IL-22 promotes liver regeneration after portal vein ligation.

Background: Insufficient remnant liver volume (RLV) after the resection of hepatic malignancy could lead to liver failure and mortality. Portal vein ligation (PVL) prior to hepatectomy is subsequently introduced to increase the remnant liver volume and improve the outcome of hepatic malignancy. IL-22 has previously been reported to promote liver regeneration, while facilitating tumor development in the liver via Steap4 upregulation. Here we performed PVL in mouse models to study the role of IL-22 in liver regeneration post-PVL. Methods: Liver weight and volume was measured via magnetic resonance imaging (MRI). Immunohistochemistry for Ki67 and hepatocyte growth factor (HGF) was performed. IL-22 was analyzed by flow cytometry and quantitative polymerase chain reaction (qPCR) was used for acquisition of Il-33, Steap4, Fga, Fgb and Cebpd. To analyze signaling pathways, mice with deletion of STAT3 and a neutralizing antibody for IL-22 were used. Results: The remnant liver weight and volume increased over time after PVL. Additionally, we found that liver regenerative molecules, including Ki67 and HGF, were significantly increased in remnant liver at day 3 post-PVL, as well as IL-22. Administration of IL-22 neutralizing antibody could reduce Ki67 expression after PVL. The upregulation of IL-22 after PVL was mainly derived from innate cells. IL-22 blockade resulted in lower levels of IL-33 and Steap4 in the remnant liver, which was also the case in mice with deletion of STAT3, the main downstream signaling molecule of IL-22, in hepatocytes. Conclusion: IL-22 promotes liver regeneration after PVL. Thus, a combination of IL-22 supplementation and Steap4 blockade could potentially be applied as a novel therapeutic approach to boost liver regeneration without facilitating tumor progression after PVL.

PSMA PET-directed surgical metastasis-directed therapy in metachronous prostate cancer.

We present the case of a patient who underwent an open radical prostatectomy with pelvic lymph node dissection (Gleason 4+3, pT3a pN1 R0) in March 2017. In November 2020, prostate-specific membrane antigen (PSMA)-radioguided salvage lymph node dissection was planned due to a single left para-rectal lymph node at a [68Ga] Ga-PSMA-I&T PET. In January 2022, the [68Ga] Ga-PSMA-I&T PET showed an isolated liver lesion. Biopsy confirmed prostate adenocarcinoma. A liver segmentectomy was performed. A complete biochemical response was reported until the last follow-up (December 2022). Prostate-specific membrane antigen positron emission tomography (PSMA PET)-directed metastasis-directed therapy may be an effective treatment in selected cases, allowing a benefit in the oncological outcome.

[Splenic surgery in hematological diseases : Indications and surgical technique]. / Chirurgie der Milz bei hämatologischen Erkrankungen : Indikationen und operative Technik.

BACKGROUND: Splenic surgery in hematological disorders requires a well-weighted decision on the indications because the medical treatment has rapidly changed in recent years due to new pharmaceutical approaches. OBJECTIVE: Summary of the indications, surgical procedures and perioperative management regarding operative interventions on the spleen in hematological disorders. MATERIAL AND METHODS: Selective literature search and summary of reviews and guideline recommendations. RESULTS: In hematological disorders surgical procedures of the spleen (splenectomy and partial splenectomy) are an important part of the repertoire in the treatment. In recent years the indications for surgery have become narrower because of new forms of medicinal treatment. Especially in hereditary spherocytosis, immune thrombocytopenia and symptomatic splenomegaly and hypersplenism it is still of importance. The minimally invasive splenectomy is regarded as the gold standard. The spleen has an important immune and sequestration function, therefore preoperative and postoperative infectious and thromboembolic events have to be anticipated and prevented. A close interdisciplinary cooperation with hematologists is essential for an optimal outcome of patients. CONCLUSION: The minimally invasive splenectomy and partial splenectomy are part of the surgical repertoire in the diagnostics and treatment of hematological disorders. Because of novel medicinal approaches the therapeutic protocols are continuously changing. A close cooperation with hematologists is important for the optimal evaluation of the indications and the perioperative management.

CD4+ T cell-derived IL-22 enhances liver metastasis by promoting angiogenesis.

Metastasis is a cancer-related systemic disease and is responsible for the greatest mortality rate among cancer patients. Interestingly, the interaction between the immune system and cancer cells seems to play a key role in metastasis formation in the target organ. However, this complex network is only partially understood. We previously found that IL-22 produced by tissue resident iNKT17 cells promotes cancer cell extravasation, the early step of metastasis. Based on these data, we aimed here to decipher the role of IL-22 in the last step of metastasis formation. We found that IL-22 levels were increased in established metastatic sites in both human and mouse. We also found that Th22 cells were the key source of IL-22 in established metastasis sites, and that deletion of IL-22 in CD4+ T cells was protective in liver metastasis formation. Accordingly, the administration of a murine IL-22 neutralizing antibody in the establishment of metastasis formation significantly reduced the metastatic burden in a mouse model. Mechanistically, IL-22-producing Th22 cells promoted angiogenesis in established metastasis sites. In conclusion, our findings highlight that IL-22 is equally as important in contributing to metastasis formation at late metastatic stages, and thus, identify it as a novel therapeutic target in established metastasis.

IL-22BP controls the progression of liver metastasis in colorectal cancer.

Background: The immune system plays a pivotal role in cancer progression. Interleukin 22 binding protein (IL-22BP), a natural antagonist of the cytokine interleukin 22 (IL-22) has been shown to control the progression of colorectal cancer (CRC). However, the role of IL-22BP in the process of metastasis formation remains unknown. Methods: We used two different murine in vivo metastasis models using the MC38 and LLC cancer cell lines and studied lung and liver metastasis formation after intracaecal or intrasplenic injection of cancer cells. Furthermore, IL22BP expression was measured in a clinical cohort of CRC patients and correlated with metastatic tumor stages. Results: Our data indicate that low levels of IL-22BP are associated with advanced (metastatic) tumor stages in colorectal cancer. Using two different murine in vivo models we show that IL-22BP indeed controls the progression of liver but not lung metastasis in mice. Conclusions: We here demonstrate a crucial role of IL-22BP in controlling metastasis progression. Thus, IL-22 might represent a future therapeutic target against the progression of metastatic CRC.

RAI3 expression is not associated with clinical outcomes of patients with non-small cell lung cancer.

PURPOSE: Retinoic acid inducible protein 3 (RAI3) has been suggested as prognostic biomarker in several cancer types. The present study aimed to examine the role of RAI3 expression in non-small cell lung cancers (NSCLCs). METHODS: RAI3 protein expression was evaluated by immunohistochemistry in tissue microarray (TMA) sections from a retrospective cohort of more than 600 surgically resected NSCLCs and results were compared with clinicopathological features and follow-up data. RESULTS: While membranous RAI3 immunostaining was always strong in benign lung, strong RAI3 staining was only detectable in 14.7% of 530 interpretable NSCLCs. Within NSCLC subtypes, immunostaining intensity for RAI3 was significantly decreased in large cell lung cancers (LCLCs) and squamous cell carcinomas (SQCCs) relative to lung adenocarcinomas (LUACs) (P < 0.0001 each). However, RAI3 staining was neither associated with pathological features of NSCLCs nor with survival of patients (P = 0.6915). CONCLUSION: Our study shows that RAI3 expression was not associated with clinical outcomes of NSCLC patients and cannot be considered as prognostic marker in lung cancer patients.

Potential role of the bitter taste receptor T2R14 in the prolonged survival and enhanced chemoresponsiveness induced by apigenin.

Bitter taste receptors (T2Rs) are G protein­coupled receptors originally detected in the gustatory system. More recently, T2Rs have been shown to be expressed in extra­oral cells eliciting non­gustatory functions. Emerging evidence has suggested a potential role for T2R signaling in diverse pathophysiological conditions, including cancer. -The aim of the present study was to evaluate the expression of T2R14 in pancreatic ductal adenocarcinoma (PDAC) and to assess its involvement in the anticancer effects induced by apigenin, a natural ligand of T2R14. For this purpose, T2R14 expression was explored in PDAC tumor tissue and tumor­derived cell lines. Using the cell lines expressing the highest levels of T2R14, its effects on chemoresponsiveness and migration upon activation with apigenin were investigated in vitro. To the best of our knowledge, the present study was the first to confirm the expression of the T2R family member T2R14 in PDAC. Patients with relatively high levels of T2R14 expression exhibited significantly prolonged overall survival compared with that of patients with low T2R14 expression. Furthermore, novel functions for apigenin were revealed; notably, apigenin was shown to elicit cytotoxic, anti­migratory and chemosensitizing effects to 5­fluoruracil (5­FU) and to 5­FU, leucovorin, irinotecan and oxaliplatin in pancreatic cancer cells. In conclusion, the present study extended the evidence for the anticancer effects of apigenin and strongly indicated the functional relevance of T2R14 in PDAC, even though their respective underlying pathways appear to be independent of each other.

A Critical Role of the IL-22-IL-22 Binding Protein Axis in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) ranks among the five most common cancer entities worldwide and leads to hundred-thousands of deaths every year. Despite some groundbreaking therapeutical revelations during the last years, the overall prognosis remains poor. Although the immune system fights malignant transformations with a robust anti-tumor response, certain immune mediators have also been shown to promote cancer development. For example, interleukin (IL)-22 has been associated with HCC progression and worsened prognosis in multiple studies. However, the underlying mechanisms of the pathological role of IL-22-signaling as well as the role of its natural antagonist IL-22 binding protein (IL-22BP) in HCC remain elusive. Here, we corroborate the pathogenic role of IL-22 in HCC by taking advantage of two mouse models. Moreover, we observed a protective role of IL-22BP during liver carcinogenesis. While IL-22 was mainly produced by CD4+ T cells in HCC, IL-22BP was abundantly expressed by neutrophils during liver carcinogenesis. Hepatocytes could be identified as a major target of this pathological IL-22-signaling. Moreover, abrogation of IL-22 signaling in hepatocytes in IL22ra1flox/flox × AlbCre+ mice reduced STEAP4 expression-a known oncogene-in HCC in vivo. Likewise, STEAP4 expression correlated with IL22 levels in human HCC samples, but not in healthy liver specimens. In conclusion, these data encourage the development of therapeutical approaches that target the IL-22-IL-22BP axis in HCC.

The Extracellular Matrix: A Key Accomplice of Cancer Stem Cell Migration, Metastasis Formation, and Drug Resistance in PDAC.

Pancreatic ductal adenocarcinoma (PDAC) is rich in dense fibrotic stroma that are composed of extracellular matrix (ECM) proteins. A disruption of the balance between ECM synthesis and secretion and the altered expression of matrix remodeling enzymes lead to abnormal ECM dynamics in PDAC. This pathological ECM promotes cancer growth, survival, invasion, and alters the behavior of fibroblasts and immune cells leading to metastasis formation and chemotherapy resistance, which contribute to the high lethality of PDAC. Additionally, recent evidence highlights that ECM, as a major structural component of the tumor microenvironment, is a highly dynamic structure in which ECM proteins establish a physical and biochemical niche for cancer stem cells (CSCs). CSCs are characterized by self-renewal, tumor initiation, and resistance to chemotherapeutics. In this review, we will discuss the effects of the ECM on tumor biological behavior and its molecular impact on the fundamental signaling pathways in PDAC. We will also provide an overview of how the different ECM components are able to modulate CSCs properties and finally discuss the current and ongoing therapeutic strategies targeting the ECM. Given the many challenges facing current targeted therapies for PDAC, a better understanding of molecular events involving the interplay of ECM and CSC will be key in identifying more effective therapeutic strategies to eliminate CSCs and ultimately to improve survival in patients that are suffering from this deadly disease.

Management of Esophageal Cancer-Associated Respiratory-Digestive Tract Fistulas.

Respiratory-digestive tract fistulas are fatal complications that occur in esophageal cancer treatment. Interdisciplinary treatment strategies are still evolving, especially in anatomical treatment stratification. Thus, this study aims to evaluate general therapeutic strategies for this rare condition. Medical records were reviewed for esophageal cancer-associated respiratory-digestive tract fistula patients treated between January 2008 and September 2021. Fistulas were classified according to being surgery- and tumor-associated. Treatment strategies, clinical success, and survival were analyzed. A total of 51 patients were identified: 28 had tumor-associated fistulas and 23 surgery-associated fistulas. Risk factors for fistula development such as radiation (OR = 0.290, p = 0.64) or stent implantation (OR = 1.917, p = 0.84) did not correlate with lack of symptom control for RDF patients. In contrast, advanced lymph node metastasis as another risk factor was associated with persistent symptoms after treatment for RDF patients (OR = 0.611, p = 0.01). Clinical success significantly correlated with bilateral fistula repair in surgery-associated fistulas (p = 0.01), while tumor-associated fistulas benefited the most from non-surgical (p = 0.04) or combined surgical and non-surgical intervention (p = 0.04) and a bilateral fistula repair (p = 0.02) in terms of overall survival. The therapeutic strategy should aim for bilateral fistula closure. A multidisciplinary, stepwise approach might have the best chance for restoration or symptom control with optimized overall survival in selected patients.

Completion of FLOT Therapy, Regardless of Tumor Regression, Significantly Improves Overall Survival in Patients with Esophageal Adenocarcinoma.

Esophageal cancer is the eighth most common cancer worldwide, with poor prognosis and high mortality. The combination of surgery and systemic therapy provide the best chances for long-term survival. The purpose of this study was to analyze the impact of the FLOT protocol on the overall survival of patients following surgery for esophageal adenocarcinoma, with a focus on the patients who did not benefit in terms of pathological remission from the neoadjuvant therapy. A retrospective analysis of all the patients who underwent esophagectomies from 2012 to 2017 for locally advanced adenocarcinomas of the esophagus at a tertiary medical center was performed. The results show that the completion of systemic therapy, regardless of the tumor regression grading, had a significant positive impact on the overall survival. The patients with complete regression and complete systemic therapy showed the best outcomes. Anastomotic insufficiency did not negatively impact the long-term survival, while complications of the systemic therapy led to significantly reduced overall survival. We conclude that adjuvant systemic therapy should, when possible, always be completed, regardless of the tumor regression, following an esophagectomy.

CD147 expression lacks prognostic relevance in esophageal cancer.

INTRODUCTION: The role of CD147 as an important indicator of tumor prognosis remains controversially discussed in literature. We focused on the prognostic significance of CD147 expression in esophageal cancer patients. While some studies report that CD147 is an unfavorable prognostic factor in esophageal squamous cell carcinoma, others showed no significant correlation. However, only one study draws attention to the significance of CD147 in esophageal adenocarcinoma, which is one of the most rapidly increasing neoplasms in the western world. METHODS: To finally clarify the impact of CD147 as a prognostic factor, especially for esophageal adenocarcinomas, we analyzed CD147 expression in a tissue microarray of 359 esophageal adenocarcinomas and 254 esophageal squamous cell cancer specimens. For the immuno-histochemical analysis, we used a primary antibody specific for CD147. Staining intensity and proportion of positive tumor cells were scored (negative, weak, moderate, strong staining). These findings were compared to normal esophageal tissue and correlated to the histopathological tumor phenotype and survival data. RESULTS: CD147 expression was detectable in weak intensities in benign esophageal tissue (85.78%) and expressed in predominately moderate to strong intensities in esophageal cancer (88.34%). Strong CD147 immunostaining was linked to increased infiltration depth (p = 0.015) and differentiation (p = 0.016) in esophageal squamous cell cancer but revealed no significant correlation with histopathology of adenocarcinoma. Moreover, CD147 intensity was unrelated to overall survival in this collective for both subtypes of esophageal cancer. CONCLUSION: Thus, our data show that CD147 has no prognostic value, neither in esophageal adenocarcinoma nor squamous cell carcinoma.

Evaluation of the Hamburg-Glasgow Classification in Pancreatic Cancer: Preoperative Staging by Combining Disseminated Tumor Load and Systemic Inflammation.

This study aims to compare the Hamburg Glasgow Classification (HGC) to Union for International Cancer Control (UICC) classification in patients with pancreatic ductal adenocarcinoma (PDAC). As adequate tumor classification is only possible after tumor resection and histological evaluation, only 20% of patients with PDAC receive accurate tumor staging. Thus, an accurate preoperative staging system is still missing but urgently needed. Systemic inflammation and tumor dissemination are important factors regarding the oncological outcome. HGC integrates both into a preoperative staging system, by combining C-reactive protein (CRP), albumin, and disseminated tumor cells (DTC) in the bone marrow. In this prospective study, 109 patients underwent surgical exploration for suspected PDAC. All patients underwent a preoperative bone marrow aspiration for DTC detection. HGC showed significant preoperative risk stratification for overall survival (OS) (p-value < 0.001) and progression-free survival (PFS) (p-value < 0.001). These results were comparable to the UICC survival stratification for OS and PFS (p-value = 0.001 and 0.006). Additionally, in non-metastatic PDAC, HGC III-IV was associated with shorter OS and PFS (p-value < 0.001, respectively) when compared to HGC I-II. Therefore, the HGC is a promising preoperative prognostic staging classification for accurate and simple outcome stratification in patients with PDAC.

High Serum Levels of Wnt Signaling Antagonist Dickkopf-Related Protein 1 Are Associated with Impaired Overall Survival and Recurrence in Esophageal Cancer Patients.

Dickkopf-related protein 1 (DKK1), an antagonist of the canonical Wnt pathway, has received tremendous attention over the past years as its dysregulation is said to be critically involved in a wide variety of gastrointestinal cancers. However, the potential clinical implications of DKK1 remain poorly understood. Although multimodal treatment options have been implemented over the past years, esophageal cancer (EC) patients still suffer from poor five-year overall survival rates ranging from 15% to 25%. Especially prognostic factors and biomarkers for risk stratification are lacking to choose the most beneficial treatment out of the emerging landscape of different treatment options. In this study, we analyzed the serum DKK1 (S-DKK1) levels of 91 EC patients prior to surgery in a single center study at the University Medical Center Hamburg-Eppendorf by enzyme-linked immunosorbent assay. High levels of S-DKK1 could be especially observed in patients suffering from esophageal adenocarcinoma which may promote the hypothesis of a crucial role of DKK1 in inflammation. S-DKK1 levels of ≥5800 pg/mL were shown to be associated with unfavorable five-year survival rates and the presence of CTCs. Interestingly, significantly lower S-DKK1 levels were detected in patients after neoadjuvant treatment, implying that S-DKK1 may serve as a useful biomarker for treatment monitoring. Multivariate analysis identified S-DKK1 as an independent prognostic marker with respect to overall survival in EC patients with a hazard ratio of 2.23. In conclusion, our data implicate a negative prognostic role of DKK1 with respect to the clinical outcome in EC patients. Further prospective studies should be conducted to implement S-DKK1 into the clinical routine for risk stratification and treatment monitoring.

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.

Multicenter Experience in Robot-Assisted Minimally Invasive Esophagectomy - a Comparison of Hybrid and Totally Robot-Assisted Techniques.

BACKGROUND: Oncological esophageal surgery has evolved significantly in the last decades. From open esophagectomy over (hybrid) minimally invasive surgery, nowadays, robot-assisted minimally invasive esophagectomy (RAMIE) approaches are applied. Current techniques require an analysis of possible advantages and disadvantages indicating the direction towards a novel gold standard. METHODS: Robot-assisted Ivor Lewis esophagectomies, performed in the period from April 2017 to June 2019 in five German centers (Berlin, Cologne, Hamburg, Kiel, Mainz), were included in this study. Pre-, intra-, and postoperative parameters were assessed. Cases were grouped for hybrid (H-RAMIE) versus totally robot-assisted (T-RAMIE) approaches. Postoperative parameters and complications were compared using risk ratios. RESULTS: A total of 175 operations were performed as T-RAMIE and 67 as H-RAMIE. Patient age (median age 62 years) and sex (83.1% male) were similarly distributed in both groups. Median duration of esophagectomy was significantly lower in the T-RAMIE group (385 versus 427 min, p < 0.001). The risks of "overall morbidity" (32.0 versus 47.8%; risk ratio [RR], 95% confidence interval (CI): 1.5, 1.1-2.1; p = 0.026), "anastomotic leak" (10.3 versus 22.4%; RR, CI: 2.2, 1.2-4.1; p = 0.020), and "respiratory failure" (1.1 versus 7.5%; RR, CI: 6.5, 1.3-32.9; p = 0.019) were significantly higher in case of H-RAMIE. CONCLUSIONS: In the five participating German centers, T-RAMIE was the preferred procedure (72.3% of operations). In comparison to H-RAMIE, T-RAMIE was associated with a significantly reduced risk of postoperative morbidity, anastomotic leak, and respiratory failure as well as a significantly reduced time necessary for esophagectomy.

Combination of Side-Swing Flap With Negative-Pressure Wound Therapy Is Superior to Open Excision or Flap Alone in Children With Pilonidal Sinus-But at What Cost?

Background: Pilonidal sinus (PS) disease frequently occurs in adolescents and young adults, and in many cases involves wide excision or local flaps as treatment. These treatments are associated with a significant recurrence rate, a long healing time, and thus absence from school or work. The hybrid technique, which is a combination of side-swing plasty with negative-pressure wound therapy (NPWT) may improve these outcomes. The aim of the study was to compare the latter with other current methods. Methods: Children presenting with a pilonidal sinus to two referral centers for pediatric surgery from January 2017 till June 2019 and subsequent (1) slide-swing plasty, (2) open excision, or (3) slide-swing plasty in combination with NPWT were included in this retrospective study. Type of therapy, number of interventions, duration of hospitalization, complications, and recurrence rate were recorded. In addition, data was retrieved from the national diagnosis-related group for inpatient statistics, for all patients who underwent surgery for pilonidal sinus in 2015 and 2016. Results: In total, 85 children were included, with a mean age of 15 years and a near equal gender distribution (53% female). The minimum follow-up was 1 year. In 56% open resection was performed, while 18% underwent a slide-swing plasty and 26% a slide-swing plasty in combination with NPWT. While the hybrid technique was superior regarding recurrence rate in comparison to open excision (24 vs. 5%, p = 0.047), it had significantly longer hospital stay [17.41 (15.63) vs. 3.65 (1.68) days, p < 0.001] and number of interventions [4.14 (4.07) vs. 1.04 (0.29), p < 0.001]. Conclusions: Management of PS disease using slide-swing plasty in combination with NPWT is an effective treatment and is associated with low recurrence rate and minimal morbidity. However, this type of treatment is accompanied by an elongated hospitalization time and more frequent interventions. A diligent case by case evaluation and thorough patient counseling is thus necessary when choosing the right technique for the treatment of PS disease.

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.

Prospective Comparison of the Prognostic Relevance of Circulating Tumor Cells in Blood and Disseminated Tumor Cells in Bone Marrow of a Single Patient's Cohort With Esophageal Cancer.

OBJECTIVE: Aim of this prospective study was to evaluate the prognostic significance of disseminated tumor cells (DTCs) and circulating tumor cells (CTCs) in 1 cohort of patients with esophageal cancer (EC). BACKGROUND: Hematogenous tumor cell dissemination is a key event in tumor progression, and clinical significance of DTCs and CTCs are controversially discussed in the literature. However, evaluation of both biomarker in 1 patient's cohort has not been described before. METHODS: In this prospective, single-center study, 76 patients with preoperatively nonmetastatic staged EC were included. The CellSearch system was used to enumerate CTCs. Bone marrow was aspirated from the iliac crest and cells were enriched by Ficoll density gradient centrifugation. DTCs were immunostained with the pan-keratin antibody A45-B/B3. RESULTS: Fifteen of 76 patients (19.7%) harbored CTCs, whereas in 13 of 76 patients (17.1%), DTCs could be detected. In only 3 patients (3.9%), CTCs and DTCs were detected simultaneously, whereas concordant results (DTC/CTC negative and DTC/CTC positive) were found in 54 patients (71.1%). Surprisingly, only patients with CTCs showed significant shorter overall and relapse-free survival (P = 0.038 and P = 0.004, respectively). Multivariate analyses revealed that only the CTC status was an independent predictor of overall and relapse-free survival (P = 0.007 and P < 0.001, respectively). CONCLUSIONS: This is the first study analyzing CTC and DTC status in 1 cohort of nonmetastatic patients with EC. In this early disease stage, only the CTC status was an independent, prognostic marker suitable and easy to use for clinical staging of patients with EC.