intraductal papillary mucinous neoplasm was made, and the patient underwent total pancreatectomy. Pathological examination showed a collision tumor constituted by a ductal adenocarcinoma involving the whole pancreas and a neuroendocrine tumor located in the duodenal peripancreatic wall and the head of the pancreas. There was one peripancreatic lymph node metastasis from the ductal adenocarcinoma and eight node metastases from the neuroendocrine tumor. These findings suggested a diagnosis of collision of neuroendocrine and ductal adenocarcinomas of the pancreas. The postoperative course was uneventful. Conclusions: The coexistence of pancreatic endocrine and exocrine tumors is very uncommon. When present, problems in differential diagnosis may arise between mixed exocrine-endocrine carcinoma or the collision of separate tumors

Relationship between Protein Oxidation Biomarkers and Uterine Health in Dairy Cows during the Postpartum Period

High neutrophil (PMN, Polymorphonuclear neutrophil) counts in the endometrium of cows affected by endometritis, suggests the involvement of oxidative stress (OS) among the causes of impaired fertility. Protein oxidation, in particular, advanced oxidation protein products (AOPP), are OS biomarkers linked to PMN activity. To test this hypothesis, the relationship between protein oxidation and uterus health was studied in thirty-eight dairy cows during the puerperium. The animals were found to be cycling, without any signs of disease and pharmacological treatments. PMN count was performed either through a cytobrush or a uterine horn lavage (UHL). Cows were classified into four groups, based on the uterine ultrasonographic characteristics and the PMN percentage in the uterine horns with a higher percentage of high neutrophil horn (HNH). They were classified as: Healthy (H); Subclinical Endometritis (SCE); Grade 1 Endometritis (EM1); and Grade 2 Endometritis (EM2). AOPP and carbonyls were measured in plasma and UHL. UHL samples underwent Western blot analysis to visualize the carbonyl and dityrosine formation. Plasma AOPP were higher (p < 0.05) in EM2. AOPP and carbonyl group concentrations were higher in the HNH samples (p < 0.05). Protein concentration in the UHL was higher in the EM2 (p < 0.05). Carbonyl and dityrosine formation was more intense in EM1 and EM2. Protein oxidation observed in the EM2 suggests the presence of an inflammatory status in the uterus which, if not adequately hindered, could result in low fertility

Temperature and humidity index (THI) affects salivary cortisol (HC) and dehydroepiandrosterone (DHEA) concentrations in growing bulls following stress generated by performance test procedures

The hypothalamus-pituitary–adrenal axis response to a challenge was proposed for genetic selection of robust and resilient animals. As ACTH (adrenocorticotropic hormone) test and hormone measurements in blood may result impractical, it may be useful to measure salivary hormones in response to natural stressors, after an accurate biological validation, to control factors that could contribute to the response. We evaluated whether animal handling during performance test affects salivary HC and DHEA secretion and could be used for selection. We tested the effects of habituation to repeated handling and THI as putative bias. Bull calves (N = 273) undergoing performance test were sampled at 8–9 and 11–13 months (N = 101), 8–9 months (N = 131), or 11–13 months (N = 41). On each test day (D0), calves were isolated, conducted to a squeeze chute and immobilized for 6 min. Saliva samples were collected in the morning after feed administration (T0), and after 6 min immobilization in the squeeze chute (T1) for HC and DHEA measurement. Environmental temperature and relative humidity were recorded every hour from 1:00 h to 24:00 h during the 6 days before the performance test and on D0. Salivary HC and DHEA concentrations were higher in T1 (p < 0.01), although a clear individual positive response to handling could be observed in less than 10% of subjects. The mixed model revealed: (i) HC and HC/DHEA were higher in Young bulls (p < 0.05). (ii) The time of T0 sample collection significantly affected DHEA (p < 0.01) and HC/DHEA (p < 0.05). (iii) THI affected both steroids (p < 0.001) but not HC/DHEA. Spearman correlations suggested that THI weakly affected salivary HC at T0 only (ρ = 0.150, p < 0.01), while moderate statistically significant correlations were found between DHEA and THI at T0 (ρ = 0.316, p < 0.001), and T1 (ρ = 0.353, p < 0.001). Salivary HC and DHEA in response to handling procedures might identify subpopulations of subjects with sensitive HPA axis. Habituation to repeated handling played a role, as the hormone response was lower in older animals. Chronic exposure to high THI had a minor effect on salivary HC visible at T0. A more intense THI effect was observed on salivary DHEA concentrations at both T0 and T1, which should be worth of further investigations

Demonstration in human cadavers of feasibility of ileoproctostomy performed entirely through a transanal route

Innovative surgical techniques are frequently developed in animal models before of trials in surgical patients. However, these experimental approaches do not permit a perfect evaluation of feasibility due to obvious anatomical differences between humans and animals. The Body Donation Program of the University of Padua has recently developed studies of feasibility on human cadavers of new surgical approaches. Natural Orifice Transluminal Endoscopic Surgery (NOTES) is an innovative kinf of surgery which utilizes a flexible endoscope to enter the abdominal, pelvic or thoracic cavities through the body’s natural orifices and then through an internal incision. Skin incisions are thus unnecessary and, as a consequence, tissue trauma, postoperative pain, and incision-related complications are minimized and less anaesthesia is required. The aim of the present study was to verify in human cadavers the technical feasibility of a new NOTES technique, i.e., ileoproctostomy performed entirely through a transanal access. This surgical procedure was previously performed only in a porcine model. The procedure was carried out in three human cadavers (two males and a female). One cadaver was fresh. The other cadavers were fixed through infusion of Thiel’s solution through the larger arteries. A Transanal Endoscopic Microsurgery (TEM) device and endoscopic instruments were utilized. The study demonstrated that ileoproctostomy through a transanal access is technically feasible in humans. The principal steps of the procedure were: placement of the TEM device; rectal perforation above the peritoneal reflection; peritoneoscopy using a standard gastroscope; grasping the small bowel with retrieval forceps and pulling it through the rectal hole; suturing the ileum and the rectum together with two semi-circular continuous sutures utilizing the TEM device; opening the ileal loop from the rectal side followed by endoscopic exploration. Although still at an experimental stage, ileoproctostomy through a transanal access is technically feasible in humans. In planning new procedures, a fundamental step is represented by feasibility tests on donated corpse

Surgical oncological emergencies in octogenarian patients

BackgroundSurgical oncological emergencies represent a frequent challenge in acute settings, with postoperative courses characterized by high morbidity and mortality. An accurate selection of patients who could benefit from surgery is essential to avoid unnecessary invasive treatment. In this study, we tried to determine if advanced age (&gt;80 years) represents a risk factor for negative short-term outcome in patients undergoing emergency surgery for acute abdominal oncological illness.MethodsWe retrospectively analyzed the records of patients who underwent emergency oncological surgery at the Department of Acute Care Surgery of Padua General Hospital from January 2018 to December 2022. One hundred two cancer patients were included in the study. Among them, 42 were aged ≥80 years (41%). Multiple preoperative and postoperative parameters were recorded, and the follow-up period was at least 90 days. Multivariate logistic regression analyses were used to identify factors associated with short-term postoperative outcomes.ResultsIn the octogenarian group, 30-day mortality was 11% vs. 9.5% in the younger group [p = not significant (ns)] and 90-day mortality was 17.6% in the octogenarian group vs. 20.5% in the younger group (p = ns). Postoperative morbidity and hospital length of stay were not significantly different in the two groups. Low albumin levels [odds ratio (OR) 30.6, 9.51–87.07] and elevated lactate dehydrogenase (LDH) levels (OR 26.4, 9.18–75.83) were predictive for short-term mortality in surgical oncological emergencies.ConclusionAdvanced age is not a risk factor for negative outcomes in surgical oncological emergencies. Therefore, surgical options should be considered in octogenarians with oncological emergencies and acceptable clinical conditions. Serum albumin levels and LDH can help predict the postoperative outcome after surgery for oncological emergencies

Advanced oxidation protein products (AOPP) inhibit bovine neutrophil activity in vitro.

Advanced oxidation protein products (AOPP) are novel markers of protein oxidation that were first described and characterized in plasma of uremic patients. Their formation is mainly dependent from chlorinated agents related to neutrophil and monocyte activation, thus being also considered a good indicator of the inflammatory response. In addition, AOPP can activate both human neutrophils and monocytes in vitro. The observation that AOPP were higher in plasma of cows affected by late embryonic loss raised our interest in the biological role of AOPP in dairy cattle. The aim of this work was to study the effects of AOPP on bovine neutrophil activation in vitro. Standard AOPP-BSA was produced by oxidizing bovine serum albumin (BSA) with hypochlorous acid. Bovine neutrophils were isolated by Ficoll gradient from peripheral blood obtained from healthy dairy heifers aged 10-13 months (N=10). The effects of either BSA or AOPP-BSA in the culture medium were tested in neutrophils either stimulated or unstimulated with phorbol myristate acetate (PMA,1 ug/ml) over a 3-hour period. PMA-stimulated and unstimulated neutrophils incubated without proteins in the culture medium were used as the control. Myeloperoxidase (MPO)-dependent formation of ROS was measured by chemiluminescence using luminol as substrate during the whole incubation period at 5-minute intervals, and results were analysed as the area under the curve (AUC). Parallel experiments were conducted to assess cell viability using both LDH and MTT assays. AOPP-BSA failed to trigger any response in the unstimulated bovine neutrophils. The ROS generation in PMA-stimulated was significantly lower (P<0.05) in neutrophils cultured with AOPP-BSA (AUC: 4860\ub135 CPS*min) in comparison to those cultured with both BSA (AUC: 14528\ub153) and without protein in the culture medium (AUC:7342\ub148 CPS*min). Cell viability, measured by the MTT assay, was significantly lower in PMA-stimulated neutrophils incubated with AOPP-BSA (P<0.05). Potential effects of BSA and AOPP-BSA on luminol reaction were studied in a cell-free system, by activating the MPO enzyme with increasing concentration of hydrogen peroxide in presence of either BSA or AOPP-BSA. The AUC observed in presence of BSA (13004\ub170 CPS*min) was not significantly different from that measured in presence of AOPP-BSA (14993\ub165 CPS*min).The results of this study suggested that AOPP-BSA inhibits the response of bovine neutrophil to PMA activation possibly by affecting cell viability. Moreover, it is noteworthy to underline that the bovine neutrophil response to AOPP-BSA observed in this study was totally different than that reported for the human neutrophils

Characterization of advanced oxidation protein products (AOPP) production by bovine neutrophils

Advanced oxidation protein products (AOPP) are novel markers of protein oxidation first characterized in uremic patients and related to hypochlorous acid (HOCl) production by activated neutrophils. To establish how oxidants contribute to the pathology of inflammation it is important to identify physiologically relevant targets of oxidation and to develop specific biomarkers to quantify the oxidative damage. Here, we characterized the relative reactivity of HOCl (0-25 mM) and cumene hydroperoxyde (CuOOH; 0-100 mM) with bovine serum albumin (BSA), bovine gamma globulins (b\uf067G) and whole bovine plasma. HOCl concentrations higher than 25 mM induced a massive protein denaturation, b\uf067G being the most susceptible. AOPP levels significantly increased in a dose-dependent manner in both HOCl-treated BSA and b\uf067G (P<0.01), whereas AOPP levels in plasma were significantly higher than the unexposed control only at 25mM HOCl concentration (P<0.05). The AOPP yield was lower when CuOOH was the oxidant agent. The AOPP levels were significantly higher (P<0.01) than the unexposed control when BSA was treated with 10 mM CuOOH, and b\uf067G and plasma were treated with 100 mM CuOOH. A significant (P<0.05) dose-dependent dityrosine and carbonyl group formation was observed in both BSA and b\uf067G exposed to HOCl. A significant dose-dependent dityrosine production was induced by CuOOH in BSA (P<0.01), b\uf067G (P<0.001) and whole plasma (P<0.05). Strong positive correlations were observed between AOPP and dityrosine in HOCl-treated BSA (r=0.977, P<0.001), b\uf067G (r=0.962, P<0.001) and plasma (r=0.811, P<0.01). Correlations between AOPP and dityrosine were weaker CuOOH-treated BSA (r=0.572, P<0.05), b\uf067G (r=0.812, P<0.01) and plasma (r=0.672, P<0.05)

Advanced oxidation protein products are generated by bovine neutrophils and inhibit free radical production in vitro

Despite the recognised importance of oxidative stress in the health and immune function of dairy cows, protein oxidation markers have been poorly studied in this species. The current study aimed to characterise markers of protein oxidation generated by activated bovine neutrophils and investigate the biological effects of advanced oxidation protein products (AOPP) on bovine neutrophils. Markers of protein oxidation (AOPP, dityrosines and carbonyls) were measured in culture medium containing bovine serum albumin (BSA) exposed to neutrophils. The effect of AOPP-BSA on generation of reactive oxygen species (ROS) was assessed by chemiluminescence. Activation of caspases-3, -8 and -9 and the presence of DNA laddering were used as apoptosis markers. Greater amounts of AOPP were generated by phorbol myristate acetate (PMA)-activated than non-activated neutrophils (1.46 ± 0.13 vs. 0.75 ± 0.13 nmol/mg protein, respectively; P < 0.05). Activated neutrophils and hypochlorous acid generated slightly different patterns of oxidized protein markers. Exposure to AOPP-BSA did not stimulate ROS production. Activated neutrophils generated a lesser amount of ROS when incubated with AOPP-BSA (P < 0.001). Activation with PMA induced a loss of viable neutrophils after 3 h, which was greater with AOPP-BSA incubation (P < 0.05). Detectable amounts of active caspases-3, -8 and -9 were found in nearly all samples but differences in caspase activation or DNA laddering were not observed comparing treatment groups. Apoptosis was unlikely to be responsible for the greater loss of PMA-activated neutrophils cultured in AOPP-BSA and it is possible that primary necrosis occurred. The results suggest that accumulation of oxidized proteins at an inflammatory site might result in a progressive reduction of neutrophil viability