Neoadjuvant radiochemotherapy (RCT) and lately total neoadjuvant therapy (TNT) improved local recurrence rates of rectal cancer significantly compared to total mesorectal excision (TME) alone. Yet the occurrence and impact of late local recurrences after many years appears to be a distinct biological problem. We included n = 188 patients with rectal cancer after RCT and radical resection in this study; n = 38 of which had recurrent disease (sites: local (8.0%), liver (6.4%), lung (3.7%)). We found that 68% of all recurrences developed within the first two years. Four patients, however, experience recurrence >8 years after surgery. Here, we report and characterize four cases of late local recurrence (10% of patients with recurrent disease), suggesting that neoadjuvant therapy in principle delays local recurrence.

BACKGROUND:Hyperthermic intraperitoneal chemotherapy (HIPEC) following cytoreductive surgery is a radical but effective treatment option for patients with peritoneal carcinomatosis (PC). Unfortunately, a standardized HIPEC protocol is missing impeding systematic comparisons with regard to minimal effective temperatures.OBJECTIVE:The purpose of the present study was to systematically analyse the precise minimal temperature needed for potentiation of chemotherapy effects in vitro and for patient survival.METHODS:We established a cell line-based model to mimic HIPEC conditions used in clinical practice, and evaluated intracellular drug concentrations and long-term survival using different temperatures ranging from 38 to 42 °C combined with cisplatin or doxorubicin. In parallel, we evaluated the temperature reached in the clinical setting by measuring inflow and outflow, as well as in two locations in the peritoneal cavity in 34 patients. Finally, we determined the influence of different HIPEC temperatures on survival.RESULTS:Long-term survival of cells treated with either cisplatin or doxorubicin was further improved only at temperatures above 40 °C. In patients, during HIPEC, constant temperatures were reached after 10 min in the peritoneal cavity. A temperature above 40 °C for at least 40 min was achieved in 68 % of patients over the 60 min duration of HIPEC. Importantly, we observed a significantly enhanced overall survival (OS) and progression-free survival (PFS) in those patients reaching temperatures above 40 °C.CONCLUSIONS:Hyperthermia significantly potentiated the chemotherapy effects only at temperatures above 40 °C in vitro. Importantly, this temperature threshold was also critical for OS and PFS of PC patients.

The German NOTES registry (GNR) is the largest published database for natural orifice transluminal endoscopic surgery (NOTES) worldwide. Although transvaginal cholecystectomy is the most frequent procedure in the GNR, the number of colorectal resections is increasing. The objective of this study was to analyze the first 139 colonic procedures of the GNR.

Intraoperative neuromonitoring (IONM) facilitates recurrent laryngeal nerve (RLN) identification, but various studies affirm virtually unchanged postoperative RLN palsy rates. Several authors meanwhile suggest continuous intraoperative neuromonitoring (CIONM) via vagal nerve stimulation (VNS) to improve RLN protection. However, knowledge of side effects of electrical VNS derives mainly from its therapeutic applications in the fields of neurology and psychiatry. The presented study was conducted to further evaluate the safety of CIONM and identify possible VNS related side effects.

Mast cells are key effector cells of immediate type allergic reactions. Upon activation they release a broad array of pre-stored and de novo synthesized mediators including immunoregulatory cytokines and chemokines. Here, we analyzed the chemokine profile expressed by mature human mast cells. Human mast cells were isolated from intestinal tissue and cultured with stem cell factor (SCF) in the presence or absence of IL-4 for 10d. Cells were stimulated by cross-linking of the high affinity IgE receptor (FcεRI) and/or by SCF. Chemokine and chemokine receptor mRNA expression was determined by real-time RT-PCR and chemokine release was measured by multiplex bead immunoassay. Out of 43 chemokines and 19 chemokine receptors human intestinal mast cells express 27 chemokines and nine chemokine receptors. Twelve chemokines (CCL1, CCL2, CCL3, CCL4, CCL5, CCL7, CCL18, CCL20, CXCL2, CXCL3, CXCL8, and XCL1) were more than four-fold up-regulated in response to FcεRI cross-linking. Combination of pre-culture with IL-4 and/or stimulation with SCF in addition to FcεRI cross-linking further increased the antigen-dependent expression of mRNA for most chemokines. In contrast, the expression of CCL20, CXCL2, and CXCL3 was strongly inhibited by IL-4 treatment. In conclusion, human intestinal mast cells express a broad spectrum of different chemokines underlining their important role as immunoregulatory cells. Furthermore, combined treatment with IL-4 and SCF increases the antigen-mediated expression and release of multiple chemokines, but IL-4 priming inhibits the expression of CCL20, CXCL2, and CXCL3.

Background The two most relevant pathologies of long-term peritoneal dialysis (PD) are simple sclerosis and encapsulating peritoneal sclerosis (EPS). The histological differentiation of those two entities is difficult. The Aim of the study was to establish a method to standardize and facilitate the differentiation between simple sclerosis and EPS Methods We investigated 58 peritoneal biopsies - 31 EPS patients and 27 PD patients. Two blinded investigators analyzed 20 histological characteristics in EPS and PD patients. Results The following findings were significantly more common in EPS than in patients on PD without EPS: fibroblast like cells (FLC) (p<0.0001), mesothelial denudation (p<0.0001), decreased cellularity (p = 0.008), fibrin deposits (p<0.03), Fe deposits (p = 0.05), podoplanin vascular (p<0.0001), podoplanin avascular (p<0.0001). Using all predictor variables we trained the classification method Random Forest to categorize future cases. Podoplanin vascular and avascular were taken together (p<0.0001), FLC (p<0.0001), mesothelial denudation (p = 0.0005), calcification (p = 0.0026), acellular areas (p = 0.0094), and fibrin deposits (p = 0.0336) showed up as significantly important predictor variables. Estimated misclassification error rate when classifying new cases turned out to be 14%. Conclusion The introduced statistical method allows discriminating between simple sclerosis and EPS. The misclassification error will likely improve with every new case added to the database.

Background. Encapsulating peritoneal sclerosis (EPS) is a rare but devastating complication of peritoneal dialysis composed of chronic abdominal pain, chronic ileus, and severe malnutrition. Operative therapy for EPS is a complex procedure, including perionectomy and enterolysis (PEEL): In contrast to simple adhesiolysis, PEEL comprises a restitution of intestinal passage and prevention of recurrent disease by decapsulation and partial deserosation.Methods. We reviewed the treatment of patients with EPS at our referral center regarding perioperative morbidity, mortality, and long-term outcome. Only patients who underwent PEEL were included. Preoperative general status was ascertained by APACHE-II score and body mass index. Postoperative morbidity was stratified into minor and major complications.Results. Between the years 2003 and 2010, 26 of 45 patients with late-stage EPS underwent PEEL. Median age was 54 years, APACHE-II score was 15, and body mass index was 21 kg/m(2). To achieve intestinal function, 9 bowel resections with immediate anastomoses were necessary. Eleven patients (37%) received a complete parietal peritonectomy. Overall morbidity was 44%, with minor complications in 2 patients (7%) and major complications in 11 patients (31%). Three patients (10%) died within the first year after operative treatment.Conclusion. PEEL is a treatment option that can be performed with low mortality and acceptable morbidity. It is a precondition that these patients are treated in specialized referral centers. (Surgery 2013;153:219-24).

Despite recent advances in NOTES, NOS, SILS and related techniques, the feasibility of performing extensive surgery is still limited. Colon surgery usually requires additional access sites or complex technical means for triangulation and retraction. A method is presented that enables single-port colon surgery, supported by flexible colonoscopy. Single-port sigmoidectomy was performed in five cases on the porcine model. Flexible colonoscopy was used to manoeuvre the colon and expose its mesentery for dissection. The specimen was retrieved transrectally by invagination. Single-port sigmoidectomy supported by colonoscopy was feasible in all cases. The method provided a fixed framework, excellent organ guidance and exposition of the mesentery and enabled bowel-close mesocolic preparation. The access angle for preparation and visualisation could be altered during the procedure using the colonoscope. During autopsy on day 21, competent anastomotic healing with only rare interenteric adhesions was observed. One animal had a small preperitoneal abscess in the umbilical region while demonstrating completed skin healing. Flexible colonoscopy provided a fixed reference frame that enabled single-port preparation and dissection of the sigmoid colon. Under colonoscopic guidance, the access angle for dissection could be adapted according to the surgeon's needs. The procedures could be performed safely and effectively.

Mast cells play a key role in allergic and non-allergic disease by releasing a broad array of mediators. Soluble N-ethyl-maleimide-sensitive factor attachment protein receptors (SNAREs) are necessary for membrane fusion events during mast cell exocytosis. We have shown recently that the SNAREs SNAP-23, syntaxin (STX)-4, vesicle associated membrane protein (VAMP)-7, and VAMP-8 are required for release of pre-stored histamine by mast cells. Here we analyze the involvement of different SNARE isoforms in exocytosis of de novo synthesized chemokines in mast cells isolated from human intestine. Following IgE receptor cross-linking, mast cells released substantial amounts of the chemokines CXCL8, CCL2, CCL3, and CCL4. Measurement of SNARE mRNA expression revealed only a moderate up-regulation of mRNA for STX-4 after stimulation for 1.5h. Inhibition of SNAP-23 or STX-3 abolished IgE mediated release of the chemokines CXCL8, CCL2, CCL3, and CCL4. In contrast, blocking of STX-2, or VAMP-3 did not affect the chemokine release. Inhibition of STX-4 or VAMP-8 resulted in a reduced release of CXCL8, but not of CCL2, CCL3, or CCL4. Inhibition of STX-6 attenuated the release of CXCL8 and CCL2, inhibition of VAMP-7 that of CCL3. In summary, STX-3 and SNAP-23 are crucial for the release of all chemokines in mature human mast cells whereas other SNAREs affect only release of selected chemokines.

Introduction. Continuous intraoperative neuromonitoring (CIONM) via vagal nerve stimulation allows real-time surveillance of the recurrent laryngeal nerve during thyroid surgery. However, for effective CIONM, subtle changes in recurrent laryngeal nerve conductivity have to be detected. A newly developed stimulation electrode that provides stable nerve stimulation and safe application is presented. Methods. For electrode validation, current distribution was simulated with the finite element method. Mechanical characteristics were assessed through bench testing. Clinical evaluation was initiated with 11 thyroid surgeries. Results. Experimental and clinical results led to the development of a tripolar gold/polyimide electrode mounted onto a backstrap-shaped silicone body. It facilitated rapid electrode implantation and extraction (median implantation time 4 ± 19 seconds). Peak extraction force was 570 mN. Median supramaximal stimulation currents were 2.00 ± 0.95 mA and resulted in reliable electromyogram responses (median 3.1 ± 3.0 mV). No intraoperative electrode dislocations occurred, and no postoperative nerve palsy was observed. Conclusion. The new backstrap vagal stimulation electrode meets the requirements for reliable CIONM.

A series of investigations proposed that patients’ preference on minimal invasive and scarless surgery may be influenced by age, sex, and surgical as well as endoscopic history of the individual patient. However, it is unknown which psychological criteria lead to the acceptance of increased personal surgical risk or increased personal expenses in patients demanding scarless operations. We investigated whether individual body image contributes to the patient’s readiness to assume higher risk in favor of potentially increased cosmesis.

Background. Continuous intraoperative neuromonitoring (CIONM) via vagal nerve stimulation (VNS) is a new option for recurrent laryngeal nerve (RLN) protection during thyroid surgery. The aim of this study was to evaluate the safety of VNS for CIONM and to assess its effects on the autonomic nervous system (ANS) through analyzing heart rate variability (HRV).Methods. In a prospective, nonrandomized controlled study 5 patients received VNS for CIONM and 5 were operated on with conventional intermittent intraoperative neuromonitoring (IONM). HRV was analyzed in accord with patient-specific reference values.Results. VNS resulted in significantly altered ANS balance. Relative parasympathetic activity increased during VNS. Yet, no relevant cardiac arrhythmias or hemodynamic alterations were observed during VNS.Conclusion. HRV analysis revealed a distinct impact of VNS for CIONM on ANS balance. VNS caused parasympathetic predominance that was not countered by increased sympathetic activity. (C) 2010 Wiley Periodicals, Inc. Head Neck 33: 976-984, 2011

A major obstacle in no-scar surgery is the extraction of large, bulky or rigid specimen. Thus, a method is needed that allows for extraction of large specimens without situs contamination in women and men. It should enable safe treatment of infectious or malignant disease while preserving pathologic workup. Five patients suffering from diverticulitis with expected bulky and rigid specimen were enrolled into this early series. Preparation was performed transumbilically in single-port technique. To prevent new scar formation, the incision was limited to the base of the umbilicus without extension onto the sound abdominal skin. A functionally and topologically extracorporeal compartment was created within the abdomen by introduction and insufflation of a tear-proof impermeable retrieval bag. The specimen was sliced in a controlled fashion inside the compartment along a pre-marked geometry. Controlled specimen dissection in a dedicated intraabdominal resection compartment was feasible. The dissected specimen could be retrieved through the 1.5 cm umbilical incision without spillage of material. The geometry of the extracted organ was reconstructed in detail allowing for uncompromised pathological workup. Extraction of bulky and rigid specimen is possible through natural orifices by the proposed controlled dissection method enabling the pathologist to reconstruct anatomical affiliation.

BACKGROUND:Minimal invasive surgery has led to a significant decrease in surgical trauma, pain, recovery time and improved cosmesis compared with open surgery. However, scar development and the risk of hot spots for infections and hernias are still present. Natural orifice surgery (NOS) promises to offer even further reduction in invasiveness and thus may lead to even faster recovery. The goal of this study was to establish a NOS colonic resection by using commercially available standard surgical instruments avoiding major abdominal incisions.METHODS AND RESULTS:This article reports a new triluminal hybrid NOS approach for sigmoid and colonic resection (Tri-Port-NOS-SIG), established using rigid laparoscopic instruments through the umbilicus, the vagina, and the rectum, without any major abdominal incision. The specimen was retrieved through the anus avoiding dilatation of the vagina. In an early series of 5 patients the first patient was a 37-year-old woman with a 10-year history of recurrent diverticulitis. She recovered quickly and was discharged on postoperative day 2. She returned to sports activity on day 12 postoperatively and to her heavy-duty job on day 16. The following 4 patients also recovered well and were discharged on postoperative days 7 (2 patients), 8, and 11, respectively. One patient experienced a temporary, mild paresthesia of the left lower dorsal leg, most likely because of intraoperative positioning. No major complications occurred.CONCLUSION:Tri-Port-NOS-SIG offers a feasible scarless approach for abdominal resections using commercially available surgical instruments in experienced hands.

Background. The authors hypothesized that by combining transumbilical, transvaginal, and transrectal accesses, complex bowel operations, including proctocolectomy with restorative jejunal pouch reconstruction, might be possible. Methods and Results. Out of a series of 30 natural orifice surgery (NOS) operations performed at the authors' institution in the past 12 months, proctocolectomy with ileoanal pouch reconstruction was planned for 3 female patients (31 years, BMI = 30; 50 years, BMI = 31; 30 years, BMI = 21) with extensive disease of ulcerative colitis, and they were operated via a 3-lumenal NOS approach. The first 2 patients received a proctocolectomy with a J-pouch formation. A 3-stage procedure was planned for the third patient, and she received a total colectomy. The colonic specimen was retrieved through the anus obviating dilation of the vagina. The J-pouch was prepared through a horizontal 2-cm incision, which later served as the protective loop ileostomy site. Conclusion. Trilumenal NOS proctocolectomy is feasible and safe providing a solution to overcome the lack of triangulation using a single-lumen approach.

Existing nerve monitoring devices in thyroid surgery are - except for one - mainly intermittently working nerve identification tools. We present a new vagal electrode which allows true continuous monitoring of the recurrent laryngeal nerve (RLN). The electrode was designed as a tripolar hybrid cuff electrode consisting of polyimide, gold and platinum layers embedded in a flexible silicon cuff which can be opened at the long side for introducing the nerve. It is fully implantable and atraumatic. The evoked potentials are sensed by standard thyroid electrodes. Real-time signal analysis and audio feedback are achieved by specially designed software. Homogeneous and stable signals were recorded throughout the operations. Thus real-time computer-based signal analysis was possible. Evoked potentials reached 300-900 mV. Mean time to place the cuff electrode was 5.5 min. The nerve was stimulated a mean of 63 min (range 55-99 min). No RLN lesions were detected postoperatively. The new vagal electrode was easy to handle and led to stable and reproducible signals. The stimulation current could be kept extremely low due to the special geometry of the electrode. It offers the possibility for uninterrupted, continuous laryngeal nerve monitoring in thyroid surgery. In an ongoing clinical trial its compatibility as an add-on for existing nerve monitoring devices is being tested.

Background. A variety of tools has been developed to identify nerve structures and to lower the risk of nerval injury during thyroid surgery. These tools are usually based on intermittent electrophysiological tracing of the nerves, but its use is still associated with permanent recurrent laryngeal nerve (RLN) injury. We are now presenting the results of the implementation of a novel real-time nerve monitoring system, based on a new vagal nerve cuff electrode.Methods. Nineteen consecutive Patients scheduled for thyroid surgery (17 with benign, 2 with malignant disease), were enrolled in this observational trial. The flexible cuff electrode was implanted during each operation and atraumatically surrounded the vagal nerve. The evoked potentials were sensed by standard thyroid electrodes. Electrical stimulation and recording were achieved through a multichannel electromyogrophy (EMG) system. The signal analysis was performed in real-time by specially designed software.Results. The cuff electrode did not cause any complications during or after the surgery. In. all patients, stable and reproducible signals were easily evoked. The mean time required to place the electrode was 6 5 min. The mean overall vagal nerve stimulation time was 65 min. No permanent RLN lesions were detected in any patient. One patient with a postoperative bleeding from a strap muscle vein required a wound revision, which was performed without nerve monitoring. This patient experienced a temporary partial impairment of the left vocal cord. No hypoparathyroidism was observed in. any patient postoperatively.Conclusions. The presented technique of real-time continuous RLN monitoring by stimulation of the vagal nerve is ftasible, safe, reproducible, and easy to perform. In addition, this new system is compatible with existing equipment and can be used as an add-on with conventional nerve monitoring devices during thyroid surgery.

In patients with inflammatory bowel disease herpes simplex virus infection has been described as a major cause of morbidity and mortality, especially in immunocompromised individuals. Here we present the case of a 35-year old woman with an exacerbation of ulcerative colitis caused by herlpes simplex virus infection (HSV-2). The diagnosis was confirmed histologically following subtotal colectomy. After intravenous treatment with aciclovir for 2 weeks postoperative hematochezia stopped. Herpes simplex virus colitis is a rare but potentially fatal complication of immunosuppressive treatment in patients with inflammatory bowel disease. Prompt diagnosis and efficient antiviral therapy are mandatory to improve prognosis.

Purpose: Cyclooxygenase-2 (COX-2) expression in human colorectal cancer and adenoma tissue seems to be higher than in normal mucosa. However, data about the relation between COX-2 expression and patient survival are inconclusive as yet. Therefore, we studied COX-2 expression in surgery tissue and survival time in a cohort of 747 colorectal cancer patients.Experimental Design: Surgical specimens of primary colorectal cancer from 747 individuals were immunostained for COX-2 and evaluated under a transmission light microscope, COX-2 expression was scored according to intensity and extent of staining, resulting in the COX-2 immunoreactivity score (IRS-COX2). All possible cutoff points for IRS-COX2 were analyzed for a relation between COX-2 expression and patient survival.Results: Both univariable and multivariable analysis have shown that the COX-2 expression in human tumor epithelial cells was unrelated to overall patient survival and to disease-free survival, irrespectively of the cutoff point for IRS-COX2. The survival rates for 1, 3, 5, and 10 years were 81.0%, 66.8%, 60.2%, and 49.8% (median: 117.3 months; 95% confidence interval, 102.3-132.0), respectively. In the multivariable analysis, only node and metastasis were significantly related to overall patient survival. Similar results were obtained when stage IV and rectal cancer patients were excluded from the analysis.Conclusions: COX-2 expression in tumor epithelial cells does not seem to be related to survival of colorectal cancer patients. Besides COX-2, there are several targets, such as the peroxisome proliferator-activated receptors, that are involved in carcinogenesis and may be modulated by nonsteroidal anti-inflammatory drugs. Further studies are needed to determine their prognostic relevance.

Bereits heute sind schon Software-Programme für die 3D-Analyse und die Therapieplanung parenchymatöser Organe, insbesondere der Leber, für den klinischen Einsatz verfügbar und werden bereits im OP eingesetzt. Die Aufarbeitung der CT-Datensätze mit Segmentierung der Organstrukturen ist allerdings sehr zeit- und personalaufwändig. Die computergenerierten Resektionsvorschläge werden bereits erfolgreich in den OP-Situs übertragen. Dieser Übertragungsschritt soll in Zukunft durch eine Echtzeit-OP-Navigation erfolgen. Die Mehrzahl der Navigationsprojekte stützen sich auf intraoperativen 2D- und 3D-Ultraschall sowie auf optische Registrierungsverfahren. Elektromagnetische Registrierungssensoren werden nur vereinzelt erprobt, da sie sehr störanfällig auf Metallgegenstände reagieren. Wenn ein Registrierungsprozess abgeschlossen ist, gelten die Daten nur so lange, wie das Organ nicht bewegt wird. Im Falle von nichtrigiden Organen wie der Leber muss daher ein Daten-Update in Echtzeit und in kurzen Zeitabständen erfolgen. Ein solches System, das eine Navigation über einen längeren Zeitraum sicherstellt, ist zur Zeit nicht verfügbar. Die Validierung der Planungsdaten existiert bisher nur in Ansätzen. Die Ergonomie, d. h. die Verfügbarkeit der Daten in intuitiv erfassbarer und manipulierbarer Weise, muss noch erheblich verbessert werden. Die Zukunft gehört möglicherweise einem intelligenten Skalpell, das seine Dissektionsaktivität herabsetzt, wenn der geplante Resektionspfad verlassen wird. Die Endverantwortung der Operation wird jedoch auch in Zukunft beim Chirurgen verbleiben.