SARS-CoV-2 Blood RNA Load Predicts Outcome in Critically Ill COVID-19 Patients.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA loads in patient specimens may act as a clinical outcome predictor in critically ill patients with coronavirus disease 2019 (COVID-19). METHODS: We evaluated the predictive value of viral RNA loads and courses in the blood compared with the upper and lower respiratory tract loads of critically ill COVID-19 patients. Daily specimen collection and viral RNA quantification by reverse transcription quantitative polymerase chain reaction were performed in all consecutive 170 COVID-19 patients between March 2020 and February 2021 during the entire intensive care unit (ICU) stay (4145 samples analyzed). Patients were grouped according to their 90-day outcome as survivors (n=100) or nonsurvivors (n=70). RESULTS: In nonsurvivors, blood SARS-CoV-2 RNA loads were significantly higher at the time of admission to the ICU (P=.0009). Failure of blood RNA clearance was observed in 33/50 (66%) of the nonsurvivors compared with 12/64 (19%) survivors (P<.0001). As determined by multivariate analysis, taking sociodemographic and clinical parameters into account, blood SARS-CoV-2 RNA load represents a valid and independent predictor of outcome in critically ill COVID-19 patients (odds ratio [OR; log10], 0.23; 95% CI, 0.12-0.42; P<.0001), with a significantly higher effect for survival compared with respiratory tract SARS-CoV-2 RNA loads (OR [log10], 0.75; 95% CI, 0.66-0.85; P<.0001). Blood RNA loads exceeding 2.51×103 SARS-CoV-2 RNA copies/mL were found to indicate a 50% probability of death. Consistently, 29/33 (88%) nonsurvivors with failure of virus clearance exceeded this cutoff value constantly. CONCLUSIONS: Blood SARS-CoV-2 load is an important independent outcome predictor and should be further evaluated for treatment allocation and patient monitoring.

Associations between pancreatic expression quantitative traits and risk of pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal cancers. Its poor prognosis is predominantly due to the fact that most patients remain asymptomatic until the disease reaches an advanced stage, alongside the lack of early markers and screening strategies. A better understanding of PDAC risk factors is essential for the identification of groups at high risk in the population. Genome-wide association studies (GWAS) have been a powerful tool for detecting genetic variants associated with complex traits, including pancreatic cancer. By exploiting functional and GWAS data, we investigated the associations between polymorphisms affecting gene function in the pancreas (expression quantitative trait loci, eQTLs) and PDAC risk. In a two-phase approach, we analysed 13 713 PDAC cases and 43 784 controls and identified a genome-wide significant association between the A allele of the rs2035875 polymorphism and increased PDAC risk (P = 7.14 × 10-10). This allele is known to be associated with increased expression in the pancreas of the keratin genes KRT8 and KRT18, whose increased levels have been reported to correlate with various tumour cell characteristics. Additionally, the A allele of the rs789744 variant was associated with decreased risk of developing PDAC (P = 3.56 × 10-6). This single nucleotide polymorphism is situated in the SRGAP1 gene and the A allele is associated with higher expression of the gene, which in turn inactivates the cyclin-dependent protein 42 (CDC42) gene expression, thus decreasing the risk of PDAC. In conclusion, we present here a functional-based novel PDAC risk locus and an additional strong candidate supported by significant associations and plausible biological mechanisms.

Patient Characteristics and Clinical Course of COVID-19 Patients Treated at a German Tertiary Center during the First and Second Waves in the Year 2020.

In this study, we directly compared coronavirus disease 2019 (COVID-19) patients hospitalized during the first (27 February-28 July 2020) and second (29 July-31 December 2020) wave of the pandemic at a large tertiary center in northern Germany. Patients who presented during the first (n = 174) and second (n = 331) wave did not differ in age (median [IQR], 59 years [46, 71] vs. 58 years [42, 73]; p = 0.82) or age-adjusted Charlson Comorbidity Index (median [IQR], 2 [1, 4] vs. 2 [0, 4]; p = 0.50). During the second wave, a higher proportion of patients were treated as outpatients (11% [n = 20] vs. 20% [n = 67]), fewer patients were admitted to the intensive care unit (43% [n = 75] vs. 29% [n = 96]), and duration of hospitalization was significantly shorter (median days [IQR], 14 [8, 34] vs. 11 [5, 19]; p < 0.001). However, in-hospital mortality was high throughout the pandemic and did not differ between the two periods (16% [n = 27] vs. 16% [n = 54]; p = 0.89). While novel treatment strategies and increased knowledge about the clinical management of COVID-19 may have resulted in a less severe disease course in some patients, in-hospital mortality remained unaltered at a high level. These findings highlight the unabated need for efforts to hamper severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) transmission, to increase vaccination coverage, and to develop novel treatment strategies to prevent mortality and decrease morbidity.

Genome-wide scan of long noncoding RNA single nucleotide polymorphisms and pancreatic cancer susceptibility.

Pancreatic ductal adenocarcinoma (PDAC) is projected to become the second cancer-related cause of death by 2030. Identifying novel risk factors, including genetic risk loci, could be instrumental in risk stratification and implementation of prevention strategies. Long noncoding RNAs (lncRNAs) are involved in regulation of key biological processes, and the possible role of their genetic variability has been unexplored so far. Combining genome wide association studies and functional data, we investigated the genetic variability in all lncRNAs. We analyzed 9893 PDAC cases and 9969 controls and identified a genome-wide significant association between the rs7046076 SNP and risk of developing PDAC (P = 9.73 × 10-9 ). This SNP is located in the NONHSAG053086.2 (lnc-SMC2-1) gene and the risk allele is predicted to disrupt the binding of the lncRNA with the micro-RNA (miRNA) hsa-mir-1256 that regulates several genes involved in cell cycle, such as CDKN2B. The CDKN2B region is pleiotropic and its genetic variants have been associated with several human diseases, possibly though an imperfect interaction between lncRNA and miRNA. We present a novel PDAC risk locus, supported by a genome-wide statistical significance and a plausible biological mechanism.

Prognostic value of positive histological margins in patients with pancreatic head ductal adenocarcinoma and lymph node involvement: an international multicentric study.

BACKGROUND: Resection margin status and lymph node (LN) involvement are known prognostic factors for patients who undergo pancreatoduodenectomy for pancreatic ductal adenocarcinoma (PDAC). This study aimed to compare overall survival (OS) and disease-free survival (DFS) by resection margin status in patients with PDAC and LN involvement. METHODS: A retrospective international multicentric study was performed including four Western centers. Multivariable Cox analysis was performed to identify prognostic factors of OS and DFS. Median OS and DFS were calculated using Kaplan-Meier curves and compared using log-rank tests. RESULTS: A cohort of 814 PDAC patients with pancreatoduodenectomy were analyzed. A total of 651 patients had LN involvement (80%). On multivariable analysis R1 resection was not an independent factor of worse OS and DFS in patients with LN involvement (HR 1.1, p = 0.565; HR 1.2, p = 0.174). Only tumor size, grade, and adjuvant chemotherapy were associated with OS and DFS. Median OS and DFS were similar between patients with R0 and R1 resections (23 vs. 20 months, p = 0.196; 15 vs. 14 months, p = 0.080). CONCLUSION: Resection status was not identified as predictor of OS or DFS in PDAC patients with LN involvement. Extensive surgery to achieve R0 resection in such patients might not influence the disease course.

Polygenic and multifactorial scores for pancreatic ductal adenocarcinoma risk prediction.

BACKGROUND: Most cases of pancreatic ductal adenocarcinoma (PDAC) are asymptomatic in early stages, and the disease is typically diagnosed in advanced phases, resulting in very high mortality. Tools to identify individuals at high risk of developing PDAC would be useful to improve chances of early detection. OBJECTIVE: We generated a polygenic risk score (PRS) for PDAC risk prediction, combining the effect of known risk SNPs, and carried out an exploratory analysis of a multifactorial score. METHODS: We tested the associations of the individual known risk SNPs on up to 2851 PDAC cases and 4810 controls of European origin from the PANcreatic Disease ReseArch (PANDoRA) consortium. Thirty risk SNPs were included in a PRS, which was computed on the subset of subjects that had 100% call rate, consisting of 839 cases and 2040 controls in PANDoRA and 6420 cases and 4889 controls from the previously published Pancreatic Cancer Cohort Consortium I-III and Pancreatic Cancer Case-Control Consortium genome-wide association studies. Additional exploratory multifactorial scores were constructed by complementing the genetic score with smoking and diabetes. RESULTS: The scores were associated with increased PDAC risk and reached high statistical significance (OR=2.70, 95% CI 1.99 to 3.68, p=2.54×10-10 highest vs lowest quintile of the weighted PRS, and OR=14.37, 95% CI 5.57 to 37.09, p=3.64×10-8, highest vs lowest quintile of the weighted multifactorial score). CONCLUSION: We found a highly significant association between a PRS and PDAC risk, which explains more than individual SNPs and is a step forward in the direction of the construction of a tool for risk stratification in the population.

Genome-wide association study identifies an early onset pancreatic cancer risk locus.

Early onset pancreatic cancer (EOPC) is a rare disease with a very high mortality rate. Almost nothing is known on the genetic susceptibility of EOPC, therefore, we performed a genome-wide association study (GWAS) to identify novel genetic variants specific for patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) at younger ages. In the first phase, conducted on 821 cases with age of onset ≤60 years, of whom 198 with age of onset ≤50, and 3227 controls from PanScan I-II, we observed four SNPs (rs7155613, rs2328991, rs4891017 and rs12610094) showing an association with EOPC risk (P < 1 × 10-4 ). We replicated these SNPs in the PANcreatic Disease ReseArch (PANDoRA) consortium and used additional in silico data from PanScan III and PanC4. Among these four variants rs2328991 was significant in an independent set of 855 cases with age of onset ≤60 years, of whom 265 with age of onset ≤50, and 4142 controls from the PANDoRA consortium while in the in silico data, we observed no statistically significant association. However, the resulting meta-analysis supported the association (P = 1.15 × 10-4 ). In conclusion, we propose a novel variant rs2328991 to be involved in EOPC risk. Even though it was not possible to find a mechanistic link between the variant and the function, the association is supported by a solid statistical significance obtained in the largest study on EOPC genetics present so far in the literature.

Oligometastases in pancreatic cancer (Synchronous resections of hepatic oligometastatic pancreatic cancer: Disputing a principle in a time of safe pancreatic operations in a retrospective multicenter analysis).

The aim of the present review was to analyze the current data on surgery of synchronous liver metastases in pancreatic ductal adenocarcinoma (PDAC) in curative intent. A review of the literature was carried out to identify the current international concepts regarding surgery of liver metastases of PDAC and, furthermore, we addressed the current challenges of resection of liver metastases of PDAC. Resection of liver metastases in PDAC may provide survival benefit without compromising safety and quality of life in a highly selected group of patients.

FOXO1 overexpression and loss of pSerine256-FOXO1 expression predicts clinical outcome in esophageal adenocarcinomas.

The function of Forkhead box O 1 (FOXO1) and pSerine256-FOXO1 immunostaining in esophageal cancer is unclear. To clarify the prognostic role of nuclear FOXO1 and cytoplasmic pSerine256-FOXO1 immunostaining, a tissue microarray containing more than 600 esophageal cancers was analyzed. In non-neoplastic esophageal mucosae, FOXO1 expression was detectable in low and pSerine256-FOXO1 expression in high intensities. Increased FOXO1 and decreased pSerine256-FOXO1 expression were linked to advanced tumor stage and high UICC stage in esophageal adenocarcinomas (EACs) (tumor stage: p = 0.0209 and p < 0.0001; UICC stage: p = 0.0201 and p < 0.0001) and squamous cell carcinomas (ESCCs) (tumor stage: p = 0.0003 and p = 0.0016; UICC stage: p = 0.0026 and p = 0.0326). Additionally, overexpression of FOXO1 and loss of pSerine256-FOXO1 expression predicted shortened survival of patients with EACs (p = 0.0003 and p = 0.0133) but were unrelated to outcome in patients with ESCCs (p = 0.7785 and p = 0.8426). In summary, our study shows that overexpression of nuclear FOXO1 and loss of cytoplasmic pSerine256-FOXO1 expression are associated with poor prognosis in patients with EACs. Thus, evaluation of FOXO1 and pSerine256-FOXO1 protein expression - either alone or in combination with other markers - might be useful for prediction of clinical outcome in patients with EAC.

Expression of ICAM-1, E-cadherin, periostin and midkine in metastases of pancreatic ductal adenocarcinomas.

Development and progression of malignant tumors is in part characterized by the ability of a tumor cell to overcome cell-cell and cell-matrix adhesion and to disseminate in organs distinct from that in which they originated. This study was undertaken to analyze the clinical significance of the expression of the following cell-cell and cell-matrix adhesion molecules in pancreatic ductal adenocarcinomas (PDACs) and synchronous liver metastases: intercellular adhesion molecule 1 (ICAM-1), E-cadherin, periostin, and midkine (MK). ICAM-1, E-cadherin, periostin and MK expression was analyzed by immunohistochemistry on a tissue microarray containing 34 PDACs and 12 liver metastasis specimens. ICAM-1 expression was predominantly localized in the membranes of the cells and was found in weak to moderate intensities in PDACs and liver metastases. E-cadherin expression was absent in the majority of PDACs and corresponding liver metastases. The secreted proteins periostin and MK were expressed in various intensities in primary cancers and liver metastases. Statistical analysis demonstrated that the expression levels of the analyzed markers were neither significantly associated with metastasis in PDACs nor with clinical outcome of patients. Our study shows that the expression of the cell-cell and cell-matrix adhesion molecules ICAM-1, E-cadherin, periostin and MK was not significantly linked to metastatic disease in PDACs. Moreover, our study excludes the analyzed markers as prognostic markers in PDACs.

Hamburg-Glasgow classification: preoperative staging by combination of disseminated tumour load and systemic inflammation in oesophageal carcinoma.

BACKGROUND: The aim of this study was to establish a new preoperative staging classification and evaluate its comparability to the post-operative tumour stage, lymph node invasion and metastasis (TNM) classification. To date, adequate, preoperative staging in patients with oesophageal carcinoma (EC) is still missing but urgently needed. Systemic inflammation and disseminated tumour load have a pivotal role in recurrence and oncological outcome. To improve the clinical staging, we merged the Glasgow Prognostic Score (GPS) and disseminated tumour cells (DTC) into a new sufficient preoperative staging classification, the Hamburg-Glasgow classification (HGC). METHODS: In this prospective, single-centre study, 326 patients following curative oesophagectomy were included. From all patients preoperative bone marrow was aspirated from the iliac crest to detect DTCs by immunostaining with the pan-keratin antibody A45-B/B3. HGC was subdefined into four prognostic groups on the basis of C-reactive protein (CRP), albumin and DTC. The three prognostic groups of the GPS were supplemented by DTC detection status. Results were correlated with clinicopathological parameters and clinical outcome. RESULTS: Increasing HGC significantly correlated with lymph node invasion (P=0.022), post-operative pathohistological TNM staging (P=0.001) and tumour recurrence (P=0.001). The four HGC prognostic groups displayed a gradual decrease in overall as well as disease-free survival (P<0.001, each). Hamburg-Glasgow classification was a strong, significant independent predictor of overall survival and disease-free survival (P<0.001, both) in multivariate analysis. CONCLUSIONS: Hamburg-Glasgow classification seems to be a promising preoperative additive staging classification for accurate and simple outcome stratification.

Allogenic Blood Transfusion is Associated with Poor Perioperative and Long-Term Outcome in Esophageal Cancer.

BACKGROUND: Esophageal resection for cancer (EC) is still associated with considerable mortality and morbidity rates. Allogenic blood transfusion (aBT) is associated with poor short-term and long-term outcome in surgical oncology. We aimed to evaluate the effect of aBT in a homogeneous population of EC patients undergoing esophagectomy without perioperative treatment. METHODS: We analyzed 565 esophagectomies performed due to EC. Allogenic blood transfusion was correlated to clinicopathological parameters, perioperative mortality and morbidity as well as the long-term outcome. Results are presented as adjusted odds ratio (OR) or hazard ratio (HR) with 95 % confidence interval (95 % CI). RESULTS: Patients receiving aBT (aBT(+)) had no higher tumor stages or higher rates of lymph node metastasis (P = 0.65 and 0.17, respectively) compared to patients without aBT (aBT(-)). Allogenic blood transfusion was strongly associated with perioperative morbidity (OR 1.9, 95 % CI 1.1-3.5, P = 0.02) and mortality (OR 2.9, 95 % CI 1.0-8.6, P = 0.04). Tumor recurrence rate was significantly higher in aBT(+) patients (P = 0.001). The disease-free and overall survival were significantly longer in aBT(-) compared to aBT(+) patients (P = 0.016 and <0.001, respectively). Patients receiving aBT had almost doubled risk for tumor recurrence (HR 1.8, 95 % CI 1.2-2.5, P = 0.001) and death (HR 2.2, 95 % CI 1.5-3.2, P < 0.001). CONCLUSION: Allogenic blood transfusion has a significant impact on the natural course of EC after complete resection. The poor short-term and long-term outcome warrants further evaluation of the underlying molecular mechanisms induced by allogenic blood transfusion in cancer patients.

Prognostic Significant or Not? The Positive Circumferential Resection Margin in Esophageal Cancer: Impact on Local Recurrence and Overall Survival in Patients Without Neoadjuvant Treatment.

OBJECTIVE: The aim of this study is to investigate the impact of the circumferential resection margin (CRM) in esophageal cancer on survival and recurrence in patients without pretreatment. BACKGROUND: Whereas the infiltration of the proximal or distal resection margin is associated with poor survival and higher recurrence, studies looking at the role of the circumferential resection margin on survival and local recurrence after esophagectomy are conflicting. METHODS: Influence of CRM infiltration according to the College of American Pathologists (CAP) and Royal College of Pathologists (RCP) on long-term survival of 180 patients with resected pT3 tumors and without neoadjuvant therapy was analyzed. RESULTS: A positive CRM was found in 76 (42.4%) patients according to RCP and 44 (24.4%) patients according to CAP. The CRM status had neither according to CAP nor according to RCP a significant impact on overall survival (P = 0.317 and 0.655, respectively), local recurrence (P = 0.716 and 0.900, respectively), or distant tumor relapse (P = 0.303 and 0.471, respectively).Lymphatic tumor spread found in 129 (71.7%) patients was an independent prognosticator (P = 0.002). In 137 (76.1%) patients who had a transthoracic esophagectomy a CRM infiltration was significantly lower according to CAP compared with 43 (23.9%) patients who had a transhiatal esophagectomy (P = 0.026). CONCLUSIONS: CRM was found to have no impact on survival and recurrence in esophageal cancer. Therefore, the possible impact of neoadjuvant pretreatment in locally advanced tumors should be considered with caution in terms of an improved resectability.

Non-trauma Emergency Pancreatoduodenectomies: A Single-Center Retrospective Analysis.

OBJECTIVE: To retrospectively assess the frequency and indications for emergency pancreatoduodenctomies in a tertiary referral center. METHODS: Pancreatoduodenectomies between January 2005 and January 2014 were retrospectively assessed for emergency indications defined as surgery following unplanned hospital admission in less than 24 h. Data on indications and on the intraoperative as well as the post-operative course were collected. RESULTS: Out of 583 pancreatoduodenectomies during the interval, a total of 10 (1.7 %) were performed as an emergency surgery. Indications included uncontrollable bleeding, duodenal and proximal jejunal perforations, and endoscopic retrograde cholangiopancreatography-related complications. Three of the 10 (30.0 %) patients died during the hospital course. In one patient, an intraoperative mass transfusion was necessary. No intraoperative death occurred. All but one patient were American Society of Anesthesiologists class three or higher. In two cases, the pancreatic remnant was left without anastomosis for second-stage pancreatojejunostomy. Median operation time was 326.5 min (SD 100.3 min). Hospital stay of the surviving patients was prolonged (median 43.0 days; SD 24.0 days). CONCLUSION: Emergency pancreatoduodenectomies are non-frequent, have a diverse range of indications and serve as an ultima ratio to cope with severe injuries and complications around the pancreatic head area.

The PER (Preoperative Esophagectomy Risk) Score: A Simple Risk Score to Predict Short-Term and Long-Term Outcome in Patients with Surgically Treated Esophageal Cancer.

Esophageal resection in patients with esophageal cancer (EC) is still associated with high mortality and morbidity rates. We aimed to develop a simple preoperative risk score for the prediction of short-term and long-term outcomes for patients with EC treated by esophageal resection. In total, 498 patients suffering from esophageal carcinoma, who underwent esophageal resection, were included in this retrospective cohort study. Three preoperative esophagectomy risk (PER) groups were defined based on preoperative functional evaluation of different organ systems by validated tools (revised cardiac risk index, model for end-stage liver disease score, and pulmonary function test). Clinicopathological parameters, morbidity, and mortality as well as disease-free survival (DFS) and overall survival (OS) were correlated to the PER score. The PER score significantly predicted the short-term outcome of patients with EC who underwent esophageal resection. PER 2 and PER 3 patients had at least double the risk of morbidity and mortality compared to PER 1 patients. Furthermore, a higher PER score was associated with shorter DFS (P < 0.001) and OS (P < 0.001). The PER score was identified as an independent predictor of tumor recurrence (hazard ratio [HR] 2.1; P < 0.001) and OS (HR 2.2; P < 0.001). The PER score allows preoperative objective allocation of patients with EC into different risk categories for morbidity, mortality, and long-term outcomes. Thus, multicenter studies are needed for independent validation of the PER score.

Glasgow Prognostic Score may be a prognostic index for overall and perioperative survival in gastric cancer without perioperative treatment.

BACKGROUND: Systemic inflammation is a key factor in tumor growth. C-reactive protein and albumin are parameters of systemic inflammation from the Glasgow Prognostic Score (GPS). The purpose was to evaluate the prognostic role of GPS in a homogeneous population of gastric cancer patients undergoing surgical treatment only. METHODS: Patients underwent operations between 2009 and 2014. Those who had received perioperative treatment or had other malignancies or inflammatory diseases were excluded. Eighty-eight patients met all inclusion criteria (age >18 years, documented preoperative serum levels of albumin and C-reactive protein, histologically proven gastric cancer, curative operation, including lymphadenectomy). C-reactive protein and albumin levels were retrieved from our prospective database. GPS was correlated with clinicopathologic characteristics and outcome. RESULTS: Increasing GPS was linked to aggressive tumor biology in terms of tumor size (GPS 0: 51.2% T1 and T2, 48.8% T3 and T4; GPS 1: 23.8% T1 and T2, 76.2% T3 and T4; GPS 2: 23.1% T1 and T2, 76.9% T3 and T4; P = .026), synchronous distant metastases (GPS 0: 47.1% M0, 0.0% M1; GPS 1: 25.9% M0, 0.0% M1; GPS 2: 27.1% M0, 100.0% M1; P = .030), venous vessel invasion (GPS 0: 91.2% V0, 8.8% V1; GPS 1: 66.7% V0, 33.3% V1; GPS 2: 55.0% V0, 45.0% V1; P = .008), resection margin status (GPS 0: 97.4% R0, 2.6% R1; GPS 1: 90.0% R0, 10.0% R1; GPS 2: 77.3% R0, 22.7% R1; P = .044), reduced overall survival (GPS 0: median 25.2 months [range 0.4-106.0]; GPS 1: 15.3 [0.2-59.5]; GPS 2: 5.8 [0.1-55.3]; P = .016) with median overall survival in the whole cohort being 16.2 months (range 0.1-106.0) and perioperative mortality (GPS 0: 0.0% of perioperative deaths, GPS 1: 20.0%, GPS 2: 80.0%; P = .036). Furthermore, GPS was identified as an independent prognosticator of overall survival (P = .033). A gradual decrease in survival between GPS subgroups was evident. CONCLUSION: GPS represents an independent prognostic factor for long-term outcome in resected gastric cancer patients without perioperative treatment and is strongly associated with perioperative mortality.

Locally advanced esophageal carcinoma: is there still a role of surgery alone without neoadjuvant treatment?

OBJECTIVE: The aim of this study is to evaluate the impact of upfront surgery without neoadjuvant pretreatment on survival in patients with clinically staged locally advanced esophageal carcinoma before the new era of neoadjuvant therapy regimes. MATERIAL AND METHODS: This is a retrospective analysis of prospectively collected data of patients with clinically advanced esophageal cancer (cT3) and without neoadjuvant treatment who underwent transthoracic esophagectomy (TTE) in curative intent between 1992 and 2009. Locally advanced esophageal cancer was defined based on presurgical computertomography, endoscopy, and endosonography findings as a tumor infiltrating the paraesophageal tissue or the adjacent structures, with or without lymph node affection. RESULTS: Histological subtypes included 131 squamous cell carcinomas (SCC) and 81 adenocarcinomas (AC). Complete resection (R0) was achieved in 84.0% of all 212 patients. Thirty-day mortality rate was 7.1%. Final pathology revealed 50 patients (23.5%) with pT1 or pT2 carcinomas which were preoperatively overstaged. Median overall survival following TTE for SCC was 13.7 months (95% CI; 10.1-17.2 months) and 24.8 months (95% CI; 14.5-35.1 months) for AC, respectively (p = 0.007). The 5-year survival rates were 14% for SCC and 26% for AC, respectively. In median, 27 lymph nodes were resected. On multivariable analyses, histological type, tumor localization, tumor grading, and resection status remained independent factors influencing overall survival. CONCLUSION: Our results in the treatment of patients with locally advanced esophageal carcinoma undergoing primary TTE are comparable to the results reported for patients undergoing neoadjuvant chemo-radio-therapy followed by surgery in the pre-CROSS-study era. Histological subtypes show different survival rates and should therefore be separately examined in future trials.

Salvage Completion Pancreatectomies as Damage Control for Post-pancreatic Surgery Complications: A Single-Center Retrospective Analysis.

BACKGROUND: Post-pancreatic surgical morbidity is frequent but often manageable by less invasive means than re-operation. Yet, some complications can become hazardous and life threatening. Herein, the results of a completion pancreatectomy (CP) to cope with severe post-operative pancreatic fistulas (POPF) and bleeding complications after major pancreatic resections for suspected pancreatic malignancy are presented. METHODS: CPs to treat severe post-pancreatic index-surgery complications between January 2002 and January 2012 were selected out of a prospective database. Indications for CP as well as perioperative data were prospectively collected and retrospectively assessed. RESULTS: In 20 of 521 Kausch-Whipple Resections (3.8%), a CP was necessary to treat post-index surgery morbidity. Indications included insufficiency of the pancreaticojejunal anastomosis with resulting POPF in 14 (70.0%) patients, severe bleeding complications in 6 (30.0%) patients, and a severe portal vein thrombosis in 1 (5.0%) patient. In 7 (35.0%) of the 20 patients, the course was complicated by remnant pancreatitis. Eleven (55.0%) of the 20 patients died during the hospital stay. Median time to re-operation did not significantly differ between survivors and in-hospital deaths (10.0 vs. 8.0 days; p = 0.732). Median hospital stay of the surviving patients was 31.0 (range 10-113) days. Re-operations following CPs were necessary in 5 (55.6%) of the 9 patients who survived and in 9 (81.8%) out of 11 patients who died. CONCLUSIONS: Post-pancreatic resection complications can become hazardous and result in severely ill patients requiring maximum therapy. CP in these cases has a high mortality but serves as an ultima ratio to cope with deleterious complications.

Cyclin D1 is a strong prognostic factor for survival in pancreatic cancer: analysis of CD G870A polymorphism, FISH and immunohistochemistry.

BACKGROUND AND OBJECTIVE: Cyclin D1 is an important regulator protein for the G1-S cell cycle phase transition. The aim of this trial was to evaluate the impact of the CCND1 polymorphism G870A and corresponding protein expression and CCND1 amplification on the survival of the patients. METHODS: 425 patients with ductal pancreatic adenocarcinoma who underwent resection were included after histopathological confirmation. DNA was analyzed for Cyclin D1 polymorphisms, immunhistochemical examination and fluorescence in situ hybridization analysis of the tumor were performed. RESULTS: Overall, the mean survival was 22.9 months (20.5-25.3). The survival in patients with Cyclin D1 G870A polymorphism Adenine/Adenine was 15.1 months (95% CI 11.3-18.9), 21.5 months (17.4-25.6) for Adenine/Guanine, and 29.4 months (95% CI 23.8-35.0) for Guanine/Guanine (P = 0.003). A shorter survival was associated with strong/moderate protein expression in immunohistochemistry (IHC) compared to weak/no expression (P = 0.028). Additionally, a significant coherency between unfavourable polymorphism (AA/AG) and increased protein expression was detected (P = 0.005). CONCLUSIONS: A strong impact on survival of Cyclin D1 G870A polymorphism and the detected corresponding protein expression was found. The biological mechanism of CCND1 in carcinogenesis has not been fully examined; but at present Cyclin D1 seems to be an interesting biomarker for the prognosis of ductal adenocarcinoma.

Preoperative Pancreatic Resection (PREPARE) score: a prospective multicenter-based morbidity risk score.

OBJECTIVES: Development of a simple preoperative risk score to predict morbidity related to pancreatic surgery. BACKGROUND: Pancreatic surgery is standardized with little technical diversity among institutions and unchanging morbidity and mortality rates in recent years. Preoperative identification of high-risk patients is potentially one of the rare avenues for improving the clinical course of patients undergoing pancreatic surgery. METHODS: Using a prospectively collected multicenter database of patients undergoing pancreatic surgery (n=703), surgical complications were classified according to the Clavien-Dindo classification. A new scoring system for preoperative identification of high-risk patients that included only objective preoperatively assessable variables was developed using a multivariate regression model. Subsequently, this scoring system was prospectively validated from 2011 to 2013 (n=429) in a multicenter setting. RESULTS: Eight independent preoperatively assessable variables were identified and included in the scoring system: systolic blood pressure, heart rate, hemoglobin level, albumin level, ASA (American Society of Anesthesiologists) score, surgical procedure, elective surgery or not, and disease of pancreatic origin or not. On the basis of 3 subgroups (low risk, intermediate risk, high risk), the proposed scoring system reached an accuracy of 75% for correctly predicting occurrence or nonoccurrence of major surgical complications in 80% of all analyzed patients within the validation cohort (c-statistic index=0.709, P<0.001, 95% confidence interval=0.657-0.760). CONCLUSIONS: We present an easily applied scoring system with convincing accuracy for identifying low-risk and high-risk patients. In contrast to other systems, the score is exclusively based on objective preoperatively assessable characteristics and can be rapidly and easily calculated.