Robotic versus transanal total mesorectal excision in sexual, anorectal, and urinary function: a multicenter, prospective, observational study.

PURPOSE: Improved long-term survival after low anterior resection (LAR) for rectal cancer highlights the importance of functional outcome. Urogenital and anorectal dysfunction is frequently reported after conventional LAR. Advanced minimally invasive techniques such as robotic (RoTME) and transanal total mesorectal excision (TaTME) might improve functional results by precisely dissecting and preserving autonomic nerves. We compared functional outcomes after RoTME or TaTME in a multicenter study. METHODS: One hundred twenty patients (55 RoTME/65 TaTME) were prospectively included in four participating centers. Anorectal (Wexner and low anterior resection syndrome (LARS) Score), urinary (International Consultation on Incontinence-Male/Female Lower Urinary Tract Symptoms Score (ICIQ-MLUTS/ICIQ-FLUTS) and International Prostate Symptom Scale (IPSS)), and sexual (International Index of Erectile Function (IIEF), Female Sexual Function Index (FSFI)) outcomes at 12 months after surgery were compared to preoperative scores. The response rate to the 1-year postoperative functional assessment by questionnaire was 79.5%. RESULTS: RoTME enabled better anorectal function compared to TaTME (LARS score 4.3 ± 2.2 vs. 9.8 ± 1.5, p = 0.038, respectively). TaTME proved superior at preserving male urinary function, while female urinary function was comparable in both groups, with only mild postoperative impairment (RoTME vs. TaTME, respectively: ICIQ-MLUTS 13.8 ± 4.9 vs. 1.8 ± 5.8, p = 0.038; ICIQ-FLUTS Incontinence Score - 0.3 ± 1.0 vs. - 0.2 ± 0.9, p = 0.844). Both techniques demonstrated comparable male (RoTME - 13.4 ± 2.7 vs. TaTME - 11.7 ± 3.4, p = 0.615) and female (RoTME 5.2 ± 4.6 vs. TaTME 10.5 ± 6.4, p = 0.254) sexual function. CONCLUSION: After adjustment for risk factors, RoTME provided better anorectal functional results, whereas TaTME was better at preserving male urinary function. Overall, both techniques demonstrated only mild postoperative functional impairment.

Liver surgery-specific complications are an independent factor influencing long-term survival following major hepatectomy.

BACKGROUND: A severity grading system for liver surgery-specific complications, given the acronym FABIB, has been standardized to increase the feasibility and comparability of academic reports in liver surgery. Whether the FABIB score is associated with long-term survival following major hepatectomy has not been previously investigated. METHODS: 297 consecutive patients who had undergone major hepatectomy between 2012 and 2019 were recruited. The postoperative complications were documented according to the FABIB system and, for comparison purposes, Clavien-Dindo classification. Their influence on 90-day mortality and long-term survival was analyzed retrospectively. RESULTS: Taking the relevant confounders into account, the FABIB score was a robust factor associated with long-term survival after major hepatectomy: patients with high FABIB scores (≥6) had a 2.415-fold higher risk of death compared to patients with low FABIB scores (≤2) (P = 0.002). In contrast to that, the Clavien-Dindo Classification (grade III + IV vs. grade I + II) was not associated with survival in our cohort (P = 0.873). CONCLUSION: Liver surgery-specific complications, measured by the FABIB system, impact long-term survival after major hepatectomy independent of relevant confounders. We propose the FABIB score as a composite endpoint for randomized controlled trials and a quality assessment tool in liver surgery.

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.

Surgical Treatment of Chronic Pancreatitis: The State of the Art.

Chronic pancreatitis is a common disease accompanied with considerable morbidity and mortality. Complications associated with chronic pancreatitis, such as pseudocysts, stenosis of adjacent anatomic structures or pain that cannot be managed conservatively, may be treatable surgically or interventionally by endoscopy. Surgery is superior to endoscopy in regard to long-term pain management. Duodenum preserving pancreatic resection is the surgical procedure of choice in patients with inflamed changes of the head of the pancreas. The best timing of surgery, the ideal standardized perioperative management are the focus of current research.

CD10 Expression Correlates with Earlier Tumour Stages and Left-Sided Tumour Location in Colorectal Cancer but Has No Prognostic Impact in a European Cohort.

The role of CD10 expression in colorectal cancer has been controversially discussed in the literature. Some data suggest a predictive capacity for lymph node and liver metastases, thus influencing overall survival (OS) and disease-free survival (DFS). This study aims to analyse the relationship between CD10 expression and overall survival (OS) in a European cohort. To determine the association of CD10 expression with tumour phenotype, molecular features, and prognosis, a tissue microarray of 1469 colorectal carcinomas was analysed using immunohistochemistry and was compared with matched clinicopathologic data. CD10 expression correlated with earlier tumour stages (p = 0.017) and left-sided colon cancer (p < 0.001). However, no correlation was found between CD10 expression and lymph node involvement (p = 0.711), tumour grading (p = 0.397), or overall survival (p = 0.562). Even in the subgroup analysis of tumour or nodal stage, CD10 did not affect overall survival, although it was significantly associated with p53 and nuclear ß-catenin expression (p = 0.013 and p < 0.001, respectively). CD10 expression correlates with earlier tumour stages, colon cancer location, and indicators of aggressive CRC subtypes. However, we can exclude CD10 as a relevant independent prognosticator for CRC.

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.

[Routine computed tomography body composition analysis-experience in intensive care patients]. / Routinecomputertomographie zur Analyse der Körperzusammensetzung ­ Erfahrungen bei Intensivpatient:innen.

The assessment of the nutritional status of patients in the intensive care unit is recommended in current guidelines and should include the assessment of muscle status. A suitable method is the analysis of routine computed tomography (CT) scans, which are frequently performed in critically ill patients. With the help of special software, individual CT slices are processed and various parameters such as muscle area, muscle density or even the percentage of adipose tissue are displayed and quantified. It has been shown that cross-sectional acquisition of skeletal muscle in the lumbar spine correlates very well with total body muscle. There are defined, albeit population-based, cut-off values that can be used to establish diagnosis of sarcopenia. Monitoring of individualized nutritional therapy can be accomplished by assessment of repetitive CT examinations. The steadily growing body of data confirms that the method can make a valuable contribution to the assessment of body composition in intensive care medicine. Most of the currently available software requires time-consuming processing of the CT. Automated programs, which are now occasionally available and eliminate the need for most manual processing, may make the method even more attractive in the future. Ultimately, the risk of intensive transport to the CT or radiation exposure may be only justified for medical indications. Nevertheless, whenever CT is available for medical reasons, it should also be exploited for composition analysis.

Socioeconomic Deprivation Is Not Associated with Outcomes after Esophagectomy at a German High-Volume Center.

In Germany, socioeconomically deprived citizens more often develop esophageal carcinoma, since typical risk factors follow the social gradient. Therefore, we hypothesized that socioeconomic deprivation might also be associated with advanced tumor stages and comorbidities at the time of surgery. As a consequence, socioeconomic deprivation may be related to postoperative complications and reduced overall survival. Therefore, 310 patients who had undergone esophagectomy for cancer in curative intent between 2012 and 2020 at the University Medical Center Hamburg-Eppendorf (UKE) were included in this study. Socioeconomic status (SES) was estimated using the purchasing power of patients' postal codes as a surrogate parameter. No association was found between SES and tumor stage or comorbidities at the time of surgery. Moreover, SES was neither associated with postoperative complications nor overall survival. In conclusion, socioeconomic inequalities of patients treated at a high-volume center do not affect treatment outcomes.

Muscle quality, not quantity, is associated with outcome after colorectal cancer surgery.

INTRODUCTION: Emerging evidence suggests that deconditioned patients benefit most from prehabilitation before colorectal cancer surgery. So far, selecting patients with poor muscle status and high perioperative risk remains challenging. Therefore, this study evaluates the potential of the CT-derived Skeletal Muscle Index (SMI), representing muscle mass, and of the Muscle Radiation Attenuation (MRA), a measure of muscle quality, for risk stratification in colorectal cancer patients. METHODS: In this retrospective, single-center observational study, 207 patients with resection of colorectal adenocarcinoma between January 2016 and December 2020 were included. The Charlson comorbidity index (CCI), postoperative complications, length of hospital stay, and survival were recorded. Data were analyzed using multivariable linear, logistic, and Cox proportional hazards regression models adjusted for age, sex, BMI, CCI, neoadjuvant therapy, tumor stage, and surgery type. RESULTS: An increase of the MRA was associated with fewer postoperative complications (anastomotic leakage and pneumonia) and lesser severity according to the Clavien-Dindo classification, shorter hospital stays, and prolonged survival (Hazard ratio: 0.63 [95%CI: 0.49-0.81], p < 0.001). No relevant associations were found between the SMI and postoperative complications, length of hospital stay, or survival. CONCLUSION: The easy-to-raise MRA serves as a more reliable tool than the SMI for identifying high-risk patients with poor muscle status before colorectal surgery. Those patients may benefit most from prehabilitation, which has to be proven in future interventional trials.

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.

Risk stratification of cirrhotic patients undergoing esophagectomy for esophageal cancer: A single-centre experience.

BACKGROUND: Concomitant liver cirrhosis is a crucial risk factor for major surgeries. However, only few data are available concerning cirrhotic patients requiring esophagectomy for malignant disease. METHODS: From a prospectively maintained database of esophageal cancer patients, who underwent curative esophagectomy between 01/2012 and 01/2016, patients with concomitant liver cirrhosis (liver-cirrhotic patients, LCP) were compared to non-liver-cirrhotic patients (NLCP). RESULTS: Of 170 patients, 14 cirrhotic patients with predominately low MELD scores (≤ 9, 64.3%) were identified. Perioperative outcome was significantly worse for LCP, as proofed by 30-day (57.1% vs. 7.7, p<0.001) and 90-day mortality (64.3% vs. 9.6%, p<0.001), anastomotic leakage rate (64.3 vs. 22.3%, p = 0.002) and sepsis (57.1 vs. 21.5%, p = 0.006). Even after adjustment for age, gender, comorbidities, and surgical approach, LCP revealed higher odds for 30-day and 90-day mortality compared to NLCP. Moreover, 5-year survival analysis showed a significantly poorer long-term outcome of LCP (p = 0.023). For risk stratification, none of the common cirrhosis scores proved prognostic impact, whereas components as Bilirubin (auROC 94.4%), INR (auROC = 90.0%), and preoperative ascites (p = 0.038) correlated significantly with the perioperative outcome. CONCLUSION: Curative esophagectomy for cirrhotic patients is associated with a dismal prognosis and should be evaluated critically. While MELD and Child score failed to predict perioperative mortality, Bilirubin and INR proofed excellent prognostic capacity in this cohort.

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.

Importance of computed tomography muscle quality and continuous versus cut-off-based sarcopenia detection in major hepatic surgery.

Background: The role of the computed tomography (CT)-derived skeletal muscle index (SMI) as a parameter of muscle quantity on the outcome after major liver resection remains contradictory and that of the muscle radiodensity attenuation (MRA) as a parameter of muscle quality has not been sufficiently evaluated. This observational study aimed to investigate the influence of metric SMI and MRA values and cut-off-based CT sarcopenia detection on liver-surgery specific complications measured by the new FABIB (liver failure, ascites, biliary leakage, infection, bleeding) score and survival after hemihepatectomy. Methods: A total of 183 patients with major hepatectomy were retrospectively included. The SMI and MRA were determined from the abdominal muscle area of preoperative CT scans. Patients were classified as sarcopenic by the SMI and MRA cut-off values of Prado et al., Martin et al., and van der Werf et al. Postoperative complications were documented according to the Clavien-Dindo classification and FABIB score. The relation of the continuous, non-categoric SMI and MRA values and of the cut-off-based sarcopenia detection to the postoperative complications and survival was analyzed by multivariable linear, logistic, and Cox proportional hazards regression. Results: A higher MRA was associated with less severe postoperative complications in the Clavien-Dindo [-0.59 (95% CI: -0.95 to -0.23), P=0.002] and the FABIB score [-0.65 (95% CI: -1.19 to -0.12), P=0.017]. An increase of the SMI did not result in less severe complications in the Clavien-Dindo [0.14 (95% CI: -0.27 to 0.55), P=0.503] or FABIB score [0.17 (95% CI: -0.42 to 0.76), P=0.572]. For patients classified as sarcopenic by the cut-off-based systems no relevant relation to postoperative complications was found. Overall survival was better for a higher MRA [hazard ratio (HR): 0.75 (95% CI: 0.58-0.97), P=0.029], as long-term survival was for a higher SMI [HR: 0.68 (95% CI: 0.47-0.96), P=0.031]. Only below van der Werf's MRA cut-off the probability of overall and long-term survival was reduced [HR: 2.32 (95% CI: 1.18-4.54), P=0.015; 2.68 (95% CI: 1.25-5.74), P=0.011]. Conclusions: The MRA has a stronger influence on complications in the Clavien-Dindo classification and the liver-surgery specific FABIB score than the SMI. Continuous, non-categoric MRA and SMI values are superior to cut-off-based systems in predicting the outcome after major hepatic surgery.

Are muscle parameters obtained by computed tomography associated with outcome after esophagectomy for cancer?

BACKGROUND & AIMS: Esophageal cancer patients often suffer from cancer-related malnutrition and, as a result, sarcopenia. Whether sarcopenia worsens the outcome after esophagectomy is unclear. Inconsistent study results are partly caused by varying cut-off values used for defining sarcopenia. To overcome this challenge, a new statistical approach is proposed in this study: analyzing the linear association of computer tomography derived muscle parameters with important clinical short- and long-term outcomes post esophagectomy, regardless of cut-offs. METHODS: Skeletal muscle index (SMI), quantifying muscle mass, was assessed with computed tomography (CT) in 98 patients undergoing esophagectomy. Muscle radiation attenuation (MRA) was measured to evaluate muscle quality. To evaluate the influence of the SMI and MRA on post-surgery complications, logistic regression models were used. To analyze the relationship of lengths of stay to muscle parameters, the competing risk approach introduced by Fine and Gray was applied. For survival analysis, log-rank test and Cox proportional hazards regression modeling were used. RESULTS: Neither a relevant association of SMI nor MRA with pneumonia and esophagoenteric leak were observed. Furthermore, no relevant association to lengths of stay in intensive care or hospital were detected. If the SMI increased, the odds for pleural effusion and pleural empyema decreased, but the odds of a pulmonary embolism increased. Univariate, unadjusted long-term survival analysis revealed that lower MRA and lower SMI were associated with shorter survival (P = 0.03). However, if the analysis was adjusted for confounders, e.g., Charlson Comorbidity Index, no relevant association regarding long-term survival was detected. CONCLUSION: Consequently, poor muscle status, determined by CT imaging, does not justify denying a patient an oncologic resection. The Charlson Comorbidity Index, however, was superior for preoperative risk stratification.

Integrin alpha-V is an important driver in pancreatic adenocarcinoma progression.

BACKGROUND: Mesothelial E- and P-selectins substantially mediate the intraperitoneal spread of Pancreatic ductal adenocarcinoma (PDA) cells in xenograft models. In the absence of selectins in the host, the integrin subunit alpha-V (ITGAV, CD51) was upregulated in the remaining metastatic deposits. Here we present the first experimental study to investigate if ITGAV plays a functional role in PDA tumor growth and progression with a particular focus on intraperitoneal carcinomatosis. METHODS: Knockdown of ITGAV was generated using an RNA interference-mediated approach in two PDA cell lines. Tumor growth, intraperitoneal and distant metastasis were analyzed in a xenograft model. Cell lines were characterized in vitro. Gene expression of the xenograft tumors was analyzed. Patient samples were histologically classified and associations to survival were evaluated. RESULTS: The knockdown of ITGAV in PDA cells strongly reduces primary tumor growth, peritoneal carcinomatosis and spontaneous pulmonary metastasis. ITGAV activates latent TGF-ß and thereby drives epithelial-mesenchymal transition. Combined depletion of ITGAV on the tumor cells and E- and P-selectins in the tumor-host synergistically almost abolishes intraperitoneal spread. Accordingly, high expression of ITGAV in PDA cells was associated with reduced survival in patients. CONCLUSION: Combined depletion of ITGAV in PDA cells and E- and P-selectins in host mice massively suppresses intraperitoneal carcinomatosis of PDA cells xenografted into immunodeficient mice, confirming the hypothesis of a partly redundant adhesion cascade of metastasizing cancer cells. Our data strongly encourage developing novel therapeutic approaches for the combined targeting of E- and P-selectins and ITGAV in PDA.

Robotic rectal resection preserves anorectal function: Systematic review and meta-analysis.

BACKGROUND: Improving survival rates in rectal cancer patients has generated a growing interest in functional outcomes after total mesorectal excision (TME). The well-established low anterior resection syndrome (LARS) score assesses postoperative anorectal impairment after TME. Our meta-analysis is the first to compare bowel function after open, laparoscopic, transanal, and robotic TME. METHODS: All studies reporting functional outcomes after rectal cancer surgery (LARS score) were included, and were compared with a consecutive series of robotic TME (n = 48). RESULTS: Thirty-two publications were identified, including 5 565 patients. Anorectal function recovered significantly better within one year after robotic TME (3.8 [95%CI -9.709-17.309]) versus laparoscopic TME (26.4 [95%CI 19.524-33.286]), p = 0.006), open TME (26.0 [95%CI 24.338-29.702], p = 0.002) and transanal TME (27.9 [95%CI 22.127-33.669], p = 0.003). CONCLUSIONS: Robotic TME enables better recovery of anorectal function compared to other techniques. Further prospective, high-quality studies are needed to confirm the benefits of robotic surgery.

Clinical Significance of Circulating Tumor Cells in Gastrointestinal Carcinomas.

The idea of a liquid biopsy to screen, surveil and treat cancer patients is an intensively discussed and highly awaited tool in the field of oncology. Despite intensive research in this field, the clinical application has not been implemented yet and further research has to be conducted. However, one component of the liquid biopsy is circulating tumor cells (CTCs) whose potential for clinical application is evaluated in the following. CTCs can shed from primary tumors to the peripheral blood at any time point during the progress of a malignant disease. Following, one single CTC can be the origin for distant metastasis at later cancer stage. Thus, CTCs have great potential to either be used in cancer diagnostics and patient stratification or to function as a target for new therapeutic approaches to stop tumor dissemination and metastasis at the very early beginning. Due to the biological fundamental role of CTCs in tumor progression, here, we provide an overview of CTCs in gastrointestinal cancers and their potential use in the clinical setting. In particular, we discuss the usage of CTC for screening and stratifying patients' risk. Moreover, we will discuss the potential role of CTCs for treatment specification and treatment monitoring.

Serum Midkine is a clinical significant biomarker for colorectal cancer and associated with poor survival.

Colorectal carcinoma (CRC) is one of the most common carcinomas worldwide. Early detection is crucial for reducing morbidity and mortality. Several promising studies described the use of midkine (MK) as a tumor marker. This study aimed to investigate a larger collective to ascertain if the preoperative serum midkine level (S-MK) is suitable as a marker for screening and if S-MK correlates with tumor progression and localization. It was also investigated for the first time whether patients with high S-MK show poor survival. This prospective single-center study included 299 patients with CRC. The preoperative serum midkine level (S-MK) was determined using ELISA. Established tumor markers Carcinoembryonic antigen (CEA) and Carbohydrate antigen 19-9 (CA 19-9) were collected for comparison. The median follow-up period was 65 months. S-MK was significantly elevated in patients with CRC (P < .001). The receiver operation characteristic (ROC) curve has an area under the curve (AUC) of 0.868 (P < .001). A cut-off value of 56.42 pg/mL results in a sensitivity of 84.3% and a specificity of 75.4%. In the one-way analysis of variance (ANOVA), there were no significant correlations between S-MK and tumor progression, localization. Furthermore, no significant correlation to CEA und CA 19-9 could be found. Kaplan-Meier survival analysis was able to show for the first time that patients with S-MK of more than 225 pg/mL have a significantly shorter survival. Multivariate Cox regression showed that only CEA was an independent prognostic factor for survival. S-MK helps estimate the prognosis for CRC and is a valuable component for developing a multimarker panel for screening and surveillance.

Increase of CD45-positive Immune Cells in Liver Parenchyma Indicates a More Favorable Prognosis for Patients With Barrett's Cancer.

BACKGROUND: Despite advances in perioperative management, the 5-year survival rate of patients with esophageal adenocarcinoma (Barrett's cancer) is poor. Adjuvant immunotherapies are currently the subject of clinical trials. The prognostic role of tumor-infiltrating T-lymphocytes (TILs) expressing CD45 has only been investigated in primary tumors. The significance of TILs in the target organs of distant metastases, in particular the liver, is unclear. This study examined the influence of CD45-positive cells in liver parenchyma and primary tumors on cumulative survival. MATERIALS AND METHODS: The density of CD45-positive cells was analyzed immunohistochemically using tissue microarrays. Sixty-five patients for whom a liver biopsy was available in addition to the primary tumor were included in the study. Liver metastases were found in 21 patients. The results of the immunohistochemical analysis were correlated with patient's outcomes. The Cox proportional hazard model was used to compute mortality hazard ratio in consideration of clinical variables. RESULTS: Elevated density of CD45-positive cells in the liver biopsy corresponded with a better cumulative survival rate (p<0.001), while no significant differences were found for primary tumors. Multivariate Cox regression analysis showed that a high density of CD45-positive cells in the liver parenchyma was an independent prognostic parameter of longer overall survival (hazard ratio(HR)=0.432, p=0.048). CONCLUSION: The density of CD45-positive cells in the liver parenchyma is an easily measured prognostic biomarker that can identify patient subgroups with a better prognosis. In addition, the density of CD45-positive cells in the liver may assist as a criterion for selecting patients with a high potential for response to adjuvant immunotherapy.