COLOR II. A randomized clinical trial comparing laparoscopic and open surgery for rectal cancer.

INTRODUCTION: Laparoscopic resection of rectal cancer has been proven efficacious but morbidity and oncological outcome need to be investigated in a randomized clinical trial. TRIAL DESIGN: Non-inferiority randomized clinical trial. METHODS: The COLOR II trial is an ongoing international randomized clinical trial. Currently 27 hospitals from Europe, South Korea and Canada are including patients. The primary endpoint is loco-regional recurrence rate three years post-operatively. Secondary endpoints cover quality of life, overall and disease free survival, post-operative morbidity and health economy analysis. RESULTS: By July 2008, 27 hospitals from the Netherlands, Belgium, Germany, Sweden, Spain, Denmark, South Korea and Canada had included 739 patients. The intra-operative conversion rate in the laparoscopic group was 17%. Distribution of age, location of the tumor and radiotherapy were equal in both treatment groups. Most tumors are located in the mid-rectum (41%). CONCLUSION: Laparoscopic surgery in the treatment of rectal cancer is feasible. The results and safety of laparoscopic surgery in the treatment of rectal cancer remain unknown, but are subject of interim analysis within the COLOR II trial. Completion of inclusion is expected by the end of 2009. TRIAL REGISTRATION: Clinicaltrials.gov, identifier: NCT00297791 (www.clinicaltrials.gov).

[Intravesical Bacillus Calmette Guerin treatment of bladder tumors and carcinoma in situ]. / Intravesikal Bacillus Calmette-Guérin-behandling af tumor og carcinoma in situ i blaeren.

Intravesical Bacillus Calmette-Guérin (BCG) has been used in the treatment of transitional neoplasia of the bladder since 1976. The indications for BCG-treatment are: 1. Carcinoma in situ (CIS), 2. Prophylaxis and 3. Treatment of tumor(s). This paper reviews the treatment schedules, results, side effects, mode of actions and the efforts at improvement of the treatment. In conclusion, the results in CIS are satisfactory, especially in primary CIS. In prophylaxis, efficacy has been demonstrated in small randomized trials against recurrence of tumor, rate of progression and survival. Unfortunately, the characteristics of the tumor(s) treated by BCG are heterogenous (stage, concomitant CIS) and the numbers of patients are small, making it difficult to determine whether there is an effect in all patients or only a subgroup. Tumor treatment with intravesical BCG is only indicated in patients not fit to undergo transurethral resection. Treatment of CIS with BCG is well established, but the exact indications for prophylaxis and tumor treatment are not known. The optimal treatment schedule has probably not been established, and further studies are necessary in an effort to improve the efficacy.

[10-22 years follow-up after truncal vagotomy and drainage of chronic duodenal ulcer]. / 10-22 år efter trunkal vagotomi og draenage for kronisk ulcus duodeni.

Long-term observation with a minimum 10 years on patients treated for duodenal ulcer is rare. This paper presents the long-term results of truncal vagotomy and drainage with a observation time of 16.8 years (range 10.1-22.4). A total of 146 patients were investigated. The side effects of the operation were moderate and only four per cent had unsatisfactory results at observation time. The recurrence rate was 25.5 per cent. Only 50 per cent of the recurrences were seen after the first eight years. A long follow-up time is therefore recommended in follow-up study of treatment of duodenal ulcer.

[The intraprostatic spiral. Long-term results in 150 consecutive patients]. / Den intraprostatiske spiral. Langtidsresultater hos 150 konsekutive patienter.

The clinical results of treatment of infravesical prostatic obstruction with an intraurethral coil in 150 consecutive patients are reported (previously published in (7)). The median follow-up time was 8.6 months (range 0 to 60 months). In 89 patients the spiral was removed after an average of four months (range 0 to 50 months); on account of dysfunction of the spiral in 58 cases, planned prostatectomy in 17 cases and unrelated to the spiral (stroke etc.) in 14 cases. A total of 34 patients died with the coil in situ. Approximately two-thirds of the patients had no or few voiding symptoms, while one fourth had moderate symptoms, leaving only approximately 10% with severe prostatism. Chronic bacteriuria was noted in 51 patients but was not a clinical problem. Migration occurred 65 times in 47 patients but this only led to coil removal in eight. Calcification of the coil was noted mainly after long-term treatment and we recommend replacement of the coil after two years. We conclude that the intraprostatic spiral is a useful alternative to an indwelling catheter. Life-long follow-up is, however, necessary in most patients.

[Is the clinical diagnosis of acute appendicitis good enough?]. / Er den kliniske diagnose god nok ved appendicitis acuta?

In order to estimate the specificity of the clinical diagnosis of acute appendicitis, case records of 148 patients, who underwent appendectomy or who were diagnosed as having periappendicular abscess during one year at a regional hospital in Denmark were analyzed. Operations without finding acute appendicitis occurred in 25.4 per cent of the patients. The group of women in the fertile age (12-50 years) was prone to unnecessary surgery (51.9 per cent in this group had a normal appendix). In children, men and non-fertile women only a few patients had unnecessary surgery. Belated diagnoses (perforation and/or abscess) were found truly in 10.7 per cent of the cases, and, with a significant higher incidence, in elderly patients (age greater than 50 years). The possibilities of diminishing the incidence of unnecessary surgery and belated diagnoses are discussed.

[Aggressive fibromatosis]. / Aggressiv fibromatose.

Fibromatosis can be classified in two groups: Superficial fibromatosis without capacity for infiltration and deep fibromatosis with variable capacity for infiltrative growth. One of the deep fibromatoses is aggressive fibromatosis which is a local infiltrating process never known to metastasize. Two cases of aggressive fibromatosis are presented and histological characteristics and prognosis are reviewed. Once the diagnosis aggressive fibromatosis is established, surgical removal of the lesion by large excision is the only sufficient treatment.

Has PET/CT a role in the characterization of indeterminate lung lesions on staging CT in colorectal cancer? A prospective study.

PURPOSE: CT has been found superior to chest x-ray to detect lung malignances. However, indeterminate lung lesions (ILL) are found in 4-42% by using CT in staging colorectal cancer (CRC) patients. Our aim was to examine the frequency of ILL on staging CT and the rate of the ILL being malignant, and to investigate if PET/CT was useful in pointing out the malignant cases. METHODS: A prospective analysis of 238 consecutive patients operated for CRC followed median 24 months. All the patients had a preoperative staging CT. Patients with ILL had a PET/CT scan performed 3 months postoperatively and low dose chest CT performed 6, 12, 18 and 24 months postoperatively. RESULTS: Twenty percent of the patients had ILL. Four of these patients (8.5%) had lung metastases detected median 9 months postoperatively, while 2 (4.3%) had other lung malignancies. One patient had TB. In patients with normal staging chest CT 10 of the 185 patients (5.4%) developed lung metastases detected median 16 months postoperatively. This was significantly later than in patients with ILL (p < 0.001), but with regard to the number of patients developing lung metastases no significant difference was found between the groups (p = 0.12). CONCLUSIONS: Even though a relative low number of ILL turn out to be malignant it seems advisable to use PET/CT scan in the follow-up to detect lung metastases as early as possible to better the prognosis. For the same reason all CRC patients should have chest CT included in their follow-up 6-12 months postoperatively.

Long-term efficacy of intravesical bacillus Calmette-Guerin for carcinoma in situ: relationship of progression to histological response and p53 nuclear accumulation.

PURPOSE: We assessed the influence of the histological response to intravesical bacillus Calmette-Guerin (BCG) and the prevalence of p53 nuclear accumulation on the clinical behavior of patients with carcinoma in situ. MATERIALS AND METHODS: Of 60 patients with Bergquist grade 3 carcinoma in situ 13 had primary and 47 had secondary carcinoma in situ. Patients received 6 weekly instillations and nonresponders received an additional 6 instillations at 2-week intervals. No maintenance was administered. Median followup was 48 months. The p53 nuclear accumulation was detected by immunohistochemical analysis with antibody PAb 1801. RESULTS: The complete histological response rate to BCG therapy was 64%, which decreased to 52% at 4 years. BCG was more effective for treatment of primary than secondary carcinoma in situ (complete response rate 85 versus 57%, respectively). The 45% progression rate was related to the initial histological response occurring in 26% of patients with a complete versus 77% with a partial and no response. Consequently, the progression rate was only 8% for primary versus 57% for secondary carcinoma in situ. Of the patients receiving only 1 course of BCG 40% had progression compared to 62% of those who received 2 courses. Patients in whom both courses failed had a progression rate of 89%. Intravesical BCG converted the p53 nuclear immunoreactivity from positive to negative in 73% of the 26 patients expressing reactivity before treatment, of whom 68% also had a complete response. The progression rate was related to the prevalence of p53 nuclear reactivity after but not before treatment (90% of patients with versus 37% without p53 nuclear accumulation had progression). All 3 complete responders with p53 nuclear reactivity after BCG had progression, which suggests that molecular genetic change may precede histological change. Complete responders without p53 nuclear accumulation after BCG treatment experienced the lowest progression rate (21%). CONCLUSIONS: Our results suggest that patients with a persistent complete histological response and without p53 nuclear accumulation after BCG treatment can be followed conservatively. Cystectomy should be considered in all other patients.

The intraprostatic spiral: clinical results in 150 consecutive patients.

The clinical results of treatment of infravesical prostatic obstruction with an intraurethral coil in 150 consecutive patients are reported. A total of 80 patients had urinary retention and 70 had severe prostatism. Median observation time was 8.2 months, with a range of 0 to 40 months. In 75 patients the spiral was removed after a median of 4 months (range 0 to 30 months) because of planned prostatectomy in 17, urinary retention in 16, incontinence in 10, local discomfort in 7, no symptomatic improvement in 13 and causes not related to the spiral (stroke and so forth) in 7. Migration occurred 55 times in 42 patients but this only led to coil removal in 5. A total of 23 patients died with the coil in situ. Voiding symptoms improved considerably in the majority of the patients. Approximately two-thirds of the patients had no or few symptoms, while a fourth had moderate symptoms, leaving only approximately 10% with severe prostatism. Chronic bacteriuria was noted in 52 patients but was not a clinical problem. Calcification on the top and inside of the coil was noted mainly after long-term treatment, and probably necessitated exchange of the coil after 2 to 3 years. We conclude that the prostatic spiral is a useful alternative to an indwelling catheter. However, life-long followup is necessary in most patients.

Memokath: a second generation of intraprostatic spirals.

Memokath (Engineers & Doctors A/S, Hornbaek, Denmark) is a new intraprostatic spiral composed of titanium nickel alloy with shape memory effect. We describe the use of this spiral in 30 consecutive patients with prostatic outflow obstruction. Their median age was 79 years and all were either in a high risk group for surgery or had refused surgery. The spiral was inserted under sterile conditions via a delivery catheter under ultrasonic guidance. When flushed with hot water (45 degrees C or above) one section of the spiral expands in the prostatic apex and maintains the spiral in position. When cooled with cold water (10 degrees C or below) the spiral becomes supersoft, making removal easy. With a follow-up of 0.2 to 9 months (median 3) we report a success rate of 83%. Five patients discontinued treatment, 3 because of urinary retention, 1 because of progressive obstructive symptoms and 1 following persistent urinary incontinence. No migration of the spiral was observed. Encrustations have appeared and seem to be a persistent problem. Most patients were satisfied with the procedure, which provided a quick, safe and effective method of relieving infravesical prostatic obstruction. Follow-up is short and late complications have yet to be assessed.

Intravesical Bacillus Calmette-Guérin with the Danish strain for treatment of carcinoma in situ of the bladder.

We report our experience of the treatment of carcinoma in situ (CIS) using intravesical therapy with the Danish Bacillus Calmette-Guérin (BCG) strain 331 (SSI). Forty-two patients received treatment, 11 had primary and 31 secondary CIS. The median follow-up period was 26 months (range 3-68). Patients received 6 weekly instillations (1 course) and non-responders an additional 6 instillations at 2-week intervals (2 courses). The complete response rate was 59% for 1-course patients, 33% for the 2-course patients and 68% for the entire series. Patients were considered treatment failures if they suffered progression to invasive cancer, metastasis or died from transitional cell carcinoma. BCG treatment was more effective in primary than in secondary CIS, with a complete response rate of 80% versus 65% and with no failures versus 35%. Patients with persistent CIS after the first course of BCG had a greater risk of failure than responders: 50% versus 17%. Patients with persistent CIS after the second course had a 75% failure rate. This suggests that cystectomy should be considered for non-responders following a 6-week course and recommended to those not responding to 2 courses. Ten patients had CIS in the prostatic urethra. All responded to BCG treatment; 2 suffered from recurrent CIS 1 associated with invasive urethral tumour. The incidence and severity of side effects were similar to those reported with other strains of BCG. One patient with primary CIS failed to complete the treatment owing to "BCG-itis".

Post transfusion purpura and anti-Zwb (-P1A2).

The first two cases of post transfusion purpura (PTP) due to recognized antibodies against the platelet specific antigen Zwb (P1A1) are described. In both cases, the antibodies were detectable in the platelet enzyme immuno-assay (ELISA), while the platelet specific alloantibodies could be ascertained neither in the platelet suspension immunofluorescence test (PSIFT) nor in the platelet fixation test (CFT) due to coexisting potent multispecific HLA-antibodies. The two sera reacted in parallel (coefficient of correlation, r = 0.87; P less than 10(-5) and the reactions of the two sera were negatively associated with the Zwa-antigen (P = 0.0002 and 0.003, respectively). Thus, PTP may be caused not only by anti-Zwa (-P1A1) but also by anti-Zwb.

Differentiation between neurogenic and prostatic obstruction using the intraprostatic spiral. A case report.

Insertion of a urethral spiral is a simple, reversible method to distinguish between prostatic obstruction and neurogenic dysfunction. A patient with indwelling catheter for seven years was treated with the urethral spiral. This established a normal voiding pattern, confirming prostatic hypertrophy to be the cause of obstruction. Later TUR-P was successfully performed.

Occlusive dressing versus petroleum gauze on drainage wounds.

Two different wound dressings were tested on human drainage wounds. Improved healing was observed under an occlusive, oxygen-impermeable hydrocolloid dressing compared with petroleum gauze. Infection tendency was not increased under the occlusive dressing.

AgNOR counts and histological grade in stage pTa bladder tumours: reproducibility and relation to recurrence pattern.

Silver-stained nucleolar organizer regions (AgNORs) were studied in 90 patients with a single, primary, non-invasive papillary bladder tumour (stage pTa). All tumours were locally resected and patients were followed for 5 years (n = 68) or until the development of an invasive recurrence (n = 22). AgNOR counts showed wide overlaps between the different tumour grades. Furthermore, AgNOR counts were unable to predict the non-invasive recurrence pattern (none, single, multiple). Almost equivalent invasive recurrence rates were found among the following AgNOR counts and Bergkvist grades: AgNOR less than or equal to 5 (0%) and grade I (5%); AgNOR greater than 5, but less than or equal to 8 (20%); and AgNOR greater than 8 (77%) and grade III (67%). Combining the two parameters showed that an AgNOR count greater than 8 resulted in a 75 and 80% invasive recurrence rate in grade III and II tumours respectively. The reproducibility for AgNOR counting was moderate (kappa = 0.52) and no better than Bergkvist grading (kappa = 0.50).

Intraprostatic spiral during waiting time for transurethral prostatectomy.

When benign prostatic hyperplasia results in voiding problems such as acute or chronic urinary retention, transurethral prostatectomy is often necessary. We have evaluated 24 patients, treated with an intraprostatic spiral, during waiting time for transurethral prostatectomy. The spiral treatment was a success in 21 patients. Three patients had a transurethral prostatectomy before scheduled time due to spiral failure, 2 with urinary retention, 1 with severe local discomfort. We conclude that spiral treatment of symptomatic benign prostatic hyperplasia while waiting for transurethral prostatectomy has a high success rate and is recommended as a favorable alternative to an indwelling urethral catheter.

Post-transfusion purpura (PTP) due to anti-Zwb (-PlA2): the significance of IgG3 antibodies in PTP.

The first two patients with post-transfusion purpura (PTP) due to platelet antibodies against the Zwb antigen are reported. The anti-Zwb specificity could be demonstrated only with an enzyme-linked immunosorbent assay (ELISA) but not with the immunofluorescence or the complement fixation test due to coexistent potent multispecific HLA antibodies. One of the patients had never received blood transfusion until 24 d before the development of thrombocytopenic purpura. In both patients, anti-Zwb of IgG1 and IgG3 subclasses defined by monoclonal antibodies were present during the thrombocytopenic period but the antibodies of IgG3 subclass disappeared concomitantly with clinical improvement. The association between the IgG3 subclass of anti-Zw antibodies and the destruction of autologous platelets in Zw-immunized individuals was investigated further. All of four PTP patients had anti-Zw antibodies of the IgG1 and IgG3 subclasses during the thrombocytopenic period while all of 20 mothers of children affected with alloimmune neonatal thrombocytopenia (AINT) had anti-Zwa of only the IgG1 and not IgG3 subclass at the time of delivery of thrombocytopenic children (P less than 10(-4). Thus, the destruction of autologous platelets in PTP is associated with the presence of anti-Zw of the IgG3 subclass which may be of importance in the pathogenesis of PTP.