Biomedical subjects

John R T Monson

Publications and source records attributed to John R T Monson.

At least 19 recordsLinked to original sources

PubMed2007

Mesorectal grades predict recurrences after curative resection for rectal cancer.

PURPOSE: Local recurrence after curative excision for rectal cancer is frequently regarded as a failure of surgery. The macroscopic quality of the excised mesorectum after total mesorectal excision has been proposed as a means of assessment of the adequacy of surgery. This study was designed to determine the utility of mesorectal grading in prediction of local and overall recurrence after curative surgery. METHODS: All patients undergoing resection for primary adenocarcinoma of the rectum had a mesorectal grading prospectively applied to their resection specimens, according to the classification proposed by Quirke et al. (Grades 1-3; 3 is the best). The outcome of patients undergoing potentially curative surgery from 2001 to 2003 was reviewed. Prognostic significance of mesorectal grades was determined by multivariate regression analyses. RESULTS: A total of 130 patients with a median follow-up of 26 (range, 17-42) months were studied. The local and overall recurrences were 8.4 and 15 percent, respectively. The mesorectum was reported as Grade 3 in 61 patients (47 percent), Grade 2 in 52 patients (40 percent), and Grade 1 in 17 patients (13 percent). Patients with Grade 1 mesorectum had 41 percent local recurrence and 59 percent overall recurrence, respectively. However, patients with Grade 2 and Grade 3 mesorectum had 5.7 and 1.6 percent local recurrences, respectively, and 17 and 1.6 percent overall recurrence, respectively. By Cox's regression analysis, grade of mesorectum independently influenced both local and overall recurrences. CONCLUSIONS: The macroscopic quality of mesorectum after curative excision of rectal cancer is an important predictor of local and overall recurrences. The mesorectal grades may be of value in decisions regarding postoperative adjuvant therapy.

Adenocarcinoma↗

PubMed2006

Transanal endoscopic microsurgery: where are we now?

AIMS: This review of literature aimed to assess the role and establish the current status of transanal endoscopic microsurgery (TEM) in the management of benign and malignant rectal lesions. METHODS: A review of the literature was undertaken through the Medline database and by cross-referencing previous publications, thus identifying 54 relevant publications on TEM in the management of rectal lesions. Aggregated results of various parameters were calculated but statistical comparisons deemed unsuitable due to heterogeneity of data. RESULTS: The TEM procedure is associated with good functional results, morbidity of 4% and zero procedure-related mortality. The local recurrence rates after TEM excision is 4.5% (range 0-14) for benign rectal lesions, 6% (0-13) for T(1) cancers, 14% (range 0-50) for T(2) cancers and 20% (range 14-67%) for T(3) cancers. Local recurrences after TEM can be surgically salvaged with good disease free survival rates. CONCLUSIONS: The TEM procedure clearly offers the benefits of good exposure of the operative field allowing extremely precise dissection and access to high rectal lesions unresectable by other methods. For pTis and low risk pT(1) lesions, the oncological results are comparable to the more traditional formal resection. The routine use of TEM for high-risk pT(1) and higher stage lesions is not an oncologically sound choice at the present moment.

Adenoma↗

PubMed2006

Implication of the BRCA2 and putative "BRCA3" genes in Dukes' stage C, replication error-negative colon cancer.

BACKGROUND: Although BRCA genes have been implicated in certain tumors, particularly breast tumors, their role in colon tumorigenesis has not been fully explored. We aimed to investigate the association of the BRCA2 and putative "BRCA3" genes in a homogeneous series of right-sided colon cancer specimens. METHODS: Twenty-three Dukes' stage C, replication error-negative carcinomas were selected from patients with right-sided colon cancer. After histological examination and microdissection, DNA was extracted from normal colon and carcinoma from each patient. Five microsatellite markers spanning the region of BRCA2 and BRCA3 on chromosome 13 (D13S218, D13S219, D13S165, D13S156, and D13S160) and two markers intragenic to BRCA2 and BRCA3 (D13S171 and D13S1308, respectively) were used. Polymerase chain reaction products were analyzed by using a fluorescent allele imbalance assay. RESULTS: Markers demonstrating the highest allelic imbalance were D13S1308 (53%), D13S171 (33%), and D13S160 (37%). CONCLUSIONS: The intragenic markers D13S1308 (BRCA3) and D13S171 (BRCA2) on chromosome 13 demonstrated a high frequency of allelic imbalance in primary colon carcinoma. This suggests an involvement of BRCA2 and putative BRCA3 in colon tumorigenesis in right-sided, replication error-negative, Dukes' stage C cancers. Further studies are needed to confirm the precise role of these genes, and any prognostic significance, in colon cancer.

Alleles↗

PubMed2006

Reduction in adhesive small-bowel obstruction by Seprafilm adhesion barrier after intestinal resection.

INTRODUCTION: Although Seprafilm has been demonstrated to reduce adhesion formation, it is not known whether its usage would translate into a reduction in adhesive small-bowel obstruction. METHODS: This was a prospective, randomized, multicenter, multinational, single-blind, controlled study. This report focuses on those patients who underwent intestinal resection (n = 1,701). Before closure of the abdomen, patients were randomized to receive Seprafilm or no treatment. Seprafilm was applied to adhesiogenic tissues throughout the abdomen. The incidence and type of bowel obstruction was compared between the two groups. Time to first adhesive small-bowel obstruction was compared during the course of the study by using survival analysis methods. The mean follow-up time for the occurrence of adhesive small-bowel obstruction was 3.5 years. RESULTS: There was no difference between the treatment and control group in overall rate of bowel obstruction. The incidence of adhesive small-bowel obstruction requiring reoperation was significantly lower for Seprafilm patients compared with no-treatment patients: 1.8 vs. 3.4 percent (P < 0.05). This finding represents an absolute reduction in adhesive small-bowel obstruction requiring reoperation of 1.6 percent and a relative reduction of 47 percent. In addition, a stepwise multivariate analysis indicated that the use of Seprafilm was the only predictive factor for reducing adhesive small-bowel obstruction requiring reoperation. In both groups, 50 percent of first adhesive small-bowel obstruction episodes occurred within 6 months after the initial surgery with nearly 30 percent occurring within the first 30 days. Additionally no first adhesive small-bowel obstruction events were reported in Years 4 and 5 of follow-up. CONCLUSIONS: The overall bowel obstruction rate was unchanged; however, adhesive small-bowel obstruction requiring reoperation was significantly reduced by the use of Seprafilm, which was the only factor that predicted this outcome.

Adolescent↗

PubMed2006

Is routine magnetic resonance imaging justified for the early detection of resectable liver metastases from colorectal cancer?

PURPOSE: This study was designed to determine whether routine follow-up by magnetic resonance imaging improves the detection of resectable liver metastases from colorectal cancer and patients' survival. METHODS: Patients who underwent curative surgery for colorectal cancer were included in a program of liver surveillance by routine magnetic resonance imaging, in addition to the standard follow-up protocol consisting of clinical examination and biochemical tests. The median follow-up was 41 (interquartile range, 30-53) months, with a median magnetic resonance imaging surveillance period of 20 (interquartile range, 12-27) months. Cases were analyzed for mode of diagnosis, resectability, and overall survival. RESULTS: Liver metastases were found in 37 (13 percent) of 293 patients studied. Magnetic resonance imaging diagnosed hepatic metastases with 84 percent sensitivity and 90 percent specificity. In 28 (76 percent) patients, carcinoembryonic antigen and/or liver function tests were abnormally elevated and 5 patients (14 percent) were symptomatic. Hepatic resection was possible in only nine patients (24 percent). Magnetic resonance imaging detected all resectable cases, whereas traditional follow-up would have missed three (33 percent) cases suitable for surgery. CONCLUSIONS: Although magnetic resonance imaging surveillance increased the number of patients suitable for liver resection by 50 percent, these represented only 1 percent of the patients included in the study. Whether these results are enough to justify the allocation of expensive resources is controversial.

Adult↗

PubMed2006

Mismatch repair, p53 and chromosomal aberrations in primary colorectal carcinomas.

Colorectal carcinoma progresses via at least two genetic pathways. Microsatellite instability, due to defective mismatch repair genes, characterizes one pathway and gross chromosomal instability another. The involvement of p53 and mismatch repair gene abnormalities within these pathways has not been fully explored. We aimed to investigate the relationships of p53 and mismatch repair gene defects on gross chromosomal aberrations detected by comparative genomic hybridization in 49 colorectal carcinomas. Tumours demonstrating loss of expression for hMLH1 or hMSH2 proteins demonstrated a highly significant attenuation in the number of gross chromosomal aberrations (p = 0.007) and were less likely to show p53 overexpression (p = 0.02). Within the mismatch repair normal tumours, p53 status did not affect the total number of chromosomal aberrations but p53 overexpression was significantly associated with a higher frequency of amplifications at 8q22-ter and at 13q21-22. Colorectal cancer demonstrates distinct molecular phenotypes and should be sub-classified accordingly.

Adaptor Proteins, Signal Transducing↗

PubMed2006

Routine follow-up by magnetic resonance imaging does not improve detection of resectable local recurrences from colorectal cancer.

OBJECTIVE: To determine if routine follow-up by magnetic resonance imaging (MRI) improves the detection of resectable local recurrences from colorectal cancer. SUMMARY BACKGROUND DATA: Surgical treatment offers the best prospect of survival for patients with recurrent colorectal cancer. Unfortunately, most cases are often diagnosed at an unresectable stage when traditional follow-up methods are used. The impact of MRI surveillance on the early diagnosis of local recurrences has yet to be ascertained. METHODS: Patients who underwent curative surgery for rectal and left-sided colon tumors were included in a program of pelvic surveillance by routine MRI, in addition to the standard follow-up protocol. Cases were then analyzed for mode of diagnosis, resectability, and overall survival. RESULTS: Pelvic recurrence was found in 30 (13%) of the 226 patients studied. MRI detected 26 of 30 (87%) and missed 4 of 30 (13%) cases with local recurrence. Of the latter, 3 were anastomotic recurrences. In 28 (14%) patients, local recurrence was suspected by an initial MR scan but cleared by subsequent MRI or CT-guided biopsy. Recurrent pelvic cancer was diagnosed by MRI with 87% sensitivity and 86% specificity. In 19 (63%) cases, CEA was abnormally elevated, and 9 patients (30%) were symptomatic. Surgical resection was possible in only 6 patients (20%). There was no difference between MRI and conventional follow-up tests in their ability to detect cases suitable for surgery. CONCLUSIONS: Pelvic surveillance by MRI is not justified as part of the routine follow-up after a curative resection for colorectal cancer and should be reserved for selectively imaging patients with clinical, colonoscopic, and/or biochemical suspicion of recurrent disease.

Adult↗

PubMed2005

Laparoscopy for colorectal malignancy.

Laparoscopy for colorectal pathology is technically demanding with a steep learning curve. In expert hands, there is no doubt that there is a place for laparoscopy in the operative armamentarium for the treatment of benign disease. The question of its application in the treatment of carcinoma is more difficult to address. The evidence available suggests that laparoscopic resection is a feasible and appropriate option for the treatment of colorectal carcinoma. The skill and technology to perform the procedure are developing apace, and level 1 evidence to support it is tantalizingly close. This paper will outline the development of the technique, the operative approach, and the available evidence for its use in the treatment of carcinoma.

Anastomosis, Surgical↗

PubMed2005

Local excision of rectal cancer: review of literature.

In selected patients, local excision of rectal cancer may be an alternative to radical surgery such as abdominoperineal excision of the rectum or anterior resection. Local excision carries lower mortality and morbidity, without the functional disturbance or alteration in body image that can be associated with radical surgery. There are several techniques of local therapy for rectal cancer, with most experience being available in transanal excision. Transanal endoscopic microsurgery is also used but experience with this newer technique is limited. Patient selection is the most important factor in successful local excision, however specific criteria for selecting patients have not been universally accepted. Review of the published literature is difficult because of the variation in adjuvant therapy regimes and follow-up strategies, as well as results reported in terms of local recurrence and survival rates. There is increasing evidence to suggest that local excision should be restricted to patients with T1 stage rectal cancer without high-risk factors. The place for local excision in patients with T2 or high-risk T1 tumours requires prospective, randomised multi-centre trials comparing radical surgery with local excision, with or without adjuvant therapy.

Chemotherapy, Adjuvant↗

PubMed2004

A case-control study of laparoscopic right hemicolectomy vs. open right hemicolectomy.

PURPOSE: The purpose of our study was to examine all laparoscopic right hemicolectomies performed for cancer in our unit and to compare them with a case-control series of open right hemicolectomies, with emphasis on long-term survival. METHODS: In a retrospective case-control series of right hemicolectomies, those done laparoscopically were compared with an age-matched and stage-matched series of patients who underwent open surgery. Survival was analyzed with the Kaplan-Meier method. RESULTS: Ninety-nine patients were included in the study, 33 laparoscopic and 66 open. Mean age 69.7 years. Dukes staging was the same between the two groups and mean follow-up period was 65.7 months. There were six laparoscopic conversions. The number of days patients were kept nil by mouth was significantly less in the laparoscopic cohort, with a mean of 2.4 days vs. a mean of 3.65 days (P = 0.005, Mann-Whitney U test). The number of days during which patients required parenteral opiates was significantly less in the laparoscopic cohort, with a mean number of days of 2.5, in contrast to 4.5 days in the open group (P = 0.008, Mann-Whitney U test). When overall survival was compared between the open and laparoscopic groups, no difference was found, with a mean overall survival of 40 months in the laparoscopic cohort and 39.4 months in the open cohort (P = 0.348, log-rank test). CONCLUSION: Laparoscopic right hemicolectomy for cancer does not compromise long-term survival and affords the advantage of a shorter period of postoperative ileus and decreased analgesia requirements.

Aged↗

PubMed2004

Prognostic implications of hMLH1 and p53 immunohistochemical status in right-sided colon cancer.

PURPOSE: Extensive research into the molecular biology of colorectal cancer has identified a plethora of molecular markers reputed to provide independent prognostic information. p53 mutational status has been associated with both improved and reduced survival; however, tumors expressing a particular phenotype associated with defective mismatch repair consistently do better. This study was designed to examine site-specific survival implications of p53 and mismatch repair status. METHODS: Mismatch repair (hMLH1 and hMSH2) and p53 status was investigated immunohistochemically in 111 proximal colon cancers along with tumor TNM stage, grade, and extramural vascular invasion. Fisher's exact test was used to assess categoric data; univariate and multivariate models compared survival between the respective tumor phenotypes. RESULTS: Thirty-two percent of tumors showed loss of expression of hMLH1 and in a multivariate analysis were associated with a significant survival advantage after adjustment for tumor stage, p53 status, and extramural vascular invasion (hazard ratio, 0.29; 95 percent confidence interval, 0.1-0.87; P = 0.027). Only two tumors showed loss of expression of hMSH2, which was not related further to survival. Aberrant p53 expression was detected in 39 percent of tumors. Such expression was found to be associated with a significantly reduced survival in univariate analysis (P = 0.037, log-rank test) but not in a multivariate model. Subgroup analysis showed no association between survival and p53 expression in mismatch repair proficient tumors. CONCLUSIONS: Loss of hMLH1 expression is an independent predicator of improved survival in this series and perhaps the underlying cause of the observed survival difference associated with p53 expression.

Adaptor Proteins, Signal Transducing↗

PubMed2004

Laparoscopy for rectal carcinoma: anterior resection.

Laparoscopic anterior resection is a technically demanding procedure with a steep learning curve. In expert hands, this procedure has a place in the operative armamentarium for the treatment of benign disease. Its application in the treatment of rectal carcinoma is more difficult to address. The evidence available suggests that laparoscopic anterior resection is a feasible and appropriate option for the treatment of rectal carcinoma. The skill and technology to perform the procedure are developing apace, and level 1 evidence to support its use is tantalizingly close. In this paper, we outline the development of the procedure, the operative approach, and the available evidence for its use in the treatment of rectal carcinoma.

Colectomy↗

PubMed2004

Novel CD43 specific phage antibodies react with early stage colorectal tumours.

Two panning strategies have been used to isolate phage antibody clones that recognise an intracellular epitope of CD43. Firstly, a naive scFv library was panned against a 15-mer CD43 synthetic peptide (RGGKRNGVVDAWAGP), and secondly the naive library was panned against native CD43, isolated from whole cell lysate of Colo205 cells, followed by selection with the synthetic CD43 peptide. Four phage antibodies (HapE8, F2, G9 and G11) were isolated and used in a preliminary immunohistochemistry study of CD43 expression on frozen colorectal adenoma and carcinoma tissue. The three antibodies HapE8, F2 and G11 showed a similar reactivity pattern, staining all adenomas and Dukes' A carcinomas, but only 2/4 Dukes' B and 1/9 Dukes' C. Antibody HapG9 similarly bound to 5/5 adenomas, but only 1/5 Dukes' A carcinoma and no tumours of a more advanced stage. No reactivity with normal colonic epithelium was observed but cross-reactivity with stromal lymphocytes was seen. These new anti-CD43 antibodies are likely to prove useful as screening tools in the detection of colorectal adenomas.

Adenocarcinoma↗

PubMed2003

Stapled versus excision haemorrhoidectomy: long-term follow up of a randomised controlled trial.

Advantages of the stapling procedure for haemorrhoids include reduced postoperative pain and shortened convalescence; however, there are few data with respect to functional and symptomatic outcome. At a dedicated clinic, we reviewed patients between Dec, 2001, and March, 2002, who had taken part in a randomised controlled trial undertaken at the unit in 1999, which compared outcomes after open or stapled haemorrhoidectomy. We noted the presence or absence of haemorrhoid specific symptoms, and assessed overall satisfaction, continence, and quality of life. Rigid sigmoidoscopy and an anorectal examination were also used to examine symptomatic recurrence and disease activity. At minimum follow-up of 33 months since surgery, both techniques seem to be equally effective.

Follow-Up Studies↗

PubMed2003

Local excision of rectal tumors.

Local excision is increasingly being used to treat rectal cancer. It appears to be an attractive option because of low morbidity and excellent functional results. Controversies remain regarding available techniques, selection criteria and results with or without adjuvant therapy. Role of salvage therapy remains uncertain. This review examines available evidence in an attempt to clarify the role of local excision in the management of rectal cancer.

Adenocarcinoma↗

PubMed2003

Identifying a region of interest in site- and stage-specific colon cancer on chromosome 13.

BACKGROUND: The role of genes on chromosome 13q has not been confirmed in colorectal tumors, in part because most series that have been studied are heterogeneous in terms of tumor site, stage, and replication error (RER) status. Using a highly homogenous series of colon tumors, our aim was to identify areas of interest on 13q that are important in carcinogenesis. METHODS: Twenty-three RER-negative tumor specimens from patients with right-sided Dukes' stage C colon tumors were selected for analysis with 10 microsatellite markers spanning 13q. The polymerase chain reaction-amplified products were analyzed by using a standard fluorescent loss of heterozygosity/allele imbalance assay. RESULTS: Markers showing the highest frequency of allelic imbalance were as follows: D13S175 (31%), D13S289 (27%), D13S263 (25%), and D13S265 (27%). The overall resolution of the map was approximately 11.4 to 11.7 cM. CONCLUSIONS: This study of right-sided, RER-negative, Dukes' stage C colon tumors showed the highest area of allelic imbalance corresponding to 13q11.2-11. This region includes LATS2 (large tumor suppressor 2 gene) and FGF9 (fibroblast growth factor 9), which may be involved in carcinogenesis.

Alleles↗

PubMed2002

The role of CD8(+) T cells in immune responses to colorectal cancer.

Cytotoxic T lymphocytes (CTL) are essential effectors of the cell-mediated immune response. The ability of CTL to specifically recognise and lyse malignant cells expressing the relevant surface antigens under optimal in vitro conditions justifies attempts to boost their number and activity through various forms of immunotherapy. Considering the high prevalence of colorectal cancer and poor survival rates for patients with advanced-stage disease, the development of new protocols based on CTL stimulation represents a genuine and promising treatment option. Significant advances in recombinant DNA technology and molecular biology have led to the identification of a number of tumour-associated antigens (TAA). These have served as vaccine constituents and/or stimuli for obtaining CTL used for adoptive immunotherapy after in vitro stimulation and expansion. The present review describes the properties and functions of CTL as effectors of the immune response against tumours, and summarises the known TAA recognised by CTL and the current status of CTL-related immunotherapeutic interventions in colorectal cancer patients.

CD8-Positive T-Lymphocytes↗

PubMed2002

Does laparoscopic abdominoperineal resection of the rectum compromise long-term survival?

PURPOSE: Laparoscopic techniques for bowel resection have not enjoyed widespread popularity. Of concern is that long-term follow-up data of cancer specific outcomes is not yet available. The aim of our study was to examine the long-term outcome of abdominoperineal resection for cancer done laparoscopically compared with a similar cohort who underwent open surgery. METHODS: A retrospective review was performed of all abdominoperineal resections done in our center between 1992 and 2000, comparing the cancer-specific outcomes of the laparoscopic cohort with the open cohort. The analysis was performed on an intention-to-treat basis and survival analysis was calculated by the techniques of Kaplan-Meier. RESULTS: Eighty-nine patients were reviewed. Twenty-eight operations were done laparoscopically, and 61 were open. The two groups were matched for age and stage of disease. There was no difference in mean length of overall survival (open = 30.3 months; laparoscopic = 40.8 months; P = 0.355 log rank). No difference in overall recurrence rate, isolated recurrence rate, or distant recurrence rates was seen nor was there any difference in the disease-free period. There was no difference in the number of lymph nodes harvested from the resected specimens, and the distance to the lateral margins or involvement of tumor in the lateral margins between the two groups was the same. The laparoscopic cohort did have a significantly shorter length of stay (mean, 13 days) compared with the open cohort (mean, 18 days), P = 0.008 Mann-Whitney U test. CONCLUSIONS: Laparoscopic abdominoperineal resection of the rectum for cancer does not compromise cancer-specific survival outcomes. The patients avoid a large abdominal wound, which improves cosmesis and presumably is responsible for the significantly shorter length of stay.

Adult↗