Anti-tumorigenic Effects of Emodin and Its' Homologue BTB14431 on Vascularized Colonic Cancer in a Rat Model.

OBJECTIVE: New drugs for cancer treatment are being sought worldwide. Therapeutic agents derived from natural substances can provide cost-efficient options. We evaluated the effect of emodin, an active natural anthraquinone derivate, and it's in-silico homologue the novel substance BTB14431 in vivo. METHOD: CC-531 colon cancer cells were implanted intraperitoneal (ip) and subcutaneous (sc) in 100 WAG/Rij rats. 28 days after tumor cell implantation, solid cancers were treated for 7 days by varying doses of BTB14431 (0.3 mg/kg body weight; 1.7 mg/kg) or emodin (2.5 mg/kg; 5 mg/kg). Treatment was applied either via an intravenous (iv) port catheter or by ip injection. Saline solution served as control. 21 days after final dose all animals were euthanized and ip tumor weight, sc tumor weight and animal body weight (bw) were determined by autopsy. Significant lower total tumor weight occurred after iv treatment with low dose BTB14431 (6.8 g; 90% confidence interval (CI) 5.3 - 8.2 g; p ≤ 0.01) and also low and high concentrations of emodin (9.4 g; CI 7.9 - 10.7 g; p ≤ 0.01 and 8.3 g; CI 7.6 - 9.3; p ≤ 0.01). Iv treatment by high dose BTB14431 did not lead to a decline in tumor weight. High dose ip treatment by emodin led to a lower overall (11.1 g; CI 10.1 - 13.8 g; p ≤ 0.01) and ip tumor weight (8.6 g; CI 6 - 10.4 g; p ≤ 0.01). Sc tumor weight was not affected. All other ip treatments did not result in changes of combined, ip or sc tumor weight. Bw decreased during iv treatment in all animals and increased after treatment was completed. Regain of bw was stronger in animals receiving low dose emodin. CONCLUSION: Our study shows promising anti-cancer properties of BTB14431 and supports the evidence regarding emodin as a natural antitumorigenic agent. Optimal dosing of iv emodin and especially BTB 14431 for maximal efficacy remains unclear and should be a subject of further research. 
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Complications After Ostomy Surgery: Emergencies and Obese Patients are at Risk-Data from the Berlin OStomy Study (BOSS).

BACKGROUND: Complications are common after ostomy surgery. Data from the Berlin OStomy Study were evaluated to determine risk factors for complications. PATIENTS AND METHODS: Patients with a bowel ostomy were questioned using a questionnaire concerning patients' characteristics and history as well as the ostomy and its complications. The questionnaire also contained a nine-fielded abdominal sketch to determine the exact ostomy location. RESULTS: Over 42 months, 2647 patients completed the questionnaire. Obese patients and patients after emergency surgery were more prone to ostomy-related complications. This result was independent of the kind of ostomy (small bowel ostomy or colostomy) and of the abdominal location. The overall ostomy complication rate was 55.6%. CONCLUSION: Significantly more complications were recorded after emergency surgery and in obese patients than after elective surgery and in non-obese patients, respectively. There was no preferential abdominal location for avoiding general ostomy complications. The results emphasized the importance of preoperative ostomy site marking by qualified personnel such as ostomy nurses or surgeons to reduce complication rates by respecting individual abdominal configurations. With an increasing prevalence of obesity, ostomy surgery will become even more challenging in the future. A division of the abdominal wall into nine regions might be helpful and more precise for describing and examining ostomy-related complications in the future.

Dose-dependent role of novel agents emodin and BTB14431 in colonic cancer treatment in rats.

BACKGROUND: BTB14431 is an in silico homolog to emodin. Both were found to possess anti-tumor effects in vitro. The aim of this work was to analyze the tumor suppressing effects of both molecules in an intraperitoneal (ip) and intravenous (iv) treated rat model (WAG-Rij). METHODS: A tumor cell suspension (CC531) was applied at the cecum after laparotomy and at the back. The rats where treated twice a day over 1 week with BTB14431, emodin and isotone sodium chloride solution (control). Treatment was applied iv or ip in a variety of dosages. Peripheral blood samples were taken before tumor application and on day 7. Twenty-one days after the last day of therapy animals were euthanized and tumor growth was evaluated. RESULTS: Data showed an insignificant decrease of tumor growth after iv and ip treatment with low doses of BTB14431 and emodin. Differential blood analysis showed apoptosis. Increased doses of emodin clearly raised mortality rate. CONCLUSIONS: Apoptosis was verified but no tumor-suppressing effects could be observed for iv and ip treatment with both agents in contrast to in vitro studies in our model. Establishing a successful ip treatment model for emotion and BTB14331 requires further studies.

Quantity-guided drain management reduces seroma formation and wound infections after radical lymph node dissection: results of a comparative observational study of 374 melanoma patients.

BACKGROUND: Lymphatic fistulas are common complications after lymph node dissections in melanoma patients. We investigated whether drain management could improve the patient's outcome. METHODS: Patients who underwent axillary or inguinal lymph node dissection (RALND or RILND) for malignant melanoma were recorded in a prospective database. Two different methods of drain management were compared. Either the drain was removed no later than the eighth postoperative day (period I, 2003-2007) or it was left in place until fluid flow was below 50 ml in 24 h for two consecutive days (period II, 2008-2011). The main outcome criterion was the incidence of seroma punctures after drain removal. RESULTS: 374 patients were analysed. The incidence of seroma punctures significantly decreased in period II. The number of patients with elevated lymphatic secretions rose by 41.3% (RALND) and 38.1% (RILND). With the exception of lymphatic fistulas, we observed significantly more local complications with need for treatment in period I (n = 104, 52%) than in period II (n = 31, 18%). In period II, the hospital stays after both procedures were significantly reduced. CONCLUSIONS: We conclude that quantity-guided drain management leads to a prolonged interval of drainage but is associated with a lower incidence of seroma formation and shorter hospital stay.

Quality of life and need for care in patients with an ostomy: a survey of 2647 patients of the Berlin OStomy-Study (BOSS).

BACKGROUND: Although ostomies are sometimes necessary, it is unclear which type of ostomy is advantageous for quality of life (QoL). In an observational study of 2647 patients, QoL after colostomy (CS) and small bowel stoma (SBS) formation was evaluated. METHODS: The European Organisation for Research and Treatment of Cancer (EORTC)-QLQ-C30 and CR-38 questionnaires were used. Patient characteristics, retrospective information about the ostomy and previous treatments, and current stoma-related complications were recorded. All questionnaires were distributed and collected by stoma therapists at the homecare company PubliCare®. RESULTS: In all, 1790 patients had a CS, and 756 had an SBS. The mean Global Health Score (mGHS-a general QoL indicator) was 52.33 in CS and 49.40 in SBS patients (p = 0.004), but the effect size (Cohen's d) was 0.1. In SBS patients, all functional scores were lower and most of the symptom scores were higher. CONCLUSIONS: QoL differed significantly for CS and SBS patients, but the effect size was marginal. The care of certain patient groups, particularly (female) patients who receive emergency surgeries, must be improved. More professional education and guidance are necessary for a larger proportion of patients. This survey provided reference data for quality of life in patients with an ostomy.

Effects of psychological interventions and patients' affect on short-term quality of life in patients undergoing colorectal surgery.

Psychological interventions can improve Quality of Life (QoL). Object of interest was if different psychological interventions influence short-term QoL after colonic resection for carcinoma. Furthermore, we wanted to see if there is a correlation between patients` preoperative affect and postoperative QoL. Sixty patients that underwent colorectal surgery were divided into three groups. Group one (n = 20) received Guided Imagery and group 2 (n = 22) Progressive Muscle Relaxation. The third group (Control, n = 18) had no intervention. Quality of Life (QoL) was measured using the EORTC QLQ-C30 and the Gastrointestinal Quality of life Index (GIQLI). Patients' affect was measured by the PANAS questionnaire. The higher the preoperative Negative Affect was, the lower were the scores for QoL on the 30th postoperative day. Patients' QoL was highest preoperatively and lowest on the third postoperative day. On the 30th postoperative day scores for QoL were almost as high as preoperative without difference between the three groups. Neither Guided Imagery nor Progressive Relaxation was influencing short-term QoL measured by the EORTC QLQ-C30 and the GIQLI questionnaire after colorectal surgery for cancer. Screening patients' with the PANAS questionnaire might help to identify individuals that are more likely to have a worse QoL postoperatively.

Mapping and confirmation of a major left ventricular mass QTL on rat chromosome 1 by contrasting SHRSP and F344 rats.

An abnormal increase in left ventricular (LV) mass, i.e., LV hypertrophy (LVH), represents an important target organ damage in arterial hypertension and has been associated with poor clinical outcome. Genetic factors are contributing to variation in LV mass in addition to blood pressure and other factors such as dietary salt intake. We set out to map quantitative trait loci (QTL) for LV mass by comparing the spontaneously hypertensive stroke-prone (SHRSP) rat with LVH and normotensive Fischer rats (F344) with contrasting low LV mass. To this end we performed a genome-wide QTL mapping analysis in 232 F2 animals derived from SHRSP and F344 exposed to high-salt (4% in chow) intake for 8 wk. We mapped one major QTL for LV mass on rat chromosome 1 (RNO1) that demonstrated strong linkage (peak logarithm of odds score 8.4) to relative LV weight (RLVW) and accounted for ∼19% of the variance of this phenotype in F2 rats. We therefore generated a consomic SHRSP-1(F344) strain in which RNO1 from F344 was introgressed into the SHRSP background. Consomic and SHRSP animals showed similar blood pressures during conventional intra-arterial measurements, while RLVW was already significantly lower (-17.7%, P<0.05) in SHRSP-1(F344) in response to a normal-salt diet; a similar significant reduction of LV mass was also observed in consomic rats after high-salt intake (P<0.05 vs. SHRSP). Thus, a major QTL on RNO1 was confirmed with significant impact on LV mass in the hypertensive background of SHRSP.

Thoracoscopic resection of a combined esophageal leiomyoma and diverticulum: a case report.

We report the case of a 66-year-old male patient with a combined esophageal leiomyoma and diverticulum. On account of the low incidence, there is little literature available with regard to the management of those conditions. Our patient underwent a simultaneous thoracoscopic enucleation of the leiomyoma and resection of the diverticulum. Though endoscopic enucleations of myoma and resections of diverticula have been described earlier, to our knowledge, we are the first, who performed those procedures in a single operation, which seems to be feasible and safe.

Continuous local analgesic therapy reduces pain after radical inguinal/iliacal lymph node dissection.

BACKGROUND: To optimize postoperative pain therapy after a radical inguinal/iliacal lymph node dissection (RILND), we investigated the influence of a continuous application of a local anaesthetic via a subfascial wound catheter in the abdominal wall in addition to a standardized systemic analgesia. MATERIALS AND METHODS: Between July 2007 and December 2009, 50 patients with stage III/IV of melanoma disease received, in an observational study, a systemic analgesic therapy. Of these patients, 30 were additionally treated with a subfascial catheter. Main outcome criterion was the pain under mobilisation at the first postoperative morning registered via a visual analogue score. Minor criteria were the analgesic requirement, the specific (surgical) complications and the day of discharge. RESULTS: Patients treated with the subfascial catheter had significant less pain at the first postoperative morning in rest (p = 0.02) and after mobilisation (p = 0.03) without increased morbidity (p = 0.45). Less patients of the treatment group needed a supplementary analgesic medication (p = 0.01) and were able to leave hospital earlier than patients of the control group (p = 0.01). CONCLUSIONS: A subfascially placed pain catheter enhances postoperative pain therapy after RILND.

Postoperative surgical complications after radical axillary lymph node dissection in melanoma disease result in increased pain.

Postoperative pain is one of the major problems caused by the operative trauma. We recorded the postoperative pain of patients who underwent a radical axillary lymph node dissection (RALND) to evaluate the quality of our standardized perioperative pain management program and the influence of surgical complications. Between August 2003 and December 2007, we registered the postoperative level of pain of 111 patients who underwent a therapeutic RALND, using a visual analog scale (VAS). Patients received standardized perioperative pain therapy according to level I of the World Health Organization (WHO) ladder of pain. We registered a VAS score of 10 in patients at rest during the first 3 postoperative days, but after mobilization of the arm, patients had significantly more pain (P < 0.0001). Patients with a postoperative surgical complication needed significantly more central analgesia to reach the same level of pain (P = 0.04) as patients without complication. Level I of the WHO ladder of pain is not enough for patients after an RALND. Patients with a postoperative complication do have increased pain, and use of only peripheral analgesia is insufficient.

Preemptive analgesia reduces pain after radical axillary lymph node dissection.

BACKGROUND: Analyzing prospective data of our melanoma patients, we registered a suboptimal pain score under mobilization after radical axillary lymph node dissection (RALND). We performed a randomized, double blinded clinical trial to investigate the effects of a preemptive Parecoxib analgesic during the perioperative course. MATERIALS AND METHODS: Between October 2006 and December 2007, 32 patients with stage III/IV melanoma underwent therapeutic RALND and were randomized into two groups. Patients received intravenously 40 mg Parecoxib or 0.9% normal saline solution 2 h before RALND. The postoperative treatment and analgetic regime was defined in the study protocol. Main outcome criterion was the pain under mobilization at the first postoperative morning registered via a visual analogue score. Minor criteria were the postoperative complications, fatigue, amount of analgesics, and the day of discharge. RESULTS: Patients receiving a preemptive analgesic had a better outcome after RALND. The pain after mobilization was significantly decreased at the first postoperative morning (P = 0.04). Patients had less fatigue as well (P = 0.05) and the amount of pain medication in the treatment group was reduced (P = 0.04). CONCLUSIONS: Preemptive application of Parecoxib enhances outcome after RALND. A preemptive analgesic with Parecoxib in the perioperative management after RALND of melanoma patients can be recommended.

Comparison of electrical velocimetry and transthoracic thermodilution technique for cardiac output assessment in critically ill patients.

BACKGROUND AND OBJECTIVE: The results of studies validating the assessment of cardiac output by pulmonary artery thermodilution and a modified algorithm using thoracic bioimpedance/electrical velocimetry in patients undergoing elective cardiac surgery are conflicting. The present observational study was designed to detect whether electrical velocimetry measurements are comparable to transthoracic thermodilution in septic patients after major general surgery. METHODS: Cardiac output was assessed simultaneously by thoracic bioimpedance measurement/electrical velocimetry and transthoracic thermodilution technique (PiCCO) in 30 patients with severe systemic inflammatory response syndrome or sepsis with haemodynamic instability being treated in the surgical intensive care unit of an university hospital. RESULTS: Thirty simultaneous measurements were taken with both methods. The Bland-Altman analysis of agreement revealed a bias of -0.3 l min(-1) with a precision of +/-1.9 l min(-1) and wide limits of agreement (-4.1-3.5 l min(-1)). The percentage error was 54%. CONCLUSION: There was poor agreement between the values of cardiac output estimation by transthoracic thermodilution and those by electrical velocimetry. Electrical velocimetry could not replace invasive monitoring in this trial.

Intraoperative application of fibrin sealant does not reduce the duration of closed suction drainage following radical axillary lymph node dissection in melanoma patients: a prospective randomized trial in 58 patients.

BACKGROUND: Patients suffering from malignant melanoma often require radical lymph node dissection of the axillary nodal basin. The effects of intraoperative application of fibrin sealant following radical axillary lymph node dissection (RALND) on the incidence of postoperative lymphatic secretion are discussed. To study the effect of intraoperatively applied fibrin sealant following RALND a randomized patient-blinded trial was carried out. METHODS: Fifty-eight patients with axillary lymph node metastases of malignant melanoma underwent therapeutic RALND and were randomized into two groups: 29 patients received 2 cc of fibrin glue intraoperatively and 29 patients were only irrigated with 0.9% saline. The amount of drainage was recorded every 24 h. The main outcome criterion was the duration of drain placement in the wound. Minor criteria were the total amount of fluid and the length of hospital stay. Statistical analysis was performed using Spearman's log-rank correlation and paired t-test. RESULTS: There was no significant difference between the nonfibrin group 5 days (range = 3.6-5.7 days) and the fibrin group 5 days (range = 4.1-8.5 days) (p = 0.701). The total amount of fluid for the nonfibrin group (410 cc, range = 362-727 cc) and that for the fibrin group (503 cc, range = 369-1098 cc) (p = 0.605) and the length of postoperative hospital stay of 6 days (range = 5.4-7) vs. 7 days (range = 5.9-10.7), respectively, were not different between both groups (p = 0.387). CONCLUSION: Considering our study results, we cannot recommend the use of 2 cc of fibrin glue intraoperatively in the prevention of lymphatic secretion in patients undergoing RALND for metastatic melanoma.