Regional vs Metropolitan. Bigger is not always better.

Nil.

Abdominal and perineal hernia rates following vertical rectus abdominis myocutaneous (VRAM) flap reconstruction - a supraregional experience.

BACKGROUND: Vertical rectus abdominis myocutaneous (VRAM) flap has proven to be a robust reconstruction method following radical pelvic surgery. Radical pelvic surgery is associated with high morbidity due to pelvic complications and non-healing perineal wounds, as a result of non-collapsible pelvic dead space and pre-operative adjuvant radiotherapy insult. VRAM flap reconstruction addresses both issues by obliterating the dead space and introducing healthy non-radiated tissue. However, flap reconstruction complications can include donor site hernias (abdominal wall), perineal hernias, and flap-specific complications. This study aimed to evaluate the abdominal and perineal hernia rates as well as radiological evidence of flap vascularity post-operatively. METHODS: We conducted a retrospective analysis of patients who underwent a VRAM flap reconstruction following radical pelvic surgery at Christchurch hospital over a 10-year period. We identified the presence of donor site hernias (abdominal wall hernias), perineal hernias, and flap vascularity on post-operative radiological imaging performed within 48 months. RESULTS: Seventy-seven patients underwent a VRAM flap reconstruction of which 60 patients met the inclusion requirements for the study (mean age was 60.3 years [range 26-89]; 31 were male and 29 were female). Eighteen patients underwent an APR and 42 underwent a partial or a complete pelvic exenteration and the majority of them (75.0%) were for rectal cancers. Available imaging was on average 21.6 months post-operatively (IQR 11.8-31.3 months). The donor site hernia rate was 16.7%, and the perineal hernia rate was 3.3%. VRAM flap appeared to have DIEA flow in 98.3% of the patients. CONCLUSION: VRAM flap reconstruction of complex pelvic defects remains a robust method of choice in complex pelvic reconstruction with little morbidity.

The prevalence of right-sided colonic diverticulosis in a New Zealand population.

BACKGROUND: Once considered to be a congenital condition, the epidemiology of right-sided colonic diverticulosis (RCD) is evolving. Acute diverticulitis (AD) is a complication of RCD which is frequently misdiagnosed as appendicitis, resulting in unnecessary surgery, as there is strong evidence supporting medical management for right-sided AD. In general, the incidence of AD correlates with the prevalence of RCD, which shows marked geographic variation. Few data reporting RCD prevalence come from Western countries, so the aim of this study is to define the prevalence of RCD in a New Zealand population. METHODS: Independent review of the imaging from 1000 consecutive patients undergoing a computed tomography Kidney/Ureter/Bladder scan for suspected urolithiasis at Christchurch Hospital between January and November 2017 was undertaken, to determine the presence or absence, and distribution of colonic diverticulosis. Patients were excluded if they had a history of colonic resection, known IBD, or were less than 18-years old. RESULTS: Thirty-one patients were excluded, leaving 969 eligible patients. Overall, 95 patients (9.8%) had RCD identified. The prevalence of RCD increased significantly with advancing age, being present in 2.3% of those aged 18-29, increasing to 20.3% in those greater than 70-years old (p < 0.001). CONCLUSION: The prevalence of RCD in a New Zealand population is relatively high and increases significantly with age. This adds support to the role of cross-sectional imaging in the evaluation of suspected appendicitis, to exclude right-sided AD. The association with advancing age supports RCD being an acquired condition rather than a congenital condition as was previously thought.

Associations Between Mutations in MSH6 and PMS2 and Risk of Surveillance-detected Colorectal Cancer.

BACKGROUND & AIMS: Lynch syndrome is the most common inherited cause of colorectal cancer (CRC). Contemporary and mutation-specific estimates of CRC-risk in patients undergoing colonoscopy would optimize surveillance strategies. We performed a prospective national cohort study, using data from New Zealand, to assess overall and mutation-specific risk of CRC in patients with Lynch syndrome undergoing surveillance. METHODS: We performed a prospective study of 381 persons with Lynch syndrome in New Zealand (98 with Lynch-syndrome associated variants in MLH1, 159 in MSH2, 103 in MSH6, and 21 in PMS2). Participants were offered annual colonoscopy starting at age 25 y, and those who underwent 2 or more colonoscopies before December 31, 2017 were included in the final analysis. Patients with previous colonic resection, history of CRC or diagnosis of CRC at index colonoscopy were excluded. RESULTS: Study participants underwent 2061 colonoscopies during 2296 person-y; the median observation-period was 4.43 y and mean-age at enrollment was 43 y. Eighteen patients developed CRC (8 with variants in MLH1, 8 in MSH2, and 2 in MSH6) after a median follow-up period of 6.5 y (range 1-16 y). Eighty-three percent of patients had a surveillance colonoscopy in preceding 24 months before diagnosis of CRC; 94% were diagnosed with stage 0-II CRC and there was no CRC-related mortality. The overall-risk of developing CRC in the 5 y after first surveillance colonoscopy was 2.49% (95% CI, 1.18-5.23); cumulative risks for CRC in patients with Lynch syndrome-associated variants in MLH1, MSH2, or MSH6 by age 70 y were 17.7%, 17.8%, and 8.5%, respectively. Age-adjusted CRC-risk in patients with variants in MSH6 was lower than in MLH1 (hazard ratio, 0.2; 95% CI, 0.04-0.94; P = .02). Of patients with CRC, 33% had an adenomatous polyp resected from same segment in which a colorectal tumor later developed. CONCLUSIONS: The risk of CRC in patients with Lynch syndrome-associated mutations in MSH6 or PMS2 was significantly lower than in patients with mutations in MLH1. Incomplete adenomatous polyp resection might be responsible for one third of surveillance-detected CRCs.

Complications and 5-year survival after radical resections which include urological organs for locally advanced and recurrent pelvic malignancies: analysis of 646 consecutive cases.

BACKGROUND: Extensive multi-visceral resection, including components of the urinary tract, is often required to achieve clear resection margins, which is now well established as a key predictor of long-term survival for locally advanced pelvic tumours. The aims of this study were to analyse major morbidity and factors predicting complications and long-term outcomes following a urological procedure within extended radical resections. METHODS: Data were collected from prospective databases at two high-volume institutions specialising in extended radical resections for locally advanced and recurrent pelvic malignancies between 1990 and 2015. The primary endpoints were general major complications (Clavien-Dindo ≥ 3) and factors influencing complications and overall survival after urological resection. RESULTS: A total of 646 consecutive patients requiring an extended radical resection for locally advanced or recurrent pelvic malignancies were identified. The median age was 63 years (range 19-89 years) and the majority were female (371; 57.4%). A urological resection was performed as part of the resection in 226 patients (35.0%). The overall 30-day major complication rate was significantly higher in the urological intervention group (23%; n = 52) compared to the non-urological group (12.9%; n = 54 patients; p = 0.001). Intestinal anastomotic leak (p = 0.001) and intra-abdominal collections (p = 0.001) were more common in the urological cohort. Ileal conduit formation was an independent predictor of major morbidity (OR 1.95; 95% CI 1.24-3.07; p = 0.004). Independent prognostic markers for poor 5-year survival following urological procedures were recurrent tumour, cardiovascular disease, previous thromboembolic event and postoperative pulmonary embolism. CONCLUSIONS: Extended radical resections which include a urological resection are associated with significantly more major morbidity than those without urological resection. Ileal conduit formation is independently associated with the development of major morbidity. Five-year overall survival is no different for patients who had or did not have urological resection as part of extended radical surgery for locally advanced or recurrent pelvic malignancy.

Complications After Extended Radical Resections for Locally Advanced and Recurrent Pelvic Malignancies: A 25-Year Experience.

BACKGROUND: The oncological role of pelvic exenteration for locally advanced and recurrent pelvic malignancies arising from the anorectum, gynaecological, or urological systems is now well-established. Despite this, the surgical community has been slow to accept pelvic exenteration, undoubtedly due to concerns about high morbidity and mortality rates. This study assessed the general major complications and predictors of morbidity following extended radical resections for locally advanced and recurrent pelvic malignancies. METHODS: Data were collected from prospective databases at two high-volume institutions specialising in beyond TME surgery for locally advanced and recurrent pelvic malignancies between 1990 and 2015. The primary outcome measures were major complications (Clavien-Dindo 3 or above) and predictors for morbidity. RESULTS: A total of 646 consecutive patients required extended surgery for local advanced pelvic malignancies. The median age was 63 (range 19-89) years, and the majority were female (371; 57.4%). One or more major complications were observed in 106 patients (16.4%). The most common major complications were intra-abdominal collection (43.7%; n = 59/135) and wound infection (14.1%; n = 19/135). The overall inpatient mortality rate was 0.46% (n = 3/646). Independent predictors for major morbidity following surgery for locally advanced or recurrent pelvic malignancies were squamous cell carcinoma of anus, sacrectomy, and blood transfusion requirement. CONCLUSIONS: This series adds increasing evidence that good outcomes can be achieved for extended radical resections in locally advanced and recurrent pelvic malignancies. A coordinated approach in specialist centres for beyond TME surgery demonstrates that this is a safe and feasible procedure, offering low major complication rates.

Evolution of pelvic exenteration surgery- resectional trends and survival outcomes over three decades.

OBJECTIVE: To examine the changes in exenterative surgery over three decades analysing oncological outcomes and whether changes in surgical approach have led to improved patient outcomes. BACKGROUND: Advances in surgical technology, perioperative care and pattern of disease recurrence have coincided with an evolutionary change in exenterative surgery. METHODS: A review of a prospectively maintained databases of pelvic exenteration surgery from 1988 to 2018  at two high volume specialised institutions. The total cohort was divided into three major time points (1988-2004, 2005-2010 and 2011 to 2018) to allow comparative analysis. Primary endpoints were overall survival in primary and recurrent disease at each time point. Secondary endpoints included anastomotic leak, blood transfusion, ileus, wound infection rates and evolution of case complexity. Data were analysed using R with a p < 0.05 considered significant. RESULTS: Six hundred and seventy patients underwent exenterative surgery. In 2011-2018 there was an increase in resection of recurrent malignancy with a continuous increase in GI malignancies resected over each time period(p < 0.001,<0.01) and a reduction in gynaecological malignancy(p < 0.001). A significant increase in sacrectomy, pelvic sidewall resection and ileal conduit reconstruction was observed (p < 0.01,<0.001).In 2005-2010 patients had increased rates of ileus and anastomotic leak(p < 0.05). Patients undergoing resection for primary disease had improved overall survival at time points 1988-2004 and 2011-2018 compared to those with recurrent disease(p = 0.007,<0.001). Overall survival was significantly improved in patients with primary versus recurrent disease(p = 0.022). CONCLUSION: There has been a significant improvement in survival in patients undergoing pelvic exenteration surgery from primary disease. Case complexity has increased without significant morbidity.

A Review of the Role of Carcinoembryonic Antigen in Clinical Practice.

Carcinoembryonic antigen (CEA) is not normally produced in significant quantities after birth but is elevated in colorectal cancer. The aim of this review was to define the current role of CEA and how best to investigate patients with elevated CEA levels. A systematic review of CEA was performed, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies were identified from PubMed, Cochrane library, and controlled trials registers. We identified 2,712 papers of which 34 were relevant. Analysis of these papers found higher preoperative CEA levels were associated with advanced or metastatic disease and thus poorer prognosis. Postoperatively, failure of CEA to return to normal was found to be indicative of residual or recurrent disease. However, measurement of CEA levels alone was not sufficient to improve survival rates. Two algorithms are proposed to guide investigation of patients with elevated CEA: one for patients with elevated CEA after CRC resection, and another for patients with de novo elevated CEA. CEA measurement has an important role in the investigation, management and follow-up of patients with colorectal cancer.

Diagnosis of abdominal tuberculosis in Christchurch New Zealand: a case series.

AIM: Abdominal tuberculosis presents with non-specific symptoms, including generalised abdominal pain. Prompt and accurate diagnosis is critical to improving outcomes and avoiding complications. We conducted a retrospective review of cases of abdominal tuberculosis presenting to Christchurch Hospital to explore the epidemiology, clinical features and diagnostic modalities used. METHOD: Cases were identified by searching for relevant ICD discharge codes from January 1996 to January 2016. Data on age, clinical presentation, investigations and microbiological results were obtained. RESULTS: There were 20 patients diagnosed with abdominal tuberculosis over the study period. The median age was 34. Thirteen patients were male (65%), seven female (35%). The majority (11) were from Asia (predominantly India), five were African, and three were New Zealand Europeans. Abdominal pain was the most common presenting symptom (70%) followed by fevers (50%) and night sweats (50%). The C-reactive protein was elevated in 15 patients (75%), anaemia was found in 11 (55%) and nine had abnormal liver function tests (45%). Abdominal ultrasound (US) and computed tomography (CT) showed generic inflammatory change in all patients in this series (100%). Laparoscopy was undertaken in 10 (50%) patients, all of which had positive laparoscopic biopsies. Ascitic fluid was obtained in nine, with stains for acid-fast bacilli uniformly negative, however three (33%) had mycobacterial growth from culture. Six colonoscopies were performed: in three (50%) culture and/or histology was positive. Three lymph node biopsies and two formal laparotomies were the remaining diagnostic techniques employed with two biopsies and one laparotomy yielding positive results. Overall, of the 20 cases, 15 (75%) were able to be definitively confirmed, with the remaining five treated presumptively for probable abdominal tuberculosis. CONCLUSION: Abdominal tuberculosis is an uncommon presentation at our institution, with an average of one case each year. The typical patient was a young immigrant from Asia or Africa. Diagnostic laparoscopy was the most common and uniformly reliable means of obtaining a definitive diagnosis.

Ten-year experience of splenic trauma in New Zealand: the rise of non-operative management.

AIM: The aim of this study was to describe the demographics, mechanisms of injury, management and outcomes in patients who suffered splenic trauma in Christchurch, New Zealand. METHODS: A retrospective study included all splenic injury patients admitted to Christchurch Public Hospital between January 2005 and August 2015. RESULTS: A total of 238 patients were included, with a median age of 26 years (4-88.7). Of these, 235 patients had blunt injuries. Eighty-nine had high-grade injuries. Yearly admissions of splenic trauma patients have gradually increased. A total of 173 (72.7%) patients were managed with observation; 28 patients (11.8%) had radiological intervention and 37 patients (15.5%) had splenectomy. Patients who died were significantly more likely to be older (median, 46.5 vs 25.2 years, p=0.04) and to have been admitted to ICU (100% vs 32%, p=<0.001). CONCLUSION: Splenic injuries have shown a steady increase in the last decade. Splenectomy rates have decreased in favour of non-operative techniques. Radiological intervention with splenic artery embolisation was successful in all selected patients with high-grade injuries.

Colorectal multidisciplinary meeting audit to determine patient benefit.

BACKGROUND: New Zealand tumour standards require discussion of all cases of colorectal cancer in a multidisciplinary meeting (MDM), but supporting evidence is lacking. The aim was to determine which patients benefit from MDM discussion. METHODS: A retrospective and prospective audit was undertaken of all patients discussed in the Christchurch Hospital colorectal MDM over 12 months to November 2014, who were compared with contemporaneous patients not discussed and identified through Hospital discharge codes. RESULTS: In total, 641 patients were identified, with 459 (70%) discussed in the MDM, on average 7 years younger than not discussed. The proportion discussed by location was 39.2% colon, 63% rectosigmoid, 98% rectal, 96.6% anal. Discussed patients were more likely to have magnetic resonance imaging (68% cf 9.3%), fluorodeoxyglucose positron emission tomography scan (18% versus 2%) and chest computerized tomography scan (50% versus 26%). For colon cancer, American Joint Committee on Cancer (AJCC) stage I and II, 91% of 68 non-discussed patients went straight to surgery compared with 48% of 27 discussed in the MDM; for AJCC stage III uptake of adjuvant chemotherapy was the same whether discussed or not. An R0 resection was achieved for 91% of discussed patients, and 96% of not discussed. A clear referrer's plan, prospectively recorded in 94 patients, was changed after the MDM in 23%. Clinical staging was changed in 20 patients (4%), none with colon cancers. CONCLUSIONS: Discussion in the MDM influenced management, but was unlikely to change management for AJCC stage I/II colon cancer, who could be spared mandatory review in the MDM and be discussed selectively as treating clinicians decide.

Chemoprevention of colorectal neoplasia.

BACKGROUND: Colorectal cancer is a common and often fatal malignancy. Currently, the modifications that alter disease outcome include early symptom recognition, population screening as well as improved surgical and adjuvant treatments. Preventative strategies have been limited with little evidence that lifestyle changes significantly alter risk. There is however a growing awareness of a potential role for chemoprevention in some patient groups. This study aimed to review the literature associated with chemoprevention in colorectal cancer. METHODS: An electronic literature search of MEDLINE and Embase databases was performed on PubMed for studies detailing the use of chemoprevention agents in colon and rectal cancer. The search was limited to clinical trials on adult humans (>16 years of age) published in English since 1990. RESULTS: The strongest evidence is for non-steroidal anti-inflammatory drugs slowing polyp progression, notably Sulindac and aspirin in patients with familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer, respectively. There is also increasing evidence that continuing use of low-dose aspirin reduces long-term incidence of colorectal cancers. Cyclooxygenase 2 inhibitors also have a potential role but cardiac toxicity currently limits their use. Folic acid, statins, antioxidants, calcium and 5-aminosalicylic acid lack evidence to support their use at present. CONCLUSIONS: Currently, there is not enough evidence to support the implementation of a chemopreventative agent for general use. However, there appears to be a role for aspirin in selected subgroups.

Ten-year review of gastrointestinal stromal tumours at a tertiary referral hospital in New Zealand.

BACKGROUND: Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumours of the gastrointestinal tract and make up 1-2% of all gastrointestinal malignancies. Traditionally, the treatment of choice for primary disease is surgical resection; however, no single surgeon or institution gets extensive exposure to these patients so appropriate decision-making is difficult, particularly since the introduction of the tyrosine kinase inhibitor imatinib, which has become an important additional management tool. METHOD: All patients were diagnosed and treated for GISTs in Christchurch Hospital (Christchurch, New Zealand) between 1 January 2000 and 31 December 2010. We maintain a prospective database of all patients with GISTs. Data on clinical and histopathological variables, management and survival outcomes were recorded. These were then reviewed. RESULTS: There were 93 patients in this study. Fifty were women. Median age was 69 (interquartile range (IQR) 59-76) years. Fifty-one tumours were located in the stomach, 27 in the small bowel, six in the colon, three in the oesophagus, one in the rectum and five were extra-gastrointestinal. In total, 22 patients received imatinib therapy; four patients with metastatic disease had imatinib as sole therapy. The median follow-up was 58 (IQR 30-90) months. The 5-year overall survival and disease-free survival (DFS) for the entire study population was 69% and 64%, respectively. The 5-year DFS was higher for all patients who have localized disease when compared with those who have metastatic disease (76% versus 28%, P-value 0.001). CONCLUSION: Surgery aiming at an R0 resection remains the mainstay of treatment. We propose the most effective way to grow the knowledge base in New Zealand is the establishment of a national register, thereby allowing better clinical decision-making by interpretation of a larger data set.

Cystoprostatectomy versus prostatectomy alone for locally advanced or recurrent pelvic cancer.

BACKGROUND: There is minimal published data evaluating the oncological outcome of rectal resection with prostatectomy alone versus rectal resection with cystoprostatectomy in patients undergoing pelvic exenteration for locally advanced or recurrent pelvic cancer. This study aims to evaluate the oncological and functional outcomes of performing rectal resection with prostatectomy alone compared with rectal resection with cystoprostatectomy in patients undergoing pelvic exenteration. METHODS: Consecutive patients undergoing pelvic exenteration for locally advanced or recurrent pelvic cancer between 1998 and 2012 were identified from a prospectively maintained database. Patients undergoing rectal resection with prostatectomy alone were compared with a control group who underwent rectal resection with cystoprostatectomy and urostomy formation. The primary outcome was overall survival. Secondary outcomes analysed in the prostatectomy group included completeness of resection, continence and erectile function. RESULTS: Eleven rectal resections with prostatectomy were compared with 20 rectal resections with cystoprostatectomy. R0 resection was achieved in 73 and 65% respectively. There was no difference in overall survival (P = 0.40). Urinary continence was achieved in 36% of prostatectomy alone patients, while 27% experienced mild incontinence. Erectile function was poor, with only one patient able to maintain normal erections. CONCLUSION: In appropriately selected patients with invasive pelvic tumours, rectal resection with prostatectomy alone provides adequate oncological outcomes. The ability to achieve an R0 resection was not compromised and overall survival is comparable with cystoprostatectomy. Urinary function is reasonable in most patients, although sexual function is compromised in almost all.

Anorectal melanoma: not a haemorrhoid.

AIM: Melanoma of the anorectum is a rare malignancy which is particularly aggressive compared to cutaneous melanoma. Due to its presenting symptoms, location and rarity there is often a delay in diagnosis. The purpose of this paper is to raise awareness of anorectal melanoma in New Zealand by presenting our institution's experience of four cases. METHODS: The presentation, management and outcomes of four cases are described. A review of the literature surrounding anorectal melanoma was also carried out. RESULTS: The four cases (3 male, 1 female, aged 30-87 years) all presented with haemorrhoidal symptoms of anal discomfort and/or outlet rectal bleeding. Three patients had metastatic disease at presentation, and the remaining patient was found to have a concurrent lymphoma which was treated with chemotherapy before he underwent excision of the melanoma. Surgical excision is the mainstay of treatment and recent literature suggests transanal excision of the primary tumour to have equivalent overall survival to abdominoperineal resection. CONCLUSION: Anorectal melanoma is rare tumour with a poor prognosis. Patients are commonly misdiagnosed as having haemorrhoids; therefore a high index of suspicion is needed to enable early diagnosis. Metastatic disease is common at presentation, and the key prognostic indicator. Local control can be obtained with transanal excision, avoiding the morbidity of abdominoperineal resection. Adjuvant therapies available at present provide little survival advantage.

Survival outcome in New Zealand after resection of colorectal cancer lung metastases.

BACKGROUND: Colorectal cancer is the second most common type of solid organ cancer in New Zealand behind prostate cancer. Even with treatment, distant disease may develop in the liver and lungs. Surgical resection of isolated liver and/or lung metastasis is now commonly considered, but survival outcomes from the latter are not well described. This study aims to review the 5-year survival and prognostic factors of patients who have resection for lung metastasis of colorectal origin. METHODS: A retrospective audit of surgical resection for lung metastasis performed by thoracic departments of several tertiary referral centres within New Zealand was performed. The study period was between 1997 and 2011. Patients were identified through operative logs, audit databases, clinical case mix codes and pathology databases. Patient demographics, preoperative and post-operative variables were recorded. All patients were followed up for survival analysis. Mann-Whitney and chi-square tests were performed for data analysis. A P-value of less than 0.05 was significant. RESULTS: There were 106 (59 male) patients. Median age was 64 (inter-quartile range (IQR) 57-73) years. Median follow-up period was 30 (IQR 16-46) months. The 5-year overall and cancer-specific survival was 40% and 43%, respectively. The only good prognostic factor for survival after lung resection was a long disease-free interval (P = 0.04) between surgery for the colorectal primary and lung metastasis. CONCLUSION: Lung resection for isolated colorectal metastases provides a reasonable 5-year survival. Outcomes from lung resection for colorectal metastases in New Zealand are comparable to that from international series.

Circulating levels and clinical significance of soluble CD40 in patients with hematologic malignancies.

BACKGROUND: CD40 plays a critical role in immunoregulation, and CD40 ligation is being investigated as a therapy for hematologic malignancies. Although soluble CD40 (sCD40) is a potential modulator of both antitumor responses and CD40-based therapies, the levels and significance of sCD40 in patients with hematologic malignancies are unknown. METHODS: The authors evaluated serum/plasma sCD40 levels using an enzyme-linked immunoassay in patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), and multiple myeloma (MM). RESULTS: Levels of sCD40 were elevated in serum (>1.697 ng/mL) or plasma (>0.649 ng/mL) from 73% of patients with CLL, 80% of patients with MCL, 40% of patients with AML, 43% of patients with MDS, and 33% of patients with MM. Multivariate analysis of patients with MM demonstrated that elevated sCD40 was a significant, independent predictor of poor survival. In multivariate analysis of patients with AML, sCD40 was a significant prognostic factor when the interaction of age and sCD40 was included as a variable. Further analysis demonstrated that elevated sCD86 levels were associated with significantly shorter survival only in AML patients younger than age 64 years. Release of sCD40 by CLL cells was induced by cross-linking with CD40 monoclonal antibody. CONCLUSIONS: Many patients with hematologic malignancies have elevated circulating levels of sCD40, and these elevated levels are associated with a poor prognosis at least in patients with MM and AML, suggesting that sCD40 may have a role in modulating antitumor responses and also may be a useful prognostic marker. In addition, the findings suggested that further studies will be required to determine the effect of circulating sCD40 on the clinical effectiveness of CD40-ligating reagents used in the treatment of hematologic malignancies.