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Based on the lack of differences in progression-free and overall survival after a median follow-up of 93 months in our HOVON-65/GMMG-HD4 trial (German part; n = 395) randomizing VAD induction (vincristin/adriamycin/dexamthasone)/tandem-transplantation/thalidomide-maintenance vs. PAD induction (bortezomib/adriamycin/dexamethasone)/tandem transplantation/bortezomib maintenance, we discern how chromosomal aberrations determine long-term prognosis by different patterns of association with proliferation and treatment-dependent response, whether responses achieved by different regimens are equal regarding prognosis, and whether subpopulations of patients could be defined as treatable without upfront "novel agents" in cases of limited resources, e.g., in low- or middle-income countries. Serum parameters and risk factors were assessed in 395 patients. CD138-purified plasma cells were subjected to fluorescence in situ hybridization ( n = 354) and gene expression profiling ( n = 204). We found chromosomal aberrations to be associated in four patterns with survival, proliferation, and response: deletion (del) del17p13, del8p21, del13q14, (gain) 1q21+, and translocation t(4;14) (all adverse) associate with higher proliferation. Of these, del17p is associated with an adverse response (pattern 1), and 1q21+, t(4;14), and del13q14 with a treatment-dependent better response (pattern 2). Hyperdiploidy associates with lower proliferation without impacting response or survival (pattern 3). Translocation t(11;14) has no association with survival but a treatment-dependent adverse response (pattern 4). Significantly fewer patients reach a near-complete response or better with "conventional" (VAD) vs. bortezomib-based treatment after induction or high-dose melphalan. These patients, however, show significantly better median progression-free and overall survival. Molecularly, patients responding to the two regimens differ in gene expression, indicating distinct biological properties of the responding myeloma cells. Patients with normal renal function (89.4%), low cytogenetic risk (72.5%), or low proliferation rate (37.9%) neither benefit in progression-free nor overall survival from bortezomib-based upfront treatment. We conclude that response level, the treatment by which it is achieved, and molecular background determine long-term prognosis. Chromosomal aberrations are associated in four patterns with proliferation and treatment-dependent responses. Associations with faster and deeper responses can be deceptive in the case of prognostically adverse aberrations 1q21+ and t(4;14). Far from advocating a return to "outdated" treatments, if resources do not permit state-of-the-art-treatment, normal renal function and/or molecular profiling identifies patient subpopulations doing well without upfront "novel agents".

First-line therapy for younger patients with peripheral T-cell non-Hodgkin lymphoma (T-NHL) consists of 6 courses of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) with or without etoposide (CHOEP), consolidated by high-dose therapy and autologous stem cell transplantation (auto-SCT). We hypothesized that allogeneic stem cell transplantation (allo-SCT) could improve outcomes. 104 patients with peripheral T-cell non-Hodgkin lymphoma, except ALK+ anaplastic large cell lymphoma, 18 to 60 years, all stages, and all age adjusted International Prognostic Index scores, except 0 and stage I, were randomized to 4 cycles of CHOEP and 1 cycle of dexamethasone, cytosine-arabinoside, and platinum (DHAP) followed by high-dose therapy and auto-SCT or myeloablative conditioning and allo-SCT. The primary end point was event-free survival (EFS) at 3 years. After a median follow-up of 42 months, the 3-year EFS after allo-SCT was 43%, as compared with 38% after auto-SCT. Overall survival at 3 years was 57% vs 70% after allo- or auto-SCT, without significant differences between treatment arms. None of the 21 responding patients proceeding to allo-SCT relapsed, as opposed to 13 of 36 patients (36%) proceeding to auto-SCT. Eight of 26 patients (31%) and none of 41 patients died of transplant-related toxicity after allo- and auto-SCT, respectively. The strong graft-versus-lymphoma effect after allo-SCT was counterbalanced by transplant-related mortality. This trial is registered at www.clinicaltrials.gov as #NCT00984412., (© 2021 by The American Society of Hematology.)

Background: Smoking is suspected to not only be a risk factor for chronic myeloid leukemia but an adverse prognostic factor for the disease as well. The objective of the current study was to investigate the impact of smoking on survival and progression to advanced phases of disease., Methods: Based on the data of the German CML Study IV, the authors analyzed the effect of smoking using a multivariate Cox model with the addition of the European Treatment and Outcome Study (EUTOS) long-term survival score variables of age, spleen size, thrombocytes, and peripheral blasts as well as sex, comorbidities, and type of treatment center., Results: The 8-year survival probability was 87% for a nonsmoking patient and 83% for a patient who smoked. The authors noted a 2.08-times higher risk of death for smokers in comparison with nonsmokers and a 2.11-times higher cause-specific hazard of disease progression. An interaction between smoking and age was found in the model for survival. No significant difference with regard to molecular response was observed., Conclusions: Even when considering differences in socioeconomic status and lifestyle between patients who smoke and nonsmokers, the current analysis demonstrated that smoking also might affect disease biology. The results of the current study indicate that patients with chronic myeloid leukemia, in particular those aged <60 years, should be encouraged to quit smoking. Cancer 2017;123:2467-71. © 2017 American Cancer Society., (© 2017 American Cancer Society.)

To tailor the nanomorphology in polymer/fullerene blends, we study the effect of electrostatic field (E-field) on the solidification of poly(3-hexylthiophene-2, 5-diyl) (P3HT):[6,6]-phenyl-C61-butyric acid methyl ester (PC 60 BM) bulk heterojunction (BHJ). In addition to control; wet P3HT:PC 60 BM thin films were exposed to E-field of Van de Graaff (VDG) generator at three different directions-horizontal (H), tilted (T), and vertical (V)-relative to the plane of the substrate. Surface and bulk characterizations of the field-treated BHJs affirmed that fullerene molecules can easily penetrate the spaghetti-like P3HT and move up and down following the E-field. Using E-field treatment, we achieved favorable morphologies with efficient charge separation, transport, and collection. We improve; (1) the hole mobility values up to 19.4 × 10 -4 ± 1.6 × 10 -4 cm 2 V -1 s -1 and (2) the power conversion efficiency (PCE) of conventional and inverted OPVs up to 2.58 ± 0.02% and 4.1 ± 0.40%, respectively. This E-field approach can serve as a new morphology-tuning technique, which is generally applicable to other polymer-fullerene systems.

Langmuir-Blodgett films of polyvinylidene fluoride trifluoroethylene - P(VDF-TrFE)-copolymers possess substantially improved electrocaloric and pyroelectric properties, when compared with conventionally spin-cast films. In order to rationalize this, we prepared single-layered films of P(VDF-TrFE) (70 : 30) using both deposition techniques. Grazing incidence wide-angle X-ray scattering (GIWAXS), reveals that Langmuir-Blodgett deposited films have a higher concentration of the ferroelectric β-phase crystals, and that these films are highly oriented with respect to the substrate. Based on these observations, we suggest alternative means of deposition, which may substantially enhance the electrocaloric effect in P(VDF-TrFE) films. This development has significant implications for the potential use of P(VDF-TrFE) in solid-state refrigeration.

Renal impairment is frequent in patients with multiple myeloma and is correlated with an inferior prognosis. This analysis evaluates the prognostic role of renal impairment in patients with myeloma treated with bortezomib before and after autologous stem cell transplantation within a prospective randomized phase III trial. Eight hundred and twenty-seven newly diagnosed myeloma patients in the HOVON-65/GMMG-HD4 trial were randomized to receive three cycles of vincristine, adriamycin, dexamethasone (VAD) or bortezomib, adriamycin, dexamethasone (PAD) followed by autologous stem cell transplantation and maintenance with thalidomide 50 mg daily (VAD-arm) or bortezomib 1.3 mg/m(2) every 2 weeks (PAD-arm). Baseline serum creatinine was less than 2 mg/dL (Durie-Salmon-stage A) in 746 patients and 2 mg/dL or higher (stage B) in 81. In myeloma patients with a baseline creatinine ≥ 2 mg/dL the renal response rate was 63% in the VAD-arm and 81% in the PAD-arm (P=0.31). The overall myeloma response rate was 64% in the VAD-arm versus 89% in the PAD-arm with 13% complete responses in the VAD-arm versus 36% in the PAD-arm (P=0.01). Overall survival at 3 years for patients with a baseline creatinine ≥ 2 mg/dL was 34% in the VAD-arm versus 74% in the PAD-arm (P<0.001) with a progression-free survival rate at 3 years of 16% in the VAD-arm versus 48% in the PAD-arm (P=0.004). Overall and progression-free survival rates in the PAD-arm were similar in patients with a baseline creatinine ≥ 2 mg/dL or <2 mg/dL. We conclude that a bortezomib-containing treatment before and after autologous stem cell transplantation overcomes the negative prognostic impact of renal impairment in patients with newly diagnosed multiple myeloma. The trial was registered at www.trialregister.nl as NTR213 and at www.controlled-trials.com as ISRCTN 64455289.

Purpose: The introduction of BEACOPP(escalated) (escalated-dose bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) has significantly improved tumor control and overall survival in patients with advanced-stage Hodgkin lymphoma. However, this regimen has also been associated with higher treatment-related mortality (TRM). Thus, we analyzed clinical course and risk factors associated with TRM during treatment with BEACOPP(escalated)., Patients and Methods: In this retrospective analysis, we investigated incidence, clinical features, and risk factors for BEACOPP(escalated)-associated TRM in the German Hodgkin Study Group trials HD9, HD12, and HD15., Results: Among a total of 3,402 patients, TRM of 1.9% (64 of 3,402) was mainly related to neutropenic infections (n = 56; 87.5%). Twenty of 64 events occurred during the first course of BEACOPP(escalated) (31.3%). Higher risk of TRM was seen in patients age ≥ 40 years with poor performance status (PS) and in patients age ≥ 50 years. PS and age were then used to construct a new risk score; those with a score ≥ 2 had TRM of 7.1%, whereas patients who scored 0 or 1 had TRM of 0.9%., Conclusion: The individual risk of TRM associated with BEACOPP(escalated) can be predicted by a simple algorithm based on age and PS. High-risk patients should receive special clinical attention.

Multiple trauma during pregnancy is a relatively rare situation which poses a great challenge for the team in charge of treatment. A concomitant disease, such as thrombotic thrombocytopenic purpura (TTP) with thrombocytic coagulopathy increases the complexity of the treatment problems. This article describes the case of a 36-year-old pregnant woman referred to this hospital suffering from multiple trauma with severe liver rupture. Stabilization was achieved after an emergency Caesarean section and packing of the liver. Recurrent massive bleeding from the liver occurred after depacking and was treated successfully with recombinant factor VIIa. The concomitant TTP was treated by transfusion of fresh frozen plasma and corticosteroids. Rapid initiation of therapy was the goal to achieve hemostasis and prevent aggravation of the coagulation disorder and an unfavourable outcome despite severe thrombocytopenia.

Purpose: We investigated whether bortezomib during induction and maintenance improves survival in newly diagnosed multiple myeloma (MM)., Patients and Methods: In all, 827 eligible patients with newly diagnosed symptomatic MM were randomly assigned to receive induction therapy with vincristine, doxorubicin, and dexamethasone (VAD) or bortezomib, doxorubicin, and dexamethasone (PAD) followed by high-dose melphalan and autologous stem-cell transplantation. Maintenance consisted of thalidomide 50 mg (VAD) once per day or bortezomib 1.3 mg/m(2) (PAD) once every 2 weeks for 2 years. The primary analysis was progression-free survival (PFS) adjusted for International Staging System (ISS) stage., Results: Complete response (CR), including near CR, was superior after PAD induction (15% v 31%; P < .001) and bortezomib maintenance (34% v 49%; P < .001). After a median follow-up of 41 months, PFS was superior in the PAD arm (median of 28 months v 35 months; hazard ratio [HR], 0.75; 95% CI, 0.62 to 0.90; P = .002). In multivariate analysis, overall survival (OS) was better in the PAD arm (HR, 0.77; 95% CI, 0.60 to 1.00; P = .049). In high-risk patients presenting with increased creatinine more than 2 mg/dL, bortezomib significantly improved PFS from a median of 13 months to 30 months (HR, 0.45; 95% CI, 0.26 to 0.78; P = .004) and OS from a median of 21 months to 54 months (HR, 0.33; 95% CI, 0.16 to 0.65; P < .001). A benefit was also observed in patients with deletion 17p13 (median PFS, 12 v 22 months; HR, 0.47; 95% CI, 0.26 to 0.86; P = .01; median OS, 24 months v not reached at 54 months; HR, 0.36; 95% CI, 0.18 to 0.74; P = .003)., Conclusion: Bortezomib during induction and maintenance improves CR and achieves superior PFS and OS.

In patients with multiple myeloma (MM), risk stratification by chromosomal abnormalities may enable a more rational selection of therapeutic approaches. In the present study, we analyzed the prognostic value of 12 chromosomal abnormalities in a series of 354 MM patients treated within the HOVON-65/GMMG-HD4 trial. Because of the 2-arm design of the study, we were able to analyze the effect of a bortezomib-based treatment before and after autologous stem cell transplantation (arm B) compared with standard treatment without bortezomib (arm A). For allanalyzed chromosomal aberrations, progression-free survival (PFS) and overall survival (OS) were at least equal or superior in the bortezomib arm compared with the standard arm. Strikingly, patients with del(17p13) benefited the most from the bortezomib-containing treatment: the median PFS in arm A was 12.0 months and in arm B it was 26.2 months (P = .024); the 3 year-OS for arm A was 17% and for arm B it was 69% (P = .028). After multivariate analysis, del(17p13) was an independent predictor for PFS (P < .0001) and OS (P < .0001) in arm A, whereas no statistically significant effect on PFS (P = .28) or OS (P = .12) was seen in arm B. In conclusion, the adverse impact of del(17p13) on PFS and OS could be significantly reduced by bortezomib-based treatment, suggesting that long-term administration of bortezomib should be recommended for patients carrying del(17p13).

Pulmonary complications together with surgical complications are the most frequent causes for morbidity and mortality after thoracoabdominal esophagectomy. The con-tinuous improvement of surgical techniques has led to a decrease in surgical complications, whereas up to 30% of the patients develop postoperative pulmonary complications such as acute lung injury (ALI) or even the more severe acute respiratory distress syndrome (ARDS), which are characterized by an acute inflammation in the lung parenchyma and the airspace. Evidence from several studies indicates that a complex network of inflammatory cytokines and mediators play a key role in mediation, amplification, and perpetuation of the process of lung injury and that the thoracotomy itself is a risk factor for developing ALI or ARDS. In this trial, the cytokine levels of IL6, IL8 and IL10 were measured and compared in 30 patients who had undergone an extended radical thoracoabdominal esophagectomy for esophageal cancer, via anterolateral thoracotomy (n=17) or posterolateral thoracotomy (n=13). Patients of both groups were similar in terms of age, sex and preoperative pulmonary function as well as in the anesthetic procedures they have undergone. All patients displayed significantly increased serum levels of IL6 and IL8 after thoracoabdominal esophagectomy. However, patients who were subjected to an anterolateral thoracotomy were reported with significantly higher serum levels of IL6 and IL8 compared to patients who had received a posterolateral thoracotomy. Thus, the choice of the thoracotomy method during the thoracoabdominal esophagectomy and the resultant cytokine levels may contribute to the occurrence of postoperative pulmonary complications and may have an impact on the extent and severity of the surgical stress.

Salinity negatively impacts plant growth and productivity, and little is known about salt responsive genes in cotton. In this study, an intra-specific backcross population of cotton (Gossypium hirsutum L.) was treated with 200 mM NaCl after which differentially expressed genes were identified by comparison between salt tolerant and susceptible segregant bulks using comparative microarray analysis. Microarray analysis identified 720 salt-responsive genes, of which 695 were down-regulated and only 25 were up-regulated in the salt tolerant bulk. Gene ontology of annotated genes revealed that at least some of the identified salt responsive transcripts belong to pathways known to be associated with salt stress including osmolyte and lipid metabolism, cell wall structure, and membrane synthesis. About 48% of all salt-responsive genes were functionally unknown. Quantitative RT-PCR was used to validate 17 selected salt responsive genes. This work represents the first study in employing microarray to investigate the possible mechanisms of the salt response in cotton. Further analysis of salt-responsive genes associated with salt tolerance in cotton will assist in laying a foundation for molecular manipulation in development of new cultivars with improved salt tolerance., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Prostheto-ureteral fistula after aortic graft surgery is a potentially life-threatening, rare pathology. We report the successful treatment of a prostheto-ureteral fistula that caused hematuria with hemorrhagic shock in two patients by explantation of aortic prosthetic grafts and implantation of a silver-bonded prosthetic graft (Intergard S, Intervascular). These cases show that this surgical procedure is effective, and that straightforward diagnostic procedures are necessary to initiate correct therapeutic approach without delay. Various different possible risk factors for the formation of a prostheto-ureteral fistula are also discussed., (Copyright 2010 Annals of Vascular Surgery Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Therapy of unresectable hepatic metastases may include tumor necrosis factor (TNF)-alpha treatment. Because of its serious systemic side effects, TNF-alpha is only used in isolated hepatic perfusion. This, however, is a technically demanding procedure with a substantial mortality rate. The infusion of TNF-alpha via the hepatic artery without hepatic isolation would be less invasive. Systemic side effects, however, have not been studied yet. Therefore, we evaluated in pigs the effects of TNF-alpha hepatic artery infusion (HAI) on systemic hemodynamics, inflammation, and organ injury., Methods: Animals were randomized in three groups. In group 1, HAI was performed with 0.9% NaCl (n = 6). In group 2, 20 microg/kg TNF-alpha (n = 6), and in group 3, 40 microg/kg TNF-alpha (n = 6) were added. HAI was performed over 15 min, followed by 120 min of observation. Finally, 250 ml hydroxyethylstarch (HAES; 6%) was administered for resuscitation and hemodynamics were analyzed for another 30 min., Results: Hepatic artery TNF-alpha infusion did not cause complications such as bleeding, cardiac depression, pulmonary dysfunction, or SIRS. TNF-alpha induced a 30% decrease of MAP and systemic vascular resistance, as well as a rise in heart rate and endexspiratory pCO(2). TNF-alpha also moderately (10-20%) lowered the cardiac preload and induced a metabolic acidosis, which, however, could easily be controlled. TNF-alpha HAI did not induce liver toxicity, and all hemodynamic changes normalized either spontaneously within the 120-min observation period, or, at least, after HAES resuscitation., Conclusions: TNF-alpha-based HAI, which may represent a minimally invasive alternative to isolated hepatic perfusion, can be performed without early systemic hemodynamic complications.

Background: This paper evaluates the prognostic and predictive impact of protein expression of various molecular markers in high-risk breast cancer (HRBC) patients with >9 involved lymph nodes, who received different chemotherapy dose-intensification strategies within a prospective randomized WSG AM-01 trial., Materials and Methods: Paraffin-embedded tumors from 236 patients, who were randomly assigned to dose-dense conventional chemotherapy with four cycles of E(90)C(600) followed by three cycles of C(600)M(40)F(600) every 2 weeks (DD) or a rapidly cycled tandem high-dose regimen with two cycles of E(90)C(600) every 2 weeks followed by two cycles of E(90)C(3000)Thiotepa(400) every 3 weeks (HD), were available for retrospective central pathological review (116 HD/120 DD). Expression of estrogen receptor (ER), progesterone receptor (PR), MIB-1, epidermal growth factor receptor, and Her-2/neu was evaluated immunohistochemically using tissue microarrays. Results were correlated with follow-up data and treatment effects by proportional hazard Cox regression models (including interaction analysis)., Results: After a median follow-up of 61.7 months, 5-year event-free survival (EFS) as well as overall survival (OS) rates for the 236 patients were significantly better in the HD arm: EFS: 62% versus 41% [hazard ratio (HR) = 0.60, 95% CI 0.43-0.85, P = 0.004]; OS: 76% versus 61% (HR = 0.58, 95% CI 0.39-0.87, P = 0.007). In multivariate analysis, HD, tumor size <3 cm, positive PR, negative MIB-1 staining, and grade 1/2 were associated with favorable outcome. Interaction analysis showed that regarding predictive effects, triple negative (ER/PR/Her-2/neu) and G3 tumors derived most benefit from HD., Conclusion: Tandem HD improves both EFS and OS in HRBC. This therapy effect may be partly attributable to superior efficacy in the subgroup of triple-negative tumors and/or G3 with their poor prognostic marker profile.

Purpose: Transanal endoscopic microsurgery (TEM) is a technique that has found its place in routine practice due to its minimal invasive character and associated low morbidity. The purpose of this study was to assess the influence of anatomical variables of rectal neoplasms as well as surgeon experience on postoperative complications in patients undergoing TEM at a tertiary care center., Methods: Data from 288 patients undergoing TEM over a 16 year period were entered in a prospective data base. Anatomical data of rectal neoplasms, operative data, and early postoperative outcome were analyzed retrospectively., Results: Overall surgical complications [OR 7.0 (1.5-45,5); p < 0.01] and bleeding [OR 222 (82 - 14316); p < 0.01] correlated with the localization of the neoplasm on the lateral wall of the rectum. Furthermore there was a trend for more surgical overall complications as well as bleeding in neoplasms with a diameter of >2 cm and neoplasms located >8 cm from the anal verge. Complications did not correlate with the number of TEM procedures performed., Conclusion: TEM resection of neoplasms located on the lateral rectal wall have a higher risk of bleeding. The learning curve for transanal endoscopic microsurgery appears to be negligible in surgeons with experience in minimal invasive surgery.

Background: In case of advanced colorectal cancer or other malignancies with pelvic involvement, tumor invasion of the ureter may afford partial ureteral resection for curative multivisceral resection. One preferable approach for the primary reconstruction of the urinary tract to preserve the ipsilateral kidney and maintain normal urinary function is transureteroureterostomy, i.e. termino-lateral anastomosis of both ureters., Materials and Methods: Between June 2001 and August 2004, 15 multivisceral en bloc resections including a distal tumor-infiltrated ureteral segment were performed. Reconstruction was achieved by transureteroureterostomy with or without additional insertion of double J stents. Clinical outcome and especially complications of the urinary tract were monitored within the follow-up-period until August 2005., Results: Post-operative course was uncomplicated in 12 cases and double J stents were removed after ultrasound control on the 14th post-operative day. Percutaneous nephrostomy was post-operatively necessary in three patients who were initially operated without insertion of double J catheters: two suffered from leakage of the transureteroureterostomy and one patient had bilateral hydronephrosis due to stenosis of the transureteroureterostomy. After 6 weeks, percutaneous nephrostomy could be removed and urine flow was uncomplicated in all three patients., Conclusion: For patients with advanced colorectal cancer or other pelvic malignancy, transureteroureterostomy is a favourable technique for definitive reconstruction of the urinary tract whenever tumor resection affords partial ureteral resection. Intra-operative insertion of double J stents into both ureters is highly recommended to prevent leakage or stenosis of the anastomosis.

Background: Surgical resection is the most effective therapy for liver cancer. Intraoperative blood loss during liver resection remains a major concern due to association with higher postoperative complications. The InLine radiofrequency ablation device (ILRFA) has achieved promising results in liver surgery with minimal blood loss and no increase of postoperative complications. In this multicentre controlled study, 108 patients undergoing liver resection were investigated., Patients and Methods: A total of 108 patients underwent liver resections in 4 medical centres; the prospective sequential cohort study consisted of 54 ILRFA and 54 ultrasonic surgical aspirator transections as the control group., Results: The type of liver resection performed was very similar in both groups. The median number of RFA deployments was 3 (range 1-12) with a median coagulation time of 9 (range 3-36) min. Median blood loss was 165+/-20 ml (range 5-675) in the ILRFA and 654+/-83 ml (range 80-3600) in the control group (p<0.001). The median transection time was 27 (2-219) min in the ILRFA group and 35 (5-62) min in controls., Conclusions: Our study indicates that ILRFA device for liver transection is effective in reducing blood loss and is safe. Precoagulation before parenchymal transection appears to be a valid concept in liver surgery. The avoidance of vascular inflow occlusion during parenchymal transection could also be of value.

Serological screening approaches have allowed for the identification of a large number of potentially relevant tumor antigens in cancer patients. Within this group, cancer testis antigens represent promising targets for cancer immunotherapy, since they are widely expressed in a variety of human cancer entities. In pancreatic cancer, however, there are only few data available about the expression pattern and serological response to cancer testis antigens and other serological-defined tumor antigens. Therefore, we investigated the IgG antibody response against 11 cancer testis antigens (SCP-1, GAGE, LAGE-1a,-1b, CT-7, NY-ESO-1, SSX-1-5) recombinantly expressed on yeast surface (RAYS) in patients with pancreatic cancer (n = 96), chronic pancreatitis (n = 18) and healthy donors (n = 48). We found in 14% of all patients antibody responses to SCP-1, but not to other cancer testis antigens (GAGE, LAGE-1a,-1b, CT-7, NY-ESO-1, SSX-1-5). Antibody response correlated with the expression of SCP-1 in the primary tumor of the respective patient as shown by RT-PCR, immunohistochemistry and Western blot. In contrast, no serological response to cancer testis antigens was observed in healthy donors. The humoral immune response against SCP-1 was associated with the size of tumor, but not with other clinico-pathological parameters such as histology, stage, presence of lymph node metastases, grading, age, gender or gemcitabine treatment. In conclusion, antibody response to cancer testis antigen SCP-1 is found in a proportion of pancreatic carcinoma patients. These results indicate that identification of additional tumor antigens by serological screening of tumor cDNA expression libraries by RAYS is a promising goal in pancreatic cancer.

Introduction: Guidelines for the treatment of complicated sigmoid diverticulitis recommend Hartmann's procedure or anastomosis with protective colostomy for Hinchey stage III diverticulitis and Hartmann's procedure only for Hinchey stage IV diverticulitis. We evaluated the outcome of patients with perforated sigmoid diverticulitis Hinchey III/IV undergoing one-stage colon resection and primary anastomosis without protective colostomy., Methods: After implementation of a protocol to treat Hinchey III/IV diverticulitis with primary anastomosis without protective ileocolostomy, the patients' data were recorded prospectively between August 2001 and August 2003 and analyzed retrospectively from a computer-related database., Results: Of 41 patients, 34 (81%) underwent one-stage sigmoid resection and primary anastomosis, 3 of 41 patients (7%) underwent primary anatomosis with protective ileostomy, and 5 of 41 patients (12%) had a Hartmann's procedure. The mortality was 11% in patients undergoing primary anastomosis and 60% in patients with Hartmann's procedure. The relative risk of co-morbidity factors for lethal outcome after sigmoid resection was 6.94 for preceding operations, 3.75 for renal failure or renal transplantation, and 3.25 for immunosuppression., Conclusions: One-stage sigmoid resection and primary anastomosis can be performed safely in nearly 90% of all patients with perforated sigmoid diverticulitis (Hinchey III/IV) by surgeons of different training levels. Patients with immunosuppression, chronic renal failure, liver cirrhosis, or previous organ transplantation or complex cardiovascular reconstructive procedures have a significantly increased risk of dying after sigmoid resection for perforated diverticulitis.

The determination of nitrogen (N) based loading rates for land application of biosolids is challenging and site specific. Over loading may contribute to environmental, agricultural, or human health problems. The objective of this study was to monitor N mineralization and losses in a moderately alkaline and calcareous desert soil amended with either anaerobically digested (AN) or lime-stabilized (LS) biosolids, and irrigated with and without urea enriched water. For Experiment 1, N inputs, leaching and residuals in soil were evaluated in an open soil column system. For Experiment 2, ammonia (NH(3)) emissions were evaluated in a closed soil column system. In Experiment 1, AN and LS biosolids increased soil ON (organic N) by three and two fold, respectively. Respective net N mineralization of ON from biosolids alone was 90% and 62% without urea, and 71% and 77%, respectively with added urea. Nitrogen leaching losses and residuals in amended soil did not account for all N inputs into the soil/biosolids system. In Experiment 2, NH(3) emissions were not significantly different among treated soils with or without added urea, except LS amended soil receiving urea. Ammonia losses did not account for unaccounted N in Experiment 1. We concluded that deep placement and rapid mineralization of AN biosolids promoted anaerobic soil conditions and denitrification, in addition to the high denitrification potential of desert soil. LS biosolids showed greater potential than AN biosolids for safe and beneficial land application to desert soils regardless of biosolids placement and the inclusion of N rich irrigation water.

Background and Objective: In analogy to industrial process management, clinical pathways have been introduced for operational process organisation in orthopedic and interventional procedures as well as for conservative treatments. Within this study, introduction and continuous, systematic application of clinical pathways at a surgical department of a university hospital was investigated., Methods: Analysis was performed by IT-based (SAP/i. s. h.med) evaluation of the registered data regarding pathway violations. Additionally, patients' records were matched with the computerized data for quality assurance of pathway documentation., Results: 501 patients were entered in 16 clinical pathways (31 +/- 39 patients per pathway). The mean period from the introduction of a distinct pathway to the data acquisition of the present study ranged from 2 to 14 months (mean 7+/-7.5 months). Pathway violations correlated with the complexity, but not with the period since the pathway was introduced. Organisational reasons next to medical reasons (i. e. delayed gastric function or wound healing) were the most frequent causes for pathway violations., Conclusion: Clinical pathways may not only be realised for operative procedures or conservative treatments, but represent a clinical and administrative management instrument at a surgical department of a university hospital for daily work routine. They are suitable as an instrument for clinical quality and risk management, as an economic control instrument in reorganisation phases as well as in the routine of surgical clinics.

Background: Breast cancer with extensive axillary-lymph-node involvement has a poor prognosis after conventional treatment. In trials with historical controls, high-dose chemotherapy produced improved outcomes. We compared an intensive double-cycle high-dose chemotherapy regimen with an accelerated conventionally dosed regimen in high-risk breast cancer in a multicentre trial., Methods: Patients with at least nine positive nodes were randomly assigned either two courses of accelerated (2-week intervals, with filgrastim support), conventionally dosed epirubicin and cyclophosphamide followed by two courses of high-dose chemotherapy (epirubicin, cyclophosphamide, and thiotepa supported by peripheral-blood progenitors) or four identical cycles of epirubicin and cyclophosphamide followed by three cycles of accelerated cyclophosphamide, methotrexate, and fluorouracil. The primary endpoint was event-free survival. Analyses were done both by intention to treat and per protocol., Findings: 403 patients were enrolled; 201 were assigned high-dose chemotherapy and 202 conventional treatment. The mean number of positive nodes was 17.6, and median follow-up was 48.6 months. 4-year event-free survival (intention-to-treat analysis) was 60% (95% CI 53-67) in the high-dose chemotherapy group and 44% (37-52) in the control group (p=0.00069). The corresponding overall survival was 75% (69-82) versus 70% (64-77; p=0.02). There were no treatment-related deaths., Interpretation: Our finding of significant improvements in both event-free and overall survival for high-dose chemotherapy compared with a dose-dense conventional regimen contrasts with the results of other studies. The discrepancy might be due partly to design differences (tandem, brief induction) between our regimen and those studied in other trials. This approach merits further study.

Heparin-induced thrombocytopenia (HIT) is a rare but potentially fatal complication of heparin therapy. The administration of heparin in patients with HIT causes platelet aggregation, thromboembolism and thrombocytopenia. Therefore, an alternative anticoagulant is recommended in these patients. We describe the use of recombinant hirudin (r-hirudin; Refludan, Pharmion Germany GmbH, Hamburg, Germany) as an anticoagulant in a patient with HIT requiring isolated limb perfusion (ILP) for in-transit metastases of malignant melanoma of the leg; r-hirudin was used in both the extracorporeal and systemic circuits. The coagulation monitoring included the activated partial thromboplastin time (aPTT) and ecarin clotting time (ECT). There were no thrombotic or bleeding complications. The dosage regimen and the strategy of monitoring of the anticoagulant activity are described. It can be concluded that ILP in patients with suspected or confirmed HIT can be safely performed with the use of r-hirudin in both the extracorporeal and systemic circuits. Monitoring of the anticoagulation effect is necessary and should preferably be performed using ECT.

Background: In a phase III study recruiting patients with stage II colon cancer the effect of adjuvant therapy with edrecolomab, a murine monoclonal antibody to the cell-surface glycoprotein 17-1A, was compared to observation alone., Patients and Methods: From January 1997 until July 2000 a total of 377 patients were postoperatively stratified according to tumor stage (T3 vs. T4) and center, and randomly allocated to either treatment with edrecolomab (cohort A, n = 183) or observation (cohort B, n = 194). Patients in cohort A received a total of 900 mg edrecolomab. The study was terminated prematurely because of discontinuation of drug supply in Germany., Results: 305 patients were eligible for the primary endpoint of overall survival and 282 patients for disease-free survival. After a median follow-up of 42 months overall survival and disease-free survival were not significantly different. Toxicity was mild., Conclusions: In the present study, postoperative adjuvant treatment with edrecolomab in patients with resected stage II colon cancer did not improve overall or disease-free survival.

History and Admission Findings: A 45-year old man with diabetes mellitus and arterial hypertension was transferred with fever of unknown origin, suspected diabetic angiopathy and sepsis. On admission the patient presented all signs of septic shock. Livid coloured injuries on his right hand and petechial bleeding in distal extremities were observed., Investigations: A different origin of sepsis was not found in transesophageal ultrasound cardiography and computed tomography of cranium, chest and abdomen., Diagnosis, Treatment and Course: Immediately after admission early goal-directed therapy was initiated. Apart from calculated antibiotic therapy intensive insulin therapy and hydrocortisone substitution was begun. The patient presented a multiple organ dysfunction syndrome. Plasma disappearance rate of indocyanine green (PDR (ICG)) on admission was 20,4 %/min (normal range > 18 %/min) and fell to 6,8 %/min within 12 hours, while central venous oxygen saturation remained normal. Despite therapy according to current guidelines for severe sepsis, the patient deteriorated. Surgical debridement was performed suspecting necrotizing fasciitis and application of recombinant human activated protein C (rhAPC) started. PDR (ICG) rapidly raised to normal values; the patient recovered and was discharged after 9 days., Conclusions: Monitoring of PDR (ICG) allows for improved bedside evaluation of liver perfusion of the critically ill and is not only able to predict prognosis but may help in decision making for supportive therapies.

Boerhaave's syndrome is a life-threatening disease with a high mortality. With regard to the heterogeneity of treatment strategies, no comparative studies exist and recommendations remain controversial. Seventeen cases of Boerhaave's syndrome operated on between 1989 and 2000 at our hospital were reviewed retrospectively to compare the time period between perforation and diagnosis, and the morbidity and mortality among the different treatment options. In addition, we conducted a meta-analysis of the literature including all series containing five or more patients and compared the findings with our own data. Our patients with a perforation history of less than 12 hours showed significantly fewer signs of sepsis compared to patients with a history of more than 12 hours. In a comparison of patients with primary repair vs. patients treated with esophageal resection or an exclusion operation, no differences were found. In the literature, patients with a long period of perforation (more than 24 hours) were treated more often with an esophageal resection than patients with primary repair. In cases of Boerhaave's syndrome, primary suturing of the esophageal perforation should be reserved only for those patients presenting within 12 hours after perforation. In all other cases, depending on the extent of the tissue damage, a two-stage esophageal resection with cervical esophagostomy and gastrostomy is recommended as the safest treatment.

Purpose: Neoadjuvant chemotherapy in locally advanced gastric cancer is effective, but is often associated with severe side effects, including fatal outcome. This study evaluates a combination of cisplatin, folinic acid and 5-fluorouracil (PLF) in terms of efficacy (R-0 resection rate) and toxicity., Methods: Twenty-five patients with locally advanced gastric cancer who after extensive staging were deemed not suitable for curative resection underwent neoadjuvant chemotherapy. Three or four cycles of cisplatin (50 mg/m(2) days 1 and 15), folinic acid (200 mg/m(2) days 1, 8, 15 and 22), and 5-fluorouracil (2,000 mg/m(2 ) days 1, 8, 15 and 22) were administered. Cases with progressive disease were taken off the study. Two weeks after finishing chemotherapy resection was performed and all patients were enrolled in a structured follow-up., Results: Of the patients, 22/25 finished chemotherapy and 20 of those underwent laparotomy. In 13/25 patients (52%) a R-0 resection and in three cases a R-1 resection were achieved. Four patients stayed irresectable. During 76 completed cycles of chemotherapy we observed five cases of WHO grade-III toxicity and no grade-IV toxicity., Conclusions: The presented PLF protocol yields R-0 resection rates comparable to protocols like EAP (etoposide, adriamycin, platinum), but with a better safety profile allowing administration in an outpatient setting. Our study supports PLF as a reference neoadjuvant treatment for gastric cancer even outside of clinical studies.

Perforated or bleeding gastric cancer is a life threatening situation that occurs in less than 10% of all patients with gastric cancer in the Western world. Three quarters of these complicated gastric carcinomas show advanced stages (UICC stages III and IV). Diagnosis is made intraoperatively only in the majority of patients. Emergency gastrectomy is superior to any type of local excision and/or local repair regarding surgical mortality and long-term survival and should be the intervention of choice. Stage-related long term survival of patients with emergency gastrectomy is comparable to that of electively resected patients. Minimalism and nihilism are therefore not appropriate in the treatment of complicated gastric cancer and are often deleterious. Subtotal gastrectomy without D2 lymphadenectomy is regarded as the adeqauate procedure in most cases.

Background: After one decade of laparoscopic resections of the colon and rectum the parameters morbidity, conversion and complications were analyzed. The analysis of the literature comprises the results of operations performed for benign and malignant indications., Methods: The analysis is based on the medline research of the past ten years. Publications in German language not listed were added. Results of multicenter studies were included if differentiation by indication and dignity could be achieved. Surveys of different operations of the colon and rectum not differentiated by the parameters to be analyzed were excluded. Publications of the early beginning of laparoscopic surgery were included even if not more than 10 cases were presented but the parameters described in detail., Results: ADENOMAS OF THE COLON: The morbidity ranges from 0-17.4%, the conversion rate is 17.4 and 18.4% in 23 respectively 38 patients. SIGMOID DIVERTICULITIS: Mortality 0-1.8%. The morbidity was 16% in the early series and was later below 10% (8.7 and 7.3%). In the beginning the conversion rate was over 10% (12.0-38.9%) with one exception (0%). It dropped below 10% (4.6-9.2%) and was 0% in a recent study of 64 patients. The reasons for conversion are: inflammatory mass, fistula; perforation and obesity. Intraoperative complications are rare. The rate of postoperative complications did not change within 10 years (9.7 to 25.0% against 7.3 to 17.0%). CROHN'S DISEASE: The morbidity is around 10% (10.6-14.0%) and is lower in series with exclusively ileocoecal resections. The conversion rate is low or zero in ileocoecal resections and raises with the degree of inflammation and the spectrum of procedures. COLON CANCER: Mortality: 0-1.9%. The morbidity ranges from 6.8 to 30% and is especially high after conversions (up to 50%). The conversion rate reflects with the range of 4.2 to 21.0% in the beginning and 1.6 to 23.5% later the experience of the individual surgeon. RECTAL CANCER: Even in large series (n = 157) the mortality of laparoscopic rectal resections is zero. The conversion rate is 0-7.6%; the morbidity 11.5 to 26.4%. REVERSAL OF HARTMANN PROCEDURE: The number of cases is low, the conversion rate is around 20%. The morbidity ranges from 14.3-41.1% with one exception (0%). RECTOPEXY: Four different techniques are applied laparoscopically. The morbidity ranges from 0 to 16%. The conversion rate is 0-2.6%, except one (16.0%)., Conclusion: After one decade of laparoscopic colorectal surgery there are advantages for benign indications (adenomas, Crohn's disease, rectopexy) when compared with open surgery. Disadvantages arise from conversions. Experience of the surgeon is a strong parameter for a successful outcome. Results of ongoing studies are awaited for malignant indications.

A traumatic abdominal wall hernia was observed in association with a colonic laceration due to a pelvic fracture. The presence of this specific combination of injuries is a rare clinical entity. CT evaluation with intravenous and bowel contrast media identified the traumatic abdominal wall hernia and the bowel entrapment.

Purpose: The aim of this study was to assess whether systemic proinflammatory cytokines (IL-6), anti-inflammatory cytokines (IL-4, IL-10), acute phase proteins (C-reactive protein), or granulocyte elastase are valuable indicators for determining the degree of surgical trauma after open vs. laparoscopic-assisted resections in Crohn's disease., Method: Eleven patients in each group (open and laparoscopic-assisted surgery) were matched for indication, surgical procedure, and Crohn's disease activity index. Serum IL-4, IL-6, and IL-10 were measured using enzyme-linked immunosorbent assay. Serum C-reactive protein was determined by immunoturbidimetric assay. Plasma granulocyte elastase was determined by immunoactivation immunoassay. Blood was sampled preoperatively, six hours after the operation, and at postoperative Days 1 to 5., Results: IL-4 was not detectable in any sample analyzed. Serum IL-6 and IL-10 levels peaked postoperatively in both groups without significant differences between laparoscopic-assisted (185.6 +/-54.1 pg/ml and 112.1 +/- 19.4 pg/ml, respectively; mean +/-standard error of the mean) and open surgery (431.1 +/-240.4 pg/ml and 196.7 +/- 56.5 pg/ml, respectively). Serum C-reactive protein levels also rose postoperatively, with a peak on the second day, but showed similar values after laparoscopic-assisted (107.1 +/- 12.1 mg/l) and open (128.3 +/- 17.5 mg/l) surgery. Plasma granulocyte elastase levels peaked on the first and second postoperative day and were found elevated almost throughout the five-day observation period. Comparison between the groups revealed significantly (P < 0.02) lower values after laparoscopic-assisted (Day 1, 46.5 +/- 8.9 microg/l; Day 2, 41.9 +/- 5.9 microg/l) when compared with open surgery (Day 1, 89.7 +/- 13.8 microg/l; Day 2, 91.4 +/- 14)., Conclusions: Serum IL-6 and IL-10 may not be ideal measures for evaluation of the degree of tissue trauma in laparoscopic-assisted and open resections in Crohn's disease, probably because of interference with disease-specific cytokine interactions. In contrast, granulocyte elastase has to be considered a strong marker discriminating the different severity of surgical trauma induced by laparoscopic-assisted vs. open resection in Crohn's disease.

Background: Actinomycosis is caused by a variety of gram-positive anaerobic or microaerophilic rods belonging to the genus Actinomyces or Propionibacterium. The production of suppurative abscesses or granulomas that eventually develop draining sinuses are hallmarks of the disease. We describe the case of a 55 year old smoker who presented himself 4 months ago with right thoracic pain and an unproductive cough. He developed a warm, red mass in the lower part of the right thorax. We performed an ultrasound guided needle aspiration and the pathologic examination revealed typical sulfur granules and masses of neutrophils in the aspirate. After surgical resection of the abscess and under high-dose therapy with penicillin G the further course of disease was uneventful., Conclusions: Although uncommon, thoracic actinomycosis should always taken into account in the differential diagnosis of chronic inflammatory processes that involve the pulmonary parenchyma or pleural space.

Background: Although it is widely proposed that surgeons, before introducing a novel laparoscopic technique in man, should practice in an appropriate animal model for acquisition of the necessary technical skills, the effectiveness of those hands-on training courses are rarely documented., Methods: In 1995 we have organized eight hands-on training courses for laparoscopic anterior interbody spine fusion in an in vivo porcine model. A total of 72 colleagues from 50 different centers of 12 countries participated, including orthopedic, trauma, visceral, neuro-, and vascular surgeons. Quality and effectiveness of the course were evaluated by a questionnaire after a 1.5- to 2.5-year period., Results: During this time, 42.2% of the participating centers had applied the new technique successfully in man. Centers which participated in the course with a team that included a skilled laparoscopic surgeon and an orthopedic or trauma surgeon introduced the technique more frequently to clinical practice (57.9%) than those represented by only one participant (30. 8%). Moreover, there was a tendency toward a more frequent introduction of the technique to clinical practice in centers associated with university hospitals (57.1% vs. 29.2%), indicating the requirement of a particular infrastructure for this complex interdisciplinary procedure. Almost all participants (98.3%) agreed that for novel surgical techniques requiring advanced technical skills, there should first be training in a large animal model before the technique is applied in man., Conclusions: Complex laparoscopic procedures (i.e., laparoscopic spine surgery) can be successfully learned by in vivo hands-on training courses. We propose that for refinements and modifications of the technique (e.g. , the lumboscopic approach), there should also first be training in a large animal model before these are applied in man.

Coincidence of an abdominal aortic aneurysm and abnormalities of the inferior vena cava is a rare condition but has significance for surgical therapy. By the preoperative use of various imaging techniques and adapted surgical procedure the risk of the operation is decreasing to a minimal level. A case of symptomatic abdominal aneurysm and left-sided infrarenal vena cava is presented and the importance of preoperative examinations and operative strategy is discussed.

Laparoscopic assisted proctocolectomy with ileoanal pouch is a technical alternative to the conventional open procedure. The aim of this technique are better cosmetics. Mobilisation of the colon is achieved laparoscopically. Rectal resection, J-pouch creation, and pouchanal anastomosis are performed via a Pfannenstiel incision. Laparoscopic assisted proctocolectomy has been performed in five selected patients, three female and two male aged 17 to 36 years. Operative time ranged from 305 to 420 minutes. Intra- and postoperative complications were not encountered. Postoperative hospital stay ranged from 13 to 16 days. On a scale from 1 to 10 the average quality of life was graded 9 and the overall satisfaction level with the results of surgery scored 10. Function was identical to open surgery in not selected patients.

286 patients with Crohn's disease were classified on the basis of the inflammatory pattern at their first operation as type 1 (Ileitis: n = 116), type 2a (segmental colitis: n = 60), and type 2b (total colitis: n = 108); 2 patients remained unclassified. At the same age at operation of 31.9 +/- 10.7 yrs symptoms were known in type 1 for 3.4 +/- 3.9 yrs, but for 7.5 +/- 5.7 yrs in type 2b. Main indication in type 1 was stenosis (56.9%), whereas in type 2b intractabilitiy (68.5%) predominated. Type 2a was intermediate concerning duration of symptoms and relationship of indications including fistulas. Standard-procedures were ileocecal resection (92.2%) in type 1, and colectomy (90.7%) in type 2b. In type 2a ileocolic resections and partial colectomies were mostly done. During the following 3.9 +/- 3.8 yrs reoperation rate due to disease progression was 13.6% in type 1, 25.5% in type 2a and 18.5% in type 2b. The cumulative risk of ileal resection at ten years due to new inflammation was significantly (p < 0.01) higher in the case of ileocolic/ileorectal anastomosis than of ileostomy (38% vs. 11%). In contrast, cumulative probability of a colorectal resection was significantly (p < 0.05) higher in type 2 (16%) when compared to type 1 (1.5%). Primary ileal loss was significantly (p < 0.01) higher in type 1 (37 +/- 23 cm) compared with type 2a (25 +/- 28 cm) and type 2b (17 +/- 21 cm). Loss of continence occurred in 0%, 3.3% and 53.7% respectively. With reoperations additional loss of ileum decreased in all types, whereas in type 2 loss of anorectal function increased. Including reoperations the rate of major complications was 9.8% and lethality was 0.8% (3/386). Resections in Crohn's disease are unavoidable due to shrinking therapeutical alternatives in the course of the disease. Owing to limited resections, loss of bowel may not exceed ileum in type 1, whereas the same resectional policy cannot avoid the total loss of the colorectum eventually in type 2. Both limited surgery and repeated resections help to maintain function as long as possible. Due to the high safety-standard the number of operations does not impair the success of the surgical concept.

Unlabelled: From Jan. 1993 to Apr. 1997 intestinal resections in Crohn's disease have been performed in 275 patients. 89 patients have been operated on laparoscopic assisted. The following parameters were analyzed: previous laparotomies, extent of resection, steroid medication, conversionrate, complications, operative time and postoperative stay. Endpoints were: conversionrate, complications, reconvalescence and overall satisfaction with the laparoscopic technique., Results: The duration of the disease ranged from 1 to 16 years (x = 6). 47 patients were under steroid medication at the time of surgery. 30 patients had undergone previous laparotomies. In 10 patients the operation had to be converted into open surgery. The following procedures have been performed: ileocaecal resections (45), anastomotic resections (14), small bowel resections (4), hemicolectomies (12), colectomies (9), loopileostomies (4), adhesiolysis (1). Minor complications occurred in 6.7% of patients, major complications in 5.6%. Operative time ranged from 70 to 420 minutes (x = 173.7). The postoperative hospital stay was 13.3 days in the average., Conclusion: The morbidity of 12.3% is not higher than in open surgery. When complications do not occur the patients benefit from early convalescence, better cosmetics and shorter hospital stay.

In a 50-year-old female patient, presenting with permanent low lumbar back pain and intermittent neurological alterations due to degenerative disc disease L4-5 and L5-/S1 we demonstrate that two-level anterior interbody fusion can be performed via laparoscopic transabdominal instrumentation using BAK interbody implants. Intervertebral disc space L5-/S1 was stabilized approaching the spine caudally of the aortic bifurcation, while disc space L4-L5 required an approach from the left lateral aspect, mobilizing the aorta and vena cava to the right. The postoperative course was without complications and allowed discharge from the hospital on day 8. X-ray control 4 months later demonstrated restoration of adequate disc space at L4-L5 and L5-/S1 and appropriate positioning of the implants.

Since 1992 laparoscopic-assisted resections have been performed in 43 patients with tumors of the right or left colon. Excluding one patient with anastomotic leak there were no harvest complications. After a mean follow-up of 25 months 26/39 patients are living without tumor progress or recurrence, none of the 39 patients have abdominal wall metastases as yet; nine patients died due to tumor progress.

39 patients with Crohn's disease underwent laparoscopic bowel resections during January 1993 to May 1995 (16 female, 23 male, with an average age of 33 years). The duration of the disease ranged from one to 18 years. 21 of the 39 patients were under steroid therapy at the time of operation. Seven patients have had ileocaecal resection for Crohn's disease. The operative technique is laparoscopically assisted. We performed: small bowel resections (8), ileocaecal resections (16), hemicolectomies (11), subtotal colectomies (2), colectomies (2). Operative time ranged from 90 to 280 min for ileocaecal resections and from 330 to 420 min for colectomies. Intraoperative complications were not encountered. Postoperatively one patient developed a subhepatic abscess which was drained under sonographic guidance on day 6. One patient was reoperated for a different disease on postoperative day 2. Two patients had fever till day 9 and 13 without clinical relevance. Two patients had delayed incision site healing. Postoperative clinical stay was 11 days. The main benefit for the patients was early mobilisation due to reduced pain. Patients experienced the small abdominal incision as a ray of hope in their chronic disease.

In rectal cancer the emphasis has moved towards sphincter saving resection. Tumor site and penetration depth decide the operative technique in low rectal cancer. 1) Resection at the upper confinement of the anal canal. 2) Intersphincteric resection at the level of the dentate line. Reconstruction is achieved by a colonic J-pouch. From 1991 to 1994 we operated on 35 patients with an average age of 58.1 years. An intersphincteric resection was performed in 11 patients whose tumor was situated between 0 and 2 cm upwards the dentate line. 24 cancers were situated between 2 and 6 cm of the dentate line and were resected at the upper confinement of the anal canal with a linear stapler. Tumor penetration depth was determined endosonographically (ES). Four patients had tumor stage ES T1, 13 ES T2 and 18 ES T3. A J-pouch of 7-9 cm size was sutured (11) or stapled (24) to the anal canal. In 10 patients who underwent intersphincteric resection the pre- and post-operative anal pressures were determined. We did not encounter major complications. In three patients a leakage at the colonal anastomosis postponed closure of the diverting colostomy. We had no anastomotic recurrence but one pelvic side recurrence. Four patients developed liver metastases; in one case resectable. Postoperative anal sphincter pressure was reduced in all cases but clinically relevant only in one. This patient has frequent major soiling, three patients have occasional minor leak. Two patients are incontinent of gas, 26 are perfect continent. One patient has bowel movements every two days, 15 one per day, 12 two per day and 3 three per day.(ABSTRACT TRUNCATED AT 250 WORDS)

An 18-year-old woman developed an acute haemolytic anaemia, acute transient renal failure and progressive hepatic failure. Coeruloplasmin and serum copper concentration were normal; a Kayser-Fleischer ring and any neurological symptoms were absent initially. Liver biopsy was contraindicated because of increased bleeding tendency. Wilson's disease was diagnosed only after the acute renal failure had regressed, on the basis of the urinary copper excretion (2890 micrograms/d, rising to 7330 micrograms/d after D-penicillamine administration). Progressive liver failure required transplantation. After it the patient quickly recovered and is now, two years later, free of disease. -This case demonstrates that Wilson's disease may be difficult to diagnose at the time of initial acute manifestation. But it can be recognized early from the pathognomonic low alkaline phosphatase and by calculation of free serum copper.

Low anterior resection of rectal cancer with preservation of the anal sphincter has comparable recurrence and survival rates when compared to abdominoperineal excision. Stool frequency and leakage rates are high after coloanal anastomosis. The colonic J-pouch improves function. Endosonographic tumor stages ES T1 and ES T2 for cancer in the distal third rectum and ES T3 tumors in die middle third rectum are indications for rectal resection with preservation of the sphincter and reconstruction with the colonic pouch. In 33 patients the technique was safe, with no deaths and no reoperation. Three diverting colostomies are not yet closed. 25 patients are perfect continent, two are incontinent for gas, three have minor and one patient major incontinence. Only one patient has more than three bowel movements in 24 hrs. For selected cancers of the distal half of the rectum total resection with preservation of the anal sphincter is a safe operation. Good function is provided by the colon J-pouch.

In a prospective randomized multicentre trial 139 patients with metastatic colorectal carcinoma (70 men, 69 women; age 35-81 years) were given palliative treatment with fluorouracil (400 mg/m2 daily for 5 days) alone or combined with folic acid (100 mg/m2 before each dose of fluorouracil). Both groups were comparable in respect of age, sex, Karnofsky index and number of localisations of metastases. The criterion for starting the treatment was progression of the malignancy or clinical symptoms caused by the tumour. Resulting remission rates (fluorouracil monotherapy vs combination with folic acid) were: complete or partial remission, 9 vs 16%; arrest of tumour growth, 20 vs 60%; progression 71 vs 24%. Peripheral side effects, such as stomatitis and diarrhoea, were similarly frequent with the two treatment regimens and reasonably tolerable. Median survival time for the fluorouracil monotherapy was 7.24 months from onset of treatment, and 9.1 months from the time that any metastases were diagnosed. The combination treatment with folic acid achieved a significantly longer median survival time (P less than 0.0001), 14.98 months from treatment onset and 16.3 months from metastasis diagnosis. The higher rate of response and the significantly prolonged survival time signify an improvement of the therapeutic profile of fluorouracil by addition of folic acid in the palliative therapy of colorectal carcinomas.

A series of seven cases of hepatic artery aneurysms is reported. Guidelines for diagnosis and therapeutic approach to this rare disease are specified based on our own results and on the work of other authors. Because of high mortality, hepatic and biliary complications in cases of ruptured hepatic aneurysms elective vascular surgery is recommended in symptomatic and asymptomatic patients. In cases of intrahepatic localization percutaneous catheter embolization may be the method of choice except for some cases of false aneurysms in transplanted livers.