Gata6+ Pericardial Cavity Macrophages Relocate to the Injured Heart and Prevent Cardiac Fibrosis.

Macrophages play an important role in structural cardiac remodeling and the transition to heart failure following myocardial infarction (MI). Previous research has focused on the impact of blood-derived monocytes on cardiac repair. Here we examined the contribution of resident cavity macrophages located in the pericardial space adjacent to the site of injury. We found that disruption of the pericardial cavity accelerated maladaptive post-MI cardiac remodeling. Gata6+ macrophages in mouse pericardial fluid contributed to the reparative immune response. Following experimental MI, these macrophages invaded the epicardium and lost Gata6 expression but continued to perform anti-fibrotic functions. Loss of this specialized macrophage population enhanced interstitial fibrosis after ischemic injury. Gata6+ macrophages were present in human pericardial fluid, supporting the notion that this reparative function is relevant in human disease. Our findings uncover an immune cardioprotective role for the pericardial tissue compartment and argue for the reevaluation of surgical procedures that remove the pericardium.

Discrimination of pancreato-biliary cancer and pancreatitis patients by non-invasive liquid biopsy.

BACKGROUND: Current diagnostics for the detection of pancreato-biliary cancers (PBCs) need to be optimized. We therefore propose that methylated cell-free DNA (cfDNA) derived from non-invasive liquid biopsies serves as a novel biomarker with the ability to discriminate pancreato-biliary cancers from non-cancer pancreatitis patients. METHODS: Differentially methylated regions (DMRs) from plasma cfDNA between PBCs, pancreatitis and clinical control samples conditions were identified by next-generation sequencing after enrichment using methyl-binding domains and database searches to generate a discriminatory panel for a hybridization and capture assay with subsequent targeted high throughput sequencing. RESULTS: The hybridization and capture panel, covering around 74 kb in total, was applied to sequence a cohort of 25 PBCs, 25 pancreatitis patients, 25 clinical controls, and seven cases of Intraductal Papillary Mucinous Neoplasia (IPMN). An unbiased machine learning approach identified the 50 most discriminatory methylation markers for the discrimination of PBC from pancreatitis and controls resulting in an AUROC of 0.85 and 0.88 for a training (n = 45) and a validation (n = 37) data set, respectively. The panel was also able to distinguish high grade from low grade IPMN samples. CONCLUSIONS: We present a proof of concept for a methylation biomarker panel with better performance and improved discriminatory power than the current clinical marker CA19-9 for the discrimination of pancreato-biliary cancers from non-cancerous pancreatitis patients and clinical controls. This workflow might be used in future diagnostics for the detection of precancerous lesions, e.g. the identification of high grade IPMNs vs. low grade IPMNs.

Survival outcome following surgical versus non-surgical treatment of colorectal lung metastasis-a retrospective cohort study.

PURPOSE: The optimal management of colorectal lung metastases (CRLM) is still controversial. The aim of this study was to compare surgical and non-surgical treatment for CRLM regarding the prognostic outcome. METHODS: This retrospective single-center cohort study included 418 patients, who were treated from January 2000 to December 2018 at a German University Hospital due to their colorectal carcinoma and had synchronous or metachronous lung metastases. Patients were stratified according the treatment of the CRLM into two groups: surgical resection of CRLM versus no surgical resection of CRLM. The survival from the time of diagnosis of lung metastasis was compared between the groups. RESULTS: Two- and 5-year overall survival (OS) from the time of diagnosis of lung metastasis was 78.2% and 54.6%, respectively, in our cohort. Patients undergoing pulmonary metastasectomy showed a significantly better 2- and 5-year survival compared to patients with non-surgical treatment (2-year OS: 98.1% vs. 67.9%; 5-year OS: 81.2% vs. 28.8%; p < 0.001). Multivariate Cox regression revealed the surgical treatment (HR 4.51 (95% CI = 2.33-8.75, p < 0.001) and the absence of other metastases (HR 1.79 (95% CI = 1.05-3.04), p = 0.032) as independent prognostic factors in patients with CRLM. CONCLUSION: Our data suggest that patients with CRLM, who qualify for surgery, benefit from surgical treatment. Randomized controlled trials are needed to confirm our findings. CLINICAL TRIAL REGISTRY NUMBER: The work has been retrospectively registrated at the German Clinical Trial Registry (DRKS00032938).

Antibiotic treatment after appendectomy for acute complicated appendicitis to prevent intrabdominal abscess and wound infections.

INTRODUCTION: The purpose of this analysis was to investigate the most appropriate duration of postoperative antibiotic treatment to minimize the incidence of intraabdominal abscesses and wound infections in patients with complicated appendicitis. MATERIALS AND METHODS: In this retrospective study, which included 396 adult patients who underwent appendectomy for complicated appendicitis between January 2010 and December 2020 at the University Hospital Erlangen, patients were classified into two groups based on the duration of their postoperative antibiotic intake: ≤ 3 postoperative days (group 1) vs. ≥ 4 postoperative days (group 2). The incidence of postoperative intraabdominal abscesses and wound infections were compared between the groups. Additionally, multivariate risk factor analysis for the occurrence of intraabdominal abscesses and wound infections was performed. RESULTS: The two groups contained 226 and 170 patients, respectively. The incidence of postoperative intraabdominal abscesses (2% vs. 3%, p = 0.507) and wound infections (3% vs. 6%, p = 0.080) did not differ significantly between the groups. Multivariate analysis revealed that an additional cecum resection (OR 5.5 (95% CI 1.4-21.5), p = 0.014) was an independent risk factor for intraabdominal abscesses. A higher BMI (OR 5.9 (95% CI 1.2-29.2), p = 0.030) and conversion to an open procedure (OR 5.2 (95% CI 1.4-20.0), p = 0.016) were identified as independent risk factors for wound infections. CONCLUSION: The duration of postoperative antibiotic therapy does not appear to influence the incidence of postoperative intraabdominal abscesses and wound infections. Therefore, short-term postoperative antibiotic treatment should be preferred.

Meta-analysis of Osteopontin splice variants in cancer.

BACKGROUND: The cytokine Osteopontin is a mediator of tumor progression and cancer metastasis. In 2006, we reported that (in addition to the full-length form -a) splice variants of Osteopontin (forms -b and -c) are produced selectively by transformed cells. Through June 2021, 36 PubMed-indexed journal articles have studied Osteopontin splice variants in various cancer patients. METHODS: Applying a categorical approach previously developed by us, here we conduct a meta-analysis of the pertinent literature. We supplement this with evaluation of the relevant entries in the TSVdb database, which focusses on splice variant expression, thus including the additional variants -4 and -5. The analysis covers 5886 patients across 15 tumors from the literature and 10,446 patients across 33 tumors from TSVdb. RESULTS: The database yields positive results more frequently than the categorical meta-analysis. The two sources are in agreement on the elevation of OPN-a, OPN-b, and OPN-c in lung cancer and the elevation of OPN-c in breast cancer as compared to healthy tissue. Specific splice variants are associated with grade, stage, or patient survival pertaining to various cancers. CONCLUSIONS: There are cases of persisting discrepancies, which require further investigation to clarify the Osteopontin splice variant utilization, so that their diagnostic, prognostic and potentially predictive potential can be brought to fruition.

The role of intraoperative swab during appendectomy in patients with uncomplicated and complicated appendicitis.

INTRODUCTION: Bacteria play an important role not only in pathogenesis of appendicitis but also in the postoperative course of patients. However, the usefulness of an intraoperative swab during appendectomy is controversial. The primary aim of this study was to investigate the impact of intraoperative swab during appendectomy on the postoperative outcome in patients with uncomplicated and complicated appendicitis. METHODS: A retrospective analysis was conducted on a consecutive series of 1570 adult patients who underwent appendectomy for acute appendicitis at the University Hospital Erlangen between 2010 and 2020. Data regarding the intraoperative swab were collected and analyzed for the entire cohort as well as for patients with uncomplicated and complicated appendicitis. RESULTS: An intraoperative swab was taken in 29% of the cohort. The bacterial isolation rate in the obtained intraoperative swabs was 51%, with a significantly higher rate observed in patients with complicated appendicitis compared to those with uncomplicated appendicitis (79% vs. 35%, p < 0.001). The presence of a positive swab was significantly associated with worse postoperative outcomes, including higher morbidity, increased need for re-surgery, and longer hospital stay, when compared to patients without a swab or with a negative swab. A positive swab was an independent risk factor for postoperative morbidity (OR 9.9 (95% CI 1.2-81.9), p = 0.034) and the need for adjustment of postoperative antibiotic therapy (OR 8.8 (95% CI 1.1-72.5), p = 0.043). However, a positive swab resulted in postoperative antibiotic therapy adjustment in only 8% of the patients with bacterial isolation in the swab. CONCLUSION: The analysis of swab samples obtained during appendectomy for acute appendicitis can help identify patients at a higher risk of a worse postoperative outcome. However, the frequency of antibiotic regime changes based on the swab analysis is low.

Four-and-a-Half LIM-Domain Protein 2 (FHL2) Induces Neuropeptide Y (NPY) in Macrophages in Visceral Adipose Tissue and Promotes Diet-Induced Obesity.

Obesity is characterized by the expansion of the adipose tissue, usually accompanied by inflammation, with a prominent role of macrophages infiltrating the visceral adipose tissue (VAT). This chronic inflammation is a major driver of obesity-associated comorbidities. Four-and-a-half LIM-domain protein 2 (FHL2) is a multifunctional adaptor protein that is involved in the regulation of various biological functions and the maintenance of the homeostasis of different tissues. In this study, we aimed to gain new insights into the expression and functional role of FHL2 in VAT in diet-induced obesity. We found enhanced FHL2 expression in the VAT of mice with Western-type diet (WTD)-induced obesity and obese humans and identified macrophages as the cellular source of enhanced FHL2 expression in VAT. In mice with FHL2 deficiency (FHL2KO), WTD feeding resulted in reduced body weight gain paralleled by enhanced energy expenditure and uncoupling protein 1 (UCP1) expression, indicative of activated thermogenesis. In human VAT, FHL2 was inversely correlated with UCP1 expression. Furthermore, macrophage infiltration and the expression of the chemokine MCP-1, a known promotor of macrophage accumulation, was significantly reduced in WTD-fed FHL2KO mice compared with wild-type (wt) littermates. While FHL2 depletion did not affect the differentiation or lipid metabolism of adipocytes in vitro, FHL2 depletion in macrophages resulted in reduced expressions of MCP-1 and the neuropeptide Y (NPY). Furthermore, WTD-fed FHL2KO mice showed reduced NPY expression in VAT compared with wt littermates, and NPY expression was enhanced in VAT resident macrophages of obese individuals. Stimulation with recombinant NPY induced not only UCP1 expression and lipid accumulation but also MCP-1 expression in adipocytes. Collectively, these findings indicate that FHL2 is a positive regulator of NPY and MCP-1 expression in macrophages and herewith closely linked to the mechanism of obesity-associated lipid accumulation and inflammation in VAT. Thus, FHL2 appears as a potential novel target to interfere with the macrophage-adipocyte crosstalk in VAT for treating obesity and related metabolic disorders.

Induction of a cytokine storm involves suppression of the Osteopontin-dependent TH1 response.

Cytokine release syndromes represent a severe turn in certain disease states, which may be caused by several infections, including those with the virus SARS-CoV-2. This inefficient, even harmful, immune response has been associated with a broad release of chemokines. Although a cellular (type I) immune reaction is efficacious against viral infections, we noted a type I deficit in the cytokine patterns produced by cytokine storms of all reported etiologies. Agents including lipopolysaccharide (LPS, bacterial), anti-CD3 (antibody) and a version of the prominent SARS-CoV-2 viral surface molecule, Spike Glycoprotein, were individually sufficient to induce IL-6 and multiple chemokines in mice. They failed to upregulate the TH1 inducer cytokine Osteopontin, and the pathophysiologic triggers actually suppressed the PMA-induced Osteopontin secretion from monocytic cells. Osteopontin administration partially reversed the chemokine elevation, more effectively so in a mouse strain with TH1 bias. Corroboration was obtained from the inverse correlation in the levels of IL-6 and Osteopontin in plasma samples from acute COVID-19 patients. We hypothesize that the inhibition of Osteopontin by SARS-CoV-2 Spike Glycoprotein or LPS represents an immune evasion mechanism employed by the pathogens of origin. The ensuing dysfunctional inflammatory response promotes a vicious cycle of amplification, resulting in a cytokine storm.

Breast cancer risk in papilloma patients: Osteopontin splice variants indicate prognosis.

BACKGROUND: Papillomas of the breast pose challenges for treatment decisions as their risk for transformation to breast cancer is low but not negligible. To spare low-risk patients the burden of substantial treatment side effects, prognostic indicators are needed for cancerous progression. The secreted metastasis mediator Osteopontin (OPN) is a marker for breast cancer aggressiveness, and its variants are prognosticators for transformation in diverse premalignant breast lesions. Here, we test whether the presence of OPN-c or OPN-exon-4 in papillomatous lesions may reflect progression risk. METHODS: By immunohistochemistry, we analyze OPN-c and OPN-exon-4 in papillomas from 114 women as well as correlations between staining and progression. In departure from prior spliced OPN biomarker publications, we utilize novel monoclonal antibodies. RESULTS: Fewer than 5% of OPN-c pathology score 0-1 (intensity) versus almost 18% of score 2-3 experienced cancer in follow-up. Nine of 12 women, who progressed, had pathology scores of 2-3 for OPN-c intensity at the time of initial diagnosis, and none had a score of 0. When developing a combined risk score from intensity plus percent positivity for OPN-c, the progression risk for patients with low score was 3.2%, for intermediate score was 5.7%, and for high score was 18.8%. Papillomas in patients, who were later diagnosed with cancer in the contralateral breast, displayed stronger staining positivity than non-progressors. CONCLUSION: OPN splice variant immunohistochemistry on biopsies of breast papillomas will allow counseling of the patients on their risk to develop breast cancer at a later time.

The B-cell inhibitory receptor CD22 is a major factor in host resistance to Streptococcus pneumoniae infection.

Streptococcus pneumoniae is a major human pathogen, causing pneumonia and sepsis. Genetic components strongly influence host responses to pneumococcal infections, but the responsible loci are unknown. We have previously identified a locus on mouse chromosome 7 from a susceptible mouse strain, CBA/Ca, to be crucial for pneumococcal infection. Here we identify a responsible gene, Cd22, which carries a point mutation in the CBA/Ca strain, leading to loss of CD22 on B cells. CBA/Ca mice and gene-targeted CD22-deficient mice on a C57BL/6 background are both similarly susceptible to pneumococcal infection, as shown by bacterial replication in the lungs, high bacteremia and early death. After bacterial infections, CD22-deficient mice had strongly reduced B cell populations in the lung, including GM-CSF producing, IgM secreting innate response activator B cells, which are crucial for protection. This study provides striking evidence that CD22 is crucial for protection during invasive pneumococcal disease.

The use of single-stapling techniques reduces anastomotic complications in minimal-invasive rectal surgery.

BACKGROUND: Leakage of rectal anastomoses is one of the most important and feared complications in colorectal surgery. Apart from patient-specific risk factors, technical aspects may influence the occurrence of anastomotic complications. This study investigated whether using single-stapling techniques (SST) instead of the double-stapling technique (DST) for minimal-invasive rectal anastomosis is associated with a lower rate of anastomotic complications. METHODS: A retrospective review of 272 patients who received a minimally invasive stapled rectal anastomosis (3-16 cm from the anal verge) at our institution from 2015 to 2020 was performed. In 131 patients, rectal anastomosis was created by SST (SST group), while 141 patients received a rectal anastomosis with crossing stapler lines (DST group). The impact of the anastomotic technique on patient outcomes was determined by uni- and multivariate analyses. RESULTS: Overall anastomotic leakage rate was 6%. Patients with SST anastomoses had a lower leakage rate than patients with DST anastomoses (3% vs. 9% in the DST group, p = 0.045). The rate of anastomotic stenosis was lower in the SST group than in the DST group (1% vs. 6%, p = 0.037). Overall morbidity and mortality did not differ between the two groups. Multivariate analysis showed that single-stapling techniques significantly reduce the risk of anastomotic leakage (OR 3.5 [1.0-11.5], p = 0.043). CONCLUSION: The use of SST for rectal anastomosis may help to reduce anastomotic complications. This finding should be confirmed by a randomized controlled trial.

Influence of interrupted versus continuous suture technique on intestinal anastomotic leakage rate in patients with Crohn's disease - a propensity score matched analysis.

PURPOSE: Intestinal anastomosis is a crucial step in most intestinal resections, as anastomotic leakage is often associated with severe consequences for affected patients. There are especially two different techniques for hand-sewn intestinal anastomosis: the interrupted suture technique (IST) and the continuous suture technique (CST). This study investigated whether one of these two suture techniques is associated with a lower rate of anastomotic leakage. METHODS: A retrospective review of 332 patients with Crohn's disease who received at least one hand-sewn colonic anastomosis at our institution from 2010 to 2020 was performed. Using propensity score matching 183 patients with IST were compared to 96 patients with CST in regard to the impact of the anastomotic technique on patient outcomes. RESULTS: Overall anastomotic leakage rate was 5%. Leakage rate did not differ between the suture technique groups (IST: 6% vs. CST: 3%, p = 0.393). Multivariate analysis revealed the ASA score as only independent risk factor for anastomotic leakage (OR 5.3 (95% CI = 1.2-23.2), p = 0.026). Suture technique also showed no significant influence on morbidity and the re-surgery rate in multivariate analysis. CONCLUSION: Our data suggest that the chosen suture technique (interrupted vs. continuous) has no influence on postoperative outcome, especially on anastomotic leakage rate. This finding should be confirmed by a randomized controlled trial.

Tumor Infiltration with CD20+CD73+ B Cells Correlates with Better Outcome in Colorectal Cancer.

Immunotherapy has become increasingly important in the treatment of colorectal cancer (CRC). Currently, CD73, also known as ecto-5'-nucleotidase (NT5E), has gained considerable interest as a potential therapeutic target. CD73 is one of the key enzymes catalyzing the conversion of extracellular ATP into adenosine, which in turn exerts potent immune suppressive effects. However, the role of CD73 expression on various cell types within the CRC tumor microenvironment remains unresolved. The expression of CD73 on various cell types has been described recently, but the role of CD73 on B-cells in CRC remains unclear. Therefore, we analyzed CD73 on B-cells, especially on tumor-infiltrating B-cells, in paired tumor and adjacent normal tissue samples from 62 eligible CRC patients. The highest expression of CD73 on tumor-infiltrating B-cells was identified on class-switched memory B-cells, followed by naive B-cells, whereas no CD73 expression was observed on plasmablasts. Clinicopathological correlation analysis revealed that higher CD73+ B-cells infiltration in the CRC tumors was associated with better overall survival. Moreover, metastasized patients showed a significantly decreased number of tumor-infiltrating CD73+ B-cells. Finally, neoadjuvant therapy correlated with reduced CD73+ B-cell numbers and CD73 expression on B-cells in the CRC tumors. As promising new immune therapies are being developed, the role of CD73+ B-cells and their subsets in the development of colorectal cancer should be further explored to find new therapeutic options.

[Pylorus-Preserving Pancreaticoduodenectomy (PPPD) with Segmental Portal Vein Resection]. / Pyloruserhaltende partielle Pankreatoduodenektomie mit segmentaler Pfortaderresektion.

INTRODUCTION: Pylorus-preserving partial pancreatoduodenectomy is a complex visceral operation, especially when simultaneous resection and reconstruction of the portal venous axis is necessary. Pancreatic anastomosis plays a decisive role in this procedure, since postoperative pancreatic fistula (POPF) is a frequent complication, with serious consequences (morbidity and mortality) for the affected patient. Various techniques are available for anastomosing the residual pancreas: the duct-to-mucosa pancreaticojejunostomy, invaginating pancreatojejunostomy, Blumgart anastomosis and pancreatogastrostomy. INDICATION: Adenocarcinoma of the pancreatic head with portal vein infiltration. PROCEDURE: Pylorus-preserving pancreaticoduodenectomy (PPPD) with portal vein resection. CONCLUSION: A standardised and structured approach to pylorus-preserving partial pancreatoduodenectomy helps the surgeon to perform this procedure safely. Performing a simultaneous portal vein resection increases the complexity of the procedure, but nonetheless, if infiltration of the portal venous axis is suspected, the indication for en-bloc resection should be given generously, as intraoperatively it is not possible to differentiate reliably between inflammatory adherence and tumour infiltration and portal vein/V.-mesenterica-superior-resection does not increase morbidity and mortality. The choice of the surgical technique for anastomosing the residual pancreas should be made by the surgeon on the basis of his expertise and, if necessary, adapted to the patient's situs, since the most important pancreatic anastomosis techniques appear to be equivalent according to the current evidence.

[Better Therapy for Pancreatic Cancer through More Radical Surgery?] / Bessere Therapie des Pankreaskarzinoms durch radikalere Chirurgie?

Despite advances in the treatment of pancreatic cancer, the survival of affected patients remains limited. A more radical surgical therapy could help to improve the prognosis, in particular by reducing the local recurrence rate, which is around 45% in patients with resected pancreatic cancer. In addition, patients with oligometastatic pancreatic cancer could also benefit from a more radical indication for surgery.Based on an analysis of the literature, important principles of pancreatic cancer surgery were examined.Even if even more radical surgical approaches such as an "extended" lymphadenectomy or a standard complete pancreatectomy do not bring any survival advantage, complete resection of the tumour (R0), a thorough locoregional lymphadenectomy and an adequate radical dissection in the area of the peripancreatic vessels including periarterial nerve plexuses should be the standard of pancreatic carcinoma resections. Whenever necessary to achieve an R0 resection, resections of the pancreas have to be extended, as well as additional venous vascular resections and multivisceral resections had to be performed. Simultaneous arterial vascular resections as part of pancreatic resections as well as surgical resections in oligometastatic patients should, however, be reserved for selected patients. These aspects of the surgical technique in pancreatic carcinoma mentioned above must not be neglected from the point of view of an "existing limited prognosis". On the contrary, they form the absolutely necessary basis in order to achieve good survival results in combination with system therapy. However, it may always be necessary to adapt these standards according to the age, comorbidities and wishes of the patient.

An overview of proteomic methods for the study of 'cytokine storms'.

Introduction: The cytokine storm is a form of excessive systemic inflammatory reaction triggered by a myriad of factors that may lead to multi-organ failure, and finally to death. The cytokine storm can occur in a number of infectious and noninfectious diseases including COVID-19, sepsis, ebola, avian influenza, and graft versus host disease, or during the severe inflammatory response syndrome.Area covered: This review mainly focuses on the most common and well-known methods of protein studies (PAGE, SDS-PAGE, and high- performance liquid chromatography). It also discusses other modern technologies in proteomics like mass spectrometry, soft ionization techniques, cytometric bead assays, and the next generation of microarrays that have been used to get an in-depth understanding of the pathomechanisms involved during the cytokine storm.Expert opinion: Overactivation of leukocytes drives the production and secretion of inflammatory cytokines fueling the cytokine storm. These events lead to a systemic hyper-inflammation, circulatory collapse and shock, and finally to multiorgan failure. Therefore, monitoring the patient's systemic cytokine levels with proteomic technologies that are redundant, economical, and require minimal sample volume for real-time assessment might help in a better clinical evaluation and management of critically ill patients.

Pancreatoduodenectomy with or without prophylactic falciform ligament wrap around the hepatic artery for prevention of postpancreatectomy haemorrhage: randomized clinical trial (PANDA trial).

BACKGROUND: Postpancreatectomy haemorrhage (PPH) is a rare but potentially fatal complication after pancreatoduodenectomy. Preventive strategies are lacking with scarce data for support. The aim of this study was to investigate whether a prophylactic falciform ligament wrap around the hepatic and gastroduodenal artery can prevent PPH from these vessels. METHODS: In a randomized, controlled, multicentre trial, patients who were scheduled for elective open partial pancreatoduodenectomy with pancreatojejunostomy between 5 November 2015 and 2 April 2020 were randomly allocated in a 1 : 1 ratio to undergo pancreatoduodenectomy with (intervention) or without (control) a falciform ligament wrap around the hepatic artery. The primary endpoint was the rate of clinically relevant PPH from the hepatic artery or gastroduodenal artery stump within 3 months after pancreatoduodenectomy. Secondary endpoints were the rates of associated postoperative complications, for example postoperative pancreatic fistula (POPF) and PPH. RESULTS: Altogether, 445 patients were randomized with 222 and 223 in each group. Among the patients included in modified intention-to-treat analysis (207 in the intervention group and 210 in the control group), the primary endpoint was observed in six of 207 in the intervention group compared with 15 of 210 in the control group (2.9 versus 7.1 per cent respectively; odds ratio 0.39 (95 per cent c.i. 0.15 to 1.02); P = 0.071). Per protocol analysis showed a significant reduction in the intervention group (odds ratio 0.26 (95 per cent c.i. 0.09 to 0.80); P = 0.017). A soft pancreas texture (43 per cent) and the rate of a clinically relevant POPF were evenly (20 per cent) distributed between the groups. The rate of any clinically relevant PPH including the primary endpoint and other bleeding sites was not significantly different between intervention and control groups (9.7 versus 14.8 per cent respectively). CONCLUSION: A falciform ligament wrap may reduce PPH from the hepatic artery or gastroduodenal artery stump and should be considered during pancreatoduodenectomy. REGISTRATION NUMBER: NCT02588066 (http://www.clinicaltrials.gov).

Defining early recurrence in patients with resected primary colorectal carcinoma and its respective risk factors.

PURPOSE: There is no evidence-based definition of early recurrence following resection of colorectal cancer. The purpose of this study is to define a point that discriminates between early and late recurrence in patients who have undergone colorectal cancer resection with curative intent and to analyze associated risk factors. METHODS: A retrospective single-center cohort study was performed at a university hospital recognized as a comprehensive cancer center, specializing in colorectal cancer surgery. Patient data were retrieved from a prospectively maintained institutional database. Included patients underwent resection for primary, non-metastatic colorectal carcinomas with curative intent between 1995 and 2010. Aims of the study were (1) to define the optimal cut-off point of recurrence-free survival based on overall survival using a minimum p value approach and (2) to identify patterns of initial recurrence and putative risk factors for early recurrence using regression models. RESULTS: Recurrence was diagnosed in 412 of 1893 patients. Statistical analysis suggested that a recurrence-free survival of 16 months could be used to distinguish between early and late recurrence based on overall survival (p < 0.001). Independent risk factors for early recurrence included advanced pT categories (pT3,4/ypT3,4) and positive lymph node status (pN+/ypN+). Early recurrence was independent of site of recurrence and was associated with worse prognosis. CONCLUSIONS: Recurrence of colorectal carcinoma within 16 months after primary treatment should be labeled as "early." Tumor categories pT3,4/ypT3,4 and positive lymph node status pN+/ypN+ are predictive of early recurrence.

Colorectal cancer in Crohn's colitis is associated with advanced tumor invasion and a poorer survival compared with ulcerative colitis: a retrospective dual-center study.

PURPOSE: Colorectal cancer is a well-recognized complication of inflammatory bowel diseases (IBD), such as ulcerative colitis (UC) and Crohn's colitis (CC). In this study, we assess the clinico-pathological features and outcomes of patients with colorectal cancer from UC in comparison with CC. METHODS: Data of all patients with colitis-associated cancer (CAC) who underwent surgery at Erlangen or Würzburg University Clinic between 1995 and 2015 were selected. Clinical, histopathological, and survival data were analyzed retrospectively. RESULTS: Of all 88 patients with CAC, 20 patients had Crohn's colitis and 68 patients had ulcerative colitis. We observed a young median age at tumor diagnosis (49.5 years UC; 45.5 years CC, p = 0.208) in both diseases and a long median disease duration before CAC (19 years UC; 18 years CC; p = 0.840). Patients with CC suffered more often from rectal cancer (14 (70.0%) in CC; 23 (33.8%) in UC; p = 0.005) and advanced tumor stages (8 (47.0%) pT4 in CC; 14 (25.0%) pT4/ypT4 in UC; p = 0.008). Five-year overall survival rate was 39.3% for CC and 67.1% for UC (p = 0.009 for difference between the groups). Survival did not differ significantly between UC and CC in the multivariate analysis after correction for UICC tumor stage. CONCLUSION: CAC in CC showed advanced tumor stages associated with reduced survival compared with CAC in UC. This may be explained by less intense surveillance in patients with CC leading to delayed cancer diagnosis.

Osteopontin splice variants and polymorphisms in cancer progression and prognosis.

Osteopontin (OPN) is an extracellular matrix protein that is overexpressed in various cancers and promotes oncogenic features including cell proliferation, survival, migration, and angiogenesis, among others. OPN can participate in the regulation of the tumor microenvironment, affecting both cancer and neighboring cells. Here, we review the roles of OPN splice variants (a, b, c) in cancer development, progression, and prognosis, and also discuss the identities of isoforms 4 and 5. We also discussed how single-nucleotide polymorphisms (SNPs) of the OPN gene are an additional factor influencing the level of OPN in individuals, modulating the risks of cancer development and outcome.