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Biomedical subjects

J C Coffey

Publications and source records attributed to J C Coffey.

At least 19 recordsLinked to original sources
PubMed2006

Cancer surgery: risks and opportunities.

In the recent past, several papers have pointed to the possibility that tumour removal generates a permissive environment in which tumour growth is potentiated. This phenomenon has been coined "perioperative tumour growth" and whilst it represents a departure in terms of our attitude to the surgical process, this concept was first hinted at by Paget(1) himself. Despite this, the time interval immediately before and after cancer surgery (i.e. the perioperative period) remains an underutilised interval during which chemotherapeutic regimens are rarely implemented. Herein, we present a summarised review of the literature that supports the concept that tumour removal may potentiate the growth of residual neoplastic disease. We also outline current knowledge regarding underlying mechanisms and in this manner highlight potential therapeutic entry points. Finally, we emphasise the urgent need for trials of agents that could protect patients against the harmful host-tumour interactions that may occur during the perioperative period.

Humans↗
PubMed2006

Rapid intraoperative parathyroid hormone assay--more than just a comfort measure.

BACKGROUND: Minimally invasive radio-guided parathyroidectomy (MIRP) has been embraced as an acceptable therapeutic approach to primary hyperparathyroidism. Preoperative sestamibi scanning has facilitated this technique. Here we evaluate the addition of a rapid intraoperative parathyroid hormone (iPTH) assay for patients undergoing MIRP. METHODS: A series of 51 patients underwent sestamibi localization of parathyroid glands followed by MIRP for primary hyperparathyroidism. Using peripheral venous samples, iPTH levels were measured prior to gland excision, as well as post-excision at 5, 10, and 15 minutes, taking a 50% reduction in iPTH level as indicative of complete excision. Next, changes in serum iPTH were compared with preoperative and postoperative changes in serum calcium, as well as levels of intraoperative ex-vivo radiation counts taken by hand-held gamma probe. RESULTS: In this series, a drop of greater than 50% in iPTH levels was observed in 94% of patients (n=48). Moreover, a significant drop in iPTH occurred within 10 minutes of excision in the majority (n=42) of cases (P<0.004). Changes in iPTH were comparable with the therapeutic reduction in calcium levels, as well as with the change in intraoperative ex-vivo gamma counts. CONCLUSIONS: This study demonstrates that the addition of an iPTH assay to MIRP provides a quick and reliable intraoperative diagnostic modality in confirming correct adenoma removal. Moreover, it precludes the requirement of frozen section.

Adult↗
PubMed2006

Sentinel lymph node biopsy: is it possible to reduce false negative rates by excluding patients with nodular melanoma?

OBJECTIVE: The aim of this study was to review the outcome of sentinel lymph node biopsy (SLNB) in patients with melanoma and to delineate whether patients with nodular melanoma are more likely to develop nodal recurrence despite negative SLNB. METHODS: Consecutive patients with cutaneous melanoma undergoing SLNB were identified from a departmental database between 1997 and 2005. Factors including demographic data, site, histological subtype, depth and outcome were examined. RESULTS: Of 131 patients, 103 were node negative and eligible for study. The median age was 53 (16-82) years with 46 patients being male (45%) and 57 female (55%). Primary melanoma sites included lower limb (49; 48%), upper limb (29; 28%), head (12; 11%), trunk (7; 7%) and back (6; 6%). The median Breslow thickness was 2mm. Superficial spreading accounted for 43% of melanoma with nodular accounting for 42%. Median follow-up was 40 (3-90) months. Of 20 relapses, seven recurred in the same nodal basin, three were satellite recurrences, one recurred with both satellite and nodal lesions simultaneously, and nine experienced haematogenous spread. Of the eight patients who developed recurrence in the same nodal basin, four were of nodular histological subtype (p=NS). All of the three patients with satellite lesions had nodular melanoma histologically (p=0.02). When nodal and satellite recurrences were combined, eight of 11 were histologically nodular (p=0.01). CONCLUSIONS: This study indicates that lymphatic recurrence occurs more often in SLNB negative patients with nodular melanoma. Further evaluation of the inclusion criteria for sentinel node biopsy is warranted.

Adolescent↗
PubMed2005

Provider volume and outcomes for oncological procedures.

BACKGROUND: Oncological procedures may have better outcomes if performed by high-volume providers. METHODS: A review of the English language literature incorporating searches of the Medline, Embase and Cochrane collaboration databases was performed. Studies were included if they involved a patient cohort from 1984 onwards, were community or population based, and assessed health outcome as a dependent variable and volume as an independent variable. The studies were also scored quantifiably to assess generalizability with respect to any observed volume-outcome relationship and analysed according to organ system; numbers needed to treat were estimated where possible. RESULTS: Sixty-eight relevant studies were identified and a total of 41 were included, of which 13 were based on clinical data. All showed either an inverse relationship, of variable magnitude, between provider volume and mortality, or no volume-outcome effect. All but two clinical reports revealed a statistically significant positive relationship between volume and outcome; none demonstrated the opposite. CONCLUSION: High-volume providers have a significantly better outcome for complex cancer surgery, specifically for pancreatectomy, oesphagectomy, gastrectomy and rectal resection.

Health Facility Size↗
PubMed2005

Can surgery for cancer accelerate the progression of secondary tumors within residual minimal disease at both local and systemic levels?

BACKGROUND: Surgical removal remains the principal treatment modality in the management of lung cancer. Our aim is to characterize the effects of tumor removal on subsequent tumor recurrence at both local and systemic levels. METHODS: C57/BL6 mice [10/group] underwent a mammary fat pad inoculation of 3LL cells [5 x 10(5)/animal] and were divided into two groups. Group 1 served as control while mice in group 2 were further subdivided into groups 2A and 2B. After 2 weeks, all mice in 2A were killed, and primary tumors and lungs were excised. At 2 weeks, primary tumors were excised completely for all mice in group 2B. These mice were then recovered and recurrent tumor growth evaluated for a further 2 weeks. Four weeks from the onset of the study, all remaining primary tumors and lungs were excised from groups 1 and 2. RESULTS: After 4 weeks undisturbed growth, primary tumors in group 1 reached a mean size of 2.85 +/- 0.33 cm. After 2 weeks growth, primary tumors in groups 2A and 2B were comparable at 1.36 +/- 0.44 m and 1.53 +/- 0.29 cm, respectively. Two weeks after primary tumor excision, recurrent tumors in group 2B had reached a mean size of 2.65 +/- 0.74 cm. Moreover, for several animals, recurrent tumors rapidly reached similar volumes to that of primary tumors in group 1. Primary tumors were typically encapsulated and nonadherent. In contrast, recurrent tumors were locally invasive and adherent to chest wall and wound. Interestingly, pulmonary metastatic burden was increased in group 2B relative to group 1. Histologic examination revealed increased mitosis in recurrent tumors when compared with primary tumors. CONCLUSIONS: Tumor removal is followed by accelerated growth of locally recurrent tumors and metastases. Moreover, recurrent tumors are more locally invasive than primary tumors. These findings strongly indicate that resection may be followed by tumor progression in residual disease.

Animals↗
PubMed2005

A characterization of anaerobic colonization and associated mucosal adaptations in the undiseased ileal pouch.

INTRODUCTION: The resolution of pouchitis with metronidazole points to an anaerobic aetiology. Pouchitis is mainly seen in patients with ulcerative colitis pouches (UCP). We have recently found that sulphate reducing bacteria (SRB), a species of strict anaerobe, colonize UCP exclusively. Herein, we aimed to correlate levels of different bacterial species (including SRB) with mucosal inflammation and morphology. METHODS: Following ethical approval, fresh faecal samples and mucosal biopsies were taken from 9 patients with UCP and 5 patients with familial adenomatous polyposis pouches (FAPP). For the purposes of comparison, faecal samples and mucosal biopsies were also taken from the stomas of 7 of the 9 patients with UC (UCS). Colonization by four types of strict anaerobes (SRB, Clostridium perfringens, Bifidobacteria and Bacteroides) as well as by three types of facultative anaerobes (Enterococci, Coliforms and Lactobacilli) was evaluated. Inflammatory scores and mucosal morphology were assessed histologically in a blinded fashion by a pathologist. RESULTS: In general, strict anaerobes predominated over facultative in the UCP (P = 0.041). SRB were present in UCP exclusively. Even after exclusion of SRB from total bacterial counts, strict anaerobes still predominated. In the UCS, facultative anaerobes predominated. Strict and facultative anaerobes were present at similar levels in the FAPP. Enterococci were present at significantly reduced levels in the UCP when compared with the UCS (P = 0.031). When levels of SRB and other anaerobic species were individually correlated with mucosal inflammation and morphology, no trends were observed. CONCLUSION: We have previously identified that SRB exclusively colonize UCP. In addition we have now identified a novel increase in the strict/facultative anaerobic ratio within the UCP compared to UCS. These stark differences in bacterial colonization, however, appear to have limited impact on mucosal inflammation or morphology.

Adenomatous Polyposis Coli↗
PubMed2003

Excisional surgery for cancer cure: therapy at a cost.

Excisional surgery is one of the primary treatment modalities for cancer. Minimal residual disease (MRD) is the occult neoplastic disease that remains in situ after curative surgery. There is increasing evidence that tumour removal alters the growth of MRD, leading to perioperative tumour growth. Because neoplasia is a systemic disease, this phenomenon may be relevant to all patients undergoing surgery for cancer. In this review we discuss the published work that addresses the effects of tumour removal on subsequent tumour growth and the mechanisms by which tumour excision may alter residual tumour growth. In addition, we describe therapeutic approaches that may protect patients against any oncologically adverse effects of tumour removal. On the basis of the evidence presented, we propose a novel therapeutic paradigm; that the postoperative period represents a window of opportunity during which the patient may be further protected against the oncological effects of tumour removal.

Chemotherapy, Adjuvant↗
PubMed2002

Sulfate-reducing bacteria colonize pouches formed for ulcerative colitis but not for familial adenomatous polyposis.

PURPOSE: Ileal pouch-anal anastomosis remains the "gold standard" in surgical treatment of ulcerative colitis and familial adenomatous polyposis. Pouchitis occurs mainly in patients with a background of ulcerative colitis, although the reasons for this are unknown. The aim of this study was to characterize differences in pouch bacterial populations between ulcerative colitis and familial adenomatous pouches. METHODS: After ethical approval was obtained, fresh stool samples were collected from patients with ulcerative colitis pouches (n = 10), familial adenomatous polyposis (n = 7) pouches, and ulcerative colitis ileostomies (n = 8). Quantitative measurements of aerobic and anaerobic bacteria were performed. RESULTS: Sulfate-reducing bacteria were isolated from 80 percent (n = 8) of ulcerative colitis pouches. Sulfate-reducing bacteria were absent from familial adenomatous polyposis pouches and also from ulcerative colitis ileostomy effluent. Pouch Lactobacilli, Bifidobacterium, Bacteroides sp, and Clostridium perfringens counts were increased relative to ileostomy counts in patients with ulcerative colitis. Total pouch enterococci and coliform counts were also increased relative to ileostomy levels. There were no significant quantitative or qualitative differences between pouch types when these bacteria were evaluated. CONCLUSIONS: Sulfate-reducing bacteria are exclusive to patients with a background of ulcerative colitis. Not all ulcerative colitis pouches harbor sulfate-reducing bacteria because two ulcerative colitis pouches in this study were free of the latter. They are not present in familial adenomatous polyposis pouches or in ileostomy effluent collected from patients with ulcerative colitis. Total bacterial counts increase in ulcerative colitis pouches after stoma closure. Levels of Lactobacilli, Bifidobacterium, Bacteroides sp, Clostridium perfringens, enterococci, and coliforms were similar in both pouch groups. Because sulfate-reducing bacteria are specific to ulcerative colitis pouches, they may play a role in the pathogenesis of pouchitis.

Adenomatous Polyposis Coli↗
PubMed2002

Quality of life after ileal pouch-anal anastomosis: an evaluation of diet and other factors using the Cleveland Global Quality of Life instrument.

PURPOSE: Although functional results after ileal pouch-anal anastomosis are excellent, imperfections of function do occur. In this setting, quality-of-life assessment is an invaluable tool in determining overall therapeutic efficacy. We evaluated the impact of dietary restrictions, preoperative diagnosis (ulcerative colitis vs. familial adenomatous polyposis), and pregnancy (after pouch insertion) on quality of life. METHODS: After ethical approval, 64 patients were reviewed (mean age, 31 (range, 15-54) years). Long-term quality of life in patients after ileal pouch-anal anastomosis was assessed using the Cleveland Global Quality of Life instrument or Fazio score. The Cleveland Global Quality of Life score is a novel quality-of-life instrument specifically designed for patients with ileal pouches. Stool frequency and continence were recorded to establish the functional status of this group. RESULTS: Sixty-one patients (95.3 percent) complained of some form of dietary restriction and adopted a fixed dietary regimen. All such patients felt that a breach of this regimen would impinge significantly on their quality of life. Late eating and alcohol were associated with diarrhea, whereas smoking was not. Constipation was infrequently reported. The mean Cleveland Global Quality of Life score of patients with ulcerative colitis (0.81 +/- 0.13) was greater than that of patients with ulcerative colitis and a background of pouchitis (0.78 +/- 0.16; P = 0.042). Whereas postoperative stool frequency in patients with familial adenomatous polyposis was always higher than the preoperative level (4 vs. 2 movements per day; P = 0.04), the Cleveland Global Quality of Life score of this group was lower than that of ulcerative colitis patients (0.77 vs. 0.81; P = 0.047). The Cleveland Global Quality of Life score of females who had had pregnancies after pouch formation was 0.70, significantly lower (P = 0.039) than that of ulcerative colitis patients, although pouch function was similar to the general group (7 vs. 6 daily bowel movements with full continence in all parous patients). CONCLUSIONS: Most patients suffered dietary restrictions, forcing them to adopt a fixed dietary regimen. Breach of this regimen would impact on their quality of life. Hence composition of diet and timing of intake are important determinants of quality of life after ileal pouch formation. Patients with familial adenomatous polyposis and those with a history of pouchitis had poorer Cleveland Global Quality of Life scores than ulcerative colitis patients without a background of pouchitis. This indicates that they also had poorer quality of life. Parous patients had the lowest Cleveland Global Quality of Life scores, indicating the poorest quality of life. These differences did not correlate with poorer pouch function, highlighting the influence of non-pouch-related factors in quality of life after ileal pouch formation.

Adenomatous Polyposis Coli↗
PubMed2001

Upregulation of Fas-Fas-L (CD95/CD95L)-mediated epithelial apoptosis--a putative role in pouchitis?

INTRODUCTION: Ileal pouch-anal anastomosis (IPAA) remains the gold standard for patients with refractory ulcerative colitis. Pouchitis causes considerable morbidity in 40% of patients with IPAA. This study examined the role of increased epithelial apoptosis in the etiology of pouchitis. METHODS: Following ethical approval pouch biopsies taken from patients with a history of pouchitis were compared with age-matched controls from patients who were pouchitis free. Apoptosis was detected immunohistochemically using a monoclonal antibody (M30) and terminal deoxyribonucleotidyl transferase (TDT)-mediated dUTP-digoxigenin end labeling (TUNEL). Villous atrophy was assessed histologically and correlated with levels of apoptosis. Epithelial Fas-ligand (L) was also assessed immunohistochemically. RESULTS: A significant increase in TUNEL staining was seen at the epithelial but not at the lamina propria level for known pouchitis patients versus controls (0.091 vs 0.035; P < 0.01). Similarly, epithelial M30 immunoreactivity (0.225 vs 0.082; P < 0.05) and villous atrophy (0.035 vs 0.10; P < 0.05) were significantly increased in pouches with previous pouchitis when compared with normal pouches. Upregulation of Fas-L expression was characteristic of this epithelium. Mononuclear cells were strongly positive for Fas-L. Increased epithelial levels of apoptosis correlated with increased levels of villous atrophy. CONCLUSIONS: Our data suggest a role for elevated Fas-Fas-L (CD95-CD95L)-mediated epithelial apoptosis in the etiology of pouchitis. Increased levels of villous atrophy may result from increased apoptosis and thereby predispose to infection by otherwise apathogenic organisms.

Adolescent↗
PubMed1997

The regional distribution of myelin oligodendrocyte glycoprotein (MOG) in the developing rat CNS: an in vivo immunohistochemical study.

Using an immunohistochemical approach we have characterized the in vivo developmental distribution of myelin oligodendrocyte glycoprotein within the rat CNS. Myelin oligodendrocyte glycoprotein expression emerged in a non-uniform manner during the first 3 postnatal weeks. Although it was absent throughout the CNS of the newborn rat at postnatal day 0(P0), it had appeared in the spinal cord and brainstem by P7. The forebrain and cerebellum remained devoid of immunoreactivity until after P14. Myelin oligodendrocyte glycoprotein emerged at different times within the closely associated fasciculi of the dorsal funiculus. It appeared in the fasciculus cuneatus during the first postnatal week and in the fasciculus gracilis and corticospinal tracts during weeks 2 and 3 respectively. Myelin oligodendrocyte glycoprotein expression developed along a caudo-rostral gradient from spinal cord to forebrain and along an antero-posterior gradient within the CNS in general. The relationship between the onset of myelin oligodendrocyte glycoprotein expression and myelinogenesis was also investigated. In most regions, myelin oligodendrocyte glycoprotein expression lagged behind the initial appearance of myelin basic protein and Luxol Fast Blue-stained myelin by at least 1 week. These observations support the idea that myelin oligodendrocyte glycoprotein is the latest myelin protein to appear in development, only being expressed during the final stages of oligodendrocyte differentiation. Furthermore, the pattern of staggered expression within the dorsal columns indicates that localized, region-specific interactions may comprise a key element in the control of the terminal phases of oligodendrocyte differentiation.

Aging↗
PubMed1988

The assay of glandular kallikrein and prekallikrein in human mixed saliva.

The measurement of glandular kallikrein in biological fluids most often utilizes a synthetic substrate, H-D-valylleucylarginine-p-nitroanilide (S-2266), which assesses amidase activity. Although this substrate has reasonable specificity for glandular kallikrein, other tryptic-like proteases found in mixed saliva may also cause hydrolysis. The primary purpose of this study was to assess the accuracy of the use of this substrate for the measurement of glandular kallikrein in human mixed saliva. An additional objective was to determine the presence of prekallikrein in mixed saliva. The addition of soybean trypsin inhibitor (SBTI), which inhibits other tryptic-like enzymes but not glandular kallikrein, resulted in an approx. 30 per cent decrease in the hydrolysis of S-2266 by centrifuged mixed human saliva. A correlation of 0.918 was obtained between the biological assays for kinin release and amidase activity in 19 subject samples. Amidase activity increased following treatment of saliva with trypsin, indicating the presence of prekallikrein in human mixed saliva. It is concluded that S-2266 is an accurate substrate for the assay of glandular kallikrein in human mixed saliva; that the inclusion of SBTI in the assay mixture is needed to inhibit non-kallikrein proteases that may also hydrolyse the synthetic substrate; and that prekallikrein is present in mixed saliva. Thus any future studies of changes in the level of kallikrein in saliva may wish to consider the presence of both active and total levels of glandular kallikrein.

Amidohydrolases↗