Follow-up after cystectomy: regularly scheduled, risk adjusted, or symptom guided? Patterns of recurrence, relapse presentation, and survival after cystectomy.

AIMS: To evaluate the efficacy of follow-up based on the patterns of recurrence, relapse presentation and survival after cystectomy, and to define a risk adjusted follow-up schedule. PATIENTS AND METHODS: The records of 343 patients with regular follow-up after cystectomy were reviewed for primary site of recurrence, accompanying symptoms, means of recurrence diagnosis, and clinicopathological factors. Based on Cox proportional hazard models, and the results of imaging studies low and high risk groups are identified and a risk adjusted follow-up protocol is proposed. RESULTS: The risk of a recurrence was related to increasing pT, tumour positive lymph nodes, tumour positive surgical margins, and pre-operative dilatation of the upper urinary tract, and low and high risk groups were defined consequently. 84% of all recurrences occurred within 2 years, with only one recurrence beyond 2 years in the low risk group. Although the minority of all patients (34%) is asymptomatic at time of recurrence, symptomatic recurrences were adversely associated with survival. CT-scans and chest X-rays accounted for 90% of the diagnostic tools to detect a recurrence in patients without symptoms. CONCLUSIONS: Asymptomatic patients may benefit from early treatment after disease recurrence. A risk adjusted follow-up strategy based on stage of disease and additional clinicopathological factors can dichotomise patients at high and low risk for recurrence. The small benefit in survival after early detection has to be confirmed in future studies, and weighed against the available treatment options of recurrences and their subsequent costs.

Short-term outcome after cystectomy: comparison of two different perioperative protocols.

AIM: To compare the outcome of two perioperative protocols with respect to postoperative management of cystectomy patients. PATIENTS AND METHODS: Between June 2007 and November 2008, 85 consecutive patients with bladder cancer were treated with cystectomy and urinary diversion. Patients were operated in two hospitals by four urologic surgeons. In protocol A, patients were enterally fed via a postpyloric tube while the nasogastric tube (NGT) was removed directly after cystectomy and selective decontamination of the digestive tract was given until normal oral intake. In protocol B, postcystectomy management consisted of total parenteral nutrition by a central venous line and NGT removal after 24 h. Hospital stay and complications were compared between the two hospitals. RESULTS: More than half of all patients (52%) developed one or more complications within 30 days after surgery, 37% in protocol A and 71% in protocol B (p = 0.002). Higher ASA score and protocol type were the only factors significantly associated with early complications in both uni- and multivariate analyses. Length of stay was significantly shorter with protocol A as compared to protocol B, 13 days versus 19 days (p = 0.006). CONCLUSIONS: Cystectomy and urinary diversion is a procedure with considerable risk of complications. Enteral nutrition might be advantageous as compared to parenteral nutrition, showing fewer complications and shorter hospital stay. A high ASA score is associated with more early complications. Selective bowel decontamination may have an additional role in preventing infectious complications after cystectomy.

Haemovigilance: an effective tool for improving transfusion practice.

Haemovigilance is a tool to improve the quality of the blood transfusion chain, primarily focusing on safety. In this review we discuss the history and present state of this relatively new branch of transfusion medicine as well as some developments that we foresee in the near future. The top 10 results and conclusions are: (1) Haemovigilance systems have shown that blood transfusion is relatively safe compared with the use of medicinal drugs and that at least in Europe blood components have reached a high safety standard. (2) The majority of the serious adverse reactions and events occur in the hospital. (3) The majority of preventable adverse reactions are due to clerical errors. (4) Some adverse reactions such as anaphylactic reactions often are not avoidable and therefore have to be considered as an inherent risk of blood transfusion. (5) Well-functioning haemovigilance systems have not only indicated how safety should be improved, but also documented the success of various measures. (6) The type of organisation of a haemovigilance system is of relative value, and different systems may have the same outcome. (7) International collaboration has been extremely useful. (8) Haemovigilance systems may be used for the vigilance and surveillance of alternatives for allogeneic blood transfusion such as cell savers. (9) Haemovigilance systems and officers may be used to improve the quality of aspects of blood transfusion other than safety, such as appropriate use. (10) Haemovigilance systems will be of benefit also for vigilance and surveillance of the treatment with other human products such as cells, tissues and organs.

Outcome of treatment of bladder cancer: a comparison between low-volume hospitals and an oncology centre.

PURPOSE: To evaluate the effect of volume of cystectomies in the Greater Amsterdam region on postoperative outcomes. METHODS: All primary bladder tumours diagnosed between 1989 and 2003 were selected from the Amsterdam Cancer Registry, a population-based cancer registry (population 3.0 million). For all patients who underwent cystectomy during 1989-2003 at 20 participating hospitals, medical records were reviewed for information on postoperative mortality, locoregional recurrences and relative risk of death. To assess the effect of volume, outcomes at an oncology centre and low-volume hospitals were compared. RESULTS: During 1989-2003 a total of 1,185 cystectomies were performed in 20 hospitals of the Greater Amsterdam region. Postoperative mortality was 3.2%. During 1989-1997, 8% of cystectomies were performed at the oncology centre, increasing to 30% in 1998-2003. Although postoperative mortality at this centre decreased from 4.0% in 1989-1997 to 1.1% in 1998-2003, the latter percentage was not statistically significantly different from the other hospitals during 1998-2003 (OR 0.3; P = 0.09). No statistically significant difference in locoregional recurrence rate and in the relative risk of death was observed between the oncology centre and all other hospitals combined. CONCLUSIONS: We observed a lower postoperative mortality rate in the oncology centre compared to the low-volume hospitals; however, this difference did not reach statistical significance. We could neither prove a statistically significant relation between hospital volume, local recurrence rate and survival after cystectomy. To answer the question if centralisation of cystectomies is beneficial more procedures have to be compared.

Survival after cystectomy for invasive bladder cancer.

AIM: To determine the difference in survival after cystectomy between patients presenting with primary muscle infiltrating bladder cancer and patients with progression to muscle infiltration after treatment for initial non-muscle-invasive bladder cancer (NMIBC). PATIENTS AND METHODS: We retrospectively analyzed the files of 188 patients who underwent cystectomy for transitional cell carcinoma between 1987 and 2005. Two groups were defined: patients presenting with muscle-invasive tumours and those progressing to muscle invasion after initial treatment. This second group was further divided into low-intermediate and high risk according to the EAU grouping for NMIBC. RESULTS: The 5-year disease specific survival (95% confidence intervals) for all patients was 50%(42-59%); 49%(40-60%) in the primary muscle infiltrating group and 52%(37-74%) in the progressive group (p = ns). The 5-year disease specific survival in the progressive group according to EAU risk groups was 75%(58-97%) for the initially diagnosed low-intermediate risk tumours and 35%(17-71%) for the initially diagnosed high-risk tumours (p = 0.015). The percentage of patients with non-locally confined tumours (pT3/4-N0//any pT-N+) was 31%//45% and 24%//46% in the primary muscle infiltrating and progressive group, respectively. CONCLUSIONS: Despite close observation of patients treated for non-muscle-invasive bladder cancer, the survival of patients who progress to muscle invasion is not better than survival of patients presenting with primary muscle infiltrating cancer. Patients with high-risk non-invasive tumours (EAU risk-categories) who progress to muscle-invasive disease have a worse prognosis compared to patients with low or intermediate risk tumours.

Underreporting of major obstetric haemorrhage in the Netherlands.

Major obstetric haemorrhage (MOH) is the main cause of severe maternal morbidity, incidence being estimated at 4.5 per 1000 deliveries. Cases are not routinely registered in the Netherlands. The objective of this study is to quantify the degree of underreporting of MOH in a large nationwide survey of severe acute maternal morbidity in the Netherlands (LEMMoN) and to estimate the true incidence of MOH in the Netherlands. Retrospective cross-match of the LEMMoN-database with the databases of local blood transfusion laboratories in 65 of 98 hospitals in the Netherlands during a 20-month period, using the capture-recapture method was used. From 16 of 65 centres, the reported transfusion data could not be confirmed by a local obstetrician for logistical reasons. These centres were excluded leaving 49 hospitals available for final analysis. In both databases together, 1018 unique cases of MOH were identified. Underreporting to LEMMoN was 35%. Hence, the true incidence of MOH in the Netherlands is at least 6.1 instead of 4.5 per 1000 deliveries. The estimated underreporting of MOH of 35% is considerable. Underreporting is inherent to large observational multicentre studies and should be anticipated and quantified to facilitate fair comparison of epidemiologic data.

Long-term survival after combined modality treatment in metastatic bladder cancer patients presenting with supra-regional tumor positive lymph nodes only.

AIMS: To evaluate if combined treatment should be offered to bladder cancer patients presenting with supra-regional lymph node metastases only and a clinical complete or partial response after chemotherapy. PATIENTS AND METHODS: We identified 14 patients with supra-regional lymph node metastases out of 394 patients with transitional cell carcinoma (TCC) treated in our institute with cystectomy and regional and supra-regional lymph node dissection between 1987 and 2007. Prior to cystectomy, neoadjuvant chemotherapy had been given. The patients received a total of four cycles of platinum-based chemotherapy. RESULTS: Five patients had a CR, nine patients had a PR after neoadjuvant chemotherapy. Histopathological proof of complete response in the bladder was confirmed in all five cases. One of these five patients had a CR in the bladder but pelvic lymph nodes still contained vital tumor. Five patients had no tumor in the lymph nodes, whereas four had tumor in the lymph nodes. Eleven patients died due to bladder cancer, seven of them within 1 year after cystectomy. The 3- and 5-year disease-specific survival rates were 36% (95% CI: 10-60%) and 24% (95% CI: 0-49%). Mean follow-up was 2.5 years. CONCLUSIONS: Combination therapy consisting of neoadjuvant chemotherapy and surgery in selected patients with tumor positive supra-regional lymph nodes only can result in durable long-term survival rates (24% 5-year survival). Response evaluation after neoadjuvant chemotherapy might play a decisive role in the selection of patients undergoing subsequent surgical removal of all known tumor sites.

Protection against rheumatoid arthritis by HLA: nature and nurture.

Rheumatoid arthritis (RA) is a complex genetic disorder in which the HLA region contributes most to the genetic risk. HLA-DRB1 molecules containing the amino acid sequence QKRAA/QRRAA/RRRAA (ie, HLA-DRB1*0101, *0102, *0401, *0404, *0405, *0408, *0410, *1001 and *1402) at position 70-74 in the third hypervariable region of the DRB1 chain are associated with susceptibility to RA. HLA-DRB1 molecules containing the amino acids "DERAA" (ie, HLA-DRB1*0103, *0402, *1102, *1103, *1301, *1302 and *1304) at the same position are associated with protection from RA. Interestingly, not only inherited but also non-inherited HLA-antigens from the mother can influence RA susceptibility. A protective effect of "DERAA"-containing HLA-DRB1 alleles as non-inherited maternal antigen (NIMA) has recently been described. The underlying mechanism of this protective effect is currently unknown, although a possible explanation is covered below. In this review, an overview of the current knowledge on protection against RA is given and the inherited and NIMA effect of "DERAA"-containing HLA-DRB1 alleles are compared.

Progression of joint damage in early rheumatoid arthritis: association with HLA-DRB1, rheumatoid factor, and anti-citrullinated protein antibodies in relation to different treatment strategies.

OBJECTIVE: To determine the association of HLA-DRB1, rheumatoid factor (RF), and anti-citrullinated protein antibody (ACPA) status with progression of joint damage in early rheumatoid arthritis (RA) treated according to different treatment strategies. METHODS: The present study was conducted using data from the BeSt study (Behandelstrategieën voor Reumatoide Artritis [treatment strategies for rheumatoid arthritis]), a randomized trial comparing 4 targeted (toward achievement of a Disease Activity Score [DAS] of < or =2.4) treatment strategies: sequential monotherapy (group 1), step-up combination therapy (group 2), initial combination therapy with methotrexate, sulfasalazine, and prednisone (group 3), and initial combination therapy with methotrexate and infliximab (group 4), in 508 patients with early RA. Multivariate logistic regression analysis was used to predict progressive disease (increase of Sharp/van der Heijde score over 2 years beyond the smallest detectable change [4.6]) according to the presence or absence of the shared epitope (SE), DERAA, RF, and ACPA, with correction for other baseline characteristics. RESULTS: Progressive disease could not be predicted by presence of the SE: the odds ratio in groups 1, 2, 3, and 4, respectively, was 1.4, 2.6, 1.9, and 3.0. DERAA carriership did not protect against progressive disease (odds ratio 0.4, 1.4, 0.9, and 0.9 in groups 1, 2, 3, and 4, respectively). RF positivity and ACPA positivity predicted progressive disease in group 1 (odds ratio 4.7 [95% confidence interval 1.5-14.5] for RF and 12.6 [95% confidence interval 3.0-51.9] for ACPA), but not in groups 2-4 (for RF, odds ratio [95% confidence interval] 1.5 [0.5-4.9], 1.0 [0.3-3.3], and 1.4 [0.4-4.8] in group 2, group 3, and group 4, respectively; for ACPA, odds ratio [95% confidence interval] 3.4 [0.8-14.2], 1.7 [0.5-5.4], and 1.8 [0.5-6.8] in group 2, group 3, and group 4). CONCLUSION: In patients with early RA treated with the goal of tight control of the DAS, no significant association between HLA-DRB1 status and radiographic progression was found. RF and ACPA were predictive of progressive disease only in patients treated with sequential monotherapy. These observations suggest that effective treatment can prevent radiographic progression, even in patients with risk factors for severe damage.