Allergen-specific T cell responses to immunotherapy monitored by CD154 and intracellular cytokine expression.

BACKGROUND: A sensitive measurement of low numbers of intracellular cytokine-expressing antigen-specific T cells from peripheral blood mononuclear cells (PBMC) is possible using CD154 as a marker of recently activated T cells. This technique may have potential for monitoring peripheral blood T cell responses to immunotherapy. OBJECTIVE: To evaluate the applicability of this method for measuring changes in cytokine production by allergen-specific T cells in a clinical trial setting. METHODS: Ex vivo ragweed-specific CD154 and intracellular cytokine expression were evaluated using a subset of subjects in an environmental chamber study of allergic rhinitis immunotherapy. PBMC were collected and cryopreserved from Amb a 1-immunostimulatory oligodeoxynucleotide conjugate (AIC)-treated (n=17) and placebo-treated (n=15) ragweed-allergic subjects both after pre- and post-treatment ragweed exposures. In vitro allergen-stimulated CD3(+)CD4(+)CD154(+) T cell intracellular IL-4, IL-5, IL-13, and IFN-gamma expression were evaluated by flow cytometry. RESULTS: Compared with the T helper type 2 (Th2) cytokine expression measured after pre-treatment ragweed exposures, placebo-treated subjects demonstrated a significantly elevated ragweed- and Amb a 1-specific T cell IL-4 and IL-13 co-expression (P=0.005 and P=0.022, respectively) and a significantly elevated ragweed-specific IL-5 expression (P<0.001) following post-treatment ragweed exposures. In contrast, AIC-treated subjects demonstrated no increases in allergen-specific Th2 cytokine expression following post-treatment ragweed exposures. IFN-gamma expression remained low and un-changed in both groups. Subject reported total nasal symptom scores demonstrated modest but significant correlations with Amb a 1- and ragweed-stimulated intracellular Th2 cytokine responses. CONCLUSION: Combined CD154 and intracellular cytokine staining in PBMC can be used to sensitively monitor changes in antigen-specific T cell subset frequencies in clinical studies. Antigen-specific cytokine expression moderately correlated with the reported levels of allergic symptoms.

[The complicated stoma--late complications, conservative and surgical management]. / Das schwierige Stoma--Stomakomplikationen, konservatives und chirurgisches Management.

Creation of a stoma is related with up to 50% complications. Two main causes are recognised: stomacare and positioning of the stoma. During the first few weeks the diameter of the stoma may shrink by 1/3. In this phase without the professional aid by a stomatherapist the risk of skin problems increases with time. Late complications as prolapse, parastomal hernia and stenosis are often the result of a too lateral positioning of the stoma or of early complications as necrosis, dehiscence, retraction and parastomal abscess. If conservative treatment does not solve the problem surgical procedures are warranted. Beside local corrections replacement of the stoma may be needed. However this is a major operation. Therefore, replacement should be the last option to resolve stoma complications.

[Adrenalectomy after snowboard fall. A pheochromocytoma becomes clinically apparent in an unusual way]. / Adrenalektomie nach Snowboardsturz : Eine aussergewöhnliche Erstmanifestation eines Phäochromozytoms.

A 33-year-old snowboarder fell and underwent radiological examination, which was suspicious for a vertebral body fracture. Accidentally we found a tumour of the left suprarenal gland. Two days after the fall, he developed a hypertensive crisis with peak blood pressure levels up to 280/120 mmHg. Further endocrinologic testing indicated a pheochromocytoma which was confirmed by post-operative histology. The fall is supposed to have activated the pheochromocytoma. The course of examinations and significance of the tumour are described.

[Progress of the laparoscopic colorectal surgery with special consideration regarding cancer treatment]. / Die Entwicklung der laparoskopischen Dickdarmchirurgie mit spezieller Berücksichtigung der Karzinombehandlung.

The development of laparoscopic surgery began with the diagnostic coelioscopy in 1901 and the first appendectomy in 1983. Its worldwide spread started in 1987 with the cholecystectomy. Four years later the right hemicolectomy and sigmoid resection were also described. The initial euphoria however evaporated when the first reports of port-site-metastasis appeared. The controversy whether one should be allowed or not to operate carcinomas laparoscopically, provoked a boom in research with as result that in 2000 it had been confirmed that the incidence of port-site-metastasis was about the same as drain-site-metastasis after open procedures (0.9%). Randomized studies comparing laparoscopic interventions and open surgery showed no difference in the long-term results of colon-carcinoma. For experienced surgeons this is also the case for rectum-carcinoma. Hereby the learning curve is of great importance and has been put at 30 to 70 procedures, taken into account the duration of the operation or other criteria such as conversion to open surgery and complications. With growing experience the amount of material used during an operation goes down, which results in a lower overall cost of the minimal-invasive technique compared with open surgery. In cost calculations one should also take into account the fact that the recovery time and the return to every-day life is generally quicker for patients after laparoscopic surgery while overall they also have a significant better quality of life score (SF-36) in the longer term. Currently, i.e. in 2006 the laparoscopic colorectal surgery has become an established procedure. It is thought that laparoscopic interventions give additional advantages because the immune system is less affected but this must still be confirmed through research.

[Learning curve--calculation and value in laparoscopic surgery]. / Lernkurve--Berechnung und Stellenwert in der laparoskopischen Chirurgie.

The learning curve shows the progress in mastering a new method. It is completed when the monitored parameters reach a steady state and when the final results can be compared with literature. The earlier used analysis of the performance-improvement with its "on the spots" appraisals at certain time-intervals is replaced by a continuous assessment. The multimode learning curve is particularly useful for it, because not only one parameter (f.e. operation-time), but also several important factors can be put together into one single graphic. For the operation-time, the Moving Average Method is useful. For incidents, which may happen or not like a conversion from laparoscopy to laparotomy as well as complications, the Cusum-method is of practical use. The learning curves of the technique of laparoscopic cholecystectomy, colo-rectal surgery, fundoplicatio and hernia surgery have been completed. Also, the learning curve of the industry is well advanced. Reliable data for the learning curves of individual surgeons for certain operations cannot be given, as, only now, young doctors are being trained on a large scale in laparoscopic technique as used to be the case in the open abdominal surgery. This will influence greatly the learning curves and will shorten the time till their completion. Different bias concerning the individual surgeons and their clinics prohibit the production of comparable curves. Several factors like the patient respectively his abdomen are complicating all this. That's why the learning curves cannot be used as benchmarks to compare different surgeons or clinics, as long as no valid scoring system concerning the complexity of a surgical intervention exists. Learning curves which become quality curves after reaching a steady state, can be used for the individual monitoring of a surgeon's performance and serve as a quality measurement of a clinic. The learning curves of the laparoscopic cholecystectomy, fundoplicatio, colo-rectal surgery and hernia surgery are discussed in particular The mandatory number of operations needed to learn a new method cannot yet be established today, even if all the existing data are consulted. Therefore, the learning curve is a useful instrument to monitor the individual progress and the results of a clinic in the meaning of an individual quality-management. After completion of the learning curve, a quality curve using the same parameters will be given, which shows the deviations of its own standard.

[Is open appendectomy still up-to-date?]. / Ist die offene Appendektomie noch zeitgemäss?

The acceptance of the laparoscopic technique for appendectomy can't be compared with the success in laparoscopic cholecystectomy. The discussion is still controversial. A lower rate of wound infection in comparison to open appendectomy has been proven statistically in many studies. There is no evidence of a higher rate of complications. Postoperative pain may be reduced and return to work is often earlier. Cosmesis shows better results. Operation time and hospital stay are comparable to open appendectomy. The total of direct and indirect costs is not higher with laparoscopic than with open appendectomy. Excellent indications for laparoscopic appendectomy are atypical pain in the right lower abdomen, uncertain diagnosis in fertile and elderly women, obesity and complicated appendicitis. Controlled double-blinded randomized studies are necessary in the future to define the advantages and further indications.

Comparison of resource utilization and long-term quality-of-life outcomes between laparoscopic and conventional colorectal surgery.

BACKGROUND: The outcomes of laparosopic and conventional colorectal surgery, with special reference to costs of treatment and patients' quality of life, were compared. METHODS: A partly retrospective cohort study was designed to assess the use of resources, and a follow-up interview was undertaken to evaluate patients' quality of life after both to define laparoscopic (LAP) and conventional (CON) surgery. RESULTS: The length of hospital stay was significantly lower in the LAP group (median, 11 days; interquartile range [IQR], 9-15) than in the CON group (median, 16 days; IQR, 13-23; p < 0.0001), which is reflected in lower costs of hospitalization calculated for the three most frequent surgical interventions. Statistically significant improvements were noted between the median scores in the domains of physical functioning (LAP 85 vs CON 68; p < 0.05) and vitality (LAP 85 vs CON 69; p < 0.05). CONCLUSION: Laparoscopy is a promising alternative for the treatment of patients with colorectal diseases, offering lower costs and a better quality of life in the long term.

[Standard technique of oncologic colorectal surgery]. / Standardtechnik der onkologischen Kolorektalchirurgie.

Who ever is writing about standards should put himself the question: What is a standard? How is it produced? Who is defining it? How compulsory is it? A standard should only be understood as guiding principles or as following guidelines and never as a dogma, while otherwise every operative technical or therapeutical progress is prohibited. On the basis of the onco-surgical guidelines for the colo-rectal carcinoma is shown how standards can begin to sway. The Turnbull "no-touch isolation technique" does not stand up to the criteria of the evidence based medicine. The usefulness of the high ligation of the veins and the intestinal occlusion has not been proven by any studies. The central ligature of the Arteria mesenterica inferior in left resection is wrong according more recent anatomical knowledge. Ligation near to the aorta leads obligatory to lesions of the plexus hypogastricus. Animal experiments are controversial concerning the dissemination of tumour cells during crushing of the cancer. And a prospective controlled study does not show any advantage of respecting the Turnbull criteria. Independent prognostic factors are the surgeon, the frequency of performing the procedure in the hospital concerned, the pT and N stage, the R-0 resection and according to American pathologists the pre-operative CEA titre. Also are mentioned the infiltration of veins and lymph vessels, micro metastases in lymph nodes and the grading. The resection should if possible be performed in anatomical layers, specially considering the meso-rectum. What should be done in the distal 8 cm till the pelvic floor has not yet been clarified. On the contrary, the laparoscopic surgery has definitively also found its acceptance in oncological surgery. The discussions about port-metastases and tumour-cell-dissemination by the pneumoperitoneum-gas have silenced. Already, partially better long-term results are mentioned. In the beginning of 2003, the pillars of the standard technique of oncological colo-rectal surgery are besides the orthograde intestinal flushing, the pre-operative low molecular Heparin and the antibiotic prophylaxis, the open or laparoscopic R-0 en bloc resection, the minimal safety distance in the low rectum of 1 cm, the ligature of the Arteria mesenterica inferior 2-3 cm distally to its origin from the aorta in case of left resection, respectively the Arteria ilio-colica at its origin from the Arteria mesenterica superior in case of right resection, the cytotoxic intestinal flushing in case of left resection and the flushing of the abdominal cavity as well as the port-site with Taurolin 0.5%. In case of rectum-carcinoma uT3 or uN+, a neo-adjuvant radio-chemotherapy is administered and adjuvant chemotherapy is given by positive nodal colon-carcinoma.

[Surgical therapy of fecal incontinence]. / Operative Therapie der Stuhlinkontinenz.

The algorithm of the treatment of the stool-incontinence starts with the differentiation between soiling and incontinence for flatus, liquid or formed faeces. In case of soiling, first all the causes that can be surgically solved should be treated. If this is not successful, the scheme of the incontinence-treatment should be followed. The first step is a dietary consultation, which includes prescription of appropriate drugs against diarrhoea, constipation and proctitis. The anal-physiological examinations will inform about the elasticity of the ampulla recti, which can be reduced in inflammatory processes, it will as well inform about the innervations of the ano-rectum and allow an objective sphincter pressure. If dietary therapy and drugs intake fail, the anal sphincter should be more closely examined. An endosonography or a perineal sonography and in case of a rectocele with incontinence a defecography need to be performed. In case of intact or defective sphincter a biofeedback training is started. If this is not successful, a sphincter-repair is performed in case of defective sphincter. To maintain the result the biofeedback training is continued. In case of failure as well as in case of intact sphincter that cannot be treated with the help of the biofeedback training, sacral nerve stimulation is indicated. If this does not work, the next step will be a dynamic graciloplasty or an artificial bowel sphincter. Both these methods are also indicated when the sphincter is missing. If this fails an anus praeter would definitively improve the quality of life of the patients. With bedridden or heavy demented patients, the anus praeter is often the first choice of procedure. The costs of the expensive pacemaker of the sacral nerve stimulation or the dynamic graciloplasty as well as the artificial bowel sphincter scare the insurances. Talking about cost and benefit these appliances are interesting as already in two years the costs a permanent anus praeter is causing are higher than the price of these medical appliances. In this overview article, different surgical procedures are described considering their indications, results and operative principles. The step-by-step use of the proposed algorithm leads to an optimal treatment of the stool-incontinence.

[The learning curve in surgery: possibilities and limits of this method]. / Lernkurve in der Chirurgie: Möglichkeiten und Grenzen dieser Methode.

The learning curve is a graphic representation of the relationship between the experience of a surgeon and one or more performance indicators. The operation time alone is an insufficient indicator to assess the performance of a surgeon. The procedure time has to be set in relation to the complication rate and in laparoscopic surgery to the conversion rate. Techniques to visualize the changes over time are the moving average method for the operation time and the Cusum method for dichotomous outcomes, like the conversion and the complication rates. At the time when the learning curve reaches the plateau phase this representation can be used to assess the quality of a surgeon or a team in one hospital. As far as there is no validated complexity scale for laparoscopic procedures available it is difficult to compare patient populations between different hospitals. Out of this reason the learning curve is no legitimate instrument to rank surgeons or different hospitals.

[Early postoperative nutrition after laparoscopic and open colorectal resection]. / Frühpostoperative Ernährung nach laparoskopischen und offenen Kolorektalresektionen.

BACKGROUND: Discussions concerning postoperative nutrition were brought up again with laparoscopic colorectal surgery. We are looking whether there is any difference between open and minimal invasive procedures with respect to the start of oral intake. METHODS: In a prospective controlled trial 152 patients were analysed after laparoscopic (n = 85) or open (n = 67) colorectal resections. At the first postoperative day fluid intake was unlimited and from the second day regular food was permitted according to the patients desire. RESULTS: No influence on the beginning of nutrition was by age, diagnoses, type of operation nor their duration. Wound infection and specially cardiopulmonal decompensation prolonged lack of appetite, however, not a pneumonia. There was no increase of anastomotic leak rate. At day 4, a highly significant difference was found between laparoscopic and open surgery with 90% and 60% of patients having started regular nutrition (p < 0.001). CONCLUSION: Early postoperative oral nutrition does not increase complication rate. Patients after laparoscopic procedures start earlier eating compared with those after conventional surgery. We recommend early postoperative oral intake after both techniques according to the patients desire.

Comorbid conditions in old patients with femur fractures.

BACKGROUND AND METHODS: The incidence of preexisting medical diseases (comorbid conditions) and their influence on the high rate of falls, associated severe injuries, operative treatment, and outcome including mortality rate, duration of hospitalization, and rehabilitation success was retrospectively evaluated in a group of 102 patients (mean age, 81 years; 81% women) with femoral fractures. A comparison of polymorbidity rates in a control group of 102 patients (mean age, 79 years; 86% women) with proximal humeral fractures was added. RESULTS: The associated polymorbidity rate among patients with femoral fractures (FF) usually was statistically significantly higher than among patients with proximal humeral fractures (PHF) despite a comparable age and sex distribution: 80% of the patients with FF presented with cardiovascular (p < or = 0.001), 41% with pulmonary (p < 0.001), 67% with gastrointestinal (p < or = 0.001), 71% with neurologic (p < or = 0.001), 55% with urologic (p < or = 0.001), 75% with musculoskeletal (p < or = 0.1), and 61% with psychiatric (p < or = 0.001) disorders and complaints. Ninety percent of the patients used different medications (diuretics, cardiac agents, anticoagulants, antidiabetic agents, steroids, hypnotics, analgesics, psychotropic agents). The postoperative mortality rate was 11%, and the mean hospitalization period was 30 days. Forty-nine percent of the patients were discharged to their homes. Only 56% of the patients with PHF, however, presented with cardiovascular, 8% with pulmonary, 11% with gastrointestinal, 8% with neurologic, 9% with urologic, 64% with musculoskeletal, and 10% with psychiatric disorders. CONCLUSION: The polymorbidity in the old patient probably is a major intrinsic cause of the high incidence of falls and associated severe femoral fractures. It influences the perioperative and postoperative medical and anesthesiologic treatment, the postoperative mortality rate, and the duration and success of the postoperative rehabilitation phase.

[Defecation problems: incontinence, constipation and impeded defecation; why and what can be done?]. / Defäkationsprobleme: Inkontinenz, Obstipation und behinderte Entleerung, weshalb und was tun?

Defaecation disorders may be subsumed in three categories: Inability to control motions = incontinence. Difficulty of evacuation = constipation [inertia coli, outlet obstruction]. Impeded defaecation: Rectocele, enterocele, intussusception. Etiology, examination and therapy are described in detail. Characteristic complaints of patients are listed and matched with probable diagnoses. Beside routine proctologic examination endosonography, estimation of transit time, endoscopy and defecography are discussed. The role of nutrition is stressed and emphasis layed on fibre and fluid intake. The advice, "take more fluid and fibres" does not help a lot, because no individual help is given. A time consuming nutrition and defaecation history has to be taken to establish nutritional support. This attention gives confidence to the patient and helps a great deal in the treatment. A checklist of the therapy of constipation and summarizing tables on different types of fibres are included. Additional conservative treatments are pelvic exercises and biofeedback training. Operative therapy is directed towards etiology of the disorder. Therefore many different methods exist and their diagnose related indication are discussed.

[Advancement flap-plasty in perianal fistulas. A reliable procedure in rectally normal and Crohn disease patients]. / Die Verschiebelappenplastik bei perianalen Fisteln. Ein zuverlässiges Verfahren bei darmgesunden und Crohn-Patienten.

The endorectal advancement flap is a safe technique for managing anorectal fistulas. The recurrence and incontinence rate (fecal soiling) is low. In Crohn's fistulae in a noninflammatory period, the results are also equivalent.

[Intraperitoneal tumor seeding in colorectal carcinoma surgery--follow-up of a comparison of laparoscopic versus open procedure]. / Intraperitoneale Tumoraussaat bei kolorektaler Karzinomchirurgie--Follow up des Vergleiches laparoskopisches versus offenes Verfahren.

Follow-up 71 patients during 20 months (12-29) operated on for colorectal cancer by laparoscopic or open surgery demonstrated no correlation between port-side metastases (1/35) or tumor recurrences (5/71) and intraperitoneal tumor cells. All these patients were cytologic-negative; however, all were initial in an advanced tumor stage (pT3-4, N1-3). We conclude from these results that free tumor cells during operation do not seem to influence outcome or the development of port-side metastases.

[Reinterventions in secondary incontinence]. / Reeingriffe bei sekundärer Inkontinenz.

Overlapping sphincter reconstruction for fecal incontinence due to perineal tears, trauma or iatrogenic injuries is the therapy of choice. If this technique fails repeatedly or more than half of the sphincter is destroyed, a gracilis muscle plasty is indicated. Incontinence caused by an ectropion must be treated by a skin flap procedure (Ferguson or VY-plasty). These techniques are described in detail. Results of 54 overlapping procedures carried out in 47 patients (30 females, 17 males, age 15-84, median 47 years) during the last 3.5 years are presented. The most frequent cause of incontinence was fistulectomy followed by perineal tears. Thirty-day success rate with excellent or good results (difficulty in controlling flatus) was 82%, decreasing to 70% at the end of follow-up. Complications were rare (7/54) and did not influence outcome except for wound healing by second intention, which resulted in a high failure rate. Superior results were achieved when the reason for incontinence was a perineal tear (81%, compared with fistulectomy (64%). In conclusion, overlapping sphincter reconstruction results in a high success rate, especially when fecal incontinence was caused by a perineal tear.

Angioplasty balloon catheters used for distraction of the ankle joint.

Arthroscopy of the ankle joint is now routinely performed in diagnostic and therapeutic interventions but is still a demanding and difficult operative procedure in this very small and tight joint. Arthroscopy can be facilitated by a sufficient distraction that gives a better overview of the joint space. However, it is still a matter of debate how to obtain the adequate distraction. Distention by manual strength as well as by the help of a technical device have been proposed. We report our experience with distraction of the ankle joint by the help of one or two intraarticularily located and secondarily insufflated angioplasty balloon catheters that are routinely used in interventional radiology. These special catheters allow a careful and controlled distention of the joint with a fixed space of distraction and, according to our limited experience, without any morbidity.