Implication of FDG-PET/CT in patients with potentially operable colorectal lung metastases.

OBJECTIVES: This prospective study assessed the role of F-18-FDG-PET/CT in clinical staging for patients with colorectal cancer planned for pulmonary metastasectomy by thoracotomy or video-assisted surgery. PATIENTS AND METHODS: In addition to conventional imaging, we performed 86 F-18-FDG-PET/CT studies in 76 patients with potentially resectable metastatic colorectal lung metastases. We then investigated the effect that PET/CT had on further clinical management. Based on the results from the 47 thoracotomies performed, we compared the number of pulmonary metastases discovered after histologic examination with the number predicted by the conventional computed tomography (CT) as an independent part of the F-18-FDG-PET/CT examination and by the F-18-FDG-PET component. RESULTS: F-18-FDG-PET/CT led to changes in treatment regime and diagnostic planning in many patients. In five patients PET/CT revealed previously undetected local recurrence of the primary colorectal cancer, in four patients hepatic metastases, in three patients bone metastases, in two patients soft-tissue metastases, and in three patients histologically preoperatively proven N2 or N3 station lymph node involvement. These all constituted exclusion criteria, and consequently the previously planned pulmonary metastasectomy was not performed. The sensitivity and positive predictive value (PPV) for detection of pulmonary metastases were 84.2% and 36.4% for CT and 75.0% and 61.6% for F-18-FDG-PET study. The calculated sensitivity, specificity, PPV, and NPV of F-18-FDG-PET/CT for detecting thoracic lymph node involvement were 85.7%, 93.0%, 66.7%, and 97.5%, respectively. Furthermore, we found that F-18-FDG-PET/CT may predict thoracic lymph node involvement based on the SUV of pulmonary nodules. CONCLUSIONS: F-18-FDG-PET/CT has a clear role in the diagnostic workup for pulmonary metastatic colorectal cancer and may save patients from futile surgery. It cannot, however, be relied on to detect all possible pulmonary and nodal metastases, which surgeons must always consider when making treatment decisions.

Effects of minimizing access trauma in laparoscopic colectomy in patients with IBD.

BACKGROUND: Laparoscopic interventions to minimize access trauma are increasingly gaining importance for both cosmetic reasons and lower postoperative morbidity. The aim of this study was to compare the clinical outcomes for different laparoscopic colectomy and proctocolectomy accesses considering IBD. A comparison was made between total laparoscopic (LR)-without an extra incision for sample--and laparoscopic-assisted resection using a small incision for retrieval of the specimen (LAR) PATIENTS AND METHODS: From 2006 to 2012, 109 IBD patients underwent minimal invasive total colectomy or proctocolectomy. Patients were subdivided according to access into LR and LAR. Perioperative outcomes were evaluated. RESULTS: 86 patients with Ulcerative Colitis (UC) and 23 with Crohn's disease (CD) were included (LR: 64 UC/13 CD, LAR: 22 UC/10 CD). Among them, there were no differences in age, BMI, sex, ASA score or pre-existing immunosuppression. Patients with LR and UC had a higher disease activity score (Truelove III LR: 42 %, LAR: 5 %; p = 0.005). The Crohn's Disease Activity Index did not differ. Patients with LR had a shorter operating time (LR: 211.5, LAR: 240 min; p = 0.002). There was no significant difference in hospital stay (LR: 11, LAR: 12.5 days; p ≥ 0.05), length of stay at the ICU (both 1 days; p ≥ 0.05), duration of required analgesia (LR: 7 days, LAR: 8 days; p ≥ 0.05), and nutritional build-up (both 5 days; p ≥ 0.05). Groups had the same overall complication rate, but surgical site infection rates tended to be higher in patients with LAR (LR: 9.1 %, LAR: 21.9 %, p = 0.07). DISCUSSION: Laparoscopic procedures for colectomy and proctocolectomy are safe and effective techniques for patients with colon involvement and IBD. Minimizing the access trauma in laparoscopic colectomy offers a potential advantage of reduced surgical site infections, especially for frequently immunosuppressed IBD patients.

Sacral neuromodulation for fecal incontinence and constipation in adult patients with anorectal malformation--a feasibility study in patients with or without sacral dysgenesis.

PURPOSE: The aim of this study was to evaluate both the feasibility and effectiveness of sacral neuromodulation for fecal incontinence and constipation in adult patients who had undergone surgical repair of anorectal malformations (ARM). METHODS: Patients with ARM with or without sacral dysgenesis who presented with fecal incontinence, constipation, or combined symptoms were treated with sacral nerve stimulation (SNS). Success of SNS was assessed by scores preoperatively and after a 3-week test period: Cleveland Clinic Incontinence Score (CCI), Surgical Working Group for Coloproctology (CACP) continence score, German version of the Fecal Incontinence Quality of Life Scale, and Cleveland Clinic Constipation Score (CCCS). The follow-up results of the patients who received a definitive pacemaker were used to evaluate the long-term effect of SNS in patients with ARM. RESULTS: Four patients with fecal incontinence and one patient with constipation (two males, three females; median age 24 years [13; 31]) were treated with SNS between May 2012 and May 2013. Four patients had a normal sacrum; one patient had a sacral dysgenesis. Preoperatively and after the test phase, median CACP continence scores were 8 [1; 10] and 11.5 [3; 16], median CCI 14 [12; 19] and 13 [11; 17], and median Fecal Incontinence Quality of Life Scale improved in all categories. For constipation, CCCSs were 16 and 7. CONCLUSION: Sacral neuromodulation is a feasible treatment modality for adult patients with ARM with a normally developed sacrum. Patients with sacrum dysgenesis are not suited for SNS because a definitive quadripolar electrode could not be anchored in the absence of a sacral bone.

An expression module of WIPF1-coexpressed genes identifies patients with favorable prognosis in three tumor types.

Wiskott-Aldrich syndrome (WAS) predisposes patients to leukemia and lymphoma. WAS is caused by mutations in the protein WASP which impair its interaction with the WIPF1 protein. Here, we aim to identify a module of WIPF1-coexpressed genes and to assess its use as a prognostic signature for colorectal cancer, glioma, and breast cancer patients. Two public colorectal cancer microarray data sets were used for discovery and validation of the WIPF1 co-expression module. Based on expression of the WIPF1 signature, we classified more than 400 additional tumors with microarray data from our own experiments or from publicly available data sets according to their WIPF1 signature expression. This allowed us to separate patient populations for colorectal cancers, breast cancers, and gliomas for which clinical characteristics like survival times and times to relapse were analyzed. Groups of colorectal cancer, breast cancer, and glioma patients with low expression of the WIPF1 co-expression module generally had a favorable prognosis. In addition, the majority of WIPF1 signature genes are individually correlated with disease outcome in different studies. Literature gene network analysis revealed that among WIPF1 co-expressed genes known direct transcriptional targets of c-myc, ESR1 and p53 are enriched. The mean expression profile of WIPF1 signature genes is correlated with the profile of a proliferation signature. The WIPF1 signature is the first microarray-based prognostic expression signature primarily developed for colorectal cancer that is instrumental in other tumor types: low expression of the WIPF1 module is associated with better prognosis.

Oral vs intravenous antibiotic prophylaxis in elective laparoscopic cholecystectomy: an exploratory trial.

INTRODUCTION: The application of perioperative intravenous antibiotic prophylaxis is often considered a necessary routine procedure. The only way to decide whether an antibiotic prophylaxis is necessary in elective gallbladder surgery is to conduct a multicenter randomized trial. The aim of this exploratory trial was to clarify whether an oral application of an antibiotic prophylaxis is a feasible and safe procedure compared to intravenous application. This exploratory trial was conducted prospective randomized, using a double-dummy design. The main target criteria included tolerance, adverse effects, pharmacokinetics, and cost of treatment. MATERIAL AND METHODS: Patients undergoing elective laparoscopic cholecystectomy were randomized double-blinded to an oral or intravenous application group of one antibiotic (gyrase inhibitor) using a double-dummy design. Exclusion criteria were acute cholecystitis, icterus, and choledocholithiasis. In addition to a tolerance analysis, the antibiotic concentration was determined in serum and bile by high-pressure liquid chromatography (HPLC). RESULTS: One hundred fifty one patients (75 patients with oral and 76 with intravenous prophylaxis) were evaluated for the tolerance analysis. Four patients (1 p.o., 3 i.v.) had adverse reactions to the antibiotics. The antibiotic serum concentration was 0.83 mg/l (p.o.) vs 8.44 mg/l (i.v.) before surgery, 0.81 mg/l (p.o.) vs 4.43 mg/l (i.v.) during surgery, and 0.69 mg/l (p.o.) vs 2.77 mg/l (i.v.) after surgery. The bile concentration was higher after oral administration with 9.20 mg/l than after intravenous application with 5.79 mg/l. The costs of medication for intravenous application were 20 times higher than those for oral application. CONCLUSION: The oral application of an antibiotic (gyrase inhibitor) was feasible and safe for perioperative antibiotic prophylaxis in laparoscopic cholecystectomy in this exploratory trial.

Genome-wide expression patterns of invasion front, inner tumor mass and surrounding normal epithelium of colorectal tumors.

Colorectal tumors have characteristic genome-wide expression patterns that allow their distinction from normal colon epithelia and facilitate clinical prognosis. The expression heterogeneity within a primary colorectal tumor has not been studied on a genome scale yet. Here we investigated three compartments of colorectal tumors, the invasion front, the inner tumor mass, and surrounding normal epithelial tissue by microdissection and microarray-based expression profiling. In both tumor compartments many genes were differentially expressed when compared to normal epithelium. The sets of significantly deregulated genes in both compartments overlapped to a large extent and revealed various interesting known and novel pathways that could have contributed to tumorigenesis. Cells from the invasion front and inner tumor mass, however, did not show significant differences in their expression profile, neither on the single gene level nor on the pathway level. Instead, gene expression differences between individuals are more pronounced as all patient-matched tumor samples clustered in close proximity to each other. With respect to invasion front and inner tumor mass we conclude that the specific tumor cell micro-environment does not have a strong influence on expression patterns: largely similar genome-wide expression programs operate in the invasion front and interior compartment of a colorectal tumor.

Transcriptional census of 36 microdissected colorectal cancers yields a gene signature to distinguish UICC II and III.

UICC stage II and III colorectal cancers (CRC) differ fundamentally in prognosis and therapeutic concepts. To analyze differential gene expression between both stages and to establish a relationship between molecular background and clinical presentation, tumor material from 36 unselected consecutive patients presenting with sporadic CRC, 18 UICC stage II and 18 UICC stage III, were laser microdissected to separate epithelial tumor cells. Gene expression levels were measured using U133A Affymetrix gene arrays. Twelve CRC associated signal transduction pathways as well as all 22,000 probe sets were screened for differential gene expression. We identified a signature consisting of 45 probe sets that allowed discrimination between UICC stage II and stage III with a rate of correct classification of about 80%. The most distinctive elements in this signature were the gene GSTP-binding elongation factor (GSPT2) and the transcription factor HOXA9. Differential expression of these genes was confirmed by quantitative real-time polymerase chain reaction (p(HOXA9) = 0.04, p(GSTP2) = 0.02). Despite the reliability of the presented data, there was no substantial differential expression of genes in cancer-related pathways. However, the comparison with recently published data corroborates the 45 gene signature showing structural agreement in the direction of fold changes of gene expression levels for our set of genes chosen to discriminate between both stages.