Proliferation and osteogenic differentiation of mesenchymal stem cells cultured onto three different polymers in vitro.

In this study, the osteoinductive and cell-binding properties of three different resorbable polymers were evaluated by human mesenchymal stem cells (MSCs). MSCs were isolated, expanded, and cultivated onto resorbable D,D,L,L-polylactide (PLLA), collagen I/III, and polygalactin-910/polydioxanone (PGPD) scaffolds in vitro. To evaluate the influence of dexamethasone, ascorbic acid, and beta-glycerolphosphate (DAG) on osteoblast differentiation, MSCs were incubated in a DAG-enriched medium. After a 28-day period in vitro, the cellular loaded polymers were digested enzymatically by papain and HCl. The Ca(2+) content of the biomembranes was evaluated by an o-kresolphthalein-complexon reaction via photometer. A PicoGreen assay was performed for dsDNA quantification. Significant differences between the number of adherent MSCs were documented (collagen > PLLA > PGPD). Compared to the initial number of adherent cells, all biomaterials induced a significant decrease in cellular adherence after 28 days in vitro. The presence of DAG-enriched culture medium stimulated the cellular proliferation for PLLA and slightly for PGPD, whereas cell proliferation was inhibited when MSCs were cultivated onto collagen I/III. In comparison with the control groups, all biomaterials (PLLA, PGPD, and collagen I/III) showed a significant increase in local Ca(2+) accumulation under DAG stimulation after 28 days in vitro. Furthermore, collagen I/III and PLLA scaffolds showed osteoinductive properties without DAG stimulation. These results were verified by immunocytochemical stainings against osteoblast-typical markers (osteopontin and alkaline phosphatase) and completed by calcified matrix detection (von Kossa staining). MSCs were identified by CD105 and CD13 antigen expression. Corresponding to an absence of CD34, CD45, and collagen II expression, we found no chondrogenic or hematopoietic cell differentiation. The results indicate significant differences for the proliferation, differentiation, adherence, and Ca(2+) accumulation between the tested polymers in a MSC culture.

Blood viscoelasticity response during carotid endarterectomy.

As demonstrated in many studies ischemic brain injury causes microcirculatory disturbances which is reflected in changes in the rheological behavior of blood. This is caused by multifactorial interaction between blood cells and damaged endothelium in the capillary network with release of tissue metabolites and by-products of cellular injury with resulting increased cellular permeability producing a volume shift into the interstitium and, subsequently, a rise in the hematocrit density. Drop in perfusion pressure produces an increase in whole blood viscosity. By means of an oscillating capillary rheometer and densimeter, the viscous and elastic parts of the complex viscosity of whole blood and plasma were measured from the ipsilateral internal jugular vein in 17 patients with unilateral occlusive carotid lesions during different stages of carotid endarterectomy. Our results show that fluid characteristics deteriorated significantly during carotid clamping with increase in whole blood viscoelasticity and plasma density, although collateral circulation was judged sufficient in the angiogram and cerebral perfusion pressure. These parameters not only returned to their initial value, but a significant amelioration was observed after installation of an intraluminal indwelling shunt as a response to improved orthograde flow and an enhanced shear velocity. We conclude that an increase in whole blood viscosity does correlate with decreased cerebral blood flow. This response is immediate. Hematocrit density increases significantly as a result of fluid shift into the interstitium. These changes are reversible if blood flow is promptly restored.

Preliminary clinical experience with polyurethane vascular prostheses in femoro-popliteal reconstruction.

Following promising results in animals, implantation of polyurethane vascular prostheses for femoral reconstruction was performed in 15 patients over a 10-month period. This prospective study was carried out to evaluate the patency, limb salvage and complications associated with this type of small diameter conduit for arterial occlusive diseases. The indications for surgery included acute and chronic ischaemia, non-healing ulceration or gangrene. There were five early occlusions, which resulted in a 1-month primary patency rate of 66% and a secondary patency rate of 80%. The mean limb salvage rate at 1 month was 80% and is 66% at the present time. Infection occurred in one patient following multiple attempts at graft thrombectomy. There were no statistically significant differences in patency rates between proximal and distal popliteal graft anastomoses. Two critical phases of healing were identified where the graft was prone to flow deterioration; at 4-6 weeks and at 4-6 months. It is concluded that although this type of graft has many interesting features, e.g. the presence of endothelial cells under poor haemodynamic conditions, excellent graft-host healing and good resistance at the suture site, further investigations on protein absorption and complement activation as well as intensive structural testing are required before further recommendations can be made.

Distal popliteal and tibioperoneal transluminal angioplasty: long-term follow-up.

The long-term efficacy of percutaneous transluminal angioplasty (PTA) for treatment of occlusive lesions involving arteries below the knee was evaluated in 168 consecutive patients. The procedure was preceded by intraarterial thrombolysis in 33 patients with failing femorodistal grafts. Indications were disabling claudication in 40 cases (24%), acute ischemia in 18 (11%), rest pain in 49 (29%), and tissue necrosis in 61 (36%). Angioplasty of tandem femoral and/or iliac lesions was performed in 58 cases (34.5%). Major complications were observed in 19 patients (11.3%) and minor complications in 12 others. Five patients died within 30 days (3%). Mean follow-up was 26.1 months (range, 4-72 months). Major amputation was required in 26 cases (15%). The cumulative clinical success at 3 years was 83% for a single stenosis, 76% for multilevel lesions, 44% following lytic therapy, 36% for segmental occlusions, and 14% for anastomotic stenoses. Infrapopliteal PTA is useful in selected patients. Factors associated with poor long-term patency include a single patent tibial artery (P = .039), acute ischemia (P = .03), anastomotic stenosis (P = .01), and, possibly, complete occlusion prior to treatment (P = .091).

Deep venous thrombosis: results of thrombectomy versus medical therapy. Presented at the 5th European-American Symposium on Venous Diseases, Vienna, Austria, Nov. 7-11, 1990.

Between 1.1.1985 and 1.1.1988, 158 patients were referred because of acute deep venous thrombosis. They were 82 women (median age 48.5) and 76 men (median age 56.5). On admission, 4 patients had already a pulmonary embolism in 3 others embolism occurred during hospitalisation. The segment involved was the isolated iliac in 10, iliofemoral in 53, isolated femoral in 7, femorotibial in 47 and isolated tibial in 41 patients. Anticoagulation and compression therapy was undertaken in 102 and mortality was 21%. At follow-up 63% had at least 1 sign of venous insufficiency, in all 16% had no sequelae and were subjectively symptom-free. Thrombolytic therapy was carried out in 25, mortality was 8%. At follow-up, 72% had at least one sign of venous insufficiency. Venous thrombectomy was performed in 31, combined in 4 with balloon dilatation of an iliac spur. Mortality was low with 3%, 58% had at least one sign of venous insufficiency at follow-up and 39% were subjectively symptom-free. Our results show that an objective assessment is insofar difficult because subjective and clinical results do not correlate; 51% with clinically verified post-therapeutic venous insufficiency had normal venous drainage in strain-gauge plethysmography, whilst 41% without subjective discomforts demonstrated an insufficient drainage. Our results show that a full restitution is seldom achieved, thrombectomy does not prevent chronic venous insufficiency. Best results were observed in isolated iliac thrombosis. We conclude that thrombectomy should be restricted to the phlegmasia caerulea dolens form of DVT, while floating thrombus and ascending thrombus extending into the vena cava should be treated with a cava filter or ligation.

Multimodality treatment for small cell bronchial carcinoma. Preliminary results of a prospective, multicenter trial. The ISC-Lung Cancer Study Group.

Preliminary results of the 1984 ISC (International Society of Chemotherapy) lung cancer studies I and II as of June 1990 are based on 146 patients with small cell bronchial carcinoma from 23 departments of thoracic surgery. All patients received surgery for cure in cTNM stages I and II followed by randomization for two different types of chemotherapy. For disease-free patients after completion of postoperative chemotherapy, prophylactic cranial irradiation (PCI) was administered. For the two different chemotherapeutic regimens, no statistically significant differences in survival (SVR) could be observed. Each patient was classified by the pTNM system. There were 63 patients with stage I, 44 patients with stage II and 38 patients with stage III disease. Four years after surgery, 63 patients with N0 disease had a SVR of 50%, 51 patients with N1 disease 31%, and 32 patients with N2 disease, 23%. No prolongation of brain-metastasis-free time for 62 patients receiving PCI was shown. It is concluded that initial surgical resection for small cell lung cancer in stages I and II followed by intensive chemotherapy is an appropriate therapeutic approach.

Surgical management of perforating diverticular disease in Austria.

Perforated diverticulitis is a much feared complication of diverticular disease and requires immediate surgical therapy to limit the incipient peritonitis and its sequelae. The ensuing surgical approach which could best irradiate the septic focus as well as restore normal intestinal continuity with less morbidity and mortality has been a matter of controversy. In the last ten years primary resection and colostomy has replaced the three-stage procedure in most cases of peritonitis. Primary anastomosis, when peritoneal involvement is well confined, has been shown to give excellent results. To assess the surgical management of perforating diverticulitis in Austria, a questionnaire was sent to leading hospitals throughout the country and information of 241 patients with perforating diverticulitis was compiled. The overall peroperative mortality was 9%, and the highest rate of complication (37.9%) was observed after primary resection and anastomosis with temporary defunctioning proximal colostomy. The mortality, as expected, is directly proportional to the extent of peritonitis; it was significantly greater among patients with generalised peritonitis and lowest among cases of covered perforation.

[Prevalence of malignancy in preoperatively undetermined solid round lesions]. / Malignomprävalenz präoperativer ungeklärter solitärer Rundherde.

We report on 20 patients submitted to surgery, with an average age of 53.9 years (+/- 8.8), in whom solitary pulmonary nodules were not amenable to preoperative diagnosis on the basis of biopsy material. It was shown that 35 per cent of the unclear solitary lesions were malignant. Provided that the medical risks of surgery can be justified, surgical clarification via a thoracotomy in patients in this age group is indicated.

[Therapy of carotid stenosis in contralateral occlusion of the internal carotid artery]. / Therapie von Karotis-Stenosen bei kontralateralem Verschluss der Arteria carotis interna.

From January 1985 up to December 1987 sixteen patients with unilateral stenosis of the internal carotid artery (ICA) and concomitant chronic contralateral carotid occlusion underwent surgical correction of the stenosis. 31.2% were asymptomatic, 18.7% had transient ischemic attacks and 50% had suffered a stroke. On the occluded side 31.2% had had a stroke. Angiography showed intracerebral shunting to the occluded side in 43.7%; 56.2% of the patients had concomitant stenoses of intracerebral vessels. Surgical correction consisted of endarterectomy and patch-plasty of the ICA-stenosis in local anesthesia under protection of an intraluminal shunt. There was no mortality and no perioperative stroke. After a mean interval of 32 months life table analysis showed a stroke-free rate of 92% from 6 to 24 months on the operated side and of 84% from 12 to 24 months on the occluded side. We conclude that ICA-endarterectomy in patients with contralateral ICA-occlusion can be done without increased perioperative risk and yields satisfactory long time results.

[Clinical and surgical therapy of phlegmasia coerulea dolens]. / Klinik und chirurgische Therapie der Phlegmasia coerulea dolens.

Venous thrombectomy was performed on 123 patients with phlegmasia coerulea dolens (blue phlebitis). Best results are obtained if treatment is initiated at the earliest stage. Arterial involvement must be closely monitored. A fasciotomy, which in some cases may involve the fascia lata, must be performed in case of compartment compression. Palma's bypass procedure and Av-fistula are indicated in some cases.

The importance of surgery as the first step in multimodality treatment of small cell bronchial carcinoma. The ISC Lung Cancer Study Group.

For patients with small cell lung cancer (SCLC) in their early stages (TNM I, II), surgery for cure was used to eliminate the primary tumour and its regional lymph-nodes followed by intermittent chemotherapy and radiotherapy within the first six postoperative months. After the pathohistological examination of the operation-specimen a two-arm-randomization was performed: standard chemotherapy (1000 mg/m2 cyclophosphamide, 50 mg/m2 doxorubicin, 1.4 mg/m2 vincristine) compared with sequential chemotherapy using three different drug-combinations (A: 1500 mg/m2 cyclophosphamide, 100 mg/m2 lomustine, 15 mg/m2 methotrexate; B: 1000 mg/m2 cyclophosphamide, 40 mg/m2 doxorubicin, 1 mg/m2 vincristine; C: 5 x 1.6 g/m2 ifosfamide plus mesna, 5 x 120 mg/m2 etopside). Thereafter disease-free patients only received prophylactic cranial irradiation (PCI: administering 3600 TD Gy/18 fractions) according to the protocols of the International Society of Chemotherapy Studies I and II. Preliminary evaluations in March 1990 of 170 patients from 24 cooperating departments for thoracic surgery showed that the projected life-table four-year-survival rate of 63 patients with SCLC at pTNM-stage I was 61%, of 54 patients at pTNM-stage II was 35%, of 13 patients at stage pT3, 4 NO, 1 MO was 59% and of 40 patients at stage pT N2 MO was 35%. The indication for surgery is emphasized for pTNM-stages I + II. For N2-lesions surgery would not be recommended in general, but the survival rate seems to indicate that this treatment was not detrimental, being rather more favourable compared with chemotherapy or radiotherapy alone. The continuation and enlargement of these studies seem not only justified, but emphatically indicated.(ABSTRACT TRUNCATED AT 250 WORDS)

[Diagnostic viewpoints in deep leg-/pelvic venous thrombosis]. / Diagnostische Gesichtspunkte bei tiefer Bein-/Beckenvenenthrombose.

In 60 to 90% of patients with deep vein thrombosis, successful recanalization with prevention of postthrombotic syndrome and decreased risk of pulmonary embolism can be achieved through early diagnosis and aggressive treatment, thrombolysis or surgical correction. In our experience, if treatment is delayed more than four days after onset, the results are unfavorable; in the latter case, provided necrotizing inflammation is not present, we treat only with anticoagulation. The indication for surgery is considered established if thrombolytic treatment is contraindicated, in the presence of necrotizing inflammation, if thrombolysis is unsuccessful and for recurrent pulmonary embolism which is carried out mostly with a caval filter. Anticoagulation alone in most patients will not lead to successful results. Sixty percent of deep vein thromboses arise ascending from lower leg thromboses. Further points of predilection are the junctions of the popliteal vein, the veins in the inguinal region and the caval bifurcation. In principle, any calf pain should suggest the possibility of beginning lower leg thrombosis. With regard to the history, it is important to know if the event is the first of its kind or recurrent (Table 1). Additionally, deep vein thrombosis may be suspected in the presence of local trauma, in women on contraceptives, in patients with hemoblastoses, after surgery in the lower pelvic or leg region and, in particular in women, in the presence of pelvic venous impediment.(ABSTRACT TRUNCATED AT 250 WORDS)

The importance of surgical and multimodality treatment for small cell bronchial carcinoma.

In a cooperative international lung cancer multimodality treatment trial, 112 patients with small cell lung cancer underwent initial surgical resection and were then randomized to receive one of two intensive postoperative chemotherapeutic regimens, followed by prophylactic cranial irradiation in the disease-free patients. Regimen A consisted of eight courses of cyclophosphamide, doxorubicin, and vincristine and regimen B of two courses of three sequential drug combinations: (1) cyclophosphamide, lomustine, and methotrexate; (2) cyclophosphamide, doxorubicin, and vincristine; and (3) ifosfamid and etoposide. In 47 patients the diagnosis was known preoperatively and in 65 it was not confirmed until the resected specimen was examined (all diagnoses were reviewed by a referee pathologist). Each patient was classified by the pathologic TNM characteristics. There were 38 patients with stage I disease, 39 patients with stage II, and 35 patients with stage IIIa disease. In stage IIIa there were nine patients with T3 N0-1 disease and 26 with T1-3 N2 disease (most N2 disease was clinically undetected until thoracotomy or was discovered only by routine histologic examination of the resected mediastinal nodes). Early survival rates at 24 months calculated by the life table method are as follows: stage I, 76%; stage II, 56%; and stage IIIa, 49% (T3 N0-1, 89%; T1-3 N2, 35%). Survival rates at 36 months are 62%, 50%, and 41% (74% and 29%), respectively. The projected 36-month survival rate for 43 patients with N0 disease is 65%; for 43 with N1 disease, 52%; and for 26 with N2 disease, 29%. No difference in survival has been noted in either chemotherapy treatment group. It is concluded that initial surgical resection for limited small cell cancer (stage I, II, and T3 N0-1) followed by intensive chemotherapy is an appropriate therapeutic approach. For T1-3 N2 disease the results are inconclusive.

[Early and late pleural decortication--indications and technique]. / Früh- und Spätkortikation--Indikation und Technik.

Our experience with 224 decortications performed between 1957 and 1987 is reported. Insufficient drainage of tuberculous and unspecific pleural empyema was the main indication. Haemothorax, pleural loculation and chronic serofibrinous pleuritis were indications of secondary importance. Mortality following decortication was on the order of 0.1% and postoperative morbidity, 3%. However, in the past 10 years there has been a general reduction of aggressive surgical treatment. Whereas decortication and thoracoplasty account for 12% and 4% respectively of our surgical pulmonary procedures, therapy with closed-tube drainage has increased to 84%.

The role of ifosfamide and cyclophosphamide in the multi-modality treatment after surgery for cure for small-cell bronchial carcinomas (SCLC).

For the optimisation of the therapy for small cell bronchial carcinomas (SCLC), surgery is used to eliminate the primary tumor and its regional lymph nodes and chemo- and radiotherapy for the general treatment of micrometastasis. After patho-histological examination of the operation specimen, randomization for two arms is performed for a standard chemotherapy (CAV) or a sequential chemotherapy using three different drug combinations. Thereafter all disease-free patients receive prophylactic cranial irradiation (PCI). Preliminary evaluations in December 1987, of 112 patients from 19 cooperating departments show that the survival rate projected for 2 yr of 43 patients at stage pT1-3 N0 M0 is 76%, of 43 patients at stage pT1-3 N1 M0 it is 63% and of 26 patients at stage pT1-3 N2 M0 it is 38%.

Anastomotic aneurysms--an unsolvable problem.

Despite the advances in reconstructive vascular surgery anastomotic pseudoaneurysms have remained a serious problem. Even if a faultless operative technique is used this complication cannot always be averted. In order to avoid rupture or thromboembolism and to improve the patient's prognosis we suggest that all pseudoaneurysms are treated surgically except in poor risk patients. Between 1981 and 1986 119 anastomotic aneurysms in 68 patients were operated on in our department. 31.0% presented as infected aneurysms. 13.1% were recurrent after preceding aneurysm repair. The most common site was the femoral region following aortobifemoral bypass. Host vessel degeneration and acute inflammation of the anastomotic site seem to be the most important causative factors. Surgical repair usually consisted of resecting the anastomosis together with part of the host artery; in septic aneurysms limb salvage was attempted using extra-anatomic bypass. Postoperative mortality was 8.8%, minor complications occurred in 10.9%; 9 patients (13.1%) had to have an amputation.

[Reconstructive interventions of the superior vena cava]. / Rekonstruktive Eingriffe an der Vena cava superior.

Twenty-nine reconstructions of the vena cava superior were performed: twice due to obliterating mediastinopericarditis, twice because of post-traumatic thrombosis, 4 times because of iatrogenic thrombosis, once because of an arteriovenous fistula and 24 times due to malignant tumours. In nine of the latter cases a large resection with prosthetic repair of the vena cava superior was necessary; one of these patients died and the others had no recurrence of thrombosis.