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.

[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.

Low molecular weight heparin (KABI 2165) as thromboprophylaxis in elective visceral surgery. A randomized, double-blind study versus unfractionated heparin.

In two randomized double-blind studies perioperative bleeding complications and thromboembolic events were assessed in 189 patients (pts) undergoing elective visceral surgery after subcutaneous administration of a low molecular weight (LMW) heparin fragment (KABI fragment 2165) or unfractionated (UF) heparin. The first study comparing 1 X 7'500 anti-factor Xa IU LMW heparin daily with 2 X 5'000 IU UF heparin was interrupted because of excessive bleeding complications (LMW heparin: 11/23 pts, UF heparin: 2/20 pts, p less than 0.01). In the second study (146 pts) the dose of LMW heparin was reduced to 1 X 2'500 anti-factor Xa IU. Bleeding complications (LMW heparin: 14.9%, UF heparin: 15.3%) and thromboembolic events (LMW heparin: 2.86%, UF heparin: 2.94%) were equal among the two groups. 2'500 anti-factor Xa IU/day of this LMW heparin fragment, corresponding to 15 mg/day, is the lowest dose of a LMW heparin used in a randomized clinical trial and was found to be a safe and efficient regimen in perioperative thrombosis prophylaxis. An advantage of LMW heparin over UF heparin is its once daily administration.

Antimicrobial management of postoperative infections in abdominal surgery: single or combination regimen?

In a prospective, controlled, randomized study, the clinical and bacteriologic efficacy of imipenem/cilastatin was compared with that of a standard combination of an aminoglycoside, amoxicillin, and clindamycin in patients with serious postoperative infections. Doses used were imipenem/cilastatin 1 gm q 8 hr, amoxicillin 2 gm q 8 hr, and clindamycin 0.6 gm q 6 hr. Aminoglycoside doses were individualized and monitored six times weekly with serum concentration assays. Sixty-three patients were entered into the study: 31 in the imipenem/cilastatin group and 32 in the combination group. Diagnoses included pneumonia (ten in the imipenem/cilastatin group and seven in the combination group), peritonitis (eight in the imipenem/cilastatin group and 15 in the combination group), and septicemia (eight in the imipenem/cilastatin group and three in the combination group). The two groups were comparable with respect to sex, age, underlying diseases, and duration of antibiotic therapy. In the imipenem/cilastatin group, 26 patients were cured and one improved (87%). In the combination group, 21 were cured and five improved (81%). Four patients receiving imipenem/cilastatin and six receiving the combination therapy failed to respond to treatment. Eighty percent of the bacterial isolates were eradicated, and 15% were suppressed in the imipenem/cilastatin group. Corresponding frequencies in the combination group were 84% and 11%, respectively. Isolated pathogens persisted in 5% of the patients in each group. It is concluded that imipenem/cilastatin appears to be an effective and well-tolerated alternative to a triple antibiotic combination in the treatment of serious postoperative infections.(ABSTRACT TRUNCATED AT 250 WORDS)

Carcinoma in a rectovaginal fistula in a patient with Crohn's disease.

A patient with Crohn's disease underwent resection for internal fistulas. Later a rectovaginal fistula developed that persisted with minimal symptoms for 10 years before causing pain and induration in the posterior vaginal wall, due to carcinoma developing within the fistula.

Natural history of perianal Crohn's disease. Ten year follow-up: a plea for conservatism.

A 10 year follow-up of 109 patients with histologic Crohn's disease and anal lesions is reported. Fourteen patients (13 percent) have died, 7 from unrelated disorders. Ten required excision of the rectum, but only 5 for perianal disease (4.5 percent). Of the remaining 85 patients, 61 have been followed up to proctoscopy and rectal biopsy. Anal skin tags were still evident in 25 of 37 patients (68 percent), but new tags have appeared in only 2 patients. Ten of 53 fissures (19 percent) were still present at 10 years, and there were no new fissures. Seven of 21 patients (33 percent) still had fistulas but were asymptomatic; the remainder of the fistulas had healed spontaneously (8) or after operation (6). New fistulas have appeared in five patients. None of the patients have been in continent. These results indicate that perianal manifestations of Crohn's disease pursue a relatively benign course and are rarely an indication for proctectomy.

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.

1.5 T MRI, CT, ultrasonography and scintigraphy in hyperparathyroidism.

The enlarged parathyroid glands of twenty-four patients with primary, and 5 with tertiary, hyperparathyroidism were prospectively studied with MRI, CT, ultrasonography and subtraction scintigraphy prior to surgery. Sensitivities in a prospective study were 63, 60, 53 and 44% for the primary, and 71, 67, 44 and 11% for the tertiary, disease form. On MRI, diseased parathyroids showed the "typical" behaviour of tumours with high signal intensity on T2-weighted and low signal intensity in T1-weighted images. On CT, the lesions were hypodense and on US hypoechoic relative to the thyroid. Retrospective analysis of MRI and CT images yielded sensitivities of 87 and 85%, respectively.

[Heart luxation following pneumonectomy]. / Herzluxation nach Pneumonektomie.

A herniation (with torsion) of the heart trough a dehiscent pericardial suture was observed on the second postoperative day after right-sided pneumonectomy, when shock symptoms developed. Chest x-ray was diagnostic and lead to rethoracotomy with successful reposition of the heart.--Another case showed an atypical bulge of the heart contour after pneumonectomy with partial pericardial resection. It was caused by pericardial fat, sutured on the defect for occlusion.

Peritoneal adhesions after laparotomy: prophylactic measures.

Abdominal adhesions are due to a locally decreased peritoneal fibrinolytic capacity occurring mainly in ischemic areas of the peritoneum. They help to guarantee the supply of blood to these areas, acting as a protective mechanism ("vascular graft"). With respect to abdominal surgery a general suppression of the ability to form adhesions would therefore seem to be questionable. We consider the currently employed or discussed methods with their advantages and disadvantages. No optimal solution to the problem of adhesions has been found so far. Nevertheless, appropriate surgical technique can permit us to control adhesion formation to a certain degree. If adhesions are unavoidable, placement of the greater omentum should be done carefully in the areas of risk.

Risk factors in abdominal surgery.

The term risk is understood to be the danger of the occurrence of an undesired, life-threatening event. The probability of this undesired event is greater in the presence of a risk factor than in its absence. In general surgery, these risk factors can be classified into five groups: The environment, the surgeon, the operation per se, the disease, and the patient himself. Abdominal surgery is especially suited to clarify and to illustrate this classification. Some typical risk factors are described, and for each group the measures for risk prevention or risk reduction are discussed.

[Opening of anorectal abscesses--with or without splitting of the fistula?]. / Eröffnung anorectaler Abscesse -- Mit oder ohne Fistelspaltung?

An anorectal abscess has to be deroofed. If, in addition, a fistula is present, it is our policy (in a teaching institution with surgeons in training) to incise it only if easily visualized and situated up to the dentate line. Of 79 anorectal abscesses drainage alone was performed in 55 (group 1) and drainage with fistulatomy in 24 (group 2). One-third of the patients in group 1 needed a secondary fistula operation, but most of the others were free of symptoms after one intervention. In group 2 all but one of the patients were cured by the combined procedure. Incontinence was observed in none.

[Treatment of anorectal fistulas: a still current problem]. / Behandlung der Anorectalfisteln: Ein immer noch aktuelles Problem.

95% of our patients have a simple fistula in ano. The majority of these fistulas were following a cryptoglandular abscess. No definitive incontinence occurred after laying open the fistula penetrating the anal sphincter and excision of the extrasphincteric part. In only 7% there was a temporary incontinence for faeces or flatus respectively. The recurrence rate was 5%. High fistulas are seldom an indication for a seaton. In 5% we found a complex fistula with supralevator or extrasphincteric extension. Thereby we usually performed a defunctioning colostomy. This became the permanent treatment for more than half of these patients.

[Is the treatment of inguinal hernia an operation for beginners?]. / Ist die Behandlung des Leistenbruches eine Anfängeroperation?

The early postoperative results of 1273 operations for inguinal hernia are reported. In addition, the late outcome of 688 operations of patients answering the questionnaires was analysed according to the surgeons stage of training. In group 1, the operator was in the first two years of his training, in group 2, he was older but had not yet achieved his title as a specialist for surgery and in group 3, all are fully trained surgeons. The postoperative complications are distributed equally among the 3 groups. Wound infection was leading in 37% to recurrent inguinal hernia. The overall figure of recurrent inguinal hernia was highest in group 2 with 7.8% (14 out of 179), followed by group 1 with 5.5% (22 out of 399) and group 3 with 4.5% (5 out of 110). Early post-operative recurrence was again highest in group 2 with 7 out of 14 compared with 9 out of 22 in group 1 and 2 out of 5 in group 3. We conclude from these results that inguinal hernia may be performed by a very young surgeon in training; supervision in those who are over the first steps, but have not completed their training has to be intensified and that asepsis has to be observed very carefully.

[Is rigid rectoscopy obsolete?]. / Ist die starre Rectoskopie obsolet?

Flexible fiberoptic sigmoidoscopy more and more replaces sigmoidoscopy with a rigid tube. In a retrospective series of 152 rigid sigmoidoscopies we analysed depth of endoscopy and findings. In 36% of patients without anaesthesia endoscopy had to be stopped at 15 cm and in further 31% at 20 cm leading to a highly significant difference to the anesthetized patients (p less than 0.0005). A good history of the present illness allows separating of bleeding carcinoma and polyps proximal to the sigmoid colon which have to be examined by colonoscopy. In routine screening for blood loss per anum it is desirable to achieve in all patients a maximal security not to overlook a finding, because of the medical costs. We have enlarged the list of indications for the rigid sigmoidoscopy by Marks et al. as a practical compromise: delineation of rectal lesions, side localization and critical rectal measurements, surveillance of disease states or anastomoses within its reach, for performing rectal biopsy and rectal polypectomy, in patients with possible contamination of the instrument, endoscopy in the anesthetized patient before a proctological operation if case history excludes a higher sited lesion. In all other cases there is an indication for colonoscopy or barium contrast enema. It is stressed that in patients with blood loss per anum the search for the source always is done by flexible fiberoptic sigmoidoscopy.

[Palliative therapy of rectal cancer by electrocoagulation]. / Die palliative Therapie des Rectumcarcinoms durch Elektrocoagulation.

Palliative therapy for rectal carcinoma is only indicated in selected patients who do not tolerate radical surgery or with very advanced disease. In a retrospective series the results of transanal electrocoagulation are analyzed. In addition patients or their relatives were questioned about the treatment related increase in quality of life and the wish of recurrent coagulation if needed. The main indication for transanal electrocoagulation was rectal stenosis, blood loss, discharge of mucosa and tumor as well as pain. Anal incontinence only gets better when it is due to discharge. However, transanal exposition bears the risk of worsening the incontinence. The electrocoagulation is favored by all continent patients before colostomy. The main indication for a colostomy was incontinence and fistula. Palliative irradiation was concentrated in patients with pain. In 59 operations upon 40 patients there was one rebleeding and one death due to sepsis resulting in a mortality of 1.7%. We conclude from our results that transanal electrocoagulation is a safe procedure in patients with rectal carcinoma who do not qualify for radical surgery.

[Ischemic colon and rectum necrosis after resection of the abdominal aorta]. / Ischämische Colon-und Rectumnekrosen nach Resektion der Aorta abdominalis.

Colorectal infarctions are a rare but serious complication following aortoiliac reconstruction. Their incidence has been reported to be about 2% in retrospective and 7-35% in prospective studies. The perioperative mortality rate reaches 40-75%. About 85% of these ischemic lesions follow resection of the infrarenal aorta because of aneurysm, only 15% after aortoiliac occlusive disease. Principal cause of the infarctions is the ligation of the inferior mesenteric artery without sufficient collateral circulation. Blood supply of the large intestine and pathogenesis of ischemic colitis are discussed in detail. The pathological and clinical presentation contains three intensity degrees. For early detection colonoscopy is useful. Prevention preoperatively consists of precise analysis of aortography, intraoperatively in perfusion control of visceral arteries. The best precaution is reimplantation of the inferior mesenteric artery into the prosthetic graft.

[Anal condylomata acuminata. A prospective comparison of HIV positive and negative patients]. / Anale Condylomata acuminata. Ein prospektiver Vergleich von HIV-positiven und -negativen Patienten.

Between July 1986 and May 1987 23 patients suffering from anal condylomata acuminata were treated at the University Hospital of Zurich. The influence of HIV-infection on the disease is described. An almost equal frequency of recurrencies between positives and negatives was observed in a three year follow-up time. However, in positive patients recurrence was earlier and much more extensive. A two-stage procedure which sometimes is advocated in very extensive lesions gave very bad results in HIV positives. We use a radical excision by electrocoagulation on the mucosa and perianally and avoid circular necrosis in the lower anal canal only. Infectious complications are not to be feared except in patients with symptomatic HIV-infection resulting in the recommendation for a antibiotic prophylaxis in such cases.