Prevalence and long-term implications of preoperative anemia in patients undergoing elective general surgery: a retrospective cohort study at a university hospital.

OBJECTIVE: The aim of this retrospective study was to assess the prevalence of anaemia in a cohort of patients undergoing elective general surgery at a university hospital. Furthermore, the authors investigated the influence of anaemia on short-term and long-term postoperative outcome. BACKGROUND: Awareness of the negative impact of preoperative anaemia on perioperative morbidity and mortality is rising. Anaemia is a potentially modifiable factor, and its therapy might improve patient outcome in elective surgery. Nevertheless, patients with preoperative anaemia frequently undergo elective surgery without receiving adequate preoperative treatment. METHODS: In this single-centre cohort study, the authors analyzed 6908 adult patients who underwent elective general surgery. Patients undergoing day-clinic surgery were excluded. In all patients, preoperative haemoglobin concentration and haematocrit was available. RESULTS: Of all patients analyzed, 32.9% were anaemic (21.0% mild, 11.8% moderate, 1.1% severe). Median time to last follow-up was 5.2 years. During the whole study period, 27.1% of patients died (1.2% died during the hospital stay); median time to death was 1.3 years. Patients with preoperative anaemia had significantly higher mortality rates ( P <0.001) and a higher probability of postoperative complications ( P <0.001). Likewise, receiving blood transfusions was associated with a higher risk of death ( P <0.001). CONCLUSION: This retrospective single-centre analysis confirmed that preoperative anaemia is common, and is a significant risk factor for unfavourable postoperative outcome. As anaemia is a modifiable risk factor, the implementation of a patient blood management concept is crucial to reduce detrimental postoperative events associated with anaemia.

Meeting actual benchmarks for short- and long-term outcomes after cytoreductive surgery for peritoneal surface malignancy at a newly established academic treatment center.

BACKGROUND: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy is a curative treatment for selected patients with peritoneal surface malignancy. Reaching actual outcomes benchmarks is challenging given the complex nature of peritoneal surface malignancy surgery. The aim of this study was to assess how the benchmarks for morbidity and oncologic outcome can be reached at a newly established program for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. METHODS: Building on existing institutional experience in complex abdominal surgery and interdisciplinary ovarian cancer treatment, a peritoneal surface malignancy center for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy was established at the Medical University of Vienna using a structured mentoring process. This is a retrospective analysis of the first 100 consecutive patients. Morbidity and mortality were assessed using the Clavien-Dindo classification, and oncologic outcomes using overall survival. RESULTS: Major morbidity and mortality were 26% and 3%, and median overall survival was 49.0 months. In patients with colorectal peritoneal metastases, the median overall survival was 35.1 months (all colorectal peritoneal metastases patients) and 48.8 months in the subgroup with Peritoneal Surface Disease Severity Score ≤3. No median overall survival could be calculated in patients with low-grade appendiceal mucinous neoplasms, appendiceal adenocarcinoma, or peritoneal mesothelioma due to >50% of patients being alive at the end of follow-up. CONCLUSION: We show that the current morbidity and oncological outcomes benchmarks can be reached within the first 100 cases of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy at a newly established peritoneal surface malignancy center. Previous institutional experience in complex abdominal surgery and a structured mentoring process are key factors in achieving this goal.

Heparin-induced thrombocytopaenia diagnostic testing after adult cardiac surgery: a single-centre experience and development.

OBJECTIVES: To assess the incidence and outcome of heparin-induced thrombocytopaenia (HIT) in patients after cardiac surgery on cardiopulmonary bypass (CPB) and to review the time course of platelet counts and the use of different immunological diagnostic tests. METHODS: All patients ≥18 years of age who underwent CPB from 2006 to 2015 and who were postoperatively admitted to our cardiac intensive care unit (ICU) were included in this retrospective study. Screening for heparin/platelet factor-4 antibodies was performed using an antibody test, which was later replaced with a screening test specific for IgG antibodies without IgA/IgM cross-reactivity. The enzyme immunoassay (EIA) for the detection of antibodies of all immunoglobulin classes against heparin/PF4 complexes was replaced with an IgG-specific EIA. HIT was confirmed by a heparin-induced platelet aggregation test until 2014. RESULTS: Among 4978 patients admitted between 2006 and 2015, 539 (11%) patients were evaluated for HIT. Patients were excluded because of age <18 years (n = 9), non-cardiac surgery without CPB (n = 10) or incomplete data (n = 3). Of the remaining 517 patients, 43 (8.3%) patients were HIT-positive. HIT incidence was 0.86%. The proportion of HIT-positive patients was similar in men and women (8.4% and 8.2%, respectively). Men and women with suspected HIT also had similar in-hospital mortality (odds ratio ≈ 1; P = 0.926). CONCLUSIONS: The incidence of HIT was lower in our study than previously reported. Novel immunological tests have improved to specifically detect IgG antibodies. Furthermore, they are able to detect anti-protamine antibodies, which may be present in patients with high clinical probability of testing negative for HIT. Incidence and clinical relevance of heparin/protamine antibodies will be subjects of future investigation.

TP53 is not a prognostic marker-clinical consequences of a generally disregarded fact.

Technological progress within the last 15-20 years has significantly increased our knowledge about the molecular basis of cancer development, tumor progression, and treatment response. As a consequence, a vast number of biomarkers have been proposed, but only a small fraction of them have found their way into clinical use. The aim of this paper is to describe the specific demands a clinically relevant biomarker should meet and how biomarkers can be tested stepwise. We name this procedure the "triple-R principle": robustness, reproducibility, and relevance. The usefulness of this principle is illustrated with the marker TP53. Since it is mutated in a broad spectrum of cancer entities, TP53 can be considered a very promising marker. Thus, TP53 has been studied in detail but there is still no explicit consensus about its clinical value. By considering our own experience and reviewing the literature, we demonstrate that a major problem of current biomarker research is disregard of whether the biomarker is prognostic or predictive. As an example, it is demonstrated that TP53 is not a prognostic marker, but rather a purely predictive marker, and that disregard of this fact has made this otherwise strong biomarker appear as not being clinically useful so far.

Circulating cell-free DNA in plasma of colorectal cancer patients - A potential biomarker for tumor burden.

BACKGROUND: Measurement of cell-free DNA (cfDNA) in plasma - the so called liquid biopsy - is a novel method for early detection of cancer. Necrotic cancer cells release various DNA fragments that can be detected in plasma or serum. The aim of our study was to investigate the concentration of circulating ALU115, LINE79 and LINE297 fragments in plasma from venous and arterial blood of colorectal cancer (CRC) patients before, during and 5 days after surgical intervention. PATIENTS AND METHODS: Thirty patients (16 female, 14 male, median age 56 years), undergoing surgery for colorectal and appendix cancer, and 17 healthy volunteers were included in this study. Plasma samples were collected from patients and healthy individuals. Qualitative polymerase chain reaction (PCR) and quantitative real-time PCR analyses were conducted using specific primers for ALU115, LINE79 and LINE297. RESULTS: The concentration of ALU115 was significantly increased in plasma of CRC patients compared to the control group (p = 0.002). Interestingly, the concentration of LINE297 was significantly higher in healthy individuals than patients (p = 0.031). We did not find any difference regarding LINE79 between the two groups (p = 0.893). The total cfDNA concentration was slightly increased in plasma after the surgery (p < 0.056), however, the difference was not significant. Interestingly, no correlation was detected between the peritoneal carcinosis index (PCI) and conventional tumor markers. CONCLUSION: According to our results, the concentration of ALU115 in cfDNA could be a potential biomarker for diagnosis of CRC. LINE79 or the conventional tumor markers CEA or CA19-9 do not seem useful for the detection of malignant tumors. Whether the amount of LINE297 in cfDNA represents a reliable biomarker for early diagnosis has yet to be confirmed.

Influence of multiple stapler firings used for rectal division on colorectal anastomotic leak rate.

BACKGROUND: Anastomotic leakage following colorectal resection remains one of the most significant complications with relevant morbidity and mortality. There is evidence that a higher number of stapler firings for rectal division can affect the leak rate in double stapling anastomosis. However, there are no data concerning compression anastomosis. We present our institutional experience addressing this issue. DESIGN: This is a retrospective review of a prospective institutional database of patients undergoing colonic and rectal resection for benign and malignant indications between January 2008 and December 2014 at the surgical department of the St. John of God Hospital, Vienna. Inclusion criteria were rectal division with linear stapling devices and construction of anastomosis to the rectal stump using a circular stapler or compression device. RESULTS: Three hundred eighty two (196 female; 51.3%) patients were included. Mean age was 65.8 years (range: 18-95) Indications for the operation included diverticular disease (44.8%), colorectal carcinoma (51.6%), inflammatory bowel disease (1.8%), and adenoma (1.8%). A laparoscopic approach was employed in 334 cases (87.4%); in 170 patients (44.9%), a compression anastomosis was created. One, two, and three or more stapler cartridges were used for rectal division in 58.4, 33.5, and 8.1%, respectively. Male gender, neoadjuvant therapy, rectal cancer as an underlying disease, laparoscopic surgical approach, and duration of operation longer than 200 min are leading causes for the usage of more than one stapler cartridge. Overall leak rate was 4.7% (18/382). The only factor associated with the occurrence of leakage was the use of three or more stapler cartridges for the closure of the rectal stump (p = 0.002). CONCLUSION: Our data support that multiple stapler firings for rectal division following colorectal resection has a major impact on anastomotic leak rate. Especially in laparoscopic surgery efforts should be made to minimize the number of stapler cartridges used.

Epithelial splicing regulatory protein 1 and 2 paralogues correlate with splice signatures and favorable outcome in human colorectal cancer.

ESRPs are master splice regulators implicated in alternative mRNA splicing programs important for epithelial-mesenchymal transition (EMT) and tumor progression. ESRP1 was identified in some tumors as good or worse predictor of outcome, but in colorectal cancer (CRC) the prognostic value of ESRPs and relation with mesenchymal splice variants is not clear. Here, we studied 68 CRC cases, compared tissue expression of ESRPs with clinical data and with EMT gene splice patterns of conditional CRC cells with deficient ESRP1 expression.Around 72% of patients showed global decreased transcript expression of both ESRPs in tumor as compared to matched non-neoplastic colorectal epithelium. Reduction of ESRP1 in tumor cells was evaluated by immunohistochemistry, associated with microsatellite stability and switch to mesenchymal splice signatures of FGFRs, CD44, ENAH and CTNND1(p120-catenin). Expression of ESRPs was significantly associated with favorable overall survival (log-rank test, P=0.0186 and 0.0408), better than prognostic stratification by tumor staging; and for ESRP1 confirmed with second TCGA cohort (log-rank test, P=0.0435). Prognostic value is independent of the pathological stage and microsatellite instability (ESRP1: HR=0.36, 95%CI 0.15-0.91, P=0.032; ESRP2: HR=0.23, 95%CI 0.08-0.65, P=0.006).Our study supports the role of ESRP1 as tumor suppressor and strongly suggests that ESRPs are candidate markers for early detection, diagnosis, and prognosis of CRC.

Constipation is not associated with diverticular disease - Analysis of 976 patients.

BACKGROUND: In the light of controversial data in the literature, the present study was designed to evaluate potential associations between colonic diverticular disease, constipation and quality of life. DESIGN: We prospectively enrolled 976 consecutive patients, who participated in the nationwide colorectal cancer screening program in four medical centers between 2008 and 2009. All patients underwent full colonoscopy and completed a standardized questionnaire. The severity of constipation was assessed by the validated Wexner constipation score. Quality of Life (QOL) was evaluated by the SF-12 health score. RESULTS: The median age was 62 years (range 22-90) and the male to female ratio was 1:1. Colonic diverticular disease was found in 290 participants (30%). Age, body mass index and diabetes mellitus were significantly associated with the presence of diverticular disease (p < 0.0001, p = 0.0007 and p = 0.0178). The median constipation score in patients with diverticular disease was 3 (range 0-18), and comparable to patients without diverticula (p = 0.1073). The physical component summary of the SF-12 was significantly reduced in patients with diverticular disease (p = 0.0038). CONCLUSION: This large population based study revealed no association between colonic diverticular disease and constipation. Notably, the presence of diverticular disease significantly impacts quality of life.

Anastomotic leakage after low anterior resection for rectal cancer: comparison of stapled versus compression anastomosis.

PURPOSE: Surgical technique and perioperative management in rectal cancer surgery have been substantially improved and standardized during the last decades. However, anastomotic leakage following low anterior resection still is a significant problem. Based on animal experimental data of improved healing of compression anastomosis, we hypothesized that a compression anastomotic device might improve healing rates of the highest-risk anastomoses. METHODS: All low anterior resections for rectal cancer performed or directly supervised by the senior author between January 2004 and June 2012 were analyzed. Only patients with a stapled or compression anastomosis located within 6 cm from the anal verge were included. Until December 2008, circular staplers were employed, while since January 2009, a novel compression anastomotic device was used for rectal reconstruction exclusively. RESULTS: Out of 197 patients operated for rectal cancer, a total of 96 (34 females, 35.4 %) fulfilled inclusion criteria. Fifty-eight (60.4 %) were reconstructed with circular staplers and 38 (39.6 %) using a compression anastomotic device. Significantly, more laparoscopic procedures were recorded in the compression anastomosis group, but distribution of gender, age, body mass index, American Society of Anaesthesiologists score, rate of preoperative radiotherapy, tumor staging, or stoma diversion rate were similar. Anastomotic leakage was observed in seven cases (7/58, 12.1 %) in the stapled and twice (2/38, 5.3 %) in the compression anastomosis group (p = 0.26). CONCLUSIONS: In this series, rectal reconstruction following low anterior resection using a novel compression anastomotic device was safe and (at least) equally effective compared to traditional circular staplers concerning leak rate.