[Surgical treatment strategies in chronic inflammation of the lower digestive tract].
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Biomedical subjects
Publications and source records attributed to E H Farthmann.
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The RNA fingerprint method was used to identify mRNAs that were differentially expressed during the development of human mesothelial cell cancer. We report the isolation of two differentially expressed clones. One clone was expressed in the metastatic mesothelioma cell line M1A and in the malignant mesothelioma cell line M1 and downregulated in normal mesothelial cells. M1 and M1A were derived from a primary and metastatic tumor of the same patient. The other clone was only expressed in normal mesothelial cells. The different expression pattern was confirmed by Northern blot analysis. One clone had a striking sequence homology to the soares pregnant uterus NbHPU homo sapiens cDNA clone. The other clone contained a high sequence homology to the human mRNA for ORF. The biological function of the corresponding genes is unknown. The specificity of expression of the two sequence tags was further examined on different cancer cell lines and normal tissues.
While there is good clinical and experimental evidence for immunological tumor control in some tumors--malignant melanomas, for instance--the immunogenicity of colorectal carcinoma (CRC) still remains unsettled. We examined surgical specimens from 4 CRC patients for T cell clones among tumor-infiltrating lymphocytes (TIL). The growth of specific lymphocyte clones in a tumor indicates an immunological response in vivo. We used a T cell receptor V beta family-specific semiquantitative PCR with additional sequencing to examine TIL for clonal expansion. In CRC, specific T cell clones could not be demonstrated. However, we observed a predominance of V beta 9 in 3 of 4 tumors.
Rectal continence preservation became feasible in treatment of cancer of the lower third of the rectum based upon technical evolutions and better understanding of tumor biology. Absolutely necessary precondition is correct preoperative staging. Operative strategy is determined by tumor stage, localization, grade and continence function. In most cases the total mesorectal excision leads to tumor-free circumferential resection margins. Distal safety margins are assured by intraoperative frozen sections. Restorative approaches are contraindicated in case of sphincter infiltration. If continence function is impaired preoperatively, restorative procedures lead to a worse functional result. The local recurrence remains the most important problem in rectal cancer surgery. Safety in resection is achieved by total mesorectal excision. The presence of distal satellite metastasis or lymph node metastasis bear a certain risk for local recurrence after partial resections of middle or upper third rectal cancer. Local resection in T1-Tumors with G1- or G2-Grading may produce comparable results.
We studied the proliferative response of tumor-infiltrating lymphocytes (TIL) from colorectal carcinomas to rIL-2 as well as their cytotoxic activity which was reduced as compared to autologous peripheral blood lymphocytes. We observed TIL to be polyclonal and asked if Fas-ligand-expressing tumor cells are responsible for the elimination of specific T-cells. Therefore we studied the expression of Fas-ligand by LS174T colon carcinoma cells which we showed to be induced by cytokines.
In this retrospective trial we analyzed the data for 200 patients with serous papillary ovarian cancer. The patients were treated with various operation strategies following an interdisciplinary conference among a surgeon, a gynecologist, and an oncologist. Mean overall survival was 26 months. It was significantly better in patients with primary and secondary debulking operations in combination with sufficient postoperative chemotherapy. The morbidity rate reached 16.8%, the overal mortality rate was 5.7%. The mortality for the first surgical intervention was 0%.
An overview of frequency, diagnosis, classification and therapy of perianal fistula in Crohn's disease is presented. There is a positive correlation with the extent of intestinal disease. The fistula as primary manifestation can present problems of differential diagnosis. Crohn fistulas may persist for an extended period of time without discomfort and complaints. Surgical treatment should be individualized for any given form of fistula. Hemorrhoidectomy in Crohn's disease associated with perianal fistulas should be avoided. Transspincteric and recto-vaginal fistulas can be treated by peranal mucosal flap with good results. In summary, neither therapeutic nihilism nor hyperactivity is justified.
Tumor cells transfected to express immunostimulatory cytokines, or admixed with similarly modified bystander cells, are able to induce immune responses against unmodified tumor cells in animal models. For treatment of human patients, a vaccine composed of autologous tumor cells and IL-2-secreting allogeneic fibroblasts was developed. Autologous tumor cells were isolated from biopsy specimens. A clone (KMST 6.14) of an immortalized human fibroblast line that stably secreted 5290 IU IL-2 per 10(6) cells and per 24 hr was obtained by cationic lipofection with an expression construct for human IL-2 and Neo(r). Fifteen patients with refractory malignant tumors received 3-4 injections of irradiated KMST6.14 and autologous tumor cells in a phase-I clinical trial. Increasing transient inflammatory responses without systemic toxicity developed at vaccination sites and after injections with irradiated tumor cells only (p < 0.05). These sites contained a dense infiltrate of CD3+ T cells with numbers of CD4+ helper cells exceeding those of CD8+ cytotoxic T cells (CTL). CD8+ T-cell lines isolated from vaccination sites of 2 malignant melanoma patients but not of renal-cell carcinoma patients exhibited a dominant lytic activity against autologous tumor cells in vitro. CD8+ T-cell clones established from the vaccination site of 1 of 2 renal-cell carcinoma patients preferentially lysed autologous and partially matched allogeneic renal-cell carcinoma cells. In conclusion, a vaccine composed of IL-2 gene-transfected allogeneic fibroblasts and autologous tumor cells is able to enhance specific anti-tumor T-cell responses in vivo without major side-effects. Malignant melanoma and renal-cell carcinoma appear to be promising entities for testing of similar approaches in future therapeutic trials.
Incisional hernias are a common complication following abdominal surgery. However, when performed correctly, the techniques utilized for direct hernia repair, Mayo's closure and plastic covering of the defect appear to be effective in the management of primary hernia closure. The recurrence rates of 30-50% continue to represent a significant challenge in the initial management of incisional hernia repair. Fortunately, there is evidence that, with correct preparation of the patient and with correct anatomical reconstruction, better results can be achieved. Also, the use of strictly applied technical skills in combination with standardized operative techniques may help to eliminate further complications and recurrences. In addition, the application of mesh or cutis transplantation to reinforce the attenuated tissue has also been shown to reduce the recurrence rate. With the diligent application of the above measures, as well as of new concepts, which at present include a promising technique called tension-adapted closure, there may be positive developments in the treatment and management of incisional hernias.
Elevated liver enzymes are a frequent clinical finding. Their significance depends on the clinical presentation and setting. Symptomatic patients with acute or chronic liver disease carry an increased surgical risk. To reduce the morbidity and mortality associated with symptomatic liver diseases the understanding of the pathophysiology of liver dysfunctions is of paramount importance for the pre-, intra- and postoperative management of such patients.
BACKGROUND: While vascular patency and overall viability of the gut can be evaluated perioperatively, damage to the mucosal barrier can hardly be judged in the perioperative setting and, moreover, will probably determine the clinical course. METHODS: In 19 consecutive cases with intestinal ischemia, the clinical course was correlated to the severity of the disease (APACHE II; Septic Severity Score, SSS), the intraabdominal and systemic inflammatory response, and the translocation of bacteria and endotoxin. RESULTS: The comparison of the 10 survivors with the nonsurviving group revealed no differences as to the length of history, serum lactate levels, white blood cell counts, body temperature, markers of the inflammatory response, or quantity and macroscopic quality of the exudate. Differences were found in intraperitoneal bacteriology (prevalence 0.37, negative predictive value for lethal outcome 0.8), endotoxin concentrations in the exudate (P = 0.02) and in the plasma (P = 0.015), fibrinopeptide A levels (exudate P = 0.036; plasma P = 0.015), PGE2 plasma concentration (P = 0.0357), and APACHE II (P = 0.0034) and SSS (P = 0.0027) values. CONCLUSION: The clinical course of ischemic bowel wall necrosis seems to depend on the severity of the disease at admission and on the integrity of the mucosal barrier rather than on inflammatory response, therapeutic measures, or supportive treatment.
Vaccination with gene-transfected tumor cells has recently been proposed as a new strategy in the immunotherapy of cancer. Since autologous tumor cells provide an optimal antigen profile, the possibility of generating single cell suspensions from renal cell carcinoma (RCC), malignant melanoma (MM), colon carcinoma (CC), and non-small-cell lung cancer (NSCLC) biopsies was investigated. One hundred and seventy-four tumor biopsies were processed by mechanic and enzymatic dissociation, yielding 1-2 x 10(6) cells/g tumor (median), irrespective of tumor type. Primary tumor cell cultures (PTCC) of > or = 10(7) cells were established from 29 of 86 (34%) RCC, 14 of 38 (37%) MM, 11 of 23 (48%) NSCLC and 4 of 27 (15%) CC specimens. The amount of non-tumor cells, as assessed by morphology and immunocytology, was generally low (< 30%) in RCC (35 of 41) and MM (11 of 17), while it exceeded 60% in 8 of 11 PTCC from NSCLC and 3 of 11 CC. A high tumor cell yield was obtained in biopsies with a high degree of vascularization and in the virtual absence of necrosis. Thus, PTCC > or = 10(7) cells were obtained in 73% of MM with a high degree of vascularization and in 22% of MM with a low degree of vascularization (p < 0.007). Long-term tumor cell cultures exceeding 20 passages were established in 24 of 86 (18%) RCC, 7 of 38 (18%) MM and 3 of 27 (11%) CC, while successful implantation in nude mice was achieved in 8 of 20 RCC and 5 of 10 MM. Thus, under the conditions described, > or = 10(7) primary tumor cells of high purity could be generated from about one third of RCC and MM biopsies, while the success rate increased to > 50 and > 70%, respectively, in samples with a high degree of vascularization generated by an optimized biopsy technique excluding necrotic parts.
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The postoperative outcome of 108 patients with soft tissue sarcoma (STS) of the extremities, the retroperitoneum, or the trunk was investigated retrospectively to identify independent factors for the over all survival and local tumor control. Chi-square single factor analysis and a Cox model were used to identify independent postoperative risk factors. Single factor analysis revealed a significant correlation with negative effect on overall survival for the variables metastasis (p < 0.0001), chemotherapy (p < 0.0009), surgical procedures (0.001), tumor size > 10 cm (p < 0.003), localization (retroperitoneum, trunk) (p < 0.03), and grading (G3/G4) (p < 0.03). Local tumor control was significantly correlated with the variable tumor size > 10 cm (p < 0.01). The Cox model showed a significant negative impact on overall survival for the factors metastasis (p < 0.002), tumor size > 10 cm (p < 0.004), grading (G3/G4) (p < 0.005), and sex (male) (p < 0.008). For local tumor control the variables were age (p < 0.006), and surgical procedures (p < 0.01).
The aim of diagnostic procedures following abdominal injuries is rapid assessment of the necessity for surgical intervention and specification of the organ lesion, thus reducing the number of negative laparotomies. The extent of the diagnostic approach must be reduced in unstable patients. Sonography is the standard procedure in stable as well as in unstable patients, both in the initial period and the subsequent follow-up. CT-scan is complementary to sonography in detecting organ lesions. Sonographically guided puncture has replaced diagnostic peritoneal lavage. Laparoscopy following blunt abdominal injuries is not useful; however, it may be helpful following penetrating abdominal trauma.
The aim of the TESUS project is to bring together several European university hospitals in a federation as well as a certain number of clinical centers in a network, the purpose of which is the online and offline transmission of surgical procedure imaging and advice. The innovation is threefold: It provides the surgeon with online information, diagnostic and therapeutic tools and expert advice, the need for which might come up before and during surgical procedures, as well as the same services in the context of teaching and training through regular staff. The developed services will be a major contribution to EU-wide standardisation of health care procedures and therapeutic approaches.
The harmonization of medical education, specialist training and continuing medical education (CME) in Europe progresses at different levels. University exchange programmes like ERASMUS and SOKRATES try to realize the European idea on the student and academic level. Specialist training is complicated by differences in responsibilities. The UEMS, based on various agreements, coordinates the harmonization process. Surgical training is represented by the European Board of Surgery (EBS). Its basic care and subspecialties have been described and European qualifications are being prepared. The content of education as well as log books, trainee qualification and training centers are regulated by position papers. Continued medical education is described in the Charter of Continued Medical Education of Specialists in which the content of training and requirements are defined.
In this retrospective trial, we examined 215 patients with bowel lesions following abdominal injuries. We analyzed the diagnostic procedures, the time to diagnosis, the subsequent surgical therapy, and complications. The diagnosis of bowel lesions remains a diagnostic challenge. All apparative diagnostic procedures (sonography, CT-scan, lavage, laparoscopy, X-ray) fail to diagnose bowel lesions. In our trial, most patients showed clinical signs of peritonitis leading to diagnosis. Ultrasonographically guided puncture was important, if clinical signs remained unclear. This study underlines the importance of repeated clinical examination for early diagnosis and treatment of bowel injury.