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Duodenal stump insufficiency after surgery for penetrating gastroduodenal ulcer is associated with substantial mortality. “Classical” technique of closing a difficult duodenal stump (Nissen–Bsteh) has, up to now, not been compared with duodenojejunostomy (DJ) in larger patient sets. This also refers to the potential benefit of a gastric and biliary diversion under such conditions. The aim of the present study was to compare classical duodenal closure (CC) with DJ and to evaluate the impact of gastric and biliary diversion on postoperative outcome after surgery for penetrating, high-risk duodenal ulcer in a matched control study. Out of 321 patients, treated for penetrating duodenal ulcer disease, the perioperative outcome of 62 DJ patients was compared with 62 patients undergoing CC matched for age, gender, biliary diversion, and the operating surgeon collective. A total of 70 patients, equally distributed between DJ and CC subsets, received temporary biliary diversion. Overall perioperative mortality was 10.5 %. However, DJ significantly reduced the mortality rate (4.8 %) associated with penetrating duodenal ulcer compared to CC (16.1 %, P

Background:Because of its retrospective character, the classification system of the International Study Group of Pancreatic Fistula (ISGPF) lacks prognostic capacity regarding fistula-related complications. This study aimed to evaluate the options and limitations of the ISGPF classification system a

Objective: Conflicting results have been reported about activated leukocyte cell adhesion molecule (ALCAM) expression in breast cancer and its prognostic value. Little is known about the role of ALCAM levels in the serum of breast cancer patients. Methods: We analyzed soluble ALCAM (sALCAM) levels in the serum of 157 primary breast cancer patients and 48 healthy women by ELISA. In addition, we determined ALCAM protein expression by Western blot analysis (n = 120) and mRNA expression by cDNA microarray analysis (n = 115) in the tumor tissue of corresponding patients. Results: sALCAM levels differed between patients and healthy controls (median 24.2 vs. 18.9 ng/ml, p < 0.001). We observed no correlation between serum levels and protein or mRNA expression in corresponding tumors (r < 0.1, p = n.s.). sALCAM levels were not correlated with histological type, grading, tumor stage, or patient age, but elevated sALCAM levels were associated with shorter disease-free survival (HR = 1.97, 95% CI 1.01–3.2, p = 0.043). Conclusions: Our results indicate that sALCAM can be detected in the serum of patients with primary breast cancer. Elevated serum levels might indicate more aggressive tumor behavior as they might be an independent factor for a worse prognosis in breast cancer patients.

Activated leukocyte cell adhesion molecule (CD166) is a member of the immunoglobulin superfamily and is aberrantly expressed in different tumors, including prostate cancer. To learn more on the prevalence and clinical significance of activated leukocyte cell adhesion molecule expression in prostate cancer, a tissue microarray containing 3261 primary prostate cancers treated by radical prostatectomy was used. A total of 2390 different prostate cancers were analyzed by immunohistochemistry in a tissue microarray format. Activated leukocyte cell adhesion molecule immunostaining in cancers was compared with clinical follow-up, which was available for 1746 patients. Membranous activated leukocyte cell adhesion molecule immunostaining was recorded in 1663 (69.6%) of cases. High activated leukocyte cell adhesion molecule expression levels were significantly associated with favorable tumor features (pT: P = .0015; pN: P = .0008; preoperative prostate-specific antigen: P = .0057) and a lower risk of a biochemical recurrence (P = .0067). Cytoplasmatic activated leukocyte cell adhesion molecule staining was usually associated with membranous staining. The small number of cancers with pure cytoplasmatic staining did not reveal any particularities with respect to clinical outcome or tumor phenotype. It is concluded that activated leukocyte cell adhesion molecule protein is almost always expressed in prostate cancer and that decreased levels of activated leukocyte cell adhesion molecule expression may lead to an aggressive behavior of tumor cells. The abundant presence of activated leukocyte cell adhesion molecule and its membranous localization in prostate cancer epithelium make activated leukocyte cell adhesion molecule a potentially attractive structure for targeted therapy.

Pancreatic cancer is one of the most devastating cancers with a 6-month median survival and a 5-year survival rate of 3-5%. Still important aspects of its aggressive biology remain elusive and advanced therapeutic regimens have not been substantially successful. We investigated the prognostic role of disseminated tumor cells (DTC) in bone marrow, a reservoir for early DTC potentially contributing to metastatic progression, of pancreatic cancer patients. After exclusion of patients with different postsurgery diagnosis or missing DTC status (n = 40) a total of 175 patients remained for final analyses. One-hundred and nineteen patients were male and 96 female with a median age of 67 years, 96 patients underwent complete resection. Bone marrow aspirates taken at primary surgery were analyzed for DTC by an immunocytochemical cytokeratin assay and correlated to survival data. Overall 13.7% of patient samples (24/175) harbored DTC in their bone marrow. Histopathological parameters did not correlate significantly. Univariate survival analysis revealed a borderline significant correlation between DTC and decreased progression-free survival (p = 0.069), and was significant for overall survival (p = 0.036). Regarding patients with resected tumors, the respective p-values were 0.058 for progression-free and 0.016 for overall survival. Importantly, the prognostic influence was independent from other risk factors as shown by multivariate analyses for progression-free (p = 0.030, HR: 2.057; CI (95%): 1.073-3.943) and overall survival (p = 0.006, HR: 2.283; CI (95%): 1.260-4.135). The presence of DTC in bone marrow is a strong and independent prognostic factor of survival in patients with pancreatic cancer. Thus, bone-targeting may be a new future therapeutic option for DTC-positive patients.

The expression of the activated leukocyte cell adhesion molecule (ALCAM and CD166) is increased in various types of cancer. We aimed to evaluate its role as a prognostic marker for esophageal cancer (EC). We retrospectively analyzed ALCAM expression in 299 primary lesions, 147 lymph node and 46 distant metastases from EC patients, on a tissue microarray using immunohistochemistry. Bone marrow samples from representative cancer patients (n = 16), taken before primary surgery, were stained by double-immunofluorescence for ALCAM and cytokeratins (CK). Blood serum samples from 236 cancer patients and 127 controls were analyzed for serum ALCAM (s-ALCAM) by ELISA. The immunohistochemical analysis showed increased ALCAM expression in the majority of lesions (primary tumor 71%, lymph node 76% and distant metastases 80%). ALCAM expression was not associated with histopathological parameters except for tumor grading (p = 0.015). ALCAM-positive patients had significantly worse recurrence-free and overall survival (OS; p = 0.002). Disseminated tumor cells (DTC) in bone marrow showed two phenotypes, ALCAM+/CK+ (36%) and ALCAM-/CK+ (64%). Multivariate analysis revealed that ALCAM expression and elevated s-ALCAM serum values are powerful prognostic variables for OS in patients with EC (hazard ratio [HR] 3.987, 95% confidence interval [95%CI] 1.906-8.340, p < 0.001 and HR 1.915, 95%CI 1.021-3.592, p = 0.043). The results of our study provide preliminary evidence for the potential clinical utility of ALCAM as a prognostic biomarker for EC, which might be a basis for future clinical application. In addition, ALCAM expression in a subset of DTC of the bone marrow indicates a potential function in the metastatic cascade of EC.

There is an assumption that multivisceral resections (MVRs) in patients with a pancreatic malignancy are associated with higher morbidity. The oncologic benefit, however, remains controversial.The aim was to identify risk factors for complications in cases of MVR in patients with pancreatic cancer. Of 1099 patients who underwent major pancreatic resection at our institution between January 1992 and October 2008, a total of 55 were treated with an MVR involving resection of one or more additional organs. This group was compared with 154 patients who had palliative bypass surgery and 303 patients who underwent standard pancreatic head resection.Multivisceral resection patients had an overall higher incidence of major surgical complications (p0.001). In-hospital mortality was comparable in all groups. Median survival after MVR was inferior to that after standard resection but was significantly better than that after palliative bypass. Univariate logistic regression analysis identified concomitant colon, kidney, and liver resections and any intraoperative transfusion as predictors of complications; in the multivariate analysis, only kidney resections and any intraoperative transfusion were confirmed predictors. In contrast, T status, kidney resection, resection of four or more organs, any postoperative transfusion, and intensive care unit stay of2 days were identified as predictors of survival in the univariate Cox regression analysis; in the multivariate analysis, only the T status was confirmed. Median survival after MVR was 16 months, after palliative bypass 6 months, and after standard resection 18 months (p0.001).Multivisceral resections are technically feasible procedures with increased survival when compared to palliative bypass procedures. The incidence of postoperative complications was increased with kidney resection and when intraoperative transfusion was required.

It has been shown that ED-B fibronectin (ED-B) is a potential target for plaque imaging. The aim of this study was to test a novel modified single chain anti-ED-B antibody (scFv) conjugated for near infrared fluorescence imaging (NIRF) with tetrasulfonated carbocyanine-maleimide (TSC-scFv) and to examine the association of ED-B with the presence of macrophages in a murine model of atherosclerosis. Expression of ED-B was observed in plaque areas in apolipoprotein E-deficient (apoE(-/-)) mice which increased with age and plaque load. Robust imaging was possible after explantation of the aorta and demonstrated a strong NIRF signal intensity in focal aortic and brachiocephalic plaque lesions, whereas no signals were found in undiseased areas. Plaque lesion ED-B was expressed by smooth muscle cell and was closely associated to macrophage infiltrates. Although not expressed by the same cell type, there was a significant correlation (p0.01) between ED-B and macrophage immunoreactivity. In vitro human coronary and mouse smooth muscle cells significantly increased ED-B expression after angiotensin II and TNF-alpha treatment. This study demonstrates that plaque NIRF imaging is feasible with a novel single chain antibody and that ED-B expression is closely associated with inflammation in experimental atherosclerosis.

The prognosis of patients with liver metastasis is generally considered dismal, and combined resections of the primary tumor and metastasectomies are not recommended. In highly selected patients, however, resections are performed. The evidence for this indication is limited. The aim of the current study was to assess the operative and oncologic outcomes of patients with combined pancreatic and liver resections of synchronous liver metastases.In a retrospective analysis of 6 European pancreas centers, we identified 69 patients with pancreatic ductal adenocarcinoma and synchronous liver metastasis who underwent simultaneous pancreas and liver metastasis resections. Patients receiving exploration without tumor resection served as the control group.Overall survival (OS) appeared to be prolonged in the group of resected patients (median 14 vs 8 months, P.001). Subgroup analysis revealed that the survival benefit of the resected patients was driven by pancreatic ductal adenocarcinomas localized in the pancreatic head (median OS 13.6 vs 7 months, P.001). Body/tail pancreatic ductal adenocarcinomas showed no benefit of resection (median OS 14 vs 15 months, P = .312). In the multivariate analysis, tumor resection was the only independent prognosticator for OS (hazard ratio 2.044, 95% confidence interval 1.342-3.114).The data of this retrospective and selective patient cohort suggested a clear survival benefit for patients undergoing synchronous pancreas and liver resections for pancreatic ductal adenocarcinoma, but due to the limitations of this retrospective study and very strong potential for selection bias, a strong conclusion for resection cannot be drawn. Prospective trials must validate these data and investigate the use of combined operative and systemic treatments in case of resectable metastatic pancreatic cancer. Is it time for a multicenter, prospective trial?

// Florian Gebauer 1, * , Suyin Gelis 1, * , Hilke Zander 1 , Karl-Frederick Meyer 1 , Gerrit Wolters-Eisfeld 1 , Jakob R. Izbicki 1 , Maximilian Bockhorn 1 , Michael Tachezy 1 1 Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany * These authors have contributed equally to this work Correspondence to: Michael Tachezy, e-mail: mtachezy@uke.de Keywords: lung cancer, NSCLC, prognostic marker, biomarker, serum Received: August 11, 2015 Accepted: January 17, 2016 Published: March 8, 2016 ABSTRACT Background: Tenascin-C is overexpressed in the stroma of most solid malignancies and may function as a diagnostic tumor marker. This study was conducted to evaluate the potential significance of Tenascin-C as a predictive marker for tumor progression in the sera of non-small cell lung cancer (NSCLC) patients. Results: Serum concentration of Tenascin-C is significantly elevated in NSCLC patients compared to healthy controls (p=0.013). The sensitivity of Tenascin-C in detecting NSCLC was 74% at a specificity of 57%. Elevated Tenascin-C serum values are associated with larger tumor size and lymph node involvement (p=0.022 and p=0.036, respectively). The Kaplan-Meyer-curves showed a significant association of Tenascin-C with the patient’s overall survival (p=0.004), but not with the recurrence-free survival (p=0.328). Methods: We quantified Tenascin-C in the sera of 103 NSCLC patients and 76 healthy blood donors by enzyme-linked immune-absorbance assay tests. Prognostic significance was determined by area under the curve analysis and Youden-index. The results were correlated with clinical, histopathological, and patient survival data (Chi-square test, Kaplan-Meier analysis, log-rank test, multivariate Cox-regression analysis). Conclusion: Although significantly elevated in patients with NSCLC, the sensitivity and specificity of the Tenascin-C serum quantification test was low. However, although failing to be an independent prognosticator in multivariate analysis, the results implicate Tenascin-C as a predictive prognostic marker for NSCLC patients. The data must be further validated in future prospective trials with larger patient cohorts.

Aim of the study was to assess the diagnostic and prognostic impact of serum EpCAM levels in patients with pancreatic adenocarcinoma (PDAC).For quantitative measurement of preoperative serum EpCAM levels, a sandwich enzyme immunoassay kit was used (ELISA). Sixty-six patients with PDAC were included in the study and for comparison 43 patients with chronic pancreatitis and 104 healthy blood donors without any clinical evidence of cancer were analyzed as well.Serum EpCAM levels differed significantly between the groups. The average value for patients with PDAC was 0.240±0.833 ng/ml, in patients with CP 0.192±0.590 ng/ml and 0.626±1.164 ng/ml in normal blood donor sera. With a cut-off level of 0.422 ng/ml EpCAM, the calculated sensitivity of detecting PDAC was 66.7% with corresponding specificity of 77.5%. A correlation with clinico-pathological data (pT, pN, M, R-status, grading, UICC stage) was not found and in addition there was no difference in overall survival between patients with high- and low-preoperative serum EpCAM levels.EpCAM can be detected in the serum in patients with PDAC though the sensitivity for detecting PDAC is low and a correlation with clinical parameters was not found.

Background: Median OS after surgery in curative intent for non-metastasized pancreas cancer ranges under study conditions from 17.9 months to 23.6 months. Tumor recurrence occurs locally, at distant sites (liver, peritoneum, lungs), or both. Observational and autopsy series report local recurrence rates of up to 87% even after potentially “curative” R0 resection. To achieve better local control, neoadjuvant CRT has been suggested for preoperative tumour downsizing, to elevate the likelihood of curative, margin-negative R0 resection and to increase the OS rate. However, controlled, randomized trials addressing the impact of neoadjuvant CRT survival do not exist. Methods/Design: The underlying hypothesis of this randomized, two-armed, open-label, multicenter, phase III trial is that neoadjuvant CRT increases the three-year overall survival by 12% compared to patients undergoing upfront surgery for resectable pancreatic cancer. A rigorous, standardized technique of histopathologically handling Whipple specimens will be applied at all participating centers. Overall, 410 patients (n=205 in each study arm) will be enrolled in the trial, taking into regard an expected drop out rate of 7% and allocated either to receive neoadjuvant CRT prior to surgery or to undergo surgery alone. Circumferential resection margin status, i.e. R0 and R1 rates, respectively, surgical resectability rate, local and distant disease-free and global survival, and first site of tumor recurrence constitute further essential endpoints of the trial. Discussion: For the first time, the NEOPA study investigates the impact of neoadjuvant CRT on survival of resectable pancreas head cancer in a prospectively randomized manner. The results of the study have the potential to change substantially the treatment regimen of pancreas cancer. Trial registration: Clinical Trial gov: NCT01900327, DRKS00003893, ISRCTN82191749

With a median survival of ⟨22 months esophageal cancer is one of the most aggressive tumors, up to 20% of node negative patients develop systemic relapse. Studies investigating the prognostic impact of tumor-micro-invasion in blood (AI) and lymphatic vessels (LVI) as well as perineural invasion (PNI) have shown inconsistent results. The aim of the present study was to investigate the prognostic value of the aforementioned factors in a large homogenously treated cohort of patients with esophageal cancer.Data from 695 patients with surgically treated esophageal cancer were analyzed. AI, LVI and PNI were determined and data were statistically correlated with clinico-pathological parameters and survival of the patients.Thirteen percent of all specimens showed an AI, 35% a LVI and 5% a PNI. The invasion factors were mostly significantly correlated with the established prognostic parameter, including bone marrow micro-metastases. Kaplan-Meier analysis revealed a prognostic impact for LVI in both cancer subtypes, while AI and PNI were significant factors in adenocarcinoma only. In multivariate analysis, none showed statistical significance. However, sub-analysis of completely resected, node negative and non-metastasized patients showed a significant prognostic impact of LVI.The prognostic significance of AI, LVI and PNI seems to be limited compared to the established prognostic parameters of the UICC staging system. In completely resected, node negative and non-metastasized patients, LVI is an independent prognostic parameter for a worse outcome. Those patients might benfit from additional treatment or more intensive follow up.

Background Aim of this study was to assess the biological function in tumor progression and metastatic process carcinoembryonic antigen-related cell adhesion molecules (CEACAM) 1, 5 and 6 in pancreatic adenocarcinoma (PDAC). Experimental Design CEACAM knock down cells were established and assessed in vitro and in a subcutaneous and intraperitoneal mouse xenograft model. Tissue and serum expression of patients with PDAC were assessed by immunohistochemistry (IHC) and by enzyme linked immunosorbent assays. Results Presence of lymph node metastasis was correlated with CEACAM 5 and 6 expression (determined by IHC) and tumor recurrence exclusively with CEACAM 6. Patients with CEACAM 5 and 6 expression showed a significantly shortened OS in Kaplan-Meier survival analyses. Elevated CEACAM6 serum values showed a correlation with distant metastasis and. Survival analysis revealed a prolonged OS for patients with low serum CEACAM 1 values. In vitro proliferation and migration capacity was increased in CEACAM knock down PDAC cells, however, mice inoculated with CEACAM knock down cells showed a prolonged overall-survival (OS). The number of spontaneous pulmonary metastasis was increased in the CEACAM knock down group. Conclusion The effects mediated by CEACAM expression in PDAC are complex, though overexpression is correlated with loco-regional aggressive tumor growth. However, loss of CEACAM can be considered as a part of epithelial-mesenchymal transition and is therefore of rather importance in the process of distant metastasis.

The aim of this study was to assess the overall survival (OS) after R0/R1 resections in patients with pancreatic ductal adenocarcinoma (PDAC) of the pancreatic head after implementation of a standardized histopathologic protocol (Leeds Pathology Protocol, LEEPP). One hundred and twenty-five patients underwent surgical resection because of PDAC of the pancreatic head. Patients were histopathologically examined according to a standardized protocol. Their oncologic outcome and clinicopathologic data were compared with those of a patient group before implementation of the LEEPP (n = 116). The R1 rate increased significantly from 13 to 52 %. There was no significant difference in OS between R0 and R1 resections. The median OS in patients with a tumor clearance of less than 2 mm from the resection margin was 15.1 months (12.1–18.1 months) versus 22.2 months (7.8–36.7 months) (P = 0.046). Multivariate analysis revealed a margin clearance or 2 mm and more as an independent prognosticator for OS. With applying the LEEPP, there was still no significant correlation between the R-status and OS in patients with PDAC. However, since a margin clearance of 2 mm or more is a predictive factor for OS, the R1 definition might have to be adapted in PDAC.

The high mortality rate of lung cancer patients is mainly due to the late stage at which lung cancer is diagnosed. For effective cancer prevention programs and early diagnosis, better blood-based markers are needed. Hence, blood-based microarray profiling of microRNA (miR) expression was performed in preoperative serum of 21 non-small cell lung cancer (NSCLC) patients and 11 healthy individuals by microfluid biochips containing 1158 different miRs. Two out of the 30 most dysregulated miRs were further validated in serum of 97 NSCLC patients, 20 patients with benign lung diseases and 30 healthy individuals by TaqMan MicroRNA Assays. Microarray profiling showed that miR-361-3p and miR-625* were significantly down-regulated in serum of lung cancer patients. Their further evaluation by quantitative RT-PCR showed that the levels of miR-361-3p and miR-625* were lower in NSCLC than in benign disease (p = 0.0001) and healthy individuals (p = 0.0001, p = 0.0005, respectively). Moreover, the levels of miR-625* were significantly lower in patients with large cell lung cancer (LCLC, p = 0.014) and smoking patients (p = 0.030) than in patients with adenocarcinoma and non-smoking patients, respectively. A rise in the levels of both miRs was observed in the postoperative samples compared with the preoperative levels (p = 0.0001). Functional analyses showed that Smad2 and TGFß1 are not dysregulated by miR-361-3p and miR-625* in the lung cell line A549, respectively. Our present pilot study suggests that miR-361-3p and miR-625* might have a protective influence on the development of NSCLC, and the quantitative assessment of these miRs in blood serum might have diagnostic potential to detect NSCLC, in particular in smokers.

BACKGROUND: This study was conducted to evaluate the expression of the activated leukocyte cell adhesion molecule (ALCAM) in pancreatic cancer (PAC) and to determine whether or not the ectodomain shedding of ALCAM (s-ALCAM) could serve as a biomarker in the peripheral blood of PAC patients. MATERIAL AND METHODS: Tissue specimens and blood sera of patients with PAC (n = 264 and n = 116, respectively) and the sera of 115 patients with chronic pancreatitis (CP) were analyzed via ALCAM immunohistochemistry and s-ALCAM ELISA tests. Results were correlated with clinical, histopathological, and patient survival data (Chi-square test, Kaplan-Meier analysis, log-rank test, respectively). RESULTS: ALCAM was expressed in the majority of PAC lesions. Immunohistochemistry and serum ELISA tests revealed no association between ALCAM expression in primary tumors or s-ALCAM and clinical or histopathological data. Neither ALCAM nor s-ALCAM showed a significant impact regarding overall survival (p = 0.261 and p = 0.660, respectively). S-ALCAM serum levels were significantly elevated compared to the sera of CP patients (p

High surgical morbidity following distal pancreatectomy, especially pancreatic fistula, remains an unsolved problem. The aim of this study was to identify potential risk factors for surgical morbidity with a focus on the development of pancreatic fistula. Clinicopathologic parameters were collected for 283 patients who underwent distal pancreatectomy between January 2000 and May 2010. Logistic regression analyses were performed to identify potential risk factors for surgical morbidity and pancreatic fistula. Spleen-preserving pancreatectomy was carried out in 12% of all cases and multivisceral resections were performed in 37.8%. For closure of the pancreatic remnant, three different techniques were used: hand-sewn suture in 44.5%, pancreaticojejunal anastomosis in 24%, and closure by stapler in 31.5%. Overall morbidity and mortality were 53 and 3.5%. Surgical morbidity was observed in 50.2% of all cases and pancreatic fistula in 24%. The stapling group had significantly higher surgical morbidity at 65.2% (p = 0.001) and the most pancreatic fistulas, though this did not reach statistical significance (p = 0.189). Univariate and multivariate logistic analyses indicated that closure by stapler [odds ratio (OR) = 3.61; p

Chemokines and their receptors are known to play important roles in the tumorigenesis of many malignancies. The aim of this study was to evaluate the prognostic impact of the expression of the chemokine receptors CXCR4 and CXCR7 in patients with pancreatic adenocarcinoma (PAC).Expression of CXCR4 and CXCR7 in specimens from 249 patients with PAC was evaluated by immunohistochemistry on a tissue microarray and matched with clinicopathological parameters and overall survival.Expression of CXCR4 was detected in 215 patients (86.4%) and CXCR7 in 47 patients (18.9%). No association between CXCR4 and CXCR7 expression was evident, although all the CXCR7 positive tumors were also CXCR4 positive. pT1/2 tumors showed a higher frequency of CXCR7 expression than pT3/4 tumors (P = 0.018), while more dedifferentiated tumors had elevated CXCR7 expression (P = 0.036). Overall and disease-free survival revealed no association with either CXCR4 or CXCR7 expression.CXCR7 is associated with tumor grade and inversely associated with tumor size and may play a potential role in tumor progression and differentiation. In contrast to previously reported data our results revealed no significant association between CXCR4 expression and clinical or pathological data.

Intraductal papillary-mucinous neoplasm (IPMN) of the pancreas is an increasingly diagnosed entity since its definition by the World Health Organization in 1996. It has a broad clinical spectrum ranging from benign to malignant tumors. Optimum treatment is controversial and a better understanding of the development of IPMN of the pancreas and identification of potential prognostic factors will help to address this. Angiogenesis plays an elementary role in the development of malignant tumors and may well also be important in the development of IPMN of the pancreas. Therefore we investigated endothelial cell marker CD31 (PECAM-1) and angiogenesis associated marker CD105 (endoglin) by immunohistochemistry.Thirty-two cases of surgically resected IPMN were chosen retrospectively and clinical data were obtained. Specimens were stained for proliferation marker (Ki-67), CD31 and CD105 by immunohistochemistry. A CD105/CD31 Angiogenesis ratio (AR) was established to determine the proliferating fraction of endothelial cells.The AR is significantly elevated in invasive IPMN of the pancreas (Mann-Whitney-U Test, p0.05) and is associated with the Ki-67-labelling-index, demonstrating synergy between tumor-growth and neovascularisation. Invasive IPMN of the pancreas is associated with significantly lower recurrence-free and overall survival.Neovascularisation plays an important role in the tumorigenesis of invasive IPMN of the pancreas, and therefore angiogenesis-associated molecules like CD105 and CD31 might be useful tools as prognostic markers. Furthermore, the results indicate a potential role for adjuvant anti-angiogenic therapies in selected patients with recurring and/or invasive IPMN of the pancreas.

As technical expertise increases, the indication for pancreatic resection for advanced pancreatic cancer has been expanded over the last years. Recently, several groups reported their series of unintentionally incomplete tumor resections and reported a potential survival benefit for patients after incomplete resection when compared with palliative bypass surgery. We investigated in a retrospective analysis whether even tumor resection that was intended to be incomplete might provide a better outcome than conventional palliative procedures. Twenty-two patients with a locally non-resectable or disseminated adenocarcinoma of the pancreas underwent a palliative intentionally incomplete resection. Outcome after resection was compared with that of 46 patients matched for age, sex, and histopathological tumor type who underwent a palliative bypass operation. Overall surgical morbidity was significantly higher in the resection group (59%) compared with the bypass group (33%, p

Systemic inflammation (SI) plays a pivotal role in cancer. C-reactive protein (CRP) and albumin as parameters of SI form the Glasgow Prognostic Score (GPS). The purpose of the study was to evaluate the potential prognostic role of GPS in a homogeneous population of esophageal cancer (EC) patients undergoing only resection.GPS was evaluated on the basis of admission blood sample taken before surgery. Patients with a CRP 10 mg/L and albumin 35 g/L were allocated to GPS0 group. If only CRP was increased or albumin decreased patients were allocated to the GPS1 and patients in whom CRP was ≥10 mg/L and albumin level ≤35 g/L were classified as GPS2. GPS was correlated to clinicopathological parameters and clinical outcome.Increasing GPS significantly correlated with more aggressive tumor biology in terms of tumor size (P 0.001), presence of regional (P = 0.01) and nonregional lymph node metastasis (P = 0.02), and higher tumor recurrence rate (P 0.001). Furthermore, GPS was identified as an independent prognosticator of perioperative morbidity (odds ratio 1.9; P = 0.03). In addition, a gradual decrease in disease-free and overall survival was evident between the three GPS subgroups. Survival differences between the GPS groups remained apparent even after stratification of the study population to underlying tumor type and nodal status. GPS was identified as a strong prognosticator of tumor recurrence (hazard ratio 2.5; P 0.001) and survival (hazard ratio 3.0; P 0.001) in EC.GPS represents a strong prognosticator of perioperative morbidity and long-term outcome in resected EC patients without neoadjuvant or adjuvant treatment.

Background Infections caused by Nocardia farcinica are uncommon and show a great variety of clinical manifestations in immunocompetent and immunocompromised patients. Because of its unspecific symptoms and tendency to disseminate it may mimic the clinical symptoms and radiologic findings of a tumour disease and the diagnosis of nocardiosis can easily be missed, because there are no characteristic symptoms. Case presentation We present a case of an adrenal gland abscess caused by subacute disseminated N. farcinica pneumonia. Conclusion An infection with N. farcinica is potentially lethal because of its tendency to disseminate -particularly in the brain- and its high resistance to antibiotics. Awareness of this differential diagnosis allows early and appropriate treatment to be administered.

Ezetimibe (EZE), an inhibitor of cholesterol absorption, reduces atherosclerosis in apolipoprotein E–deficient (apo –/– ) mice. The matrix protein ED-B fibronectin (ED-B) is upregulated in atherosclerotic lesions. Using a novel conjugate for near-infrared fluorescence (NIRF) imaging targeting ED-B, we studied the effect of EZE on plaque lesion formation in apoE –/– mice. ApoE –/– mice received EZE (5 μg/kg/d) or chow up to the age of 4, 6, and 8 months. NIRF imaging of aortic lesions was performed 24 hours after intravenous application ex vivo and in vivo. Plaque lesion formation was analyzed by histology and immunohistochemistry. Aortic lesion formation detected by Sudan staining and NIRF imaging was significantly reduced at 6 and 8 months ( p < .001). Plaque areas determined by NIRF imaging significantly correlated with Sudan staining ( p < .001). EZE treatment resulted in a significant reduction in plaque macrophage and ED-B immunoreactivity (both p < .05) in brachiocephalic lesions. There was a significant reduction in plaque size in brachiocephalic arteries in 8-month-old mice treated with EZE compared with mice during short-term treatment ( p < .05), indicating EZE plaque regression. Targeted NIRF imaging showed a correlation to histologic lesion extension during therapeutical intervention in experimental atherosclerosis.

Background Activated leukocyte cell adhesion molecule (ALCAM, CD166) is a cell membrane protein that is aberrantly expressed in different tumors, including pancreatic neuroendocrine tumors (PNET). The aim of this study was to determine the expression of ALCAM in PNET to learn more about the prevalence and clinical significance of ALCAM expression in PNET. Methods Primary tumors ( n = 38) and corresponding lymph node ( n = 5) and liver metastases ( n = 9) of patients with PNET, treated at the University Medical Center Hamburg-Eppendorf between 1993 and 2006, were analyzed via ALCAM immunohistochemistry in a tissue microarray format. The results were correlated with clinical and histopathologic data, including the WHO classification of PNET. Results The majority of primary (74%) and secondary (50%) lesions of PNET showed strong ALCAM expression. Immunohistochemistry of primary tumors revealed an association between high ALCAM expression and the hormone production status of the tumor ( P = 0.037), and an inverse correlation with metastasis status ( P = 0.041) and tumor size (cut off level 2 cm, P = 0.013). Elevated ALCAM expression was a significant positive prognostic factor for recurrence-free ( P = 0.002) and disease-specific survival ( P = 0.009) in Kaplan-Meier survival analysis (log rank test). Conclusions ALCAM is abundantly expressed in PNET and decreased expression is significantly associated with poor prognosis. ALCAM may be a potential marker for risk prediction in patients diagnosed with PNET. Further studies with larger patient collectives are required to validate the results of this study and investigate the functional role of ALCAM in PNET.

Background The chemokine CXCL12 and its receptor CXCR4 play a major role in tumor invasion, proliferation and metastasis in different malignant diseases, including esophageal carcinoma, amongst others. CXCR7 was recently identified as a novel alternate receptor for CXCL12. The aim of this study was to evaluate the prognostic impact of expression of chemokine receptor CXCR7 in patients with esophageal carcinoma (EC). Methods Expression of CXCR7 in primary tumors, lymph nodes and distant metastases of 299 patients with EC was evaluated by immunohistochemistry on a tissue microarray and compared with clinical and histopathological data. Results In esophageal cancer sections, CXCR7-specific reactivity was apparent in 45% of the squamous cell carcinomas (ESCC), but only occasionally in adenocarcinomas. No correlation between CXCR4 and CXCR7 expression was evident. We correlated expression with clinical and histopathological characteristics, but could not find any association. Conclusions Contrary to the other known CXCL12 receptor, CXCR4, CXCR7 is expressed in ESCC only, underlining the divergent mechanisms and backgrounds of EAC and ESCC. The results of the study do not indicate a significant functional role for CXCR7 in EAC or ESCC of the esophagus. However, its variable expression in the main two main types of EC needs to be further investigated.

Background L1 cell adhesion molecule (CD171) is expressed in many malignant tumors and its expression correlates with unfavourable outcome. It thus represents a target for tumor diagnosis and therapy. An earlier study conducted by our group identified L1 expression levels in primary gastrointestinal stromal tumors (GIST) as a prognostic marker. The aim of the current study was to compare L1 serum levels of GIST patients with those of healthy controls and to determine whether levels of soluble L1 in sera could serve as a prognostic marker. Methods Using a sensitive enzyme-linked immunosorbent assay (ELISA), soluble L1 was measured in sera of 93 GIST patients und 151 healthy controls. Soluble L1 levels were then correlated with clinicopathological data. Results Median levels of soluble L1 were significantly higher (p < 0.001; Mann-Whitney U test) in sera of GIST patients compared to healthy individuals. Median soluble L1 levels were particularly elevated in patients with recurrence and relapse (p < 0.05; Mann Whitney U test). Conclusion These results suggest that high soluble L1 levels predict poor prognosis and may thus be a promising tumor marker that can contribute to individualise therapy.

Introduction Omental infarction is a rare and often misdiagnosed clinical event with unspecific symptoms. It affects predominantly young and middle aged women. Case presentation This is a case report of a 26-year-old Caucasian woman with spontaneous omental infarction two weeks after normal vaginal delivery. Conclusion Omental infarction is a differential diagnosis in the postpartum acute abdomen. As some cases of omental infarction, which are caused by torsion, can be adequately diagnosed via computed tomography, a conservative treatment strategy for patients without complications should be considered in order to avoid any unnecessary surgical intervention.