Decellularised tissues obtained by a CO2-philic detergent and supercritical CO2.

Tissue decellularisation has gained much attention in regenerative medicine as an alternative to synthetic materials. In decellularised tissues, biological cues can be maintained and provide cellular environments still unmet by synthetic materials. Supercritical CO2 (scCO2 ) has recently emerged as a promising alternative decellularisation technique to aggressive detergents; in addition, scCO2 provides innate sterilisation. However, to date, decellularisation with scCO2 is limited to only a few tissue types with low cellular density. In the current study, a scCO2 technique to decellularise high density tissues, including articular cartilage, tendon and skin, was developed. Results showed that most of the cellular material was removed, while the sample structure and biocompatibility was preserved. The DNA content was reduced in cartilage, tendon and skin as compared to the native tissue. The treatment did not affect the initial tendon elastic modulus [reduced from 126.35 ± 9.79 MPa to 113.48 ± 8.48 MPa (p 〉 0.05)], while it reduced the cartilage one [from 12.06 ± 2.14 MPa to 1.17 ± 0.34 MPa (p 〈 0.0001)]. Interestingly, cell adhesion molecules such as fibronectin and laminin were still present in the tissues after decellularisation. Bovine chondrocytes were metabolically active and adhered to the surface of all decellularised tissues after 1 week of cell culture. The developed method has the potential to become a cost-effective, one-step procedure for the decellularisation of dense tissues.

The structure, thermal properties and phase transformations of the cubic polymorph of magnesium tetrahydroborate.

The structure of the cubic polymorph of magnesium tetrahydroborate (γ-Mg(BH(4))(2)) has been determined in space group Ia3d from a structural database of the isoelectronic compound SiO(2); this has been corroborated by DFT calculations. The structure is found to concur with that recently determined by Filinchuk et al. (Y. Filinchuk, B. Richter, T. R. Jensen, V. Dmitriev, D. Chernyshov and H. Hagemann, Angew. Chem. Int. Ed., 2011, DOI: 10.1002/anie.201100675). The phase transformations and subsequent decomposition of γ-Mg(BH(4))(2) on heating have been ascertained from variable-temperature synchrotron X-ray diffraction data combined with thermogravimetric and mass spectrometry measurements. At ~160 °C, conversion to a disordered variant of the ß-Mg(BH(4))(2) phase (denoted as ß') is observed along with a further unidentified polymorph. There is evidence of amorphous phases during decomposition but there is no direct crystallographic indication of the existence of Mg(B(12)H(12)) or other intermediate Mg-B-H compounds. MgH(2) and finally Mg are observed in the X-ray diffraction data after decomposition.

Prognostic value of beta1,6-branched oligosaccharides in human colorectal carcinoma.

Increase of beta1,6-branched oligosaccharides is possibly associated with tumor progression and lymph node metastasis. The aim of this study was to determine the prognostic value of beta1,6 branches in human colorectal carcinoma. Expression of beta1,6 branches was histochemically evaluated using the leukoagglutinating Phaseolus vulgaris lectin, PHA-L, in 92 clinically documented colorectal carcinomas, of which 31 had formed lymph node metastases. The follow-up time ranged between 4 and 14 years (median, 10.3 years). A PHA-L staining index (SI), taking into account staining intensity and its percentage of tumor cut surface area, was established. The carcinoma SI was highly associated with the disease-free survival (P = 0.004) and overall survival (P = 0.005). Patients with a carcinoma SI of >1, as compared to those with a SI of < or =1, were at significantly higher risk for tumor recurrence, with a shorter disease-free survival (hazard ratio = 2.59, P = 0.005) and significant higher risk of death with shorter overall survival (hazard ratio = 2.51, P = 0.007). The carcinoma SI was also associated with the presence of lymph node metastases. We conclude that PHA-L staining in human colorectal carcinoma sections provides an independent prognostic indicator for tumor recurrence and patient survival and is associated with the presence of lymph node metastases.

Total mesorectal excision for cancer of the rectum.

The concept of total mesorectal excision (TME) was first described by R. J. Heald in 1982 as a radical cancer operation based on the anatomy of fascial planes and fibrous spaces of the pelvis. The ampulla recti is invested by a fascia propria which is a part of the visceral pelvic fascia. The fascia propria is separated from the parietal pelvic fascia by the pelvirectal fibrous space, which is a compartment of the subperitoneal space of the pelvis. The lateral ligaments of the rectum divides the pelvirectal space into a prerectal and a retrorectal part. TME is defined as the resection of the rectum with its surrounding fatty and lymphatic tissue contained within the visceral sheet of the pelvic fascia. The dissection proceeds in the nearly avascular cleavage plane between the visceral and the parietal fascial sheets, allowing maximal protection of the hypogastric nerves and the inferior hypogastric plexus. Continuity of the prerectal and retrorectal parts of the field of dissection is established by dividing the lateral ligaments of the rectum slightly inside the point where they swing away from the parietal fascia of the pelvic side wall. By following this plane of dissection it is possible to achieve en bloc excision of the total mass of perirectal lymphatic and fatty tissue down to the pelvic floor.

Non-homogeneous intrahepatic drug distribution in intraportal infusional chemotherapy demonstrated by Tc-99m-MAA perfusion SPECT.

Perioperative adjuvant cytotoxic chemotherapy given through a portal vein catheter may reduce the incidence of metachronous liver metastases following curative resection of colorectal carcinoma. It has generally been assumed that positioning the tip of the catheter in the stem of the portal vein will ensure homogeneous drug distribution to the whole liver. This hypothesis has been put to the test in 10 patients receiving intraportal chemotherapy according to protocol 40/81 of the Swiss Group of Clinical Cancer Research. Catheter position in the stem of the portal vein was checked angiographically the first and last day of a 7-day chemotherapy course. Perfusion scans using 99m-Tc-MAA made during therapy were compared to static liver scans obtained with 99m-Tc sulfur colloid one day after conclusion of chemotherapy. The results were evaluated on planar scans and by SPECT. Slow infusion of the tracer substance under conditions duplicating those of cytotoxic drug infusion used in the protocol resulted in decreased or missing perfusion of the left liver lobe and gross non-homogeneous perfusion in nearly all of the patients.

Early hematological toxicity of adjuvant perioperative intraportal and intravenous chemotherapy with fluorouracil, mitomycin and heparin in colorectal cancer. Swiss Group for Clinical Cancer Research.

BACKGROUND: From 1987 to 1993 the Swiss Group for Clinical Cancer Research (SAKK) performed a randomized phase III adjuvant trial in patients with colorectal adenocarcinoma with the objective of comparing intraportal versus intravenous perioperative chemotherapy. PATIENTS AND METHODS: Patients younger than 75 years had a curative en bloc resection of their cancer and were then randomized into three arms: 1. adjuvant perioperative portal liver infusion with fluorouracil, mitomycin and heparin, 2. adjuvant subclavian intravenous infusion with the same regimen and 3. no adjuvant treatment. The hematological toxicity was evaluated by hemoglobin determination and leucocyte and thrombocyte counting before and during ten days after surgery. RESULTS: Hemoglobin showed a median decrease of 22% in the control group. This decrease is aggravated significantly by 3% through the chemotherapy. Leucocytes showed a median decrease of 7% in the control group. Perioperative chemotherapy caused a significantly higher median drop; 23% when given into the liver through the portal vein and 34% when given systemically through a subclavian catheter. Thrombocytes revealed a median decrease of 25% in the control group. Chemotherapy was not associated with a significant additional drop. CONCLUSIONS: Adjuvant perioperative chemotherapy with fluorouracil, mitomycin and Heparin as given in this study is associated with a significant mild drop in hemoglobin and leucocytes during the first 10 postoperative days. If drug dose increases are planned in future trials the addition of hematopoietic growth factors might be considered.

Coverage of enterococci in community acquired secondary peritonitis: results of a randomized trial.

INTRODUCTION: The increasing number of enterococcal infections in hospitals and reports about the development of resistance of these bacteria make it necessary to review their importance as co-pathogens in secondary peritonitis. MATERIALS AND METHODS: A prospective randomized controlled trial on primary therapy of secondary peritonitis was carried out in six centers comparing cephalosporin-based antibiotic therapy to acylaminopenicillin-based therapy. RESULTS: Enterococci were only cultured in 6 of 110 cases from the abdomen and were found in only 5 cases of postoperative complications. No differences were found between penicillin-based vs. cephalosporin-based therapy. CONCLUSION: The study supports the view that these bacteria continue to play a minor role in secondary peritonitis. The point has to be emphasized, however, that the patients under study were in relatively good condition (APACHE II median 9 for cephalosporins and 10 for penicillins) and that postoperative cases of peritonitis were excluded.

Behaviour of surgically corrected infrainguinal vein grafts.

During a period of 4 years (1988-1992) we detected in a series of 114 infrainguinal vein grafts 22 bypasses (19%) with 26 hemodynamically significant (> 50%) stenoses. The secondary cumulative patency rate of 114 bypasses was 92% at 12, 84% at 24 and 84% at 36 months. Twenty-three secondary surgical procedures consisting of vein patch angioplasty (n = 10), interposition grafting (n = 3) or jump- or sequential grafting (n = 10) were performed to correct stenoses. One graft correction was technically not feasible, resulting in graft occlusion. Two patients refused surgery. All corrected grafts were prospectively studied both by ankle brachial measurements and color flow Duplex scanning every 3 to 6 months. Cumulative graft patency after reintervention in 20 grafts was 95% at 12 months and 95% at 24 months. Mild stenosis (< 50%) of revision sites was observed in 2 grafts. No single stenosis remote of revision site developed during follow-up (mean 20.4 months), confirming the opinion that stenosed vein grafts after correction do not demonstrate a higher incidence to develop strictures than normal grafts. No tertiary procedures were necessary, as all categories of secondary procedures normalized graft and limb hemodynamics. This series demonstrates that excellent long term results after surgically corrected high grade graft lesions justify an aggressive approach to these stenoses.

Infrainguinal arterial reconstruction with autologous vein grafts: are the results for the in situ technique better than those of non-reversed bypass? A long-term follow-up study.

BACKGROUND: The aim of this study was to answer the question if the in situ technique in infrainguinal arterial reconstruction is better than the non reversed one in long-term follow-up. METHODS: Patients were included in a prospective study at operation. 387 infrainguinal arterial reconstructions in 367 patients performed from 10-88 to 12-98 were retrospectively analysed. RESULTS: 280 non-reversed and 107 in situ bypass procedures were performed. Primary patency rates at 60 months were 63.3% for non-reversed and 57.9% for in situ grafts (p=n.s.). Primary assisted patency rates were 81.8% and 84.5% respectively (p=n.s.). Limb salvage rate was not different in either group. The 30-day mortality was 1.9% in the in situ group and 0.7% in the non-reversed group (p=n.s.). CONCLUSIONS: There is no difference in outcome between in situ and non-reversed vein grafting. Absence of statistical difference between the two procedures may be mainly due to the routine use of angioscopic quality control.

Angioscopy guided in situ bypass versus angioscopy guided non reversed bypass for infrainguinal arterial reconstructions. A comparison of outcome.

In situ bypass grafting depends on an adequate ipsilateral greater saphenous vein. To profit from a tapered, valveless conduit in legs without an adequate greater saphenous vein, we routinely used the contralateral saphenous vein non reversed. In some reconstructions to the infrageniculate popliteal and the proximal anterior tibial artery we used the non reversed instead of the in situ technique because of the distance between the natural course of the saphenous vein and the recipient artery. This retrospective study compares the outcome of 48 in situ bypasses to the outcome of 66 non reversed bypasses. Endoluminal manipulations in all veins were visually controlled using an angioscope. The two groups of bypasses (in situ versus non reversed) did not differ concerning age, sex, risk factors, operative mortality, indication for surgery and distribution of the recipient arteries. There was a tendency for a lower wound complication rate in "in situ" compared to non reversed bypasses (10% versus 27%; p = 0.086). There were no differences in cumulative primary and primary assisted patency rates between the two groups after two years. We prefer the angioscopy guided in situ technique for reconstructions to infrageniculate arteries because of a low wound complication rate and excellent patency rates. In the absence of an adequate ipsilateral saphenous vein and in reconstructions to recipient arteries not presenting themselves for the in situ technique, similar results can be achieved with angioscopically prepared non reversed grafts.

Surgical treatment of hydatid disease of the liver: an experience from outside the endemic area.

BACKGROUND/AIMS: Hydatid disease is quite rare in European countries outside the endemic area around the Mediterranean Sea. Most of the cases observed in Central and Northern Europe occur in emigrants from the endemic area, whose number has been increasing over the last decade. In Switzerland about twenty-five new cases are being diagnosed per year, an incidence of about 0.33 cases per 10(5) inhabitants. Surgery remains the principal treatment modality of hydatid liver disease. There is still debate about conservative surgery as opposed to radical surgical treatment in which the cyst is totally removed including the pericyst by total cystoperi-cystectomy, partial hepatectomy or a combination of both. Surgeons working inside the endemic area tend to favor conservative methods, whereas those outside the endemic area have the tendency to favor radical surgery. This article reviews the results of surgery for liver hydatid disease obtained in a country outside the endemic area. PATIENTS AND METHODS: In our institution 24 patients (12 female, 12 male) have been treated for liver hydatid disease from 6/1983 to 2/1995. Twenty-two patients were immigrants from the endemic area. Surgery indication was primary liver hydatid disease in 23 patients, and recurrent disease in one. RESULTS: Twenty-one patients underwent radical procedures, and three were treated by cystectomy, unroofing and omentoplasty. Radical procedures were pericystectomy in 11 patients, partial hepatectomy in five and pericystectomy combined with partial hepatectomy in five. There was no operative mortality in 23 patients operated on for primary disease, but the only patient operated upon for recurrence died from anaphylactic shock. Eighteen of the 23 surviving patients could be followed up for a median time of 6.5 years (eight months to 12.5 years). Sixteen of 18 patients have remained free of recurrence. One has been reoperated for a retrocaval recurrence four years after right hepatectomy, and one patient is being observed for suspected recurrence after unroofing and omentoplasty. CONCLUSIONS: The policy of applying radical surgery whenever feasible can be followed with acceptable morbidity and near zero mortality. Radical surgery has, however, to be applied judiciously, and there is still an important role for conservative surgery.

Septic complications after biliary tract stone surgery: a review and report of the European prospective study.

We report a prospective, controlled study of the incidence of septic complications following biliary tract stone surgery. This study included a total of 280 patients operated on in eight hospitals in various European countries. In this study the computer program "Surgery" was used. Of 280 patients, 77 (27.5%) were male and 203 (72.5%) were female. The age ranged from 20 to 92 years (mean 54.8 years); 78.9% of the cases corresponded to clean-contaminated surgery; 85% of the patients received antibiotic prophylaxis with cefazolin. Twenty-one patients developed postoperative septic complications (7.5%) of which 12 (4.3%) were wound infections; five patients (1.8%) had intra-abdominal infections. The wound infection rate was 3.2% in clean-contaminated surgery, 7.7% in contaminated and 20% in dirty (p < 0.02). In laparoscopic cholecystectomy the global rate of septic complications was 3.6% vs. 12.6% in open cholecystectomy (p < 0.01); 2.4% and 6.3% wound infection respectively. The mean age of patients who developed postoperative septic complications was 61.5 years and 54.2 years old who did not develop any complications (p < 0.03). The duration of the postoperative period was 5 days in patients without infection and 13 days in patients with infection (p < 0.0001). Two patients died, one of them (0.4%) caused by sepsis. In addition to the European prospective study, a review of the problems of sepsis in biliary surgery was carried out.

[Is the cost of pedal reconstructions justified in potential amputation of the lower extremity]. / Rechtfertigt sich der Aufwand der pedalen Rekonstruktionen bei der amputations-gefährdeten unteren Extremität?

From May 1990 to April 1994 we performed 24 arterial reconstructions to pedal arteries in 23 patients. There were 12 women (52%) and 11 men (48%) suffering from chronic critical ischemia of the lower extremities. The 30 day-mortality was 9%. 3 early graft thromboses had to be corrected. This was successful in two cases, but failed in one case, making below knee amputation in this patient necessary. Another leg with a patent graft had to have a below-knee amputation due to persistent foot infection. Secondary procedures to correct graft stenoses were performed in 8 legs (33%). All patients entered a prospective surveillance program to study primary (64% at 12 months) and primary assisted patency rates (81% at 24 months). Limb salvage rate was 90% at 24 months. We think that reconstructions to pedal arteries are worthwhile in properly selected patients. Limbs can be salvaged in a high percentage improving quality of live considerably.

[Rupture of a sinus of Valsalva aneurysm in the left atrium]. / Rupture d'un anévrisme des sinus de Valsalva dans l'oreillette gauche.

Ruptures of sinus of Valsalva aneurysms are a rare complication, and very few cases of rupture in the left atrium have been described. In this clinical case we report the case of a patient hospitalised with a scenario of cardiac insufficiency revealing a very large posterior sinus of Valsalva aneurysm, associated with a bicuspid aortic valve, and rupture in the left atrium. The diagnosis was by transthoracic and transoesophageal multiplan echocardiography, and the treatment surgical, with a good result.

[Treatment of recurrent inguinal hernia by implantation of a pre-peritoneal prosthesis. Results of a prospective study]. / Die Behandlung der Rezidivinguinalhernie durch die Einlage einer präperitonealen Prothese. Resultate einer prospektiven Studie.

44 patients with 47 recurrent inguinal hernias entered a prospective study. All patients were operatively managed by a standardized technique using a polypropylene (Prolene) mesh inserted through a pre-peritoneal approach. Operating in the pre-peritoneal space avoids dissection of the scared cord and the "inlay" prosthetic mesh safely creates a new "fascia transversalis" with a low rate of recurrences. All patients were personally controlled every 6 months with a follow-up time of 12 to 60 months (mean 20.2 months). The low postoperative morbidity included only one seroma, no infection and no testicular complications. We observed one recurrence occurring 6 months after surgery (2%). The described operative technique using an inlay patch is recommended as the therapy of choice in all recurrent groin hernias.

[Full-thickness abdominal wall closure of laparoscopic trocar incision sites: a new, simplified technique]. / Der mehrschichtige Bauchwandverschluss laparoskopischer Trokareinstichstellen: eine neue, vereinfachte Technik.

Description of a safe, quick, easy and cheap technique of suture closure of laparoscopic trocar sites utilizing a reusable instrument ("hook-needle") developed for the purpose. The procedure is done under laparoscopic vision without the need for laparoscopic suture handling and results in a one stage closure of all relevant layers of the abdominal wall. Other techniques recently published for the same purpose are critically reviewed.

[Status of portal perfusion in colorectal cancer. Swiss Study Group for Clinical Cancer Research]. / Stellenwert der portalen Perfusion beim colorectalen Carcinom. Schweizerische Arbeitsgemeinschaft für Klinische Krebsforschung (SAKK).

533 patients with diagnosis of operable colorectal carcinoma were randomized to receive either a single course of portal infusion with Mitomycin-C (MMC) and 5-Fluorouracil (5-FU) starting immediately after operation, or no adjuvant treatment. Of these, 505 (94%) were evaluable. Over the median follow-up of 8 years, the adjuvant therapy reduced the risk of recurrence by 22% (Hazard ratio = 0.78%, 95% CI 0.61-0.99; P = 0.045). The relative reduction of relapse on death was similar in all subgroups (i.e. nodal status, localization). However, adjuvant portal chemotherapy proved to be most efficient in the subgroups of patients with tumor involvement of the regional lymph nodes (Dukes C) and of patients with colon cancer. Analysis of the pattern of relapse showed that most of the difference in overall and disease-free survival is to be attributed to a consistent reduction of all kinds of tumor recurrences (i.e. local relapses, liver metastases and/or other distant metastases) in the treated group, rather than to liver relapses alone. We conclude therefore, that part of significant benefit obtained for patients with operable colorectal carcinoma treated with a single course of adjuvant chemotherapy via the portal vein might be due to the additional systemic effects of the portal chemotherapy and further study of perioperative treatment with and without prolonged chemotherapy appears worthwhile.

[Existence of asymptomatic changes in left ventricular function in the diabetic. Noninvasive study]. / Existence d'altérations asymptomatiques de la fonction ventriculaire gauche chez le diabétique. Etude non invasive.

49 diabetics (D) (26 IDD and 23 NIDD) were compared to 32 controls (C). Absence of ischemic cardiopathy (IC) was confirmed by routine investigations and noninvasive cardiovascular techniques, including an exercise ECG using 12 leads and a thallium 201 scintigraphy. Our results show: a) a prolonged mean isovolumetric relaxation time (IVRT) as studied by the M mode echocardiography and phonomechanography: D = 0,10 sec +/- 0,04; C = 0,05 sec +/- 0,02; p less than 0,0001; b) a reduced mean EF slope: D = 97,48 +/- 37,08 mm / sec; C = 125,68 +/- 34,35; p less than 0,005; c) a high mean Weissler index (ratio of PEP to LVET): D = 40 +/- 0,08; C = 33 +/- 0,05; p less than 0,01. IVRT and EF slope abnormalities are related to increased myocardial stiffness and impaired LV compliance. In the absence of changes in preload and afterload, the high Weissler index reflects impaired contractility of the myocardium. These abnormalities are related neither to the duration of diabetes nor to the presence or severity of the complications. With the M mode echocardiography, mean diastolic and systolic thickness of the septum is greater in D with retinopathy than in C (p less than 0,005 and p less than 0,03 respectively); mean diastolic and systolic thickness of the posterior wall is greater in NIDD than in C (p less than 0,001 and p less than 0,025). We conclude that there is evidence of left ventricular functional abnormalities specific to diabetes and unrelated to IC and hypertension. Our findings support the hypothesis that they may be due to metabolic disorders and/or myocardial microangiopathy.