[Pain relief during and after surgical procedures : Results of an Austria-wide patient survey on postoperative pain and perioperative pain management]. / Schmerzversorgung bei chirurgischen Eingriffen : Ergebnisse einer österreichweiten Patientenbefragung zur postoperativen Schmerzsituation und zum perioperativen Schmerzmanagement.

BACKGROUND: Pain after surgery, especially on the first postoperative day, results in longer hospital stays, increased complication rates and may also cause a higher risk of pain chronification. However, the expected intensity of pain is often misjudged and therefore not adequately treated. METHODOLOGY: An Austria-wide patient survey on the pain situation on the first postoperative day and on the quality of perioperative pain management was carried out on a voluntary and anonymous basis. RESULTS: Regarding the intensity of pain a clear gender difference could be observed. Women were more prone to more severe pain than men across all age groups. This difference was most pronounced in the younger age groups (18-40 years) and in those patients showing the highest pain scores. Treatment satisfaction was correlated (high significance) with pain intensity on exercise (p < 0.01), maximum pain (p < 0.01), least pain (<0.01) and frequency of postoperative pain assessment. DISCUSSION: The risk of postoperative pain can be reduced by optimal care structures. Since patients treated in optimal care structures had significantly lower pain scores on exercise and with respect to maximum pain, the investment in the optimization of such resources should be carefully planned. Special attention should be paid to postoperative pain management in women, especially in younger female patients.

Effects of multifunctional cross-linkers on rheology and adhesion of soft nanostructured materials.

We investigate the nanostructure, the rheology and the adhesion of soft supramolecular materials elaborated by blending monofunctional and multifunctional poly(isobutene) (PIB) chains. Monofunctional PIB chains (PIBUT) are linear and unentangled polymer chains (Mn ≈ 3 kg mol-1) functionalized in the middle by a bis-urea interacting moiety, able to self-associate by four hydrogen bonds. Covalent coupling of monofunctional PIB allows us to synthesize longer chains bearing two or three interacting moieties. These chains are then added to monofunctional PIB to prepare blends containing up to 10% of multifunctional PIB (M-PIBUT). The influence of M-PIBUT on the supramolecular nanostructure, which results from the self-assembly of stickers, is studied by Atomic Force Microscopy and Small Angle X-ray Scattering at room temperature. Multifunctional and monofunctional chains are shown to interact with each other to form bundles of rod-like aggregates. The consequences of these interactions on the rheology of the blends were studied by shear tests in the linear and non linear regimes, below and above the order-disorder transition temperature. A pronounced strengthening effect of M-PIBUT is observed at room temperature: the supramolecular blends become more elastic and are more resistant to creep with increasing concentration of M-PIBUT. The effects of M-PIBUT on the nanostructure and the rheology suggest that M-PIBUT, which can link with more than one supramolecular aggregate, plays the role of a physical cross-linker. The impact of these supramolecular cross-linkers on the adhesion of the blends is studied by probe-tack tests and discussed by analyzing the in situ deformation through the debonding images.

[Interdisciplinary position paper "Perioperative pain management"]. / Interdisziplinäres Positionspapier "Perioperatives Schmerzmanagement".

Despite many positive developments, postoperative pain and its treatment is still not always given the necessary attention. Severe pain after surgical procedures affects a significant proportion of patients. This very fact is not only detrimental to the immediate recovery process, but can also form the basis for the development of chronic pain conditions.An adequate and effective management of perioperative pain requires appropriate organizational structures. This multidisciplinary paper which was initiated by the Austrian Society for Anaesthesiology and Intensive Care and the Austrian Pain Society and developed together with numerous specialist and professional societies dealing with the subject aims at supporting the organization of perioperative pain management structures and to make best use of proven concepts. Additional recommendations describe specific interventions for selected types of intervention.

Stability of murine bradykinin type 2 receptor despite treatment with NO, bradykinin, icatibant, or C1-INH.

BACKGROUND: Little is known about factors which trigger and/or contribute to hereditary angioedema or ACE-inhibitor-mediated angioedema including variations in bradykinin type 2 receptor (B2R) expression and activity. METHODS: Protein and mRNA expression of B2R and the increase of intracellular calcium (iCa) in response to bradykinin were monitored in porcine and murine endothelial cells in response to NO donors or bradykinin. B2R protein expression was evaluated in skin, heart, and lung of (i) mice with endothelial-specific overexpression of eNOS (eNOS(tg) ), (ii) in eNOS(-/-) mice and (iii) in C57BL/6 mice treated with the NO donor pentaerythritol tetranitrate (PETN), the NOS inhibitor l-nitroarginine (L-NA), plasma pool C1-INH, and the B2R antagonist icatibant. Aortic reactivity to bradykinin was investigated including eNOS(-/-) mice. RESULTS: B2R protein and mRNA expression remained unchanged in cells subjected to L-NA, NO donors, and bradykinin in a time- and concentration-dependent manner. Likewise, increases of iCa in murine brain endothelial cells remained unchanged. B2R protein levels were similar in eNOS(tg) and eNOS(-/-) as compared to transgene-negative littermates. Likewise, treatment of C57BL/6 mice with PETN, L-NA, C1-INH or icatibant did not change B2R protein expression. In aortic rings of C57BL/6 mice, bradykinin induced B2R-dependent constrictions which were attenuated by endothelial NO and abolished by diclofenac indicating the functional importance of B2R-induced activation of endothelial NO synthase and cyclooxygenase. CONCLUSION: These data suggest that alterations of B2R protein expression induced by NO, bradykinin, C1-INH, or icatibant unlikely contribute to bradykinin-induced angioedema. This finding does not rule out a role for NO in bradykinin-induced extravasation and/or angioedema.

COMPRES: a prospective postmarketing evaluation of the compression anastomosis ring CAR 27(™) /ColonRing(™).

AIM: Preclinical studies have suggested that nitinol-based compression anastomosis might be a viable solution to anastomotic leak following low anterior resection. A prospective multicentre open label study was therefore designed to evaluate the performance of the ColonRing(™) in (low) colorectal anastomosis. METHOD: The primary outcome measure was anastomotic leakage. Patients were recruited at 13 different colorectal surgical units in Europe, the United States and Israel. Institutional review board approval was obtained. RESULTS: Between 21 March 2010 and 3 August 2011, 266 patients completed the study protocol. The overall anastomotic leakage rate was 5.3% for all anastomoses, including a rate of 3.1% for low anastomoses. Septic anastomotic complications occurred in 8.3% of all anastomoses and 8.2% of low anastomoses. CONCLUSION: Nitinol compression anastomosis is safe, effective and easy to use and may offer an advantage for low colorectal anastomosis. A prospective randomized trial comparing ColonRing(™) with conventional stapling is needed.

Diagnosis, management and outcome of early anastomotic leakage following colorectal anastomosis using a compression device: is it different?

AIM: Compression anastomosis has proved to be safe for rectal reconstruction with leak rates comparable to those observed using circular stapling devices. However, there are no data on whether the metallic compression ring alters the ease of diagnosis or the treatment in cases of leakage. In this study, we present our experience with early leakage following compression anastomosis. METHOD: A prospective registry was used for data review. Patients with anastomotic leakage following compression anastomosis between November 2008 and September 2013 were included. RESULTS: In all, 197 (92 female) patients were operated using a novel compression device. Early leakage was found in 10 (5.1%) patients after a median of 5 (3-14) days. The radiologist was able to detect leakage using CT in nine out of 10 cases unequivocally. Removal of the ring was necessary in eight of the 10 cases, and salvage of the anastomosis was feasible on six occasions. In all diverted cases with a low anastomosis, a transanal repair of the defect was feasible in three cases, including a single patient with complete separation of the anastomosis. CONCLUSION: Artefacts on the CT scan caused by the compression ring did not hamper the diagnosis of anastomotic leakage. Removal of the ring in the early postoperative period is not associated with complete separation of the bowel ends. Salvage of anastomosis is feasible in most cases.

Surgical recurrence after primary ileocolic resection for Crohn's disease.

BACKGROUND: The current study was conducted to assess long-term outcomes after primary ileocolic resection for Crohn's disease (CD) and to identify factors associated with surgical relapse in the era of immunosuppressive medications. METHODS: Data were collected retrospectively on 116 consecutive patients, who underwent primary ileocolic resection for CD at a tertiary referral center between 1997 and 2006. Medical records were reviewed, and the use of immunomodulators was noted. The cumulative probability for a second operation due to recurrent CD was described by Kaplan-Meier curves. RESULTS: Ten patients (8.6 %) developed surgical recurrence after a mean follow-up period of 8.1 (±2.6) years. The percentage of patients not requiring further surgery was 96.5% and 88.0 % at 5 and 10 years, respectively. An urgent indication for surgery was significantly associated with the necessity of repeated intestinal resection (hazard ratio 5.6, 95 % confidence interval 1.2-27.0, p = 0.0145). In addition, postoperative exposure to azathioprine/6-mercaptopurine for more than 3 months decreased the probability of surgical recurrence significantly (hazard ratio 2.5, 95 % confidence interval 0.6-9.9, p = 0.0349). CONCLUSIONS: In contrast to previous studies, we observed a significant low surgical recurrence rate after primary ileocolic resection. Additionally, maintenance treatment with azathioprine/6-mercaptopurine after surgery may reduce the necessity for repeat surgical intervention.

Subharmonic lock-in detection and its optimization for femtosecond noise correlation spectroscopy.

Although often viewed as detrimental, fluctuations carry valuable information about the physical system from which they emerge. Femtosecond noise correlation spectroscopy (FemNoC) has recently been established to probe the ultrafast fluctuation dynamics of thermally populated magnons by measurement of their amplitude autocorrelation. Subharmonic lock-in detection is the key technique in this method, allowing us to extract the pulse-to-pulse polarization fluctuations of two femtosecond optical pulse trains transmitted through a magnetic sample. Here, we present a thorough technical description of the subharmonic demodulation technique and the FemNoC measurement system. We mathematically model the data acquisition process and identify the essential parameters that critically influence the signal-to-noise ratio of the signals. Comparing the model calculations to real datasets allows validating the predicted parameter dependences and provides a means to optimize FemNoC experiments.

Hypercapnia and surgical site infection: a randomized trial.

BACKGROUND: Tissue oxygenation is a strong predictor of surgical site infection (SSI). Mild intraoperative hypercapnia increases peripheral, gastrointestinal, and splanchnic tissue oxygenation and perfusion. Hypercapnia also has anti-inflammatory effects. However, it is unknown whether hypercapnia reduces SSI risk. We tested the hypothesis that mild intraoperative hypercapnia reduces the risk of SSI in patients having colon resection surgery. METHODS: With institutional review board approval and subject consent, patients having elective colon resection (e.g. hemicolectomy and low-anterior resection) expected to last >2 h were randomly assigned to intraoperative normocapnia (PE'CO2 ≈ 35 mm Hg; n=623) or hypercapnia ( PE'CO2 ≈ 50 mm Hg; n=592). Investigators blinded to group assignment evaluated perioperative SSI (Center for Disease Control criteria) for 30 postoperative days. SSI rates were compared. RESULTS: Patient and surgical characteristics were comparable among the groups. The SSI rate for normocapnia was 13.3%, and for hypercapnia, it was 11.2% (P=0.29). The Executive Committee stopped the trial after the first a priori determined statistical assessment point because of much smaller actual effect compared with the projected. However, because the actual difference found in the SSI rates (15-16%) were within the 95% confidence intervals (CIs) of the projected relative difference of 33% (95% CI -43 to +24%), our results cannot be considered as 'no difference', and cannot exclude a Type II error. Time to first bowel movement was half-a-day shorter in the hypercapnia group. CONCLUSIONS: Mild hypercapnia appears to have little or-possibly-no ability to prevent SSI after colon resection. Other strategies for reducing SSI risk should thus take priority.

Repeat endorectal advancement flap after flap breakdown and recurrence of fistula-in-ano--is it an option?

AIM: Endorectal advancement flaps are an established treatment for high transsphincteric and suprasphincteric fistulae. The outcome of a repeat procedure in the case of flap breakdown and fistula recurrence remains unclear. The aim of the study was to analyse the outcome of repeat endorectal advancement flaps. METHODS: We retrospectively analysed patients with a repeat endorectal advancement flap procedure after flap breakdown and recurrence of fistula-in-ano of cryptoglandular origin who had been treated in our unit between 1994 and 2010. RESULTS: In all, 97 patients underwent an endorectal advancement flap procedure for fistula-in-ano and, of these, nine patients (five men, four women, 9.3%) subsequently underwent a repeat procedure due to flap breakdown. Median age was 40 years (range 25-60). Median follow-up time was 85 months (range 26-136). Seven full-thickness and two mucosal flap repeat procedures were performed because of eight transsphincteric and one suprasphincteric fistulae. The repeat procedure was successful in seven (78%) patients. In one of the two patients with repeat flap failure, a third flap procedure failed again. Disturbances of postoperative faecal incontinence were observed in five (55%) patients. Overall, the median postoperative Vaizey faecal incontinence score was 1 (range 0-4). CONCLUSION: Repeat endorectal advancement flap procedures are feasible and associated with a low recurrence rate and mild postoperative faecal incontinence. Therefore, a repeat procedure is a viable option in the case of a flap breakdown and fistula recurrence.

Bridging the gap with an ileocolonic graft after extensive colorectal resections.

BACKGROUND: Ileocecal interposition (ICI) for first-line reconstruction after low anterior colorectal resection was introduced by von Flüe and Harder in 1994 (Dis Colon Rectum 37:1160-1162, 1994). We report our experience using this technique to bridge colonic gaps after significant loss of bowel length. PATIENTS AND METHODS: Between 1999 and 2009 the left-sided colon was too short for traditional isoperistaltic reconstruction in six patients treated in our hospital. Reasons for extensive bowel loss were a deficient (n = 3) or torn (n = 1) marginal artery with ischemia or repeat colorectal resections (n = 2). An ICI was done to bridge the gap and enable restoration of intestinal continuity. RESULTS: No patient died. Whenever performing a coloanal anastomosis (4/6) a loop ileostomy was raised. One patient with colonic diversion experienced graft-related complications: ischemic colitis of the interposed colonic segment, anastomotic stenosis, and a presacral sinus were observed and managed nonoperatively. Subsequent closure of the stoma was possible in all cases. A median Vaizey incontinence score of 9 (range: 4-14) was recorded in the patient with coloanal anastomosis. The average number of bowel movements per day was 1.5 (range: 0.5-6). CONCLUSIONS: When the descending colon does not reach the rectal stump or anal canal in reoperative cases or after vascular complication, ICI is a useful salvage procedure resulting in good bowel function.

10-year stability of clinical-grade serum-free γ-retroviral vector-containing medium.

More than 10 years ago, we developed an efficient protocol for serum-free retroviral transduction of human hematopoietic stem cells derived from mobilized peripheral blood. After upscaling of the methodology, serum-free retroviral gibbon-ape leukemia virus (GALV) pseudotype PG13/LN vector supernatant produced under strict good manufacturing practice (GMP) conditions was used in the first clinical gene-marking trial in Germany. In this study, we analyzed the titer and transduction efficiency of this serum-free clinical-grade retroviral supernatant 10 years after production to evaluate the long-term stability. Long-term storage and transport on dry ice resulted in modestly decreased titers and levels of transduction efficiency in CD34+ cells ranging from 38.4 to 49.1%. We conclude that the stability of retroviral vectors in serum-free medium allows extended storage and distribution of approved clinical-grade retroviral vector stocks to distant sites in multicenter clinical trials.

Treatment of perianal sepsis and long-term outcome of recurrence and continence.

AIM: The study investigated the fate of patients with perianal sepsis of cryptoglandular origin. METHOD: All patients treated for perianal sepsis between January 1994 and December 2000 were retrospectively analysed regarding recurrence and faecal incontinence. Data collection was conducted by chart review and by telephone questionnaire using the Vaizey incontinence score. RESULTS: One hundred seventy-three (58%) of 300 patients were available for follow-up at a median period of 121 (77-171) months. Fistula-in-ano was diagnosed in 156 (90%) patients. After a single surgical procedure, 55 (32%) patients had no recurrence of perianal sepsis. In 118 (68%), recurrence required multiple procedures (median 3, range 2-19). If only a single incision and drainage was performed (n = 10, 6%), no faecal incontinence occurred. Drainage with fistulotomy (n = 45, 26%) induced mild incontinence in 9% and severe incontinence in 4%. After multiple procedures that were required in 118 (68%) patients, mild and severe faecal incontinence was found in 16% and 4% of them, respectively. CONCLUSION: Treatment of anal sepsis is associated with a high recurrence rate and a substantial risk of faecal incontinence.

Short-term complications of wide-lumen stapled anastomosis after ileocolic resection for Crohn's disease: who is at risk?

AIM: There is growing evidence that stapled anastomoses are similarly effective compared to hand-sewn anastomoses in Crohn's patients. This study was designed to assess safety and limitations of wide-lumen stapled ileocolic anastomoses. METHOD: All patients with ileocolic resections for Crohn's disease perfomed between 1998 and 2006 were studied. A stapled anastomosis was constructed whenever possible. Potential risk factors for postoperative complications were recorded, retrospectively. Univariate and multivariate analyses were performed. RESULTS: In 209 out of 220 cases (95%, 132 primary operations) stapled anastomoses were performed. Eleven patients underwent a hand-sewn anastomosis owing to massive bowel dilatation (n = 7) or increased wall thickness (n = 4). There were 10 major (4.5%; surgical: 8, medical: 2) complications including two anastomotic leaks and one anastomotic bleed (all from stapled anastomoses) and one death not related to the anastomosis. Minor complications occurred in 25 patients. In multivariate analysis, major surgical postoperative complications were significantly associated with a low level of albumin (P = 0.0113) and previous resections for Crohn's disease (P = 0.0144). CONCLUSION: Stapled ileocolic anastomosis was safe in the majority of Crohn's patients. The most important limitation was technical impracticability. A low level of albumin and a history of previous resection increased the risk of postoperative complications.

Postoperative course and long term follow up after colectomy for slow transit constipation--is surgery an appropriate approach?

OBJECTIVE: Patients with slow transit constipation who do not respond satisfactorily to common medical treatment are considered candidates for colectomy. The present observational long term study was designed to assess outcome after surgery. METHOD: Twenty consecutive patients were treated by colectomy for slow transit constipation between 1996 and 2004. Preoperative and postoperative data were reviewed by using our institutional database. A questionnaire including validated scoring systems and questions about complications and subsequent surgical interventions was sent to all available patients. RESULTS: Three patients (15%) died perioperatively. Median long term follow up was 84 months. Ten patients (50%) needed further operations after colectomy: Three patients (15%) had surgery during the early postoperative period, seven patients (35%) during follow up. A total of 31 operations had to be performed in these patients. Twelve patients (86%) responded to the questionnaires. Their median Wexner constipation score was 11.5 (range 8-23). Six patients fulfilled the Rome II criteria for constipation. The median Vaizey incontinence score was 7.5 (range 0-22). The median GIQLI showed 80 points (range 32-129). CONCLUSION: Morbidity and mortality rate after colectomy were inadmissibly high. Taking into account the poor functional results, we cannot recommend colectomy for slow transit constipation.

Endoscopic anterior component separation: a novel technical approach.

PURPOSE: Open anterior release of the external oblique fascia to enable midline closure of large abdominal wall defects is associated with relevant morbidity due to extensive subcutaneous dissection. Using endoscopic techniques, wound complications can be minimized. However, identification of the correct entry point (e.g. for balloon trocar insertion) can be challenging especially in adipose patients. We therefore present a technical modification facilitating the entire procedure. METHODS: A novel technique for endoscopic anterior component separation using a trocar system allowing blunt and sharp dissection under direct vision is described. This brief communication also contains our initial experience and learning curve with this novel approach. RESULTS: Endoscopic release of the external oblique fascia was successfully performed 29 times in a total of 15 patients. Body mass index accounted for 30.8 kg/m2 (median; range 21.6-42.5). Transverse width of midline defect accounted for 7 cm (median; range 4-12). Subsequent hernia repair was successfully done using sublay mesh reinforcement (n = 13) or a laparoscopic intraperitoneal onlay mesh procedure (n = 2) with midline closure in all cases. One hematoma was seen at site of release managed conservatively. CONCLUSIONS: Using a trocar system allowing blunt and sharp dissection under direct vision may be a viable option for the endoscopic anterior component separation.

Efficacy of liver transplantation for alcoholic cirrhosis with respect to recidivism and compliance.

Many transplant centers are reluctant to accept alcoholic patients for OLT because of their supposed potential for alcoholic recidivism and poor compliance with the required immunosuppressive regimen, both of which result in graft failure. Only inconclusive data related to these arguments are available. From May 1982 to January 1993, 58 patients received OLT at our institution for end-stage cirrhosis, where alcohol was the only toxic component. The indication for OLT in these patients was considered with particular attention to recidivism and compliance. Overall survival in this group was 71% and 63% at 1 and 5 years, respectively, with an average survival time of 78 months. Actuarial survival of patients transplanted since January 1989 (n = 37) was 86% and 83% at 1 and 2 years (average survival 42 months). Nonfatal clinical endpoints were analyzed in those patients surviving at least 3 months (n = 44). Return to alcohol abuse has been documented in 14 persons at routine short-term outpatient checkups. The estimated risk for alcoholic recidivism amounts to 31%, with a median follow-up of 33 months. Compliance with immunosuppressive regimen was expressed as a dependent value of acute rejection episodes (0.3 per patient, median follow-up 33 months), chronic rejection (occurred in none of the patients), and measurements of CsA HPLC blood trough level (92.2% within the target range). The preversus postoperative improvement of employment, marital, and social status after OLT showed a statistically significant difference. Unwillingness to offer OLT to individuals with alcoholic liver disease because of failure to demonstrate 100% long-term abstinence appears difficult to defend in the face of good results in survival, compliance, and social rehabilitation.

The early response of p53-dependent proteins during radiotherapy in human rectal carcinoma and in adjacent normal tissue.

The aim of this study was to investigate the activation of the p53 pathway and the induction of apoptosis during preoperative radiotherapy in normal human rectal tissue and in rectal carcinoma. Twelve patients with rectal cancer of the lower third were enrolled in this study. Tumor specimens and adjacent normal tissue were obtained before radiation, after the third radiation cycle and from the surgically removed rectum. All specimens were analyzed be means of immunohistochemistry for expression of p53 and its downstream target genes MDM2 and p21. In normal mucosal crypts, irradiation led to p53 accumulation and MDM2 induction in more than 70% of the cells. The accumulation of p53 in basal crypts was associated with high expression of p21. Apoptosis was also induced in crypts and occurred in 15% of the cells. Activation of the p53 pathway was not seen in the resting cells at the luminal border of the epithelium. In interstitial cells, p21 was highly upregulated, whereas p53 and MDM2 showed weak expression. The level of bcl-2 was not altered during radiotherapy in healthy tissue. In rectal carcinoma cells, p53 expression was unaltered by irradiation in 11 out of 12 tumors. The p53 non-functional tumors were characterized by a weak induction of MDM2 and p21 and by the lack of apoptosis in the presence of bcl-2. Our findings demonstrate that sequential immunohistochemical analysis is suitable to detect a deregulation of the p53 pathway in human rectal cancer cells during radiotherapy. Further investigations are necessary to elucidate its value as a prognostic marker and potential predictor of therapy responsiveness.

p53 gene status and expression of p53, mdm2, and p21Waf1/Cip1 proteins in colorectal cancer.

Abrogation of the normal p53 pathway is the most common molecular alteration in human cancer. p53 Gene status can be potentially assessed through the expression of proteins known to be activated by the wild-type p53 (wt p53) system, such as mdm2 and p21Waf1/Cip1. In this study, the frequency of mdm2, p21Waf1/Cip1, and p53 protein expression was investigated using immunohistochemistry (IHC) in 88 colorectal carcinomas (CRCs). The relationship between these expressions and p53 status was examined. p53 status and the immunophenotypes characterizing these tumors were correlated with standard prognostic variables. Mutation of p53 was detected using single-strand conformational polymorphism (SSCP) analysis and sequencing. Concordance between p53 gene status and p53 immunoreactivity was seen in 62 of 88 (70.45%) carcinomas. Mdm2 expression was found in 22 of 45 (48.88%) and 5 of 43 (11.62%) of the tumors with wt p53 and mutated p53 (P<0.0001), respectively. Predominantly, higher p21Waf1/Cip1 expression was associated with wt p53 (P<0.001). All wt p53 cases that expressed mdm2 also expressed p21Waf1/Cip1. These results suggest that there is a subgroup of CRCs in which p53 is functionally active, inducing transcription of mdm2 and Waf1/Cip1. Their combined evaluation may provide important clues for planning adjuvant systemic therapy and gene therapy based on the restitution of p53 function. However, no significant association was found between the immunophenotypes and the standard prognostic variables investigated.

Significant association of strictures and internal fistula formation in Crohn's disease.

Intestinal inflammation in Crohn's disease (CD) may be complicated by the occurrence of strictures and fistulae. The pathogenesis of fistula formation is unknown. We therefore wanted to determine whether mechanical factors might contribute to the development of fistulae. Furthermore, we tried to define the path of internal fistulae through the muscular layer. For this purpose, surgical resection specimens from 42 consecutive patients with CD were prospectively studied. In gross examination the whole bowel was cut into circumferential cross sections 0.3 cm thick. Abnormal areas were histologically examined. Strictures were found in 38 patients (90.5%), and fistulae were observed in 27 (64.3%) patients. In 11 (40.7%) specimens fistulae were found within a stricture, in 15 (55.6%) at the proximal end, and in 1 (3.7%) no stricture was found. In 7 (25.9%) cases with fistulae, herniated mucosa was found within the muscularis propria or the subserosa. In 7 (25.9%) cases a blood vessel was identified near a fistula traversing the muscularis propria. From these findings we conclude that that mechanical factors may contribute to fistula formation. This is further supported by the fact that fistulae appear to traverse the muscular layer along piercing vessels.