Radical Resection in Entero-Pancreatic Neuroendocrine Tumors: Recurrence-Free Survival Rate and Definition of a Risk Score for Recurrence.

BACKGROUND: Surgery with radical intent is the only potentially curative option for entero-pancreatic neuroendocrine tumors (EP-NETs) but many patients develop recurrence even after many years. The subset of patients at high risk of disease recurrence has not been clearly defined to date. OBJECTIVE: The aim of this retrospective study was to define, in a series of completely resected EP-NETs, the recurrence-free survival (RFS) rate and a risk score for disease recurrence. PATIENTS AND METHODS: This was a multicenter retrospective analysis of sporadic pancreatic NETs (PanNETs) or small intestine NETs (SiNETs) [G1/G2] that underwent R0/R1 surgery (years 2000-2016) with at least a 24-month follow-up. Survival analysis was performed using the Kaplan-Meier method and risk factor analysis was performed using the Cox regression model. RESULTS: Overall, 441 patients (224 PanNETs and 217 SiNETs) were included, with a median Ki67 of 2% in tumor tissue and 8.2% stage IV disease. Median RFS was 101 months (5-year rate 67.9%). The derived prognostic score defined by multivariable analysis included prognostic parameters, such as TNM stage, lymph node ratio, margin status, and grading. The score distinguished three risk categories with a significantly different RFS (p < 0.01). CONCLUSIONS: Approximately 30% of patients with EP-NETs recurred within 5 years after radical surgery. Risk factors for recurrence were disease stage, lymph node ratio, margin status, and grading. The definition of risk categories may help in selecting patients who might benefit from adjuvant treatments and more intensive follow-up programs.

Neoadjuvant concurrent chemoradiotherapy with and without hyperthermia in retroperitoneal sarcomas: feasibility, efficacy, toxicity, and long-term outcome.

PURPOSE: Retroperitoneal (RPS) sarcomas are associated with poor local and abdominal tumor control. However, the benefit of preoperative radio- or chemotherapy alone for these entities is currently unclear. Moreover, as intermediate- and high-grade sarcomas have a tendency toward early metastasis, exploration of neoadjuvant strategies is of high importance. This analysis reports the results of our 20-year single-institution experience with preoperative neoadjuvant concurrent chemoradiation. METHODS: From 2000-2019, 27 patients with intermediate- or high-grade RPS (12 dedifferentiated liposarcoma, 10 leiomyosarcoma, 5 others) were treated with radiotherapy (median dose: 50.4 Gy; range 45-75 Gy) and two cycles of chemotherapy (doxorubicin 50 mg/m2 BSA/d3 q28 and ifosfamide 1.5 g/m2 BSA/d1­5 q28) in neoadjuvant intent. Chemotherapy consisted of doxorubicin alone in two cases and ifosfamide alone in one case. Fifteen patients (56%) additionally received deep regional hyperthermia. RESULTS: The median follow-up time was 53 months (±56.7 months). 92% of patients received two cycles of chemotherapy as planned and 92% underwent surgery. At 5 and 10 years, abdominal-recurrence-free survival was 74.6% (±10.1%) and 66.3% (±11.9%), distant metastasis-free survival was 67.2% (±9.7%) and 59.7% (±11.1%), and overall survival was 60.3% (±10.5%) and 60.3% (±10.5%), respectively. CTC grade III and IV toxicities were leukocytopenia (85%), thrombocytopenia (33%), and anemia (11%). There were no treatment-related deaths. CONCLUSION: Neoadjuvant chemoradiotherapy with and without hyperthermia for retroperitoneal sarcomas is feasible and provided high local control of intermediate- and high-grade sarcoma.

R0 resection following chemo (radio)therapy improves survival of primary inoperable pancreatic cancer patients. Interim results of the German randomized CONKO-007± trial.

PURPOSE: Chemotherapy with or without radiotherapy is the standard in patients with initially nonmetastatic unresectable pancreatic cancer. Additional surgery is in discussion. The CONKO-007 multicenter randomized trial examines the value of radiotherapy. Our interim analysis showed a significant effect of surgery, which may be relevant to clinical practice. METHODS: One hundred eighty patients received induction chemotherapy (gemcitabine or FOLFIRINOX). Patients without tumor progression were randomized to either chemotherapy alone or to concurrent chemoradiotherapy. At the end of therapy, a panel of five independent pancreatic surgeons judged the resectability of the tumor. RESULTS: Following induction chemotherapy, 126/180 patients (70.0%) were randomized to further treatment. Following study treatment, 36/126 patients (28.5%) underwent surgery; (R0: 25/126 [19.8%]; R1/R2/Rx [n = 11/126; 6.1%]). Disease-free survival (DFS) and overall survival (OS) were significantly better for patients with R0 resected tumors (median DFS and OS: 16.6 months and 26.5 months, respectively) than for nonoperated patients (median DFS and OS: 11.9 months and 16.5 months, respectively; p = 0.003). In the 25 patients with R0 resected tumors before treatment, only 6/113 (5.3%) of the recommendations of the panel surgeons recommended R0 resectability, compared with 17/48 (35.4%) after treatment (p < 0.001). CONCLUSION: Tumor resectability of pancreatic cancer staged as unresectable at primary diagnosis should be reassessed after neoadjuvant treatment. The patient should undergo surgery if a resectability is reached, as this significantly improves their prognosis.

The polygenic risk for obsessive-compulsive disorder is associated with the personality trait harm avoidance.

OBJECTIVE: Obsessive-compulsive disorder (OCD) is a complex psychiatric disorder with a substantial genetic contribution. While the specific variants underlying OCD's heritability are still unknown, findings from genome-wide association studies (GWAS) corroborate the importance of common SNPs explaining the phenotypic variance in OCD. Investigating associations between the genetic liability for OCD, as reflected by a polygenic risk score (PRS), and potential endophenotypes of the disorder, such as the personality trait harm avoidance, may aid the understanding of functional pathways from genes to diagnostic phenotypes. METHODS: We derived PRS for OCD at several P-value thresholds based on the latest Psychiatric Genomics Consortium OCD GWAS (2688 cases, 7037 controls) in an independent sample of OCD patients (n = 180), their unaffected first-degree relatives (n = 108) and healthy controls (n = 200). Using linear regression, we tested whether these PRS are associated with the personality trait harm avoidance. RESULTS: Results showed that OCD PRS significantly predicted OCD status, with patients having the highest scores and relatives having intermediate scores. Furthermore, the genetic risk for OCD was associated with harm avoidance across the entire sample, and among OCD patients. As indicated by mediation analyses, harm avoidance mediated the association between the OCD PRS and OCD caseness. These results were observed at multiple P-value thresholds and persisted after the exclusion of patients with a current comorbid major depressive or anxiety disorder. CONCLUSION: Our findings support the polygenic nature of OCD and further validate harm avoidance as a candidate endophenotype and diathesis of OCD.

Consensus in determining the resectability of locally progressed pancreatic ductal adenocarcinoma - results of the Conko-007 multicenter trial.

BACKGROUND: One critical step in the therapy of patients with localized pancreatic cancer is the determination of local resectability. The decision between primary surgery versus upfront local or systemic cancer therapy seems especially to differ between pancreatic cancer centers. In our cohort study, we analyzed the independent judgement of resectability of five experienced high volume pancreatic surgeons in 200 consecutive patients with borderline resectable or locally advanced pancreatic cancer. METHODS: Pretherapeutic CT or MRI scans of 200 consecutive patients with borderline resectable or locally advanced pancreatic cancer were evaluated by 5 independent pancreatic surgeons. Resectability and the degree of abutment of the tumor to the venous and arterial structures adjacent to the pancreas were reported. Interrater reliability and dispersion indices were compared. RESULTS: One hundred ninety-four CT scans and 6 MRI scans were evaluated and all parameters were evaluated by all surgeons in 133 (66.5%) cases. Low agreement was observed for tumor infiltration of venous structures (κ = 0.265 and κ = 0.285) while good agreement was achieved for the abutment of the tumor to arterial structures (interrater reliability celiac trunk κ = 0.708 P < 0.001). In patients with vascular tumor contact indicating locally advanced disease, surgeons highly agreed on unresectability, but in patients with vascular tumor abutment consistent with borderline resectable disease, the judgement of resectability was less uniform (dispersion index locally advanced vs. borderline resectable p < 0.05). CONCLUSION: Excellent agreement between surgeons exists in determining the presence of arterial abutment and locally advanced pancreatic cancer. The determination of resectability in borderline resectable patients is influenced by additional subjective factors. TRIAL REGISTRATION: EudraCT:2009-014476-21 (2013-02-22) and NCT01827553 (2013-04-09).

Ventral rectopexy with biological mesh for recurrent disorders of the posterior pelvic organ compartment.

PURPOSE: Recurrent prolapse of the posterior pelvic organ compartment presents a management challenge, with the best surgical procedure remaining unclear. We present functional outcome and patient satisfaction after laparoscopic and robotic ventral mesh rectopexy (VMR) with biological mesh in patients with recurrence. METHODS: We analyzed data from 30 patients with recurrent posterior pelvic organ prolapse who underwent VMR with biological mesh from August 2012 to January 2018. Data included patient demographics and intra- and postoperative findings; functional outcome as assessed by Cleveland Clinic Constipation Score (CCCS), Obstructed Defecation Score Longo (ODS), and Cleveland Clinic Incontinence Score (CCIS); and patient satisfaction. RESULTS: CCCS, CCIS, and ODS were significantly improved at 6-12 months postoperatively and at last follow-up. Patient satisfaction (visual analog scale [VAS] 6.7 [0 to 10]), subjective symptoms (+ 3.4 [scale - 5 to + 5]), and quality of life improvement (+ 3.0 [scale from - 5 to + 5]) were high at last follow-up. The rates of morbidity and major complications were 13% and 3%, respectively. There were no mesh-related complications or deaths. Difference in type of previous surgery (abdominal or transanal/perineal) had no significant effect on results. CONCLUSIONS: VMR with biological mesh is a safe and effective option for patients with recurrent posterior pelvic organ prolapse. It reduces functional symptoms, has a low complication rate, and promotes patient satisfaction.

Permacol™ collagen paste for cryptoglandular and Crohn's anal fistula.

BACKGROUND: Permacol™ collagen paste, an acellular crosslinked porcine dermal collagen matrix suspension, is a new treatment option for anal fistula. Data remain limited, however, and as yet only the results of one case of Crohn's fistula treated with Permacol™ paste has been reported. The aim of this study was to assess the use of Permacol™ collagen paste in patients with cryptoglandular and Crohn's perianal fistulae. METHODS: A prospective study was conducted on patients with anal fistula, treated with Permacol™ paste. Patients were followed at 1 week, 6 and 12 months, and on demand thereafter. The main focus was on fistula healing and postoperative continence. The former was defined as the absence of signs of recurrence on clinical examination, proctoscopy and rigid rectoscopy. Fecal incontinence was assessed before surgery and at each follow-up. RESULTS: Thirty patients (19 women, 11 men; mean age 46 years), 12 (40%) of whom had Crohn's disease were included. The average number of previous fistula operations was 6. All patients had ≥ 6 months of follow-up, and 24 patients (80%) had ≥ 12 months of follow-up. The healing rate in all patients was 57% (17 of 30 patients) at 6 months and 63% (15 of 24 patients) at 12 months. One patient reported a worsening of fecal incontinence at 12 months; 2 patients had adverse events (perianal pain: n = 1, fluid accumulation n = 1) requiring fistula drainage. Patient characteristics, healing, incontinence, and adverse events did not differ significantly between patients with and without Crohn's disease. CONCLUSIONS: Our data indicate that Permacol™ paste is a safe and moderately effective treatment for cryptoglandular and Crohn's fistulae.

Neoadjuvant rectal score as individual-level surrogate for disease-free survival in rectal cancer in the CAO/ARO/AIO-04 randomized phase III trial.

Background: Surrogate end points in rectal cancer after preoperative chemoradiation are lacking as their statistical validation poses major challenges, including confirmation based on large phase III trials. We examined the prognostic role and individual-level surrogacy of neoadjuvant rectal (NAR) score that incorporates weighted cT, ypT and ypN categories for disease-free survival (DFS) in 1191 patients with rectal carcinoma treated within the CAO/ARO/AIO-04 phase III trial. Patients and methods: Cox regression models adjusted for treatment arm, resection status, and NAR score were used in multivariable analysis. The four Prentice criteria (PC1-4) were used to assess individual-level surrogacy of NAR for DFS. Results: After a median follow-up of 50 months, the addition of oxaliplatin to fluorouracil-based chemoradiotherapy (CRT) significantly improved 3-year DFS [75.9% (95% confidence interval [CI] 72.30% to 79.50%) versus 71.3% (95% CI 67.60% to 74.90%); P = 0.034; PC 1) and resulted in a shift toward lower NAR groups (P = 0.034, PC 2) compared with fluorouracil-only CRT. The 3-year DFS was 91.7% (95% CI 88.2% to 95.2%), 81.8% (95% CI 78.4% to 85.1%), and 58.1% (95% CI 52.4% to 63.9%) for low, intermediate, and high NAR score, respectively (P < 0.001; PC 3). NAR score remained an independent prognostic factor for DFS [low versus high NAR: hazard ratio (HR) 4.670; 95% CI 3.106-7.020; P < 0.001; low versus intermediate NAR: HR 1.971; 95% CI 1.303-2.98; P = 0.001] in multivariable analysis. Notwithstanding the inherent methodological difficulty in interpretation of PC 4 to establish surrogacy, the treatment effect on DFS was captured by NAR, supporting satisfaction of individual-level PC 4. Conclusion: Our study validates the prognostic role and individual-level surrogacy of NAR score for DFS within a large randomized phase III trial. NAR score could help oncologists to speed up response-adapted therapeutic decision, and further large phase III trial data sets should aim to confirm trial-level surrogacy.

Ventral rectopexy with biological mesh: short-term functional results.

PURPOSE: Ventral mesh rectopexy (VMR) is an established, minimally invasive, nerve-sparing procedure for the treatment of various symptomatic morphological changes in the posterior pelvic compartment. We present the short-term functional outcome and patient satisfaction after laparoscopic and robotic VMR with biological mesh. METHODS: We analyzed data from 123 patients who underwent laparoscopic ventral mesh rectopexy (LVMR) or robotic ventral mesh rectopexy (RVMR) from August 2012 to January 2017. Included in these data were patient demographics, intra- and postoperative findings, Cleveland Clinic Constipation Score (CCCS), Obstructed Defecation Score Longo (ODS), Cleveland Clinic Incontinence Score (CCIS), and patient satisfaction as measured by visual analog scale (0-10). RESULTS: Improvements in CCCS, CCIS, and ODS were statistically significant at 6 and 12 months (p < 0.001). Patient satisfaction was excellent at 6 and 12 months (8.2/10 and 8.3/10, respectively). The overall complication rate was 14%, with a major complication rate of 2%. No mesh-related complications were observed. The need for surgical re-intervention because of relapse, symptom persistence or recurrence, or new symptoms was 3%. Outcome appears to be similar between LVMR and RVMR. CONCLUSIONS: Both LVMR and RVMR with biological mesh are safe and effective in reducing symptoms, as measured by CCCS, CCIS, and ODS, and patient satisfaction is high.

Harm avoidance and childhood adversities in patients with obsessive-compulsive disorder and their unaffected first-degree relatives.

OBJECTIVE: The etiology of obsessive-compulsive disorder (OCD) is assumed to involve interactions between genetically determined vulnerability factors and significant environmental features. Here, we aim to investigate how the personality trait harm avoidance and the experience of childhood adversities contribute to OCD. METHOD: A total of 169 patients with OCD, 157 healthy comparison subjects, and 57 unaffected first-degree relatives of patients with OCD participated in the study. Harm avoidance was assessed using the Temperament and Character Inventory, and the severity of childhood adversities was measured with the Childhood Trauma Questionnaire. RESULTS: Both patients with OCD and relatives showed elevated levels of harm avoidance compared to controls. Furthermore, patients exhibited significantly higher scores than relatives. This linear pattern was observed throughout all subscales of harm avoidance, and remained stable after controlling for the severity of depressive and obsessive-compulsive symptoms. With regard to childhood adversities, patients with OCD reported higher levels than relatives and controls. CONCLUSION: Our results provide further evidence for a diathesis-stress model of OCD. While patients and unaffected relatives share elevated levels of harm avoidance, supporting the role of harm avoidance as an endophenotype of OCD, a heightened severity of childhood adversity was only observed in patients. The assumed biological underpinnings of these findings are discussed.

[Robotic-Assisted Liver Surgery]. / Roboterassistierte Leberchirurgie.

BACKGROUND: The advantages of minimally invasive liver resections for selected patients are evident. Robots provide new innovations that will influence minimally invasive liver surgery in the future. This article presents our initial experience with this technology in our patient population. Material und Methods: In 14 patients with benign or malignant liver tumours, robotic-assisted liver surgery was performed. Selection criteria were compensated liver function and resection of ≤ 3 liver segments. Chronic liver disease or previous abdominal surgery were no exclusion criteria. RESULTS: Malignant liver tumours were removed in 10 patients (71%) and benign symptomatic liver tumors in 3 patients (21%), respectively, with histopathologically negative margins (R0). One patient suffering from HCC underwent intraoperative ablation. In one case (7%) conversion was necessary. Mean operation time was 296 min (120-458 min); mean estimated blood loss was 319 ± 298 ml. The mean hospital stay of the patients was 8 days (3-17 days). Three patients (21%) suffered from postoperative complications, which were manageable by conservative treatment (Clavien-Dindo I) in 2 cases (14%). One patient (7%) needed endoscopic treatment for postoperative bile leak (Clavien-Dindo III a). No patient died intra- or perioperatively. CONCLUSION: Robotic-assisted liver surgery is a safe procedure, which provides patients with all benefits of minimally invasive surgery. This highly advanced technology requires surgeons to strive for an increasing level of specialisation, in addition to being well-trained in liver surgery. Hence, a clear definition of the procedures and standardised teaching programs are necessary.

[Total Pancreatectomy and Islet Autotransplantation in a Child with Recurrent Pancreatitis]. / Totale Pankreatektomie und Inselautotransplantation bei einem Kind mit chronisch rezidivierender Pankreatitis.

INTRODUCTION: Hereditary pancreatitis in children is rare. The indications for surgery in these children are complications and severe pain that cannot be managed by conservative treatment. Surgical treatment options are duodenum preserving resections as well as drainage procedures. Recurrences are common following theses surgical procedures, because usually the whole pancreas is affected. The majority of the children with symptomatic hereditary pancreatitis are free of pain after total pancreatectomy. When total pancreatectomy is combined with islet autotransplantation, pancreoprivic diabetes can be attenuated or even prevented. The principle of spleen-preserving total pancreatectomy combined with subsequent islet autotransplantation is shown in a case of a 10-year-old child with chronic recurrent pancreatitis in this video. INDICATION: Symptomatic chronic hereditary pancreatitis in children. PROCEDURE: Spleen-preserving total pancreatectomy, reconstruction with hepatico-jejunostomy and duodeno-jejunostomy, islet autotransplantation via portal vein. CONCLUSION: If the surgeon has appropriate experience, spleen-preserving total pancreatectomy is a safe procedure. In combination with islet autotransplantation, it may attenuate or prevent diabetes mellitus associated with total pancreatectomy. In highly selected pediatric patients, this surgical procedure has a major benefit compared to a purely symptomatic therapy.

[Appleby operation for locally advanced tumour of the pancreatic body and tail--a video demonstration]. / Appleby-Operation bei ausgedehntem Pankreaskorpus- und -schwanztumor - Video eines Falles.

INTRODUCTION: Patients with locally advanced pancreatic cancer and arterial infiltration of the coeliac artery are often classified as irresectable and therefore treated palliatively. For a highly selected group of patients, a complete resection (R0) of a pancreatic carcinoma including resection of the coeliac trunk without arterial reconstruction can mean a survival advantage. The expertise of the surgeon in vascular and pancreatic surgery as well as the proficiency of the entire surgical and anaesthesiological team and the appropriate infrastructure of the hospital are prerequisites for the success of such complex operations. Concerning the local finding of infiltration of the aorta, the gastroduodenal artery and the mesenteric superior artery should be excluded, to ensure R0 resection and perfusion of the liver via the gastroduodenal artery after resection. Moreover, the patient has to be fit for a large abdominal operation and extrapancreatic metastases have to be excluded, especially in ductal adenocarcinoma of the pancreas. In this video, the principles of the Appleby operation are shown in a case of locally advanced neuroendocrine carcinoma of the pancreas with infiltration of the coeliac artery. INDICATION: Locally advanced pancreatic neuroendocrine carcinoma with infiltration of the coeliac artery without distant metastasis after neoadjuvant therapy. PROCEDURE: Extended multiorgan pancreatic corpus and tail resection including resection of coeliac artery, portal vein resection, splenectomy, resection of left adrenal gland, subtotal gastrectomy and oversewing of the pancreatic head, end-to-end reconstruction of the portal vein and gastro-jejunostomy (Roux-Y) and duodeno-jejunostomy. CONCLUSION: Given the appropriate experience, the Appleby procedure is a technically demanding resection in pancreatic carcinomas involving the coeliac artery without arterial anastomosis. In selected cases this operation might have advantages compared to palliative treatment.

[Arterial reconstruction in pancreatic carcinoma ­demonstration of surgical techniques]. / Arterielle Rekonstruktion beim duktalen Pankreaskarzinom­ Darstellung chirurgischer Techniken.

INTRODUCTION: For a highly selected group of patients, a complete resection (R0) of a pancreatic carcinoma including arterial resection and reconstruction can represent an advantage in survival. The expertise of the surgeon in vascular and pancreatic surgery as well as the proficiency of the entire surgical and anaesthesiological team and the appropriate infrastructure of the hospital are prerequisites for the success of such complex operations. Proximal and distal of the tumour, sufficient lengths of the vessels are needed for the vascular anastomoses. In this video, the principles of arterial resection and reconstruction are shown in two patients with advanced pancreatic carcinoma. INDICATION: This procedure is indicated for locally advanced pancreatic carcinoma with arterial infiltration without distant metastasis after neoadjuvant therapy. PROCEDURE: The procedure involves 2 steps: 1. pancreatic head resection with resection of the common hepatic artery and end-to-end anastomosis of the hepatic artery and portal vein resection; 2. left pancreatic resection including splenectomy; resection of the celiac trunk, the superior mesenteric artery; reinsertion of the superior mesenteric artery into the aorta; end-to-end anastomosis of the common hepatic artery with the stump of the celiac trunk. CONCLUSION: Given the appropriate experience, technically demanding arterial resections and reconstructions in pancreatic carcinoma are feasible and can provide superior survival for the patient compared to palliative therapy.

[Intraductal papillary mucinous neoplasm of the pancreas (IPMN)--standards and new aspects]. / Intraduktale papillär-muzinöse Neoplasien (IPMN) des Pankreas--Standards und neue Aspekte.

Intraductal papillary mucinous neoplasms (IPMN) of the pancreas belong to the heterogeneous group of cystic pancreatic lesions and have been diagnosed more frequently in recent years. Diagnosis and differentiation from other cystic lesions (pseudocysts, serous-cystic neoplasias [SCN], mucinous-cystic neoplasias [MCN], intraductal papillary-mucinous neoplasias [IPMN] and solid pseudopapillary neoplasias [SPN]) is often challenging. IPMN of the pancreas are considered as precursor lesions for the development of invasive pancreatic cancer. However, depending on the morphological (MD-IPMN, BD-IPMN) and histological subtype (intestinal, pancreatobiliary, oncocytic or gastric) the malignant potential of IPMNs varies significantly. Hence, early diagnosis and selection of the appropriate therapeutic strategy is necessary for optimal outcome and cure. There is a strong consensus for the resection of all MD-IPMN. Small BD-IPMN without signs of malignancy can be followed by observation. The increasing understanding of the histopathology and tumour biology of IPMN has led to an amendment of the 2006 International Association of Pancreatology (IAP) guidelines for the treatment of cystic pancreatic tumours. In consideration of recent data, recommendations for observation and/or follow-up of IPMN cannot be given definitely.

DNA demethylation and tri-methylation of H3K4 at the TACSTD2 promoter are complementary players for TROP2 regulation in colorectal cancer cells.

TROP2 is a powerful cancer driver in colorectal cancer cells. Divergent epigenetic regulation mechanisms for the corresponding TACSTD2 gene exist such as miRNAs or DNA methylation. However, the role of TACSTD2 promoter hypermethylation in colorectal cancer has not been investigated yet. In this study, TROP2 expression strongly correlated with promoter methylation in different colorectal tumor cell lines. Treatment with 5-Azacytidine, a DNMT1 inhibitor, led to demethylation of the TACSTD2 promoter accompanied by an increase in TROP2 protein expression. TROP2 expression correlated with promoter methylation in vivo in human colon tumor tissue, thereby verifying promoter methylation as an important factor in the regulation of TROP2 expression in colorectal cancer. When performing a ChIP-Seq analysis in HCT116 and HT29 cells, we found that TACSTD2 promoter demethylation was accompanied by tri-methylation of H3K4. In silico analysis of GSE156613 data set confirmed that a higher binding of histone mark H3K4me3 around the TACSTD2 promoter was found in TACSTD2 high expressing tumors of colon cancer patients compared to the corresponding adjacent tumor tissue. Moreover, the link between TROP2 and the H3K4me3 code was even evident in tumors showing high intratumoral heterogeneity for TROP2 staining. Our data provide novel evidence for promoter demethylation and simultaneous gains of the active histone mark H3K4me3 across CpG-rich sequences, both being complementary mechanisms in the transcriptional regulation of TACSTD2 in colon cancer. The functional consequences of TROP2 loss in colorectal cancer needs to be further investigated.

[Endovascular treatment of thoracic aneurisms: indications, techniques and results]. / Endovaskuläre Therapie des thorakalen Aortenaneurysmas: Indikationen, Technik und Ergebnisse.

UNLABELLED: CLINICAL ISSUE OF THORACIC ANEURYSMS: Aneurysms are among the most common diseases affecting the thoracic aorta, with a continuous increase in incidence over the recent decades. The main cause of thoracic aneurysms is atherosclerosis, which, due to the frequent lack of major symptoms and the potentially lethal complications such as ruptured aortic aneurysm, remains a challenge in clinical practice. STANDARD RADIOLOGICAL METHODS: CT angiography remains the imaging method of choice for acute aortic aneurysms, with MR angiography being increasingly used for follow-up imaging. THRESHOLD FOR TREATMENT: In the ascending aorta a diameter larger than 5-5.5 cm (descending aorta 6.5 cm) is regarded as the threshold for treatment. THORACIC ENDOVASCULAR AORTIC REPAIR: The continuous evolution of aortic stent grafting (i.e., thoracic endovascular aortic repair [TEVAR]) since Parodi, Palmaz and Dake has led to a steep rise in stent grafting procedures in recent years. PRACTICAL RECOMMENDATIONS: Particularly in elderly patients with multiple comorbidities, TEVAR is a valuable, less invasive option compared to open surgical repair.

[Pancreatic anastomosis -- a video comparison of different techniques]. / Die Pankreasanastomose - ein Videovergleich unterschiedlicher Anastomosentechniken.

INTRODUCTION: The pancreatic anastomosis seems to be the most difficult and dangerous anastomosis in general surgery, especially in a soft pancreas. Many techniques have been described. The techniques most often used are: anastomosis of the pancreas to the jejunum as a pancreatico-jejunostomy (duct-to-mucosa anastomosis) or as a pancreato-jejunostomy (invaginating anastomosis). Another widely used anastomosis for reconstruction after pancreatic head resection is from the stomach to the pancreas, i.e., pancreato-gastrostomy. In literature the data concerning postoperative complications (pancreatic fistula, postoperative bleeding and others) are not consistent. INDICATIONS: Reconstruction after pancreatic head resection. PROCEDURE: Anastomosis between small intestine or stomach and the pancreas. CONCLUSION: There is no gold standard for pancreatic anastomosis. Thus, of the different commonly used techniques, in our opinion, the best technique for each surgeon seems to be the one that he/she is most familiar with.

[New aspects of surgery for pancreatic cancer. Principles, results and evidence]. / Neue Aspekte in der Chirurgie des Pankreaskarzinoms. Prinzipien - Ergebnisse - Evidenz.

Ductal adenocarcinoma is the most frequent malignant tumor of the pancreas and total resection of the pancreatic tumor is still the only curative treatment option. Most tumors are located in the pancreatic head, therefore, pylorus-preserving pancreaticoduodenectomy (Whipple PPPD) is the oncological standard procedure. By concentrating pancreatic resections in specialized centers for pancreatic surgery perioperative mortality and morbidity has decreased in recent years. However, pancreatic resections remain complex and difficult operations and pancreatic anastomosis is particular challenging. To achieve complete resection (R0) resection and reconstruction of large venous vessels is often necessary. Resection of arterial vessels is rarely performed and usually does not lead to an R0 resection of the tumor. Currently adjuvant chemotherapy after total tumor resection is standard of care for all tumor stages but neoadjuvant regimes have recently been reported increasingly more often. Advances in translational research has led to a better understanding of tumor biology and new diagnostic options and therapies are expected in the near future.