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.

Increased lysophosphatidylcholine acyltransferase 1 expression is unrelated to prognosis of esophageal cancer patients.

INTRODUCTION: Lysophosphatidylcholine acyltransferase 1 (LPCAT1) has repeatedly been suggested to be associated with tumorigenesis. To evaluate the role of LPCAT1 in esophageal cancer, LPCAT1 immunostaining was analyzed on a tissue microarray containing samples from esophageal cancer patients. RESULTS: In benign esophageal tissue, LPCAT1 staining was detectable in low intensities. LPCAT1 staining was increased in malignant as compared to benign esophageal tissue and was found in high intensity in 26.4% of 288 interpretable esophageal adenocarcinomas (EACs) and in 23.2% of 211 squamous cell carcinomas (ESCCs). Increased LPCAT1 staining was linked to undifferentiated tumor grading in both subtypes of EACs and ESCCs (p = 0.0273 and p = 0.0085). CONCLUSION: However, LPCAT1 was not associated with prognosis of EAC and ESCC patients (p = 0.6838 and p = 0.4695) and thus cannot be considered a prognostic biomarker in esophageal cancers.

A single-center experience: management of patients with thymic epithelial tumors.

BACKGROUND: Thymic epithelial tumors are rare neoplasias. There are no internationally accepted standards to treat this complex oncological disease. The studies on which our knowledge is based frequently have methodological weaknesses. If the tumor is resectable, complete surgical excision is currently the first-line therapy. Thymic epithelial tumors respond to radiation. The therapeutic benefit of adjuvant radiotherapy depends on tumor stage. To validate and improve treatment, we share our current experiences with clinical management and surgical intervention. METHODS: This single-center retrospective study included 40 patients with primarily resectable thymic epithelial tumors who underwent resection with curative intent. The survival data was collected and presented according to Kaplan-Meier. Single- and multiple predictor survival analyses were carried out using the log-rank test and Cox proportional hazards model. RESULTS: Single-predictor survival analysis showed survival to be dependent on the Masaoka-Koga classification, WHO histological classification, resection status, surgical technique, and Clavien-Dindo grade for postoperative complications. Multiple predictor analysis confirms that the Masaoka-Koga stage (HR = 4.876, P = 0.032) and Clavien-Dindo grade (HR = 4.904, P = 0.011) are independent prognostic factors for survival. CONCLUSION: In addition to the Masaoka stage, the occurrence of severe postoperative complications represents an independent prognostic factor. Given the tumor's sensitivity to radiation, the use of neoadjuvant radiotherapy can be considered to downstage Masaoka-Koga stages III and higher, thus reducing surgical risks. Further prospective multicenter studies are urgently needed.

Identification of Kosakonia cowanii as a rare cause of acute cholecystitis: case report and review of the literature.

BACKGROUND: Kosakonia cowanii, formerly known as Enterobacter cowanii, is a Gram-negative bacillus belonging to the order Enterobacterales. The species is usually recognized as a plant pathogen and has only anecdotally been encountered as a human pathogen. Here we describe the rare case of a K. cowanii infection presenting as an acute cholecystitis and provide a review of available literature. Evident difficulties in species identification by biochemical profiling suggests that potentially, K. cowanii might represent an underestimated human pathogen. CASE PRESENTATION: A 61-year old immunocompromised man presented to the hospital with fever and pain in the upper right abdomen. Sonography revealed an inflamed gall bladder and several gall stones. A cholecystectomy proved diagnosis of an acute cholecystitis with a partial necrosis of the gall bladder. Surgical specimen grew pure cultures of Gram-negative rods unambiguously identified as K. cowanii by MALDI-TOF, 16S-rRNA analysis and whole genome sequencing. CONCLUSIONS: Reporting cases of Kosakonia species can shed light on the prevalence and clinical importance of this rare cause of human infection. Our case is the first to describe an infection without prior traumatic inoculation of the pathogen from its usual habitat, a plant, to the patient. This raises the question of the route of infections as well as the pathogen's ability to colonize the human gut.

Expression and serum levels of the neural cell adhesion molecule L1-like protein (CHL1) in gastrointestinal stroma tumors (GIST) and its prognostic power.

INTRODUCTION: Diagnosis of gastrointestinal stroma tumors (GIST) is based on the histological evaluation of tissue specimens. Reliable systemic biomarkers are lacking. We investigated the local expression of the neural cell adhesion molecule L1-like protein (CHL1) in GIST and determined whether soluble CHL1 proteoforms could serve as systemic biomarkers. MATERIAL AND METHODS: Expression of CHL1 was analyzed in primary tumor specimens and metastases. 58 GIST specimens were immunohistochemically stained for CHL1 on a tissue microarray (TMA). Systemic CHL1 levels were measured in sera derived from 102 GIST patients and 91 healthy controls by ELISA. Results were statistically correlated with clinicopathological parameters. RESULTS: CHL1 expression was detected in GIST specimens. Reduced tissue expression was significantly associated with advanced UICC stages (p = 0.036) and unfavorable tumor localization (p = 0.001). CHL1 serum levels are significantly elevated in GIST patients (p < 0.010). Elevated CHL1 levels were significantly associated with larger tumors (p = 0.023), advanced UICC stage (p = 0.021), and an increased Fletcher score (p = 0.041). Moreover, patients with a higher CHL1 serum levels displayed a significantly shortened recurrence free survival independent of other clinicopathological variables. CONCLUSION: Local CHL1 expression and serum CHL1 levels show a reverse prognostic behavior, highlighting the relevance of proteolytic shedding of the molecule. The results of the study indicate a potential role of serum CHL1 as a diagnostic and prognostic marker in GIST.

Endoscopic vacuum therapy versus stenting for postoperative esophago-enteric anastomotic leakage: systematic review and meta-analysis.

BACKGROUND: Esophageal anastomotic leakage still represents a challenging complication after esophageal surgery. Endoscopically placed self-expandable metal stents (SEMS) are the treatment of choice, but since the introduction of endoscopic vacuum therapy (EVT) for esophageal leakage 10 years ago, increasing evidence has demonstrated that EVT might be a superior alternative. Therefore, we performed a systematic review and meta-analysis to compare the effectiveness and related morbidity of SEMS and EVT in the treatment of esophageal leak. METHODS: We systematically searched for studies comparing SEMS and EVT to treat anastomotic leakage after esophageal surgery. Predefined end points including outcome, treatment success, endoscopy, treatment duration, hospitalization time, morbidity, and mortality were assessed and included in the meta-analysis. RESULTS: Five retrospective studies including 274 patients matched the inclusion criteria. Compared with stenting, EVT was significantly associated with a higher rate of leak closure (odds ratio [OR] 3.14, 95 % confidence interval [CI] 1.23 to 7.98), more endoscopic device changes (pooled median difference of 3.09; 95 %CI 1.54 to 4.64]), a shorter duration of treatment (pooled median difference -11.90 days; 95 %CI -18.59 to -5.21 days), and a lower mortality rate (OR 0.39, 95 %CI 0.18 to 0.83). There were no significant differences in short-term and major complications. CONCLUSIONS: Owing to the retrospective quality of the studies with potential biases, the results of the meta-analysis must be interpreted with caution. However, the analysis indicates the potential benefit of EVT, which should be further investigated with standardized and prospectively collected data.

Improved colorectal anastomotic leakage healing by transanal rinsing treatment after endoscopic vacuum therapy using a novel patient-applied rinsing catheter.

PURPOSE: Anastomotic or stump leakage is a common and serious complication of colorectal surgery. The objective of this study was to retrospectively investigate the clinical use and potential benefit of transanal rinsing treatment (TRT) using an innovative rinsing catheter (RC) after treatment with endoscopic vacuum therapy (EVT). METHODS: Patients with leakage after low colorectal surgery who had been treated with EVT were retrospectively analyzed. A subset of patients was trained to perform TRT with a specially developed RC. We investigated the rate of complete healing of the leakage, septic complications, failure of the therapy, surgical revisions, ostomy closure rate, and complications related to endoscopic therapy. RESULTS: Between February 2007 and January 2014, 98 patients with local complications after low colorectal surgery, treated with EVT, were identified. Eighty-nine patients were analyzed (the treatment of nine patients was stopped due to medical or technical problems): 31 patients were treated with EVT only (EVT group) and 58 patients with EVT followed by TRT (EVT/TRT group). Complete healing of the leakage was significantly better in the EVT/TRT group [84% vs. 58% (p < 0.009)], and significantly fewer septic complications needing surgical revision were detected [3% vs. 11% (p = 0.001)]. No significant differences regarding endoscopy-related complications and ostomy closure were found between EVT and EVT/TRT patients. CONCLUSIONS: The use of patient-administered TRT with an innovative, customized RC after EVT is technically feasible and reliable and significantly improves therapeutic results. Further prospective trials with larger patient groups are needed to validate the results of our study.

Surgical Management of Non-Malignant Esophageal Perforations: A Single-Center Analysis Over a 15-Year Period.

PURPOSE: Esophageal perforations are associated with high morbidity and mortality. Different nonoperative and operative treatment options have been proposed. This study focuses on the impact of different surgical treatments in nonmalignant esophageal perforations and tries to identify predictors of mortality in a single tertiary center over a 15-year period. METHODS: From 2002 to 2017, patients with surgically managed esophageal perforation were identified from our database. Patients with esophageal malignancies were excluded. Etiology, clinical data, treatment, and outcome were analyzed. A multivariate logistic regression analysis was performed to investigate the impact on mortality. RESULTS: A total of 72 patients were identified. The majority of perforations were iatrogenic (54.2%) followed by Boerhaave's syndrome (23.6%). Most ruptures were found in the distal third of the esophagus (59.7%) measuring <3 cm (61.1%). Patients were treated with exploration and drainage (8.3%), primary suture and patch reinforcement (36.1%), resection and restoration of continuity (25.0%), or resection without restoration of continuity (30.6%). Delayed therapy significantly correlated with sepsis (p < 0.0001) and mortality (p = 0.032). A correlation between an increasing perforation length with sepsis (p = 0.012) was observed. A higher Perforation Severity Score (PSS; OR 4.430; 95% CI 1.143-17.174; p = 0.031) and a higher American Society of Anesthesiologists (ASA) score (OR 2.923; 95% CI 1.011-8.448; p = 0.048) were associated with mortality in multivariate analysis. CONCLUSION: Esophageal perforations are associated with high mortality, and larger ruptures are associated with worse outcome. Rapid diagnosis and treatment are crucial for patient survival. Hence, PSS and ASA score help to identify high-risk patients. The advantage of surgical management lies in the rapid control of the septic focus in an already critically ill patient. Though, the kind of surgical technique needs to be adjusted to the individual situation.

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.

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.

Endogenous testosterone and exogenous oxytocin influence the response to baby schema in the female brain.

Nurturing behavior may be critically influenced by the interplay of different hormones. The neuropeptide oxytocin is known to promote maternal behavior and its reduction has been associated with postpartum depression risk and child neglect. Contrariwise, the observed decrease in testosterone level during early parenthood may benefit caretaking behavior, whereas increased testosterone may reduce attention to infants. Here we used functional magnetic resonance imaging to investigate the interactive influence of testosterone and oxytocin on selective attention to and neural processing of the baby schema (BS). 57 nulliparous women performed a target detection task with human faces with varying degree of BS following double-blinded placebo-controlled oxytocin administration in a between-subjects design. Our results support the idea that oxytocin enhances attention to the BS. Oxytocin had a positive effect on activation of the inferior frontal junction during identification of infant targets with a high degree of BS that were presented among adult distractors. Further, activation of the putamen was positively correlated with selective attention to the BS, but only in women with high endogenous testosterone who received oxytocin. These findings provide initial evidence for the neural mechanism by which oxytocin may counteract the negative effects of testosterone in the modulation of nurturing behavior.

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.

Pancreatic cancer and liver metastases: state of the art.

Pancreatic cancer is still one of the most aggressive oncological diseases with a 5-year mortality rate below 10%. Surgery remains the only curative treatment; however, most patients present with late-stage disease deemed unresectable, either due to extensive local vascular involvement or the presence of distant metastasis. In the detection of hepatic metastases, the current standard is palliative chemotherapy with fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) or nab-paclitaxel with gemcitabine. Once hepatic metastases are diagnosed, the guidelines do not recommend resection of the primary tumor. Recent findings suggest that some patients with non-resectable diseases initially have survival rates as good as those with initially resectable disease when they are able to undergo surgical resection. Synchronous resection of both the primary tumour as well as the liver metastases may be beneficial and improves the outcome.

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.