Serum midkine as non-invasive biomarker for detection and prognosis of non-small cell lung cancer.

Lung cancer continues to be the leading cause for cancer-related deaths in men and women worldwide. Sufficient screening tools enabling early diagnosis are essential to improve patient outcomes. The aim of this study was to evaluate serum midkine (S-MK) both as a diagnostic and prognostic biomarker in non-small cell lung cancer (NSCLC). This single-center analysis included 59 NSCLC patients counting 30 squamous cell cancers and 29 adenocarcinomas. Preoperative S-MK concentration was determined using ELISA. Patients were followed up to five years. S-MK was found to be significantly overexpressed in patients with NSCLC compared to healthy controls (p < 0.001). The discriminative power of S-MK to differentiate NSCLC subjects from controls was fairly high with an area under the receiver operating characteristic curve of 0.83 (p < 0.001). Optimal sensitivity of 92% and reasonable specificity of 68% was reached at a threshold of 416 pg/ml S-MK. Patients with high S-MK concentration showed a significantly shorter overall survival compared to patients with low S-MK expression (p < 0.05). In conclusion, S-MK is overexpressed in patients with NSCLC and serves as an independent prognostic factor for overall survival. S-MK may thus be considered as an additional non-invasive biomarker not only for NSCLC screening but also for outcome prediction.

Acute Mesenteric Infarction: The Chameleon of Acute Abdomen Evaluating the Quality of the Diagnostic Parameters in Acute Mesenteric Ischemia.

INTRODUCTION/OBJECTIVE: Acute mesenteric ischemia (AMI) is difficult to diagnose. Since the established parameters have low sensitivity and specificity, the aim of this study is to analyze the diagnostic quality of the established parameters of AMI. METHODS: All patients that underwent emergency surgery due to suspected diagnosis of mesenteric ischemia at the University Medical Center Hamburg-Eppendorf between 2008 and 2014 were evaluated. Overall, 275 patients were enrolled and pre-, intra- and postoperative data were evaluated. RESULTS: In 200 patients, a mesenteric ischemia was confirmed intraoperatively, and 75 patients had no ischemia. Comparing these groups, the rate of patients with pH < 7.2 (25 vs. 12%; p = 0.021) and elevated mean CRP level (175 ± 117 mg/L vs. 139 ± 104 mg/L; p = 0.019) was significantly higher in ischemic patients. There was no significant difference in the level of preoperative lactate. Concerning abdominal CT scan, a sensitivity and specificity of 61 and 68%, respectively, was found. CONCLUSION: New diagnostic parameters are needed. So far, explorative laparotomy is the only reliable diagnostic method to detect mesenteric infarction.

Microbial findings, sensitivity and outcome in patients with postoperative peritonitis a retrospective cohort study.

BACKGROUND: Acute postoperative peritonitis resulting from previous abdominal surgery is still a severe and potentially fatal disease, which is associated with high morbidity and mortality. The aim of the present study was to evaluate patients' outcome after postoperative peritonitis and identify the most effective empiric antibiotic regimes. METHODS: 422 patients with acute postoperative peritonitis as a result to earlier abdominal operation (e.g. anastomotic leakage) were analyzed retrospectively focusing on the origin of the peritonitis, microbial flora and resistance patterns. Furthermore, mortality was estimated according to sensitivity results of the tested antibiotics. RESULTS: In 50% of the patients, anastomotic leakage was located in the colon. The predominantly cultured microorganisms were Escherichia coli and Enterobacteriaceae. The combination of meropenem and vancomycin was effective in 96% of these microbes. The frequently used combinations of piperacillin/sulbactam and cefotaxime/metronidazole were effective in only 67% and 43%, respectively. CONCLUSIONS: We were able to show that the currently used antibiotic regimes with piperacillin/sulbactam and cefotaxime/metronidazole are ineffective in a relevant number of patients with anastomotic leakage. Only meropenem or meropenem/vancomycin cover most of the microbes predominant in postoperative peritonitis.

Decentralized colorectal cancer care in Germany over the last decade is associated with high in-hospital morbidity and mortality.

PURPOSE: Despite several national initiatives, centralization of cancer care in Germany remains insufficient for most malignancies. Currently, there is a plethora of centers, including 290 voluntary certified and audited colorectal cancer (CRC) centers by the end of 2017, in the nation with many patients still being treated outside of such centers. This study aimed to assess morbidity and mortality rates of surgical procedures for primary colorectal CRC in Germany over the last decade through a comprehensive unbiased analysis. PATIENTS AND METHODS: We performed an analysis of the national diagnosis-related group inpatient statistics from 2005 to 2015 including all German hospitals. All patients who underwent surgeries for primary CRC during the study period were included. RESULTS: A total of 351,028 cases were analyzed (61.6% colonic and 38.4% rectal resections). The mortality rate of colonic resections remained high during the study period (4.9% in 2005 vs 4.5% in 2015; P=0.57). Reduced perioperative mortality after rectal surgery was observed only after 2012 compared to previous years (3.8% in 2005 vs 3.0% in 2015; P<0.001), with no further improvement. In-hospital morbidity such as anastomotic leak, wound infections, hemorrhage, pneumonia, deep vein thrombosis, and lung embolism did not improve for either rectal or for colonic surgery, but in contrast, most outcomes deteriorated over time. CONCLUSION: The present study challenges the current national health policies aiming to improve outcomes of surgical patients. CRC care in Germany remains decentralized with high in-hospital morbidity and mortality rates. New national strategies focusing on the implementation of centralization and high-quality CRC care are urgently needed.

Duodenum-preserving pancreatic head resection: A retrospective analysis of the Hamburg Modification.

BACKGROUND: Chronic pancreatitis remains a challenging inflammatory disease, causing progressive, irreversible fibrosis of the pancreatic parenchyma. Several surgical options for treatment have been established, but duodenum-preserving pancreatic head resections seem to be the most favorable option other than pancreatoduodenectomy. The aim of this retrospective analysis is to evaluate the outcomes of the Hamburg modification of duodenum-preserving pancreatic head resections. METHODS: We retrospectively evaluated-for long-term outcomes concerning pain control, quality of life, and symptom control-500 consecutive patients suffering from painful chronic pancreatitis who had undergone the Hamburg modification of the duodenum-preserving pancreatic head resection. Additionally, the patients were compared with a database of 104 patients who underwent duodenum-preserving pancreatic head resections according to Beger or Frey. RESULTS: After a mean follow-up of 10 years, overall survival was 90% in those patients having undergone the Hamburg modification. Regarding analgetic medications, the median pain score for frequency of pain attacks, measured by a visual analog scale and inability to work, was 0 (0-100), and the global quality of life revealed a median of 92 (0-100). In addition, we found that a high rate of patients continued consuming alcohol after the operation (37.9%). The rate of redo surgery owing to the recurrence of chronic pancreatitis was 7.6% after this Hamburg modification. CONCLUSION: Duodenum-preserving pancreatic head resections provide adequate outcomes in terms of pain control, quality of life, and symptom control. In this retrospective analysis, the Hamburg modification was found to be a good alternative to other forms of duodenum-preserving pancreatic head resections. The choice of a certain modification of the duodenum-preserving pancreatic head resection may depend on the surgeon's expertise and the individual needs of the patient.

Minimally invasive surgery for colorectal cancer remains underutilized in Germany despite its nationwide application over the last decade.

Minimally invasive surgery (MIS) has superior short-term outcomes than open surgery (OS) for colorectal cancer (CRC). However, a nationwide dataset has not been analysed to confirm these findings. We evaluated the distribution and outcomes of MIS for CRC from 2005 to 2015; all in-patients with CRC surgery procedure codes were identified from hospital data, which are entered into the nationwide diagnosis-related group database and forwarded anonymised to the Federal Bureau of Statistics. We determined absolute MIS, morbidity, and mortality rates for specific sub-categories, including procedure type. We identified 345,913 in-patient files. The MIS rate increased from 6.4% (n = 2366; 2005) to 28.5% (n = 8363; 2015), with the highest rates for sigmoid colon (38%) and rectal (39%) resections. The overall conversion rate was 14.4%, without noticeable improvement over time. International Classification of Disease codes related to postoperative complications were documented more frequently after OS than after MIS. OS was associated with a higher mortality rate (4.7%) than MIS (1.8%) (P < 0.001), even after stratifying patients according to the resection site. Use of MIS remains low in Germany compared with that in other European countries. Underutilization of MIS has to be addressed in the future by promoting structured training programs and standardization of laparoscopic surgery.

Sustained function in atrophying liver tissue after portal branch ligation in the rat.

BACKGROUND: Preoperative segmental portal vein occlusion has become a common method to prevent liver failure after extended hepatic resection. To date, it is not elucidated whether atrophy by portal deprivation with concomitant contralateral regeneration leads to impaired liver function. We addressed this question by examining the expression of liver function proteins related to glucose homeostasis and acute-phase response in a corresponding animal model. MATERIALS AND METHODS: Male Wistar rats were subjected to either portal branch ligation (PBL), partial hepatectomy (PH), or sham operation (SO). The mRNA expression and chronological distribution of glucose-6-phosphatase (G6P), glucagon receptor (GR), glceraldehyd-3-phosphate-dehydrogenase (GAPDH), albumin, fibronectin, and C1-esterase-inhibitor (C1-Inh) genes were examined by Northern-blot hybridizations. Determinations of serum-glucose and glycogen staining by periodic acid and Schiff were performed to analyze changes in glucose mobilization and storage. RESULTS: In regenerating liver tissue after PH and PBL, we detected a selective reduction of transcripts encoding G6P during the prereplicative period 6 and 12 h after surgery and a contemporary drop in serum glucose levels. This impairment proved to be more distinct after PH than after PBL. Compared with the residual liver after PH, the level of glycogen disappearance was lower after PBL in the regenerating lobe. In the portal-deprived liver tissue, the expression of genes coding for G6P, GR, GAPDH, albumin, fibronectin, and C1-Inh was not altered compared with the SO group. CONCLUSIONS: Overall, portal-deprived liver tissue undergoing atrophy retains its liver-specific differentiation and function and helps to maintain homeostasis during the fast regeneration of the non-occluded liver lobe.

Absence of adhesion triggers differential FAK and SAPKp38 signals in SW620 human colon cancer cells that may inhibit adhesiveness and lead to cell death.

BACKGROUND: Upon adhesion, anchorage-dependent cells transmit survival signals from the matrix into the cell. Loss of anchorage leads to anoikis. Resistance to anoikis may influence tumor progression and metastasis. To better understand the pathways that regulate the choice between adhesion and cell death, we examined FAK, c-Src andMAPKinase activities in SW620 human colon cancer cells. METHODS: SW620 cell suspensions were first allowed to adhere to collagen I for 30 minutes and adherent cells were subsequently counted. FAK, p38, c-Src and ERK1/2 phosphorylation were assessed by Western blot in adherent cells and in cells prevented from adhesion by plating unto BSA-pacificated dishes. p38 and FAK were inhibited by SB203580 (20 microM) or by specific FAK antisense nucleotides or FAK siRNA, respectively, and adhesion quantitated. Apoptosis (anoikis) after lack of adhesion was measured colorimetrically in control cells and in cells treated with SB203580. RESULTS: Adhesion to collagen I nearly doubled FAK phosphorylation at Y397, the autophosphorylation site, and decreased p38 activation by 60% (p<0.001) but did not affect FAK phosphorylation at Y576, the c-Src dependent site. Lowering FAK expression with FAK antisense decreased adhesion to collagen I; the larger decrease in FAK expression obtained with the siRNA (43 +/- 2%) resulted in significantly greater inhibition of adhesion not only to collagen I but also to collagen IV and fibronectin. The p38 inhibitor diminished anoikis and enhanced adhesion. Interestingly, the SB compound also significantly inhibited FAK phosphorylation at Y397 (23 +/- 3% in adherent, 30 +/- 4% in non-adherent cells at 30 minutes and 35 +/- 4% in adherent, 46 +/- 14% in non-adherent cells after 6 hours, p<0.05 for each) and greatly enhanced phosphorylation of ERK1/2, a putative anti-apoptotic component of the MAPK cascade. CONCLUSIONS: In the absence of adhesion, SW620 cells exhibit increased p38 but decreased FAK activation, signals that may promote cell death. Our observations with the p38 inhibitor SB203580 indicate that inside-out signals, from p38 to FAK, may regulate both adhesion and anoikis in SW620 cells. In addition, the data suggest the presence of cross-talk between the pro-apoptotic p38 and anti-apoptotic ERK1/2 pathways.