A meta-analysis comparing side to end with colonic J-pouch formation after anterior resection for rectal cancer.

BACKGROUND: A meta-analysis of published literature comparing J-pouch with side to end anastomosis after anterior resection (AR) for rectal cancer. METHODS: Electronic databases were searched from January 1980 to March 2009. A systematic review was performed to obtain a summative outcome. RESULTS: Four randomized controlled trials involving 273 patients were analysed. One hundred and thirty-eight patients were in the J-pouch and 135 in the side to end anastomosis (STEA) group. No significant difference in surgically related outcomes was established (hospital stay, operative time, estimated blood loss, overall morbidity and mortality). Resting pressures at 24 months post-operatively were lower in J-pouch group compared with STEA and approached statistical significance [random effects model: SMD = -1.23, 95% CI (-2.47, -0.01), z = -1.94, P = 0.053]. No statistical difference was found in volumetric parameters (Volume at which the patient first experiences a sensation to defaecate and maximal tolerable volume). No statistical difference except urgency at 6 months [P < 0.05] was elicited in functional outcomes (use of enemas, bowel medications, pads, incomplete defaecation and stool frequency) between J-pouch and STEA groups. CONCLUSIONS: J-pouch or STEA are acceptable and safe options after AR for rectal cancer. Either approach may be considered according to surgeon choice. A randomized controlled trial including a larger number of patients is required to strengthen the evidence.

An isolated lump in right groin: an unusual initial presentation of Crohn's disease.

BACKGROUND: Retroperitoneal abscess, extending to the groin as an isolated tender lump, is rare as the first manifestation of Crohn's disease. CASE PRESENTATION: This report describes a young, fit and healthy 22 year-old woman with no previous history of gastrointestinal disorder, who presented with an isolated, tender lump in her right groin as the initial presentation of Crohn's disease. The patient, after a conventional incision and drainage of the abscess, was readmitted with enterocutaneous fistula at the right groin. After radiological investigations, she underwent a laparotomy, which showed jejunal perforation through ileocaecal mesentery producing retrocaecal abscess. There was also a suspicious fistulous connection between jejunum and ileo-caecal junction. A segmental small bowel resection and a limited right hemicolectomy with primary anastomoses were performed. The patient made an uneventful post-operative recovery and was discharged home on the fifth post operative day. CONCLUSION: Crohn's disease could manifest as an isolated, tender groin lump which has not been described in the published literature so far. Since retroperitoneal abscess remains a rare but serious complication of Crohn's disease, aggressive operative therapy should be ensued without delay in order to remove the source of the abscess. Groin abscess could conceal surprises and should always be investigated radiologically before proceeding to incision and drainage.

Perforated caecal volvulus: an unusual complication after anterior resection for colorectal carcinoma.

AIM: To discuss an unusual and rare complication of perforated caecal volvulus (CV) following open anterior resection. METHODS: A retrospective review of the case notes of a patient. RESULTS: CV is a well known but rare cause of bowel obstruction. Chronic constipation, distal colonic obstruction and post-operative ileus are potentially aggravating factors for the development of CV in anatomically susceptible patients. The anatomical susceptibility for CV was noticed during the first operation but prophylactic caecopexy was not performed due to lack of evidence in the literature. This patient developed CV after anterior resection and subsequently underwent a second laparotmy for right hemicolectomy. CONCLUSION: CV is a known but rare case of postoperative bowel obstruction. The role of prophylactic caecopexy could be discussed in order to avoid the development of postoperative CV in anatomically susceptible patients.

Internet information on colorectal cancer: commercialization and lack of quality control.

OBJECTIVE: The objective of this study was to evaluate the effectiveness of the internet as a source of information for colorectal cancer (CRC). METHOD: Six of the most common search engines (Yahoo, Google, MSN search, Alta Vista, Excite and Lycos) were used for the search of the generic term 'CRC'. First 300 links were analysed and classified by information type, provider, readership and commercial orientation. RESULTS: The average time delay was 1.70 s before matches were located. A total of 3.2827 million matches on CRC were found using the six search engines ranging from 700 (Excite) to 1 417 000 (Lycos) websites. Approximately 50% of the links were based on information from textbooks or governmental websites. Commercial companies giving information about private hospitals and products provided over 50% of the websites on CRC. The distribution of target readers was uneven, although a majority of websites were delivering CRC information to public and patients. Readability of information was difficult to comprehend by the public. CONCLUSION: The internet is becoming an essential tool for disseminating information about CRC to consumers. Half of the links on CRC are commercially oriented, containing information on goods or private health services. Less than 1% information is being provided by professional societies. To provide relevant CRC information, key consensus criteria for evaluating healthcare-related websites have to be established. There is an urgent need for CRC information on the internet to be regulated through the establishment of government-funded organizations (e.g. NHS) or professional societies (e.g. ACPGBI).

Autologous bone marrow transplantation for children with AML in first remission.

In Children's cancer group (CCG) 2891, newly diagnosed patients with AML were randomized between standard and intensive timing induction therapies. Patients in first remission who lacked an HLA matched family donor were randomized between an autologous bone marrow transplantation (ABMT) where marrow was purged with 4 hydroperoxycyclophosphamide and consolidation chemotherapy. One hundred and thirty seven patients received an ABMT. Myeloid and platelet engraftment occurred at a median of 44 and 42 days, respectively. Disease-free survival (DFS), relapse-free survival and overall survival at 8 years post induction were 47% (95% confidence interval (CI): 38-55), 50% (CI: 42-59) and 55% (CI: 46-63), respectively. Multivariate analysis of DFS showed WBC <50 000/microl and having received intensively timed induction therapy were associated with improved DFS. Recipients who received intensive timed induction therapy and whose WBC was less than 50 000/microl had a DFS at 8 years of 62% (CI: 49-73). Conversely, recipients who received intensive timed induction therapy patients whose WBC was > or =50 000/microl had a DFS of 33% (CI: 17-50), P=0.003. The results confirm previous studies that ABMT is effective post remission therapy for pediatric patients with AML in first remission.

Intraoperative oesophageal Doppler guided fluid management shortens postoperative hospital stay after major bowel surgery.

BACKGROUND: Occult hypovolaemia is a key factor in the aetiology of postoperative morbidity and may not be detected by routine heart rate and arterial pressure measurements. Intraoperative gut hypoperfusion during major surgery is associated with increased morbidity and postoperative hospital stay. We assessed whether using intraoperative oesophageal Doppler guided fluid management to minimize hypovolaemia would reduce postoperative hospital stay and the time before return of gut function after colorectal surgery. METHODS: This single centre, blinded, prospective controlled trial randomized 128 consecutive consenting patients undergoing colorectal resection to oesophageal Doppler guided or central venous pressure (CVP)-based (conventional) intraoperative fluid management. The intervention group patients followed a dynamic oesophageal Doppler guided fluid protocol whereas control patients were managed using routine cardiovascular monitoring aiming for a CVP between 12 and 15 mm Hg. RESULTS: The median postoperative stay in the Doppler guided fluid group was 10 vs 11.5 days in the control group P<0.05. The median time to resuming full diet in the Doppler guided fluid group was 6 vs 7 for controls P<0.001. Doppler patients achieved significantly higher cardiac output, stroke volume, and oxygen delivery. Twenty-nine (45.3%) control patients suffered gastrointestinal morbidity compared with nine (14.1%) in the Doppler guided fluid group P<0.001, overall morbidity was also significantly higher in the control group P=0.05. CONCLUSIONS: Intraoperative oesophageal Doppler guided fluid management was associated with a 1.5-day median reduction in postoperative hospital stay. Patients recovered gut function significantly faster and suffered significantly less gastrointestinal and overall morbidity.

Long-term results of children with acute myeloid leukemia: a report of three consecutive Phase III trials by the Children's Cancer Group: CCG 251, CCG 213 and CCG 2891.

The Children's Cancer Group (CCG) conducted three Phase III prospective clinical trials for children with de novo acute myeloid leukemia between the years 1979 and 1995. A total of 1903 eligible children ages birth to 21 years of age were enrolled on CCG 251 (n=485), CCG 213 (n=532) and CCG 2891 (n=886). Follow-up is ongoing, with medians of 7.9, 10.9 and 8.6 years, respectively. These three clinical trials developed dose- and time-intensive induction regimens based upon high-dose cytarabine and daunomycin and randomly assigned patients to allogeneic bone marrow transplantation in first remission if an HLA-matched related donor was identified. Despite dose- and time-intensive induction regimens, remission induction rates remained relatively stable at 77-78%. However, overall survival, event-free survival and disease-free survival (DFS) increased for patients receiving intensive-timing induction therapy in comparison to patients who received standard-timing induction, regardless of the type of postremission therapy. Outcomes were best for patients receiving intensive-timing induction followed by matched related donor allogeneic transplantation with DFS of 65+/-9% at 6 years. These three clinical trials have established a strong foundation for the development of future studies focusing on further risk group stratification and the development of novel, molecularly-targeted therapies.

Treatment-related myelodysplastic syndrome/acute myeloid leukemia in survivors of childhood cancer--an update.

Treatment-related myelodysplastic syndrome/acute myeloid leukemia (t-MDS/t-AML) is a devastating complication of treatment for childhood cancer. However, the major cause of premature death of children treated for cancer remains their primary cancer. The understanding of the presentation, incidence, predisposing risk factors and pathobiology of t-MDS/t-AML is increasing. This increased understanding has not yet been translated into improved outcomes of therapy for t-MDS/t-AML. However, newer approaches are under study.

Postremission therapy for children with acute myeloid leukemia: the children's cancer group experience in the transplant era.

We reviewed consolidation therapy results and analyzed postremission outcomes for 1464 children less than 21 years old at diagnosis in five consecutive Children's Cancer Group acute myeloid leukemia trials between 1979 and 1996. Children in remission were allocated to allogeneic bone marrow transplantation (BMT) (N=373) in first remission, if a matched family donor was available. Remaining children were assigned consolidation chemotherapy (N=688) or autologous purged BMT (N=217), or withdrew from study before assignment, or with unknown data (N=186). Overall and disease-free survival were superior for children assigned allogeneic transplants. High (>50,000/microl) diagnostic white blood cell (WBC) count was prognostic for inferior outcome, but French-American-British (FAB) subtypes were not. Inv(16) is a favorable karyotypic feature for children in first remission and t(8;21) is not. Allogeneic transplantation benefit was evident in most children, including those with high or low diagnostic WBC count, each FAB subtype, and t(8;21), but was not seen in children with inv(16). Therefore, these data suggest reserving matched related donor allogeneic transplantation for children with inv(16) for second remission, but not those with t(8;21).

Pre-operative short-course radiotherapy is associated with faecal incontinence after anterior resection.

OBJECTIVE: To determine the contribution of total mesorectal excision (TME), short-course pre-operative radiotherapy (SCRT), the level of the anastomosis and other putative contributory factors to the incidence and degree of faecal incontinence after anterior resection of the rectum. PATIENTS AND METHODS: Survivors of anterior resection of the rectum performed between February 1996 and February 2001, with a functioning anastomosis, were asked to complete a telephone questionnaire regarding their current bowel habit. Faecal incontinence was scored using the St. Mark's Incontinence Score. RESULTS: The median age of 124 patients who completed the questionnaire was 76 years. Of these, 104 patients had neoplastic disease, 66 (53%) patients exhibited some degree of incontinence, median St. Marks' Score 6, interquartile range 3-10. There was a significant association between the anastomotic level, and the St. Mark's Score (P < 0.0001, linear regression). Male sex (P = 0.047), SCRT (P = 0.0014) and an anastomotic leak (P = 0.038) were associated with significantly higher incontinence scores. Age, splenic flexure mobilization, TME, anastomotic configuration or use of a temporary stoma had no detectable independent effect on incontinence scores. CONCLUSIONS: Poor functional outcome following anterior resection was associated with a low anastomosis, SCRT or an anastomotic leak. The finding that SCRT was a predictor of postoperative incontinence emphasizes the need for stringent patient selection for this treatment modality.

Colonoscopic surveillance after curative colorectal resection: results of an empirical surveillance programme.

INTRODUCTION: Colonoscopic surveillance after colorectal cancer resection is widely practised despite little evidence that it improves survival. The optimum protocol for colonoscopic follow-up after colorectal cancer resection has not yet been elucidated. We audited the outcome of an empirical colonoscopic follow-up programme in a cohort of patients who underwent colorectal resection with a minimum of five years follow-up to establish patterns of metachronous neoplasia and suitable surveillance intervals. METHODS: The colonoscopic records, biopsy results and follow-up details of patients diagnosed with colorectal cancer between June 1990 and June 1996 were reviewed. The number and type of metachronous neoplastic lesions diagnosed was recorded. Rates of development of new neoplasms were estimated by calculating the time from operation to their first discovery. Factors predictive of further development of polyps or cancer were sought. Results were compared to published reports of intensive follow-up programmes. RESULTS: Seven hundred and ninety-eight patients underwent colorectal resection with curative intent during the study period. 226 patients had one or more follow-up colonoscopies (mean time post resection 48.8 months). In total 352 colonoscopies, encompassing 1437 patient years of surveillance, were performed. Nine metachronous cancers in eight patients, five of which were asymptomatic were diagnosed by colonoscopy at a mean of 63 months. Three asymptomatic recurrences were diagnosed but all were inoperable. 70 (31%) patients had adenomatous polyps diagnosed after a mean time from operation of 34 months for simple adenomatous polyps and 21 months for those with advanced features. Patients with multiple polyps or advanced polyps at the initial colonoscopy were more likely to form subsequent polyps. Only 5.8% of patients with a single adenoma or a normal colon formed an advanced adenoma over the next 36 months of surveillance. CONCLUSION: The results of an empirical colonoscopic follow-up programme compared favourably to the results of the intensive programmes reported in the literature. Most patients are at very low risk of developing significant colonic pathology over the first five years after resection. Colonoscopic surveillance intervals need not be less than five years unless the patient has multiple adenomas or advanced adenomas at the first colonoscopy. Three yearly surveillance intervals are most probably adequate in these individuals.

Prognostic variables in newly diagnosed children and adolescents with acute myeloid leukemia: Children's Cancer Group Study 213.

The objective of this study was to identify biologic parameters that were associated with either exceptionally good or poor outcome in childhood acute myeloid leukemia (AML). Among the children with AML who entered Children's Cancer Group trial 213, 498 patients without Down syndrome or acute promyelocytic leukemia (APL) comprise the basis for this report. Univariate comparisons of the proportion of patients attaining complete remission after induction (CR) indicate that, at diagnosis, male gender, low platelet count (< or =20 000/microl), hepatomegaly, myelodysplastic syndrome (MDS), French-American- British (FAB) category M5, high (>15%) bone marrow (BM) blasts on day 14 of the first course of induction, and +8 are associated with lower CR rates, while abnormal 16 is associated with a higher CR rate. Multivariate analysis suggests high platelet count at diagnosis (>20 000/microl), absence of hepatomegaly, < or =15% day 14 BM blast percentage, and abnormal 16 are independent prognostic factors associated with better CR. Univariate analysis demonstrated a significant favorable relationship between platelet count at diagnosis (>20 000/microl), absence of hepatomegaly, low percentage of BM blasts (< or =15%), and abnormal 16 with overall survival. Absence of hepatomegaly, < or =15% day 14 BM blast percentage, and abnormal 16 were determined to be independent prognostic factors associated with better survival.

Loss of heterozygosity in childhood de novo acute myelogenous leukemia.

A genome-wide screening for loss of heterozygosity (LOH), a marker for possible involvement of tumor suppressor genes, was conducted in 53 children with de novo acute myelogenous leukemia (AML). A total of 177 highly polymorphic microsatellite repeat markers were used in locus-specific polymerase chain reactions. This comprehensive allelotyping employed flow-sorted cells from diagnostic samples and whole-genome amplification of DNA from small, highly purified samples. Nineteen regions of allelic loss in 17 patients (32%) were detected on chromosome arms 1q, 3q, 5q, 7q (n = 2), 9q (n = 4), 11p (n = 2), 12p (n = 3), 13q (n = 2), 16q, 19q, and Y. The study revealed a degree of allelic loss underestimated by routine cytogenetic analysis, which failed to detect 9 of these LOH events. There was no evidence of LOH by intragenic markers for p53, Nf1, or CBFA2/AML1. Most lymphocytes lacked the deletions, which were detected only in the leukemic myeloid blast population. Analysis of patients' clinical and biologic characteristics indicated that the presence of LOH was associated with a white blood cell count of 20 x 10(9)/L or higher but was not correlated with a shorter overall survival. The relatively low rate of LOH observed in this study compared with findings in solid tumors and in pediatric acute lymphoblastic leukemia and adult AML suggests that tumor suppressor genes are either infrequently involved in the development of pediatric de novo AML or are inactivated by such means as methylation and point mutations. Additional study is needed to determine whether these regions of LOH harbor tumor suppressor genes and whether specific regions of LOH correlate with clinical characteristics. (Blood. 2001;98:1188-1194)

Biological aspects of neuroblastomas identified by mass screening in Quebec.

BACKGROUND: Neuroblastoma has several characteristics that suggest that preclinical diagnosis might improve outcome. Therefore, the Quebec Neuroblastoma Screening Project was undertaken from 1989 to 1994 to examine infants at 3 weeks and 6 months by measuring urinary catecholamine metabolites. PROCEDURE: Over the 5-yr period, 45 tumors were detected by screening, 20 were identified clinically prior to the third week, and 64 were identified clinically at a later time. We analyzed available tumors for Shimada histopathology, tumor ploidy, MYCN copy number and serum ferritin. RESULTS: Of the tumors detected by screening, only 2 of 45 tested had unfavorable histology, 2 of 45 had diploid or tetraploid DNA content, 0 of 43 had MYCN amplification, and 4 of 44 had elevated serum ferritin. All of these patients are alive and well. The 20 patients detected prior to the 3-week screen had similar biological characteristics. In contrast, of the patients detected clinically after 3 weeks of age, 19 of 51 testedhad unfavorable histology, 25 of 66 had diploid or tetraploid tumors, 12 of 56 had MYCN amplification, and 14 of 54 had elevated ferritin. CONCLUSIONS: The difference between the screened and clinically detected cases was highly significant for each biological variable. Preliminary data on other biological variables, such as neurotrophin expression and allelic loss on 1 p in these patients are consistent with the above findings. These data suggest that mass screening for neuroblastoma at or before 6 months of age detects almost exclusively tumors that have favorable biological characteristics, many of which might have regressed spontaneously. Thus, continued mass screening for neuroblastoma at 6 months is unlikely to accomplish its intended goal, and should probably be discontinued.

Glutathione S-transferase polymorphisms and outcome of chemotherapy in childhood acute myeloid leukemia.

PURPOSE: Glutathione S-transferase theta (GSTT1) and mu (GSTM1) genes are polymorphic, the genes being absent in approximately 15% and 50% of the population, respectively. Because glutathione S-transferases may be involved in the metabolism of chemotherapy drugs, we hypothesized that presence or absence of the genes may influence the outcome of treatment for childhood acute myeloid leukemia (AML). PATIENTS AND METHODS: We genotyped GSTT1 and GSTM1 in 306 children with AML receiving chemotherapy on Children's Cancer Group therapeutic studies. Outcomes were compared in those with and without GSTT1 and GSTM1 genes. RESULTS: Patients with the GSTT1-negative genotype had reduced survival compared with those with at least one GSTT1 allele (GSTT1 positive) (52% v 40% at 5 years; log-rank P =.05). A multivariate model of survival adjusted for age group, sex, WBC count, chloroma, CNS involvement, and French-American-British group confirmed the increased risk of death in the GSTT1-null cases (relative risk, AQ 1.6; P =.02). The frequency of death in remission was increased in GSTT1-negative cases compared with GSTT1-positive cases (24% v 12%, log-rank P =.05). The frequency of relapse from end of induction was similar in GSTT1-negative and GSTT1-positive cases (38% v 35%, log-rank P =.5). CONCLUSION: Children who lacked GSTT1 had greater toxicity and reduced survival after chemotherapy for AML compared with children with at least one GSTT1 allele. If confirmed in further studies, GSTT1 genotype might be useful in selecting appropriate chemotherapy regimens for children with AML.

A comparison of allogeneic bone marrow transplantation, autologous bone marrow transplantation, and aggressive chemotherapy in children with acute myeloid leukemia in remission.

Intensive, myelosuppressive therapy is necessary to maximize outcomes for patients with acute myeloid leukemia (AML). A comparison was made of 3 aggressive postremission approaches for children and adolescents with AML in a randomized trial, CCG-2891. A total of 652 children and adolescents with AML who achieved remission on 2 induction regimens using identical drugs and doses (standard and intensive timing) were eligible for allocation to allogeneic bone marrow transplantation (BMT) based on matched related donor status (n = 181) or randomization to autologous BMT (n = 177) or to aggressive high-dose cytarabine-based chemotherapy (n = 179). Only 115 patients (18%) refused to participate in the postremission phase of this study. Overall compliance with the 3 allocated regimens was 90%. At 8 years actuarial, 54% +/- 4% (95% confidence interval) of all remission patients remain alive. Survival by assigned regimen ("intent to treat") is as follows: allogeneic BMT, 60% +/- 9%; autologous BMT, 48% +/- 8%; and chemotherapy, 53% +/- 8%. Survival in the allogeneic BMT group is significantly superior to autologous BMT (P =.002) and chemotherapy (P =.05); differences between chemotherapy and autologous BMT are not significant (P =.21). No potential confounding factors affected results. Patients receiving intensive-timing induction therapy had superior long-term survival irrespective of postremission regimen received (allogeneic BMT, 70% +/- 9%; autologous BMT, 54% +/- 9%; chemotherapy, 57% +/- 10%). Allogeneic BMT remains the treatment of choice for children and adolescents with AML in remission, when a matched related donor is available. For all others, there is no advantage to autologous BMT; hence, aggressive nonablative chemotherapy should be used.

Prevalence and prognostic significance of Flt3 internal tandem duplication in pediatric acute myeloid leukemia.

The Flt3 gene encodes a tyrosine kinase receptor that regulates proliferation and differentiation of hematopoietic stem cells. An internal tandem duplication of the Flt3 gene (Flt3/ITD) has been reported in acute myelogenous leukemia (AML) and may be associated with poor prognosis. We analyzed diagnostic bone marrow specimens from 91 pediatric patients with AML treated on Children's Cancer Group (CCG)-2891 for the presence of the Flt3/ITD and correlated its presence with clinical outcome. Fifteen of 91 samples (16.5%) were positive for the Flt3/ITD. Flt3/ITD-positive patients had a median diagnostic white count of 73 800 compared with 28 400 for the Flt3/ITD-negative patients (P =.05). The size of the duplication ranged from 21 to 174 base pairs (bp). Nucleotide sequencing of the abnormal polymerase chain reaction products demonstrated that all duplications involved exon 11 of the Flt3 gene and also preserved the reading frame. Lineage restriction analysis revealed that Flt3/ITD was not present in the lymphocytes, suggesting a lack of stem cell involvement for this mutation. None of the Flt3/ITD-positive patients had unfavorable cytogenetic markers, and there was no predominance of a particular FAB class. The remission induction rate was 40% in Flt3/ITD-positive patients compared with 74% in Flt3/ITD-negative ones (P =.005). The Kaplan-Meier estimates of event-free survival at 8 years for patients with and without Flt3/ITD were 7% and 44%, respectively (P =.002). Multivariate analysis demonstrated that presence of the Flt3/ITD was the single most significant, independent prognostic factor for poor outcome (P =.009) in pediatric AML.

Therapy for acute myeloid leukemia: intensive timing of induction chemotherapy.

Children's Cancer Group (CCG) study 2891 for children with previously untreated acute myeloid leukemia enrolled more than 1200 patients between 1989 and 1995. This study showed that increased dose intensity during induction therapy improved survival for all patients except those with Down syndrome, where it proved harmful. Although increased dose intensity improved survival, it did not improve remission induction rate, indicating that the quality of remissions varies. This finding complicates the evaluation of postremission therapy options, which CCG 2891 also evaluated. Survival with related-donor allogeneic bone marrow transplantation was superior to survival with both purged autologous bone marrow transplantation and a more standard chemotherapy consolidation, whereas survival for autologous transplantation and chemotherapy was equivalent.