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Esophageal adenocarcinoma (EAC) is a malignant tumor with poorly understood molecular mechanisms. This study endeavors to elucidate how the long non-coding RNAs (lncRNAs) MALAT1, MANCR and PSMA3-AS1, as well as the microRNA miR-101, exhibit specific expression patterns in the pathogenesis and prognosis of EAC. A total of 50 EAC tissue samples (tumors and lymph nodes) and a control group comprising 26 healthy individuals were recruited. The samples underwent quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analyses. The relative expression levels of MALAT1, MANCR, PSMA3-AS1, and miR-101 were ascertained and correlated with various clinicopathological parameters including TNM staging, tumor characteristics (size and grade of the tumor) lymphatic invasion, disease-free (DFS) and overall survival (OS) of EAC patients. Quantitative analyses revealed that MALAT1 and MANCR were significantly upregulated in EAC tumors and positive lymph nodes when compared to control tissues (p < 0.05). Such dysregulations correlated positively with advanced lymphatic metastases and a higher N stage. DFS in the subgroup of patients with negative lymph nodes was higher in the setting of low-MANCR-expression patients compared to patients with high MANCR expression (p = 0.02). Conversely, miR-101 displayed a significant downregulation in EAC tumors and positive lymph nodes (p < 0.05), and correlated negatively with advanced tumor stage, lymphatic invasion and the grade of the tumor (p = 0.006). Also, patients with low miR-101 expression showed a tendency towards inferior overall survival. PSMA3-AS1 did not demonstrate statistically significant alterations (p > 0.05). This study reveals MALAT1, MANCR, and miR-101 as putative molecular markers for prognostic evaluation in EAC and suggests their involvement in EAC progression. [ABSTRACT FROM AUTHOR]

Background and Objectives: Encouraging data have been reported from referral centers following gastrointestinal cancer surgery. Our goal was to retrospectively review patient outcomes following gastrectomy for gastric or gastroesophageal junction (GEJ) cancer at a high-volume unit of the University of Athens. Methods: The enrollment period was from June 2003 to September 2018. Disease-free survival (DFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Cox proportional hazard models were constructed to identify variables independently associated with time-to-event outcomes. Results: A total of 205 patients were analyzed. R0 resection was achieved in 183 (89.3%) patients and was more likely to occur following neoadjuvant chemotherapy (p = 0.008). Recurrence developed in 46.6% of our cohort and the median disease-free survival was 31.2 months. On multivariate analysis, only staging (HR = 2.15; 95% CI: 1.06–4.36) was independently associated with increased risk of recurrence. All-cause mortality was 57.2% and the median time of death was 40.9 months. On multivariate regression, staging (HR: 1.35; 95% CI: 1.11–1.65) and recurrence (HR: 2.87; 95% CI: 1.32–6.22) predicted inferior prognosis. Conclusions: Gastrectomy at the University of Athens has yielded favorable outcomes for patients with GEJ cancer. [ABSTRACT FROM AUTHOR]

Background: Short bowel syndrome (SBS) remains an unsolved issue in modern medicine. Numerous experimental surgical techniques have been proposed in the attempt to increase the intestinal absorptive capacity. Materials and Methods: Ten female Landrace pigs, divided in two groups of 5 (A and B), were explored through a midline incision. A spindle-shaped vascularized full-thickness gastric wall flap (GWF) consisting of part of the major curvature with the gastroepiploic arch preserved was de-epithelialized and then placed as a "patch" to cover an antimesenteric border defect of either a nonfunctional blind intestinal loop (group A) or a functional intestinal loop of the gastrointestinal tract (group B). A spindle-shaped curved, rigid, low density polyethylene (LDPE) splint was sutured on the external surface of the patch in order to prevent shrinkage of GWF and collapse of the intestinal wall in group A. Results: There was a decrease of both dimensions of the patch. Microscopically a thin layer of columnar epithelial cells covered the center of the patch, evolving in shorter, blunt, poorly developed villi with increasing maturation laterally. The patch surface was covered by nearly 90%. In the three animals that died prematurely the coverage of GWF was negligent or suboptimal directly dependent on the length of survival. Conclusions: The hereby-described patching technique demonstrated the growth of intestinal neomucosa on the GWF. The capability of the stomach to provide large flaps and the advantages of the use of native tissues render this animal model valuable for the future research in the field. [ABSTRACT FROM AUTHOR]

Objective: Disease-related malnutrition is a debilitating condition frequently observed in patients with cancer. The aim of the current study was to prospectively examine postoperative changes in nutritional and functional status of patients undergoing surgery for gastric, esophageal, and gastroesophageal junction cancer. Methods: Participants were prospectively recruited from September 2015 to September 2019. The assessment of malnutrition was based on the Patient-Generated Subjective Global Assessment tool. The functional assessment included the evaluation of muscle strength and physical performance, while muscle mass assessment was based on Skeletal Muscle Mass Index (SMI) derived from the analysis of computed tomography scans. The follow up of patients was scheduled at six months postoperatively. Results: A total of 98 patients were analyzed. Mean patient age was 60.79 ± 10.19 years and 80.6% were males. The mean unintentional weight loss at 6months was 11.7 ± 8.0%. Patients who underwent McKeown esophagectomy reported the greatest weight loss postoperatively (16.2 ± 9.6%), whereas the lowest rate of weight loss was observed in patients who underwent partial gastrectomy (5.6 ± 6.7%). The rate of severe malnutrition declined at six months postoperatively (39.7% vs 27%). Muscle strength and physical performance were significantly deteriorated at 6months postoperatively, except for the group of partial gastrectomy, while SMI significantly decreased in all groups of patients except for McKewon esophagectomy group. Finally, the prevalence of low muscle mass increased significantly from 43.5% in the preoperative period to 66.7% at the follow-up. Conclusions: Our study revealed a significant deterioration in gastroesophageal cancer patient nutritional and functional status at six months postoperatively. The high prevalence of malnutrition and low muscle mass requires systematic follow-up and multidirectional monitoring in order to ensure the successful rehabilitation of these patients. [ABSTRACT FROM AUTHOR]

Background: Pyometra (P) leads to sepsis and multiple organ dysfunction syndrome. Toll-like receptors (TLRs) recognize pathogens which can cause P. The aim of this study was to investigate TLR-7 and -9 via the MYD88 pathway and the nuclear factor kappa B (NFκB) response in the uterus of a P mouse model before and after ovariohysterectomy (RP) as well as potential lung injury. Materials and Methods: 200 female C57BL/6J mice were randomly divided into groups (N = 10/subgroup; sham 1, 2, 3, 7; P1, 2, 3, 7; 1RP1, 2, 3, 7; 2RP1, 2, 3, 7; 3RP1, 2, 3, 7) according to the day of euthanasia. Pathogens were administrated in the groups P and RP in order to induce P. Results: Alterations in blood chemistry, histopathology, and RT-qPCT analysis before (P) and after RP were observed. Significant correlations were also found between MYD88, NFκB, and TLR9 in P and RP groups in the lungs and in RP groups in the uterus, suggesting that the immune system responded via the TLR9-MYD88 pathway. Conclusions: This is the first report of immunohistochemical TLR-7 and -9 localization and of TLR-7, -9, MYD88, and NFκB mRNA expression in the uterus causing lung injury in a P mouse model. [ABSTRACT FROM AUTHOR]

Abstract A 60-year-old Caucasian male underwent a total pancreatectomy for a mixed type pancreatic intraductal papillary mucinous neoplasm (IPMN) arising in the main and secondary pancreatic ducts. During surgery, a subserosal polypoid mass was noted at the greater curvature of the gastric antrum and was enucleated. This mass was proven to be heterotopic pancreatic tissue with cystic neoplasia of the IPMN histologic subtype. Through an extensive search of the literature, we found that this is the first case ever reported with simultaneous existence of IPMN changes, in the main and secondary ducts of the orthotopic pancreas and in the heterotopic pancreatic tissue of the gastric wall.

Oncologic patients often suffer from malnutrition which in turn, might have negative impact on treatment outcomes. The Geriatric Nutritional Risk Index (GNRI), as an index of impaired nutritional status, has emerged as a significant prognostic factor for short-and long-term outcomes in cancer patients. The aim of the current systematic review is to determine whether the GNRI is an independent prognostic factor of postoperative complications and survival in cancer patients. A systematic search was conducted to identify studies, published from 2005 to 2019, which assessed associations between GNRI and short- and long-term outcomes in cancer patients. Eighteen studies fulfilled the eligibility criteria and were included in the analysis. Low scores of GNRI were associated with increased risk for developing postoperative complications and impaired survival of cancer patients in most studies. Our findings support the use of the GNRI in the clinical practice, since it is a simple and reliable tool for assessing nutritional status in oncologic patients. More prospective, multi-centered studies are warranted to confirm the current results, as well as the role of nutritional support in improving the prognosis of cancer patients. [ABSTRACT FROM AUTHOR]

Abstract Background To investigate the changes of the neoplastic microenvironment during the different morphological alterations of hyperplastic and pre-invasive breast lesions. Methods 78 in situ ductal carcinomas of all degrees of differentiation, 22 atypical ductal hyperplasias, 25 in situ lobular carcinomas, 18 atypical lobular hyperplasias, 32 ductal epithelial hyperplasias of usual type and 8 flat atypias were immunohistochemically investigated for the expression of vascular endothelial growth factor (VEGF), smooth muscle actin (SMA) and CD34, while microvessel density (MVD) was counted using the anti-CD31 antibody. Results VEGF expression was strongly correlated with MVD in all hyperplastic and pre-invasive breast lesions (p < 0.05). Stromagenesis, as characterized by an increase in SMA and a decrease in CD34 positive myofibroblasts was observed mostly around ducts harboring high grade in situ carcinoma and to a lesser extent around moderately differentiated DCIS. In these two groups of in situ carcinomas, a positive correlation between MVD and SMA (p < 0.05) was observed. On the contrary, CD34 was found to be inversely related to MVD (p < 0.05). No statistically significant changes of the stromal fibroblasts were observed in low grade DCIS neither in any of the other lesions under investigation as compared to normal mammary intra- and interlobular stroma. Conclusion Angiogenesis is observed before any significant fibroblastic stromagenesis in pre-invasive breast lesions. A composite phenotype characterized by VEGF positive epithelial cells and SMA positive/CD34 negative stromal cells, is identified mostly in intermediate and high grade DCIS. These findings might imply for new therapeutic strategies using both anti-angiogenic factors and factors selectively targeting tumor stroma in order to prevent the progression of DCIS to invasive carcinoma.

The aim of this study is to describe outcomes of esophageal cancer surgery in a quaternary upper gastrointestinal (GI) center in Athens during the era of the Greek financial crisis. We performed a retrospective analysis of patients that underwent esophagectomy for esophageal or gastroesophageal junction (GEJ) cancer at an upper GI unit of the University of Athens, during the period January 2004–June 2019. Time-to-event analyses were performed to explore trends in survival and recurrence. A total of 146 patients were identified. Nearly half of the patients (49.3%) underwent surgery during the last 4 years of the financial crisis (2015–2018). Mean age at the time of surgery was 62.3 ± 10.3 years, and patients did not present at older ages during the recession (P  = 0.50). Most patients were stage III at the time of surgery both prior to the recession (35%) and during the financial crisis (39.8%, P  = 0.17). Ivor–Lewis was the most commonly performed procedure (67.1%) across all eras (P  = 0.06). Gastric conduit was the most common form of GI reconstruction (95.9%) following all types of surgery (P  < 0.001). Pre-recession anastomoses were usually performed using a circular stapler (65%). Both during (88.1%) and following the recession (100%), the vast majority of anastomoses were hand-sewn. R0 resection was achieved in 142 (97.9%) patients. Anastomosis technique did not affect postoperative leak (P  = 0.3) or morbidity rates (P  = 0.1). Morbidity rates were not significantly different prior to (25%), during (46.9%), and after (62.5%) the financial crisis, P  = 0.16. Utilization of neoadjuvant chemotherapy (26.9%, P  = 0.90) or radiation (8.4%, P  = 0.44) as well as adjuvant chemotherapy (54.8%, P  = 0.85) and irradiation (13.7%, P  = 0.49) was the same across all eras. Disease-free survival (DFS) and all-cause mortality rates were 41.2 and 47.3%, respectively. Median DFS and observed survival (OS) were 11.3 and 22.7 months, respectively. The financial crisis did not influence relapse (P  = 0.17) and survival rates (P  = 0.91). The establishment of capital controls also had no impact on recurrence (P  = 0.18) and survival (P  = 0.94). Austerity measures during the Greek financial crisis did not influence long-term esophageal cancer outcomes. Therefore, achieving international standards in esophagectomy may be possible in resource-limited countries when centralizing care. [ABSTRACT FROM AUTHOR]

Staged esophagectomy was developed in the mid-twentieth century in an attempt to reduce high rates of postoperative morbidity and mortality. Nowadays, the operation has almost been abandoned due to its significant disadvantages, especially the need for multiple surgeries, inability of patients to feed between operations, and morbidity of esophageal stoma. However, staged esophagectomy is still occasionally useful for very high-risk patients and in particular cases, for example multiple cancers of the aerodigestive tract and emergent esophagectomy. Staged esophagectomy is based on the division of surgical stress into two operations, which gives the patient time to recover before final restoration. Gastric tube ischemic preparation may be a more important mechanism in staged esophagectomy. This approach may survive and expand with the application of ischemic gastric pre-conditioning through embolization or laparoscopic ligation of the gastric arteries, which is a less explored and promising technique. [ABSTRACT FROM AUTHOR]

Objective: Malnutrition is common in patients who underwent upper gastrointestinal cancer surgery. Our goal was to explore postoperative compliance with oral nutritional supplementation and define barriers to consumption in patients with esophageal, gastroesophageal junction, and gastric cancer.Methods: Participants were prospectively recruited from September 2015 to November 2018. Preoperative nutritional status was assessed using the Patient Generated Subjective Global Assessment. Malnourished patients and patients at risk for malnutrition were offered oral nutritional supplementation at the time of hospital discharge. Compliance was evaluated 1 month after hospital discharge.Results: A total of 78 patients were analyzed. Mean patient age was 62.8 ± 10.7 years and 83.3% were males. Εsophagectomy and gastrectomy were performed in 60.3% and 39.7% of the patients respectively. Twenty-eight (35.9%) participants reported consuming all prescribed supplements, whereas 50 (64.1%) patients were noncompliant with their prescribed oral nutritional supplementation regimen. The main barriers to oral nutritional supplementation compliance were bloating (compliant vs. noncompliant patients: 17.9% vs. 58%, p < 0.001), early satiety (compliant vs. noncompliant patients: 25% vs. 52.32%, p < 0.001), flavor or texture dislike (compliant vs. noncompliant patients: 7.1% vs. 34%, p < 0.001), and diarrhea (compliant vs. noncompliant patients: 10.7% vs. 24%, p < 0.001). No other statistically significant differences were identified between the two groups.Conclusions: Postoperative compliance to oral nutritional supplementation is low in patients who underwent upper gastrointestinal cancer surgery. Patient education and support as well as providing a range of oral nutrition supplement flavors, texture, and compositions may be useful in increasing adherence to oral nutritional supplementation regimens. [ABSTRACT FROM AUTHOR]

Background/Aim: Esophagobronchial fistula is a common complication of advanced esophageal cancer, related to respiratory distress and mortality. Esophageal bypass has been successfully utilized for palliation, as bridging to definitive chemoradiotherapy. The aim of this study is to present an extremely difficult case of a mid-esophageal squamous cell carcinoma complicated with aerodigestive fistula that was treated using 3D laparoscopic-assisted esophageal bypass with curative intent. Case Report: A 49year-old female patient presented with T4b esophagealsquamous cell carcinoma and esophagobronchial fistula. Laparoscopic-assisted V-shaped retrosternal esophageal bypass using a gastric conduit was started, which was converted to open surgery due to respiratory distress. The patient was able to undergo chemoradiotherapy treatment. Conclusion: 3D laparoscopic-assisted esophageal bypass can be a safe and feasible approach in patients with advanced midesophageal squamous cell carcinoma and esophagobroncial fistula. Additionally to the advantages of laparoscopic surgery, this operation permits oral feeding, and can be used with possible curative intent in patients with adequate response to chemoradiotherapy. [ABSTRACT FROM AUTHOR]

Background: Chronic mesenteric ischemia can be treated with either endovascular approaches or surgical revascularization. Recent data suggest that surgery leads to more durable symptom relief with similar long-term survival compared to transcatheter angioplasty. Splanchnic vessel endarterectomy has been shown to lead to longer freedom from recurrence compared to the more commonly used surgical bypass procedure. Methods: We retrospectively reviewed the medical records of patients with chronic mesenteric ischemia who were considered poor candidates for endovascular repair and therefore underwent superior mesenteric artery endarterectomy in our institution. Study period was April 2016 to April 2018. Results: A 73-year-old female and a 69-year-old male patient fulfilled our inclusion criteria. Extensive stenosis of the celiac axis and the superior mesenteric artery was found in both patients. superior mesenteric artery endarterectomy was performed in both cases. Endarterectomy was closed using a polytetrafluoroethylene patch. Both patients are alive and symptom-free at one year postoperatively with no signs of restenosis. Conclusions: Our institutional outcomes are in line with recent literature supporting superior mesenteric artery endarterectomy as a viable alternative to surgical bypass in patients with chronic mesenteric ischemia who are suboptimal candidates for endovascular angioplasty and stenting. [ABSTRACT FROM AUTHOR]

Background: There are a number of stent-grafts in the market, designed to handle difficult anatomies during endovascular aortic repair. The aim of this study is to determine which stent-graft is the most appropriate to accommodate the majority of infra-renal aortic aneurysms cases. An additional aim is to determine what stent-graft characteristics influence the suitability of the stent-graft. Research design and methods: Retrospective cohort study on the suitability of available stent-grafts for infrarenal aneurysm (AAA) repair based on real-life anatomic data. The anatomical characteristics of 235 AAA were measured manually using specialized software. All measurements were compared to the official instructions-for-use (IFU) using a purpose-specific server-side script. The proper function of the script was additionally confirmed. Results: The highest suitability rate was achieved by Medtronic Endurant. The majority of stent-grafts failed to meet the respective AAA anatomy by one IFU characteristic. Stent-grafts that failed by only one IFU characteristic by ≥80% of unsuitable cases tend to have higher suitability rates. Neck dimensions and CIA diameter are the two characteristics significantly influencing the suitability rate. Conclusions: Any stent-graft with high suitability rates should be available off-the-shelf in any vascular department in order to cover the majority of cases. For challenging cases, special advantages of the stent-grafts should be taken under consideration. [ABSTRACT FROM AUTHOR]

Background Despite therapeutic advancements, gastric cancer (GC) remains a leading cause of death worldwide. Methods This retrospective cohort study statistically analyzed the clinicopathologic characteristics, treatments and outcomes of patients with potentially resectable GC managed at our institution between 2006 and 2010. The STROBE checklist was applied. Results Preoperative assessment of 164 GC patients (male: female ratio 1.87, median age 65 years) assigned 132 (80.5%) to total (56; 42.4%) or subtotal (76; 57.6%) gastrectomy. Resection margins were microscopically tumor-free (R0) in 100 (75.8%), microscopically infiltrated (R1) in 25 (18.9%) and macroscopically infiltrated (R2) in 7 (5.3%) patients. Nodal plane dissection was D0 in 34 (25.8%), D1 in 62 (47.0%) and D2 in 36 (27.3%) patients. Early GC was diagnosed in 19 patients (14.4%). Fluorouracil-based chemotherapy was administered in 69.7% and chemoradiation in 18.2% of patients. The 5- and 10-year survival rates of patients with R0 resection were 74% and 65.4%, respectively. The 2-year survival rates for R1 and R2 resection were 28.9% and 0% respectively. The 5- and 10-year survival rates according to nodal plane dissection were 55.6% and 41.4% for D2, and 53.2% and 49.7% for D1, respectively. On multivariate analysis, T4, N3 and R1/R2 remained independent negative prognostic factors for overall survival. Microscopic or macroscopic infiltration of surgical margins was the worst adverse prognostic factor for survival. Conclusion These results are equivalent to those from centers of excellence and indicate the urgent need for improvements in the field, particularly in the development of predictive models to guide personalized therapy. [ABSTRACT FROM AUTHOR]

Background: Carotid disease is one of the many forms of cardiovascular disease, which may lead to chronic disability and death. It is a multifactorial inflammatory disease, greatly affected by an individual's habits like smoking, lack of exercise, and a diet high in fats. MicroRNAs (miRs) are known to be involved in vascular inflammation. Objectives: We aimed to analyse in a case-control study the expression profile of selected miRs from patients with symptomatic carotid disease and to examine their involvement in the disease pathogenesis. Patients and Methods: Samples from 38 symptomatic patients who underwent carotid endarterectomy were collected and adjacent healthy regions from 15 patients were used as control samples. Fold change in the expression of miR21, miR122, miR146a and miR196α was measured using reverse transcription-real time PCR. Western blot was used to quantify the levels of MMP2 protein whose gene is a target of miR21. Results: Compared to control samples, all patients showed upregulation of miR21, miR122, miR146a and miR196a. No statistical significance was found to exist from patients with high or low miRs expression and clinical/laboratory parameters. The levels of MMP2 were found to be decreased in patients when compared to control samples. Conclusions: Our results revealed miRs which showed different expression in endarterectomy specimens from patients with symptomatic carotid disease, suggesting that these miRs correlated with vascular inflammation. Furthermore, mir21 seems an appealing pharmaceutical target since by targeting MMP2 can favour a stable plaque since low levels of the protein of its gene MMP2 target prevent the fibrous cap of the atheroma from getting thinner. Thus, miR21 seems to prevent rupture but further research is required. [ABSTRACT FROM AUTHOR]

It remains uncertain whether enhanced recovery after surgery (ERAS) protocols can be safely implemented for elderly patients, especially after highly complex surgery such as pancreaticoduodenectomy (PD). The present study was designed to assess the feasibility and safety of an ERAS protocol in elderly patients undergoing PD. Starting January 2010 to February 2015, we prospectively collected data from 85 consecutive patients who underwent PD with a fast-track program. Data of patients older and younger than 70 years were compared. Endpoints were morbidity, mortality, readmissions, length of stay, and compliance with ERAS elements. Forty-five patients were less than 70 years old and 40 patients were 70 years of age or older. Both mortality (4.4% vs 5%; P = 1.000) and overall morbidity (33.3% vs 37.5%; P = 0.821) did not differ significantly between the groups. Rates of intervention and relaparotomy were similar in both groups. Length of stay (10 vs 11.8 days; P = 0.099) did not differ significantly between the groups, nor did the readmission rates (6.7% vs 5.0%; P = 0.272). There were no differences in compliance with ERAS elements between groups. An ERAS program seems feasible and can be safely implemented for elderly patients undergoing PD. [ABSTRACT FROM AUTHOR]

Background: Single-incision laparoscopic surgery has attracted a great deal of interest in the surgical community in recent years, including bariatric surgery. Single-incision laparoscopic sleeve gastrectomy (SILSG) has been proposed as an alternative to the multiport laparoscopic procedure; however, it has yet to meet wide acceptance and application.Objective: We aim to summarize existing data on SILSG and check the procedure's feasibility, technical details, safety, and, if possible, outcomes.Materials and Methods: We checked the most important databases for studies concerning SILSG and included all these that summarized the criteria placed and contained the data needed for this review. We excluded case reports.Results: Nineteen studies complied with the criteria of our review, containing a total of 1679 patients. Their mean age has been 38.91 years and the mean preoperative body mass index has been 41.8 kg/m2. In majority of cases (60.5%), a left upper quadrant incision has been preferred and in 97.6%, a commercially available multiport system has been picked. A wide variety of instruments have been used and mean operating time has been 94.6 minutes. One conversion to open surgery has been reported and 7.4% required the placement of additional ports. There was a complication rate of 7.38% (most common being bleeding with a rate of 2.5%) and a reoperation rate of 2.8%. Mean excess weight loss for a follow-up of 1 year was achieved in 53.7% of patients and was 70.06%. A tendency for less analgesia and better wound satisfaction has been reported.Conclusions: SILSG is safe and feasible. However, there is insufficient evidence to recommend it as the new gold standard for sleeve gastrectomy in the place of conventional laparoscopic sleeve gastrectomy. Randomized controlled trials are needed to analyze the results and the possible benefits of this technique. [ABSTRACT FROM AUTHOR]

Hepatobiliary and pancreatic (HBP) cancers are associated with high cancer-related death rates. Surgery aiming for complete tumor resection (R0) remains the cornerstone of the treatment for HBP cancers. The current progress in the adjuvant treatment is quite slow, with gemcitabine chemotherapy available only for pancreatic ductal adenocarcinoma (PDA). In the advanced and metastatic setting, only two targeted drugs have been approved by the Food & Drug Administration (FDA), which are sorafenib for hepatocellular carcinoma and erlotinib for PDA. It is a pity that multiple Phase III randomized control trials testing the efficacy of targeted agents have negative results. Failure in the development of effective drugs probably reflects the poor understanding of genome-wide alterations and molecular mechanisms orchestrating therapeutic resistance and recurrence. In the post-ENCODE (Encyclopedia of DNA Elements) era, cancer is referred to as a highly heterogeneous and systemic disease of the genome. The unprecedented potential of next-generation sequencing (NGS) technologies to accurately identify genetic and genomic variations has attracted major research and clinical interest. The applications of NGS include targeted NGS with potential clinical implications, while whole-exome and whole-genome sequencing focus on the discovery of both novel cancer driver genes and therapeutic targets. These advances dictate new designs for clinical trials to validate biomarkers and drugs. This review discusses the findings of available NGS studies on HBP cancers and the limitations of genome sequencing analysis to translate genome-based biomarkers and drugs into patient care in the clinic. [ABSTRACT FROM AUTHOR]

Objective. Nutritional deficiencies are common after bariatric surgery. We aimed to assess the prevalence and possible predictors of secondary hyperparathyroidism (SHPT) in bariatric patients. Methods. A total of 95 patients who had undergone Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) were assessed after a median of 3 years after surgery. Anthropometric/demographic and weight-loss parameters were compared according to the presence of SHPT, independently for men/premenopausal women and postmenopausal women. Results. SHPT was highly prevalent (men/premenopausal women, 52.1%; postmenopausal women, 31.9%). Among men/premenopausal women, multivariate analysis indicated that SHPT was predicted by (a) 25-hydroxyvitamin D levels (Exp(B) = 0.869, P-value = 0.037), independently of age, sex, smoking; (b) calcium (Exp(B) = 0.159, P-value = 0.033) and smoking, independently of age and sex; (c) magnesium (Exp(B) = 0.026, P-value = 0.046) and smoking, independently of age and sex. Among postmenopausal women, SHPT was predicted by menopausal age independently of age, smoking, and levels of 25-hydroxyvitamin D or calcium. The development of SHPT was not associated with the type of surgery. Conclusions. RYGB and SG exhibited similar effects regarding the regulation of the hypothalamus-pituitary-parathyroid axis after surgery. Vitamin D status and menopausal age appear to determine SHPT on the long term. SHPT should be sought and vigorously treated with calcium and vitamin D supplementation. [ABSTRACT FROM AUTHOR]

A 60-year-old Caucasian male underwent a total pancreatectomy for a mixed type pancreatic intraductal papillary mucinous neoplasm (IPMN) arising in the main and secondary pancreatic ducts. During surgery, a subserosal polypoid mass was noted at the greater curvature of the gastric antrum and was enucleated. This mass was proven to be heterotopic pancreatic tissue with cystic neoplasia of the IPMN histologic subtype. Through an extensive search of the literature, we found that this is the first case ever reported with simultaneous existence of IPMN changes, in the main and secondary ducts of the orthotopic pancreas and in the heterotopic pancreatic tissue of the gastric wall. [ABSTRACT FROM AUTHOR]

Warfarin-induced skin necrosis is an infrequent and well-recognized complication of warfarin treatment. The incidence was estimated between 0.01% and 0.1% whereas a paradoxal prothrombotic state that arises from warfarin therapy seems to be responsible for this life-threatening disease. To the best of our knowledge we present the first case of an old woman diagnosed with warfarin-induced skin necrosis, in whom novel oral anticoagulants and extensive surgical debridement were combined safely with excellent results. [ABSTRACT FROM AUTHOR]

Background: To investigate the changes of the neoplastic microenvironment during the different morphological alterations of hyperplastic and pre-invasive breast lesions. Methods: 78 in situ ductal carcinomas of all degrees of differentiation, 22 atypical ductal hyperplasias, 25 in situ lobular carcinomas, 18 atypical lobular hyperplasias, 32 ductal epithelial hyperplasias of usual type and 8 flat atypias were immunohistochemically investigated for the expression of vascular endothelial growth factor (VEGF), smooth muscle actin (SMA) and CD34, while microvessel density (MVD) was counted using the anti-CD31 antibody. Results: VEGF expression was strongly correlated with MVD in all hyperplastic and pre-invasive breast lesions (p < 0.05). Stromagenesis, as characterized by an increase in SMA and a decrease in CD34 positive myofibroblasts was observed mostly around ducts harboring high grade in situ carcinoma and to a lesser extent around moderately differentiated DCIS. In these two groups of in situ carcinomas, a positive correlation between MVD and SMA (p < 0.05) was observed. On the contrary, CD34 was found to be inversely related to MVD (p < 0.05). No statistically significant changes of the stromal fibroblasts were observed in low grade DCIS neither in any of the other lesions under investigation as compared to normal mammary intra- and interlobular stroma. Conclusion: Angiogenesis is observed before any significant fibroblastic stromagenesis in pre-invasive breast lesions. A composite phenotype characterized by VEGF positive epithelial cells and SMA positive/CD34 negative stromal cells, is identified mostly in intermediate and high grade DCIS. These findings might imply for new therapeutic strategies using both anti-angiogenic factors and factors selectively targeting tumor stroma in order to prevent the progression of DCIS to invasive carcinoma. [ABSTRACT FROM AUTHOR]

B Background: b ZO-1, -2, and -3 ( onula Occludens) are proteins that connect the cell cytoskeleton to Tight Junctions and Adherens Junctions. Our aim was to compare the expression of these proteins in Benign Nevi (BN) and MM cells. ZO-1 was preferentially located in the cytoplasm in BN (78.6%) but not in MM (42.9%) where it was located in both the cytoplasm and the cell membrane (57.1%, p=0.028). [Extracted from the article]

To minimize complications associated with the construction of the hand-sewn aortic anastomosis, alternative experimental methods have been pursued. This study aimed to evaluate the efficacy of experimental anastomotic devices in relation to time and point of rupture of the anastomosis in comparison to the conventional technique. An electronic search was performed using MEDLINE, Scopus, Science Direct, and Cochrane Library databases by two independent authors. Our exclusion criteria referred to studies reporting results solely from end-to-side anastomosis, results on vessels other than the aorta, studies that did not involve animal experiments, and non-English publications. The last search date was January 1, 2020. The meta-analysis included 22 studies with 34 anastomosis samples and a total of 316 animals. The pooled mean automated anastomosis time was 10.38 min, and the mean point of rupture was 32.7 N. In the subgroup analysis of automated anastomosis time by device category, the anastomotic stenting technique reported significantly lower anastomosis time but also showed significantly lower point of rupture. Comparing the efficacy of experimental devices and the hand-sewn technique, our pooled analysis showed that automated devices significantly decrease the time needed to perform the anastomosis (weighted mean difference −7.24 min). On the other hand, the automated anastomosis is also associated with decreased tensile strength (weighted mean difference −20.68 N). Although experimental devices seem to offer a faster anastomosis, they lack endurance when compared with the hand-sewn technique. Further research is needed for the development of an "ideal" anastomotic technique. [ABSTRACT FROM AUTHOR]

Background The role of hepatic hemodynamic modulation in the development of “small-for-size” syndrome (SFSS) after extended hepatectomy (EH) or living-donor liver transplantation is still controversial. We have designed an experimental study to investigate the effect of hemodynamic parameters of the liver circulation on the development of SFSS after EH in a porcine model. Methods Eighteen pigs were randomly divided into two groups: group A has received EH (75%-80%) without splenectomy, and group B with EH and simultaneous splenectomy was carried out. Portal hemodynamics, liver function tests, histologic findings, injury and survival rates were compared between groups A and B. Results The 7-d survival rate in the splenectomy group was significantly improved compared with group A (88.9% versus 44.4%, P < 0.05). Portal vein pressure, portal vein flow, and liver function tests in the splenectomy group were significantly lower than in group A immediately after splenectomy and postoperatively until the day of sacrifice. Histologic findings in group A clearly illustrate severe inflammation, bridging necrosis, ischemic cholangitis, and severe congestion, while in group B there were less serious histologic changes. Conclusions Our experimental study indicates that perioperative portal modulation can successfully prevent the manifestation of SFSS after EH. Therefore, by focusing on “flow” rather than on “size,” researchers may understand better the pathophysiology of this syndrome. [ABSTRACT FROM AUTHOR]