Bilirubin, urobilinogen, pancreas elastase and bile acid in drain fluid. The GBUP-study: Analysis of biomarkers for a colorectal anastomotic leakage.

PURPOSE: A colorectal anastomotic leakage (CAL) is a major complication after colorectal surgery and leads to high rates of morbidity and prolonged hospital stay. The study aims to evaluate the benefit of using bilirubin, urobilinogen, pancreas elastase and bile acid in the drain fluid (DF) as a predictive marker for the CAL. METHODS: From June 2015 to October 2017 100 patients, who underwent left hemicolectomy (LH), sigma resection (SR), high anterior resection (HAR), low anterior resection (LAR) or reversal of Hartmann's Procedure (ROHP) were included in this monocentric non-randomized prospective clinical trial. During the first four postoperative days (POD) the concentration of bilirubin, urobilinogen, pancreas elastase and bile acid in the DF was measured. RESULTS: In total 100 patients were recruited. 17 were excluded due to intraoperative decisions to conduct a protective stoma. 6 patients had a CAL. The patients of the control group (n = 77) and the patients who suffered from a CAL (n = 6) had no increased concentration of urobilinogen and pancreas elastase in the DF. The concentration of bile acid in the DF of the patients who suffered from a CAL differed from those of the control group on the 4th POD (p = 0.055).The concentration of bilirubin in the DF of the patients who suffered from a CAL significantly differed from those of the control group on the 1st POD (p = 0.031) and on the 3rd POD (p = 0.041). CONCLUSION: Bilirubin and bile acid in the DF may function as a predictive marker for a CAL.

Intraoperative localization of occult colorectal tumors during laparoscopic surgery by magnetic ring markers-a pilot study.

PURPOSE: Intraoperative localization of small tumors or malignant polyps has been an important issue in laparoscopic colon surgery. We have developed a new method for preoperative endoscopic tumor marking using a ring-shaped magnetic marker. METHODS: In a pilot study, 28 patients with small colonic (n = 23) or rectal tumors (n = 5) underwent endoscopic magnetic clipping prior to laparoscopic resection. A cap carrying a high-power neodymium ring magnet was mounted on the tip of a colonoscope. Near the lesion, the ring magnet was released and clipped to the colorectal wall. Standard laparoscopic instruments were used to find the magnet intraoperatively. RESULTS: Endoscopic fixation of a ring magnet next to the tumor by clipping was technically feasible in all 28 patients. Intraoperative localization of the marked lesions was successful in 27 of 28 patients (96 %). All patients underwent magnet-guided radical laparoscopic resection of the tumor with an average proximal and distal resection margin of 101 and 63 mm, respectively. In one case, the magnet could not be found due to preoperative migration. Surgical complications related to magnetic clip application or intraoperative tumor localization were not observed. However, there was one case with an intraoperative perforation of the colon by the magnet, which was obviously caused by unchecked action with a laparoscopic instrument. CONCLUSIONS: Preoperative endoscopic labeling of colonic lesions with on-the-scope magnetic markers is simple and safe. Intraoperative tumor localization during laparoscopic colorectal surgery can be achieved reliably without additional equipment such as ultrasound or fluoroscopy.

Vacuum-assisted minimally invasive biopsy of soft-tissue tumors.

BACKGROUND: Although exact histological characterization of soft-tissue tumors is essential for determining the appropriate therapy, the quality of the histological assessment is often limited by the size of the tissue samples. Incisional biopsy and core needle biopsy have been the most effective techniques for obtaining tissue samples from soft-tissue tumors. This study was performed to investigate whether vacuum-assisted biopsy can serve as a new diagnostic tool for soft-tissue neoplasms. METHODS: This retrospective study compared the characterization made with use of vacuum-assisted biopsy of soft-tissue tumors in seventy-five patients between 2004 and 2006 and the characterization made with use of incisional biopsy of tumors in a comparison group of seventy-four patients between 2000 and 2005 with the final characterization made after radical tumor excision. All vacuum-assisted and incisional biopsies were performed by the same experienced surgeons and evaluated by the same experienced pathologists at a single tumor center. The sensitivity, specificity, positive and negative predictive values, and accuracy of the preliminary characterization made with use of each method were calculated on the basis of the final characterization made after excision. RESULTS: The vacuum-assisted biopsy procedure was performed successfully in seventy-four (99%) of the seventy-five patients. The accuracy of vacuum-assisted biopsy (96%) was comparable with that of incisional biopsy (99%). Vacuum-assisted biopsy correctly characterized the tumor as benign or malignant in 96% (95% confidence interval [CI], 92% to 100%) of the seventy-five patients compared with 99% (95% CI, 96% to 100%) of the seventy-four patients who underwent incisional biopsy. Vacuum-assisted biopsy correctly characterized the tumor diagnosis in 95% (95% CI, 90% to 100%) of the patients compared with 95% (95% CI, 89% to 100%) for incisional biopsy. Vacuum-assisted biopsy correctly characterized the tumor grade in 89% (95% CI, 82% to 96%) of the patients compared with 88% (95% CI, 80% to 95%) for incisional biopsy. The sensitivity of vacuum-assisted biopsy was 93% (95% CI, 71% to 100%), the specificity and the positive predictive value were both 100%, and the negative predictive value was 91% (95% CI, 85% to 98%). The overall accuracy of vacuum-assisted biopsy was 96% (95% CI, 92% to 100%). CONCLUSIONS: Vacuum-assisted biopsy appears to be safe and provides a new tool for the diagnosis of soft-tissue tumors. One advantage of vacuum-assisted biopsy is that it can be performed with use of local anesthesia in an outpatient setting.

Ultrastaging of colon cancer by sentinel node biopsy using fluorescence navigation with indocyanine green.

PURPOSE: Lymph node status is the most important prognostic factor in colon cancer, but the role of sentinel lymph node biopsy (SLNB) as a tool for identification of micrometastatic disease and extraanatomical lymph nodes for adjuvant strategies and a tailored approach still remains unclear. Indocyanine green (ICG) fluorescence detection is a new method for SLNB allowing real-time lymphography and lymph node detection. This study was designed to evaluate the feasibility of fluorescence-guided sentinel lymph node detection in colon carcinoma. METHODS: Twenty six patients with colon adenocarcinoma were prospectively included in this study. Intraoperatively, a peritumorous injection with a mean of 2.0 ml ICG was performed, followed by lymphatic mapping and SLNB. Clinical feasibility, detection rate, and sensitivity of the method were analyzed. RESULTS: No adverse reactions occurred due to the injection of ICG. Overall, ICG fluorescence imaging identified 1.7 sentinel lymph node (SLN) in average in 25 out of 26 patients (detection rate, 96%). Metastatic involvement of the SLN was found in nine out of 11 nodal positive patients by conventional histopathology. The sensitivity of the method was 82% for colon carcinoma, respectively. CONCLUSION: ICG fluorescence imaging is a new, feasible method for SLNB of colon carcinoma and enables ultrastaging with improved accuracy but with limited validity due to the small number of cases. One advantage of this technique is real-time visualization of lymphatic vessels and SLNB without radiation exposure. Further, larger series are necessary to analyze the role of fluorescence-guided SLNB for colon cancer.

High rate of solitary sentinel node metastases identification by fluorescence-guided lymphatic imaging in breast cancer.

BACKGROUND: The lymph node status was shown to be an important prognostic factor for breast cancer, but controversial issues remain. There has been increased focus on optimizing the visualization of lymph nodes for an accurate and selective approach to axillary lymph nodes. Fluorescence-guided lymphatic imaging is a potential candidate for further research on remaining controversies. METHODS: Forty-seven patients were subject to injection of indocyanine green for navigation to the SLN based on fluorescent dye retention detection. In two groups, patients either received intended axillary lymph node dissection (ALND) and sentinel lymph node biopsy (SLNB) for superstaging or isolated SLNB for minimal-invasive staging. The prospective study was designed to evaluate the technical feasibility with focus on solitary positive SLN. RESULTS: Visualization of lymphatic vessels with bright fluorescence of the SLN was feasible in 46 of 47 patients. Eighteen of 19 nodal positive patients were correctly identified with a sensitivity of 94.7% in all patients after ALND. After immunohistochemistry, in 19 of 25 overall nodal positive patients (76%) the SLN was the only positive lymph node. CONCLUSION: Fluorescence-guided imaging using fluorescence retention detection allows transcutaneous navigation with a high rate of solitary positive SLN identification as an alternative technique for further research.

Esophageal stents for leaks and perforations.

Stenting of esophageal leaks, ie, anastomotic leaks or perforations, might be a minimally invasive alternative to surgery in most clinical situations. However, it must be emphasized that surgery should be considered if stent treatment in combination with drainage and antibiotics does not improve the clinical condition of the patient. Stent insertion should be performed as soon as possible after diagnosis of the leak.

Management of esophageal anastomotic leaks, perforations, and fistulae with self-expanding plastic stents.

OBJECTIVE: Esophageal anastomotic leaks, perforations, and fistulae are associated with considerable morbidity and mortality. The aim of the present study was to assess the efficacy of self-expanding plastic stents in the treatment of esophageal leaks. METHODS: From 2001 to 2009, 41 patients with postoperative anastomotic leaks (n = 30), esophageal perforations (n = 6), or fistulae (n = 5) were treated by endoscopic insertion of self-expanding plastic stents. The clinical outcome of the patients was analyzed, including leak healing, morbidity, and mortality. RESULTS: Self-expanding plastic stents were successfully inserted in all 41 patients without procedure-related complications. Non-ventilated patients received oral feeding an average of 3.9 days after stent placement. Complete leak healing was obtained in 27 of 30 patients (90%) with anastomotic leaks and 5 patients (83%) with perforation. Sealing of fistulae by the stents was achieved in all 5 patients, and closure of the fistula was observed in 2 patients (40%). The mean healing time was 30 days for anastomotic leaks, 15 days for esophageal perforations, and 16 days for fistulae. Stent migration occurred in 14 cases, but endoscopic reintervention and new stent placement were successful in all cases. In-hospital mortality after treatment of esophageal leaks with stents was 10%. CONCLUSIONS: In combination with effective interventional or surgical drainage, stenting is a viable option for the treatment of esophageal anastomotic leaks and perforations, but the success in tracheoesophageal fistula is limited.

Perineal colostomy with spiral smooth muscle graft for neosphincter reconstruction following abdominoperineal resection of very low rectal cancer: long-term outcome.

BACKGROUND: To avoid abdominal colostomy and improve quality of life, several types of anorectal reconstruction following abdominoperineal resection have been proposed. The aim of this study was to assess functional results and the quality of life of patients with very low rectal cancer after abdominoperineal resection and neosphincter reconstruction by perineal colostomy with a colonic muscular cuff. PATIENTS AND METHODS: Twenty-seven patients who had undergone neosphincter reconstruction with a perineal spiral cuff plasty after abdominoperineal resection were included in a retrospective study to evaluate long-term outcome. The functional results were analyzed using anal manometry and the continence score. The quality of life was measured with the global and disease-specific questionnaires European Organization for Research and Treatment of Cancer QLQ-C30 and C38. RESULTS: Median follow-up time was 105 months (range, 18-185 mo). The median Holschneider continence score of the study sample was 13 (continent), with a range of 10 (partially continent) to 16 (continent), thus demonstrating satisfactory functional results. The functional assessment was completed by neosphincter manometry which revealed a median resting vs compression pressure of 40 vs 96 cmH2O with a range of 5 to 81 cmH2O vs 49 to 364 cmH2O. The quality-of-life analyses showed an above-average score for both global health and disease-specific status. CONCLUSION: Spiral cuff colostomy with reconstruction after abdominoperineal resection of very low distal rectal cancer offers a surgical option for a selective group of patients with reasonable functional long-term results and an improved quality of life.

Expression-patterns of the RNA component (hTR)and the catalytic subunit (hTERT) of human telomerase in nonneoplastic prostate tissue, prostatic intraepithelial neoplasia, and prostate cancer.

BACKGROUND: Telomerase, a ribonucleoprotein, is composed of a RNA component (hTR) and two protein subunits. One of these subunits, the catalytic subunit (human telomerase reverse transcriptase, hTERT), represents a reverse transcriptase. hTERT-expression is closely correlated with telomerase activity. The telomerase is thought to be involved in immortalization process. By adding hexamic repeats to the end of chromosomal DNA, the telomeres, the enzyme is able to stop progresssive telomeric DNA loss that occurs during cell division due to the end replication problem that stops the mitotic clock. METHODS: Expression-patterns of hTR using radioactive in situ hybridization with (35)S-labelled RNA probes were compared with immunhistochemical staining for hTERT in 14 cases of archival paraffin-embedded samples of normal prostatic tissue, high-grade prostatic intraepithelial neoplasia (PIN), prostatic cancer, and one atypical adenomatous hyperplasia (AAH). Beside the expression-patterns each telomerase component was evaluated semiquantitatively. RESULTS: hTERT and hTR can be found in nonneoplstic tissue and are upregulated in premalignant transformated lesions. AAH showed no hTERT-expression and low hTR-expression. There is a heterogenous expression within prostatic carcinomas. CONCLUSIONS: No association was observed between the grade of the tumour differentiation and semiquantitative levels of hTR- or hTERT-expression. Telomerase is of limited value for the diagnostic of malignant or benign lesions in prostate.

Telomerase as a prognostic marker in breast cancer: high-throughput tissue microarray analysis of hTERT and hTR.

Telomerase activity (TA) has been shown to correlate with poor clinical outcome in various tumour entities, indicating that tumours expressing this enzyme may be more aggressive and that TA may be a useful prognostic marker. For breast cancer, however, TA is a controversial prognostic marker; whereas some studies suggest an association between TA and disease outcome, others do not find this association. This study used tissue microarrays (breast carcinoma prognosis arrays) containing 611 samples (each 0.6 mm in diameter) from the tumour centre of paraffin-embedded breast carcinomas to analyse the catalytic subunit of telomerase, human telomerase reverse-transcriptase (hTERT), and the internal RNA component (hTR), which are the core components of the telomerase holoenzyme complex. hTERT protein expression was obtained by immunohistochemistry (human anti-telomerase antibody Ab-2, Calbiochem), and hTR RNA was measured by radioactive in situ hybridization. hTERT and hTR expression were determined semi-quantitatively and graded (scores 1-4). Clinical data, such as histological subtype, pT stage, tumour diameter, pN stage, BRE grade, tumour-specific survival (in months), patient's age and others, were available for statistical analysis. A statistically significant correlation was found between tumour-specific survival (overall survival) and hTERT expression (p < 0.0001) or hTR expression (p = 0.00110). Tumours with higher scores (scores 3, 4) for hTR and/or hTERT were associated with a worse prognosis. In multivariate analysis, hTERT expression was an independent prognostic factor. Previous studies, focusing on analysis of TA in smaller numbers of fresh-frozen breast carcinomas by the TRAP assay, gave controversial results with respect to TA as a prognostic marker. Using tissue microarrays from 611 breast carcinomas, this study has demonstrated that increased expression levels of the telomerase core components, hTERT and hTR, are associated with lower overall survival. These findings suggest that TA should be included in future validation studies as a prognostic marker in breast cancer.