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.

Comparison of strictureplasty and endoscopic balloon dilatation for stricturing Crohn's disease--review of the literature.

BACKGROUND: Stricturing Crohn's disease is accompanied by a high-risk for bowel resection and subsequent short bowel syndrome. Strictureplasty (SP) and endoscopic balloon dilatation (EBD) have been developed to prevent, or at least delay, the requirement for resection. The goal of this study was to compare the outcome of these two procedures with regard to complications and disease recurrence. METHODS: We conducted a MEDLINE literature search to give a current overview about the safety and efficacy of EBD and SP. RESULTS: The initial search yielded 744 articles. Case reports, reviews and meta-analyses were excluded. Finally, 63 articles (SP, 40 articles; EBD, 23 articles) were used for the review. None of the studies compared the two methods directly. A total of 2,532 patients (SP, n = 1,958; EBD, n = 574) were included. The incidence of perioperative complications after SP was 11% and the incidence of major complications was 5%. The median surgical recurrence rate was 24% after a median follow-up of 46 months. The median technical success for EBD was 90%. Major complications occurred in 3% of the cases. According to an intention-to-treat protocol, the median surgical recurrence rate was 27.6%. Per-protocol analysis revealed a median surgical recurrence rate of 21.4% after a median follow-up of 21 months. CONCLUSION: Due to the lack of comparable data, there is currently no reliable information on whether one treatment option is superior to the other. Regarding the limited applicability of EBD in strictures of the small bowel, only a controlled trial would provide evidence as a basis for clinical decision making in CD strictures that are potentially treatable by EBD and SP.

Face, content and construct validity of a new realistic trainer for conventional techniques in digestive surgery.

PURPOSE: Surgical simulation modules for "open" surgery are limited in contrast to well-studied and validated laparoscopic trainers. In this study, face, content and construct validity of a devised simulation module (Berlin Operation Trainer, BOPT) for handsewn anastomoses in digestive surgery were analysed. MATERIALS AND METHODS: Participants of a skills course for digestive surgery (novices: 1-3 years of training; experts: more than 5 years of training) were timed on performing four defined handsewn digestive anastomoses on formalin fixed porcine intestine in the BOPT. Questionnaires were answered regarding impression with the simulation module concerning appearance and realism using a five-point Likert and a three-point forced choice scale. Face and content validities were evaluated based on the responses of participants and construct validity by comparing novices to experts. Data collected were analysed with Fisher's exact test and two-sample t test. RESULTS: Twenty-two novices (median: second postgraduate year) and 26 experts (median: seventh postgraduate year) were enrolled in the study. The BOPT showed strong face and content validities with average scores for satisfaction parameters above 4.2 +/- 0.41 and 4.1 +/- 0.22, respectively. Construct validity was adequate for anastomosis simulation in the BOPT based on different percentages of anastomosis complete during set time between novices and experts as shown for simple (68.2% vs. 92.3%, p = 0.038) and for difficult anastomosis (18.2% vs. 50.0%, p = 0.021). CONCLUSIONS: The BOPT is a suitable instrument for advanced surgical training for novices and experienced colleagues creating a realistic and demanding situation. Further studies have to evaluate if a more realistic preoperative training will support an effective transfer of learned techniques to the operating room.

NALP expression in Paneth cells provides a novel track in IBD signaling.

PURPOSE: Paneth cells are part of the innate mucosal immunity of the gut with possible regulatory function. This study intends to identify the gene expression pattern of the orthotopic and metaplastic Paneth cells, searching for differences between metaplastic occurrence between Crohn's disease and ulcerative colitis. METHODS: Paneth cells were collected in RNAse-free conditions via micro dissection. RNA isolation and super amplification was followed by microarray analysis of whole genome expression activity of the orthotopic and metaplastic Paneth cells. Immunohistology of beta-catenin and Frizzled-5 receptor was performed. RESULTS: Histological analysis showed no morphological or secretory change (Frizzled-5 receptor and beta-catenin) in orthotopic and metaplastic Paneth cells. Microarray analysis indicated an increased, but not mutant activation of Wnt/beta-catenin signaling and firstly showed expression of NALP 1, 7, 8 and 11 in metaplastic Paneth cells. CONCLUSIONS: Paneth cells might play a NALP-mediated role in the pathogenesis of IBD.

Regulatory (FOXP3+) T cells as target for immune therapy of cervical intraepithelial neoplasia and cervical cancer.

Regulatory (FOXP3+) T cells (Tregs) comprise a subpopulation of CD4+ T cells that suppress autoreactive immune cells, thereby protecting organs and tissues from autoimmunity. Tregs have also been detected in human malignancies and their depletion or inactivation substantially improves cellular antitumor immunity in preclinical studies. Novel therapeutic strategies for cervical cancer and precancerous cervical intraepithelial neoplasia (CIN) focus on immune-modulatory and cancer vaccination approaches. In this context, the frequency of Tregs in cervical cancer and precancerous CIN could influence therapeutic strategies. We determined the frequency of infiltrating CD4+ and CD8+ T cells as well as FOXP3+ Tregs in high-grade CIN lesions (CIN III) and cervical carcinoma compared to colon carcinoma, skin melanoma, and bronchial carcinoma. We show that human papilloma virus-derived lesions have a significantly higher number of infiltrating lymphocytes and FOXP3+ Tregs compared to three other common tumor entities. In addition we explored the therapeutic effect of agonistic anti-glucocorticoid-induced tumor necrosis factor receptor family-related protein antibodies that, by single systemic application, inactivate Tregs and induce strong intratumoral invasion of CD8+ T cells and complete tumor eradication in 70% of treated animals. The large number of Tregs in human papilloma virus-derived lesions suggests a pivotal role of Tregs for counteracting the host immune response. We therefore regard CIN and cervical cancer as prime targets for new immune-based non-invasive therapies.

Optical properties of adenocarcinoma and squamous cell carcinoma of the gastroesophageal junction.

Photodynamic therapy (PDT) is an alternative to radical surgical resection for T1a or nonresectable carcinomas of the gastroesophageal junction. Besides the concentration of the photosensitizer, the light distribution in tissue is responsible for tumor destruction. For this reason, knowledge about the behavior of light in healthy and dysplastic tissue is of great interest for careful irradiation scheduling. The aim of this study is to determine the optical parameters (OP) of healthy and carcinomatous tissue of the gastroesophageal junction in vitro to provide reproducible parameters for optimal dosimetry when applying PDT. A total of 36 tissue samples [adenocarcinoma tissue (n=21), squamous cell tissue (n=15)] are obtained from patients with carcinomas of the gastroesophageal junction. The optical parameters are measured in 10-nm steps using new integrating sphere spectrometers in the PDT-relevant wavelength range of 300 to 1140 nm and evaluated by inverse Monte-Carlo simulation. Additional examinations are done in healthy tissue from the surgical safety margin. In the wavelength range of frequently applied photosensitizers at 330, 630, and 650 nm, the absorption coefficient in tumor tissue (adenocarcinoma 1.22, 0.16, and 0.15 mm(-1); squamous cell carcinoma 1.48, 0.13, and 0.11 mm(-1)) is significantly lower than in healthy tissue (stomach 3.34, 0.26, and 0.20 mm(-1); esophagus 2.47, 0.21, and 0.18 mm(-1)). The scattering coefficient of all tissues decreases continuously with increasing wavelength (adenocarcinoma 22.8, 12.99, and 12.52 mm(-1); squamous cell carcinoma 19.44, 9.35, and 8.98 mm(-1); stomach 20.55, 13.96, and 13.94 mm(-1); esophagus 20.34, 12.56, and 12.22 mm(-1). All tissues show an anisotropy factor between 0.80 and 0.94 over the entire spectrum. The maximum optical penetration depth for all tissues is achieved in the range of 800 to 1100 nm. At the wavelength range of 330, 630, and 650 nm, the optical penetration depth is significantly higher in carcinoma tissue (adenocarcinoma 0.27, 1.54, and 1.66 mm; squamous cell carcinoma 0.23, 1.71, and 1.84 mm) than in healthy tissue (stomach 0.16, 1.10, and 1.26 mm; esophagus 0.17, 1.47, and 1.65 mm; p<0.05). Above 1000 nm, a higher absorption coefficient of tumor tissue results in a lower optical penetration depth than in healthy tissue (p<0.05). The higher absorption and scattering of the tumor tissue in the wavelength range of available photosensitizer is associated with a low optical penetration depth. This necessitates higher energy doses and long application times or repeated applications to effectively treat large tumor volumes. Photosensitizers optimized for larger wavelength range need to be developed to increase the efficacy of PDT.

Curative in situ ablation of colorectal liver metastases-experimental and clinical implementation.

INTRODUCTION: In situ ablation of colorectal liver metastases is frequently assessed for palliative treatment only. The establishment of clinically relevant lesion size and a lack of long-term survival data were regarded as main limitations to using them with curative intention. In contrast to surgical liver resection, whose oncological findings seem to have remained unchanged over the years, the in situ ablation methods have considerably changed technically and clinically in the last few years. OBJECTIVE: The aim of the paper was to point out experimental and clinical data underlining the impact of in situ ablation for potentially curative treatment of colorectal liver metastases. DISCUSSION: On the basis of experimental data, the aim of complete local tumor control (R0 ablation) can only be obtained if additional energy is applied after reaching the tumor-adapted maximal coagulation volume. Analogous to the oncological safety margin in surgical resection, we defined this decisive energy difference as the "energy safety margin" for in situ ablation. The energy safety margin is the energy that must be additionally applied after reaching the plateau in the energy/volume curve to achieve complete tumor coagulation. In addition to that, in situ ablation should be combined with temporary interruption of hepatic perfusion whenever possible to prevent intralesional recurrences. In this way, the thermoprotective mechanism of hepatic perfusion can be effectively eliminated. With restrictions, the survival data after ablation in specialized centers is comparable to surgical resection with concomitantly lower morbidity and mortality. Based on recent findings and with the corresponding expertise in the field of ablation and state-of-the-art equipment, ablation is, thus, an alternative to surgical resection. The combined application of surgical resection and ablation is also a suitable method for increasing the R0 rate and thus helps improve the prognosis of treated patients. In summary, it can be said that in situ ablation is a useful expansion of the therapeutic spectrum of liver metastases and can be applied as an alternative to or in combination with surgical resection.

Bipolar radiofrequency ablation of liver metastases during laparotomy. First clinical experiences with a new multipolar ablation concept.

BACKGROUND AND OBJECTIVE: Radiofrequency ablation (RFA) is a promising method for local treatment of liver malignancies. Currently available systems for radiofrequency ablation use monopolar current, which carries the risk of uncontrolled electrical current paths, collateral damages and limited effectiveness. To overcome this problem, we used a newly developed internally cooled bipolar application system in patients with irresectable liver metastases undergoing laparotomy. The aim of this study was to clinically evaluate the safety, feasibility and effectiveness of this new system with a novel multipolar application concept. PATIENTS AND METHODS: Patients with a maximum of five liver metastases having a maximum diameter of 5 cm underwent laparotomy and abdominal exploration to control resectability. In cases of irresectability, RFA with the newly developed bipolar application system was performed. Treatment was carried out under ultrasound guidance. Depending on tumour size, shape and location, up to three applicators were simultaneously inserted in or closely around the tumour, never exceeding a maximum probe distance of 3 cm. In the multipolar ablation concept, the current runs alternating between all possible pairs of consecutively activated electrodes with up to 15 possible electrode combinations. Post-operative follow-up was evaluated by CT or MRI controls 24-48 h after RFA and every 3 months. RESULTS: In a total of six patients (four male, two female; 61-68 years), ten metastases (1.0-5.5 cm) were treated with a total of 14 RF applications. In four metastases three probes were used, and in another four and two metastases, two and one probes were used, respectively. During a mean ablation time of 18.8 min (10-31), a mean energy of 48.8 kJ (12-116) for each metastases was applied. No procedure-related complications occurred. The patients were released from the hospital between 7 and 12 days post-intervention (median 9 days). The post-interventional control showed complete tumour ablation in all cases. CONCLUSIONS: Bipolar radiofrequency using the novel multipolar ablation concept permits a safe and effective therapy for the induction of large volumes of coagulation in the local treatment of liver metastases.

Prognostic factors for mesenteric infarction: multivariate analysis of 187 patients with regard to patient age.

Between 1980 and 2002 a total of 187 patients (105 women, 82 men) with a mean age of 71.5 years underwent surgery for acute mesenteric infarction (AMI) in our department. Arterial occlusion was found in 140 patients, splanchnic vein thrombosis in 22, and nonocclusive AMI in 25. We performed bowel resection in 61 patients, vascular surgery in 32, a combination of the two in 15, and an exploratory laparotomy in 79. The mortality rate was 70.6% (73.9% in patients >70 years and 65.2% in those <70). AMI is still a disease with a consistently high mortality rate (60-80%). Multivariate prognostic factors include the time until surgery and a markedly elevated white blood cell count and serum lactate level. Mortality and secondary disease rates are higher in the elderly, and the fact that they have to wait much longer for an operation than younger patients may be a factor. If surgery is performed early, the survival rate increases regardless of age. The most important prognostic factor and the only one that can be influenced by the surgeon remains the time interval between the onset of symptoms and surgery, Therefore diagnostic and therapeutic intervention should be performed as early as possible in patients with suspected AMI.

Effectivity of laser-induced thermotherapy: in vivo comparison of arterial microembolization and complete hepatic inflow occlusion.

BACKGROUND AND OBJECTIVES: Laser-induced thermotherapy (LITT) is a promising method for local treatment of liver metastases. The aim of this study was to compare the effect of LITT on lesion size when combined with hepatic arterial microembolization or complete hepatic blood flow occlusion. STUDY DESIGN/MATERIALS AND METHODS: In a porcine liver model, LITT (30 W 15 minutes) was performed with either normal (n = 12), partially interrupted (arterial microembolization via a hepatic artery catheter n = 12) or completely interrupted hepatic perfusion (Pringle's maneuver, n = 12). LITT lesions were macro- and microscopically assessed after liver dissection. RESULTS: Hepatic inflow occlusion led to a fourfold increase in lesion volume after arterial microembolization and a ninefold increase after complete interruption (6.3. cm3 vs. 27.1 cm3 vs. 58.8 cm3, P < 0.01). CONCLUSIONS: Interrupting hepatic perfusion significantly increases lesion volumes in LITT. This beneficial effect can also be achieved in the percutaneous application mode by LITT combined with arterial microembolization via a hepatic artery catheter.