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T Colgan

Publications and source records attributed to T Colgan.

16 recordsLinked to original sources

Immunofluorometric quantitation and histochemical localisation of kallikrein 6 protein in ovarian cancer tissue: a new independent unfavourable prognostic biomarker.

Human kallikrein 6 protein is a newly discovered human kallikrein. We determined the amount of human kallikrein 6 in extracts of 182 ovarian tumours and correlated specific activity (ng hK6 mg(-1) total protein) with clinicopathological variables documented at the time of surgical excision and with outcome (progression free survival, overall survival) monitored over a median interval of 62 months. Thirty per cent of the tumours were positive for human kallikrein 6 (>35 ng hK6 mg(-1) total protein). Human kallikrein 6-specific immunohistochemical staining of four ovarian tissues that included benign, borderline and malignant lesions indicated a cytoplasmic location of human kallikrein 6 in tumour cells of epithelial origin, although the intensity of staining was variable. Tumour human kallikrein 6 (ng hK6 mg(-1) total protein) was higher in late stage disease, serous histotype, residual tumour >1 cm and suboptimal debulking (>1 cm) (P<0.05). Univariate analysis revealed that patients with tumour human kallikrein 6 positive specific activity were more likely to suffer progressive disease and to die (hazard ratio 1.71 (P=0.015) and 1.88 (P=0.022), respectively). Survival curves demonstrated the same (P=0.013 and 0.019, respectively). Multivariate analysis revealed that human kallikrein 6 positivity was retained as an independent prognostic variable in several subgroups of patients, namely those with (low) grade I and II tumours (hazard ratio progression free survival 4.3 (P=0.027) and overall survival 4.1 (P=0.023)) and those with optimal debulking (hazard ratio progression free survival 3.8 (P=0.019) and overall survival 5.6 (P=0.011)). We conclude that tumour kallikrein 6 protein levels have utility as an independent adverse prognostic marker in a subgroup of ovarian cancer patients with otherwise apparently good prognosis.

Adult↗

How important is removal of the parametrium at surgery for carcinoma of the cervix?

OBJECTIVES: The aims of this study were (1) to determine the incidence and factors predictive for pathologic parametrial involvement in clinical stage IA1/2 and IB1 cervical cancer after radical surgery and (2) to identify a population at low risk for pathologic parametrial involvement. METHODS: All patient information was collected prospectively and extracted from a cervical cancer radical surgery database. Selection criteria for surgery were generally based upon tumor size, with the cutoff for surgery between 3 and 4 cm. Parametrial involvement (PI) was defined as either positive parametrial lymph nodes (PMLN) or malignant cells in the parametrial tissue (PT) (including lymphovascular channels) by either contiguous or discontiguous spread. Statistical analysis included the chi2 test, the Wilcoxon rank test, and the Mantel-Haentzel test. RESULTS: Between July 1984 and January 2000, 842 patients underwent radical surgery for clinical stage IA1/2 and IB1 cervical cancer at our center. Forty-nine patients (6%) had positive pelvic lymph nodes. Thirty-three patients (4%) had pathologic PI, 8 in the PMLN and 25 in the PT (none had both). PI was associated with older age (42 vs 40 years, P < 0.04), larger tumor size (2.2 vs 1.8 cm, P < 0.04), higher incidence of capillary-lymphatic space invasion (85% vs 45%, P = 0.0004), tumor grades 2 and 3 (95% vs 65%, P = 0.001), greater depth of invasion (18.0 vs 5.0 mm, P < 0.001), and pelvic lymph node metastases (44% vs 5%, P < 0.0001). The incidence of PI in patients with tumor size < or =2 cm, negative pelvic lymph nodes, and depth of invasion < or =10 mm was 0.6%. CONCLUSION: Pathologic parametrial involvement in clinical stage IA1/2 and /IB1 cervical cancer is uncommon. Acknowledging that almost all patients with pelvic lymph node metastases and a high proportion of patients with tumor invasion >10 mm will receive adjuvant radiation regardless of the radicality of surgery, a population at low risk for pathologic parametrial involvement can be identified. These patients are worthy of consideration for studies of less radical surgery performed in conjunction with pelvic lymphadenectomy.

Adult↗

Does histology influence prognosis in patients with early-stage cervical carcinoma?

BACKGROUND: The objective of this study was to examine the influence of histology on the outcome of patients with surgically treated, Stage IA-IB carcinoma of the uterine cervix. METHODS: All patient information was collected prospectively and was extracted subsequently from the University of Toronto cervical carcinoma surgery data base. Selection criteria for surgery were based on tumor size and were independent of histology. Patients with adenocarcinoma were separated into two groups: those with mucinous/endometrioid adenocarcinoma (M/E AC) and those with adenosquamous/clear cell adenocarcinoma (AS/CC AC). Statistical analysis used Wilcoxon rank tests, Mantel-Hanzel tests, chi-square tests, and Cox regression analyses. RESULTS: Between July 1984 and January 2000, 880 patients with Stage IA-IB cervical carcinoma underwent radical surgery, including pelvic lymphadenectomy, as the primary treatment. Two hundred fifty-five patients had M/E AC (29%), 81 patients had AS/CC AC (9%), and 544 patients had squamous cell carcinoma (SCC; 62%). Compared with patients who had SCC, patients with M/E AC had significantly more favorable prognostic characteristics: age (median, 39 years vs. 41 years; P < 0.03), depth of invasion (3.7 mm vs. 5.5 mm; P < 0.001), vascular space involvement (24% vs. 57%; P < 0.0001), Grade 2-3 tumor (40% vs. 78%; P < 0.0001), and pelvic lymph node metastases (4% vs. 8%; P < 0.04), respectively. Characteristics among patients with AS/CC AC tended have values similar to the median values for patients with SCC (or intermediate between the values for patients with M/E AC and the values for patients with SCC): age (38 years), depth of invasion (6 mm), vascular space involvement (40%), Grades 2-3 (70%), and pelvic lymph node metastases (6%). The 2-year and 5-year recurrence free survival rate was similar between patients with M/E AC and patients with SCC (95% vs. 94% and 90% vs. 90%, respectively); however, both were significantly superior to the rates for patients with AS/CC AC (2-year recurrence free survival rate: 86%, P < 0.03; 5-year recurrence free survival rate: 81%, P % 0.03). There were no differences in the pattern of first recurrence by histology. CONCLUSIONS: Patients with surgically treated Stage IA-IB cervical carcinoma with M/E AC and SCC histology have a similar prognosis. For patients with disease with AS/CC AC histology, the current results and the literature indicate that patients with uncommon histologies have an inferior recurrence free survival rate. Although the optimal therapy for these patients remains undefined, there is no obvious rationale for altering the treatment strategies from those currently employed for patients with M/E AC and SCC.

Adenocarcinoma↗

Changes in the demographics and perioperative care of stage IA(2)/IB(1) cervical cancer over the past 16 years.

OBJECTIVES: The aim of this study was to determine whether there have been any significant changes in the demographics and perioperative care of FIGO stage IA(2)/IB(1) cervical cancer over the past 16 years and, if so, to quantify them. METHODS: Since July 1984, all patients with FIGO stage IA(2)/IB(1) cervical cancer undergoing radical surgery by members of our division have been entered into a prospective database. Selection for surgery has been unchanged over the past 16 years. Since March 1994 and November 1996, one surgeon has performed radical vaginal trachelectomy and laparoscopic assisted radical vaginal hysterectomy, respectively. Statistical analysis used Spearman's correlation analysis, the proportional hazards regression model of Cox, and the Mantel-Hanzel test was performed. Due to the number of statistical analyses, statistical significance was defined as P < 0.01. RESULTS: Eight hundred sixty-four patients have undergone radical surgery (784 radical hysterectomy, 42 radical vaginal trachelectomy, 32 radical vaginal hysterectomy, 6 radical abdominal trachelectomy) for FIGO stage IA(2)/IB(1) carcinoma of the cervix by members of our division since 1984. There have been no changes in the median age (40 years), tumor size (2.0 cm), incidence of capillary lymphatic space involvement (47%), or positive pelvic lymph nodes (6%) over the past 16 years. The median Quetelet index (24.6), depth of tumor invasion (squamous cell carcinomas only) (6.0 mm), and proportion of patients with comorbid conditions (17%) have increased over time (P = 0.001, P = 0.003, and P < 0.001, respectively). Pathologically, there has been an increase in the proportion of adenocarcinomas (28%) and a decrease in the proportion of grade 3 tumors (28%) (P < 0.001 and P < 0.001, respectively). The median operating time (2.8 h), hospital stay (7.0 days), blood loss (600 cc), allogeneic blood transfusion (23%), postoperative infections (13%), and noninfectious complications (6%) have all decreased (P < 0.001, P < 0.001, P < 0.001, P < 0.001, P < 0.001, and P = 0.002, respectively). There has been no change in the incidence of positive surgical margins (3%), adjuvant radiation (13%), or recurrence-free survival (2 and 5 years, 94 and 90%, respectively) after a median follow-up of 45 months. CONCLUSION: Despite no substantive changes in the selection criteria for surgery and the small time interval studied (16 years), almost all indices of operative and postoperative morbidity analyzed have decreased significantly. These changes have occurred without an increase in the use of adjuvant radiation or decrease in recurrence-free survival. Although little progress has been made in the cure rates associated with surgical management of FIGO stage IA(2)/IB(1) cervical cancer during this time interval, it appears that the morbidity of surgery has decreased.

Adenocarcinoma↗

EURADOS trial performance test for photon dosimetry.

Within the framework of the EURADOS Action entitled Harmonisation and Dosimetric Quality Assurance in Individual Monitoring for External Radiation, trial performance tests for whole-body and extremity personal dosemeters were carried out. Photon, beta and neutron dosemeters were considered. This paper summarises the results of the whole-body photon dosemeter test. Twenty-six dosimetry services from all EU Member States and Switzerland participated. Twelve different radiation fields were used to simulate various workplace irradiation fields. Dose values from 0.4 mSv to 80 mSv were chosen. From 312 single results, 26 fell outside the limits of the trumpet curve and 32 were outside the range 1/1.5 to 1.5. Most outliers resulted from high energy R-F irradiations without electronic equilibrium. These fields are not routinely encountered by many of the participating dosimetry services. If the results for this field are excluded, most participating services satisfied the evaluation criteria.

Consumer Product Safety↗

EURADOS trial performance test for neutron personal dosimetry.

This paper reports on the results of a neutron trial performance test sponsored by the European Commission and organised by EURADOS. As anticipated, neutron dosimetry results were very dependent on the dosemeter type and the dose calculation algorithm. Fast neutron fields were generally well measured, but particular problems were noted in the determination of intermediate energy fields and large incident angles, demonstrating the difficulties of neutron personal dosimetry. Of particular concern from a radiological protection point of view was the large number of results underestimating personal dose equivalent. A considerable over-response was noted in a few cases.

European Union↗

EURADOS trial performance test for personal dosemeters for external beta radiation.

On the initiative of the European Dosimetry Group (EURADOS) action group 'Harmonisation and Dosimetric Quality Assurance in Individual Monitoring for External Radiation' a trial performance test for whole-body and extremity personal dosemeters broadly representative of those in use in the EU was accomplished. This paper deals with the part of the performance test concerned with exposure to beta radiation. Fifteen dosimetric services participated with whole-body dosemeters intended to measure beta doses (Hp(0.07)) of which 13 used thermoluminescent (TL) detectors and two used photographic films. Eight services participated with extremity dosemeters which all used TL detectors. A description is given of the irradiation set-up, the characteristics of the irradiation fields, the calibration quantity applied and the performance criteria used for the evaluation of the results. The paper discusses in detail the results obtained from the exercise. In particular, based on the replies to a questionnaire issued to each participant, the results are analysed in relation to important design characteristics of the dosemeters taking part in the test.

Beta Particles↗

Preliminary experience with subcutaneous human ovarian cortex transplantation in the NOD-SCID mouse.

Xenogeneic transplantation of ovarian cortex into an immunodeficient animal host may be an approach toward fertility preservation for young female patients undergoing cancer therapy. Our objective was to evaluate the development of follicles in human ovarian cortex placed s.c. in non-obese diabetic-severe combined immune deficiency (NOD-SCID) mice (n = 54). The following variables were compared: 1) male versus female mice as hosts, 2) intact versus pituitary down-regulated mice, and 3) warm versus cold tissue transport. After 2 wk, 37 of 50 (74%) of the human xenografts contained follicles. At 12 wk after transplantation, exogenous gonadotropin stimulation resulted in follicle growth in 19 of 37 (51%) of the grafts, including the development of antral follicles, which could be palpated and visualized through the mouse skin. Significantly more developing follicles were identified in male versus female mice (13 of 17 vs. 6 of 20, respectively; p = 0.013) after stimulation. No difference was found between intact and pituitary down-regulated mice as hosts. Follicular survival was significantly increased by warm versus cold tissue transport. Our results suggest that s.c. ovarian cortex xenografting into NOD-SCID mice is feasible. Primordial follicles in ovarian xenografts retain their developmental potential and form antral follicles following gonadotropin stimulation.

Animals↗

Differences in the morbidity of radical hysterectomy between gynecological oncologists.

A multivariate analysis was performed on 405 patients who underwent radical hysterectomy and pelvic lymphadenectomy by eight surgeons for stage IB cervical carcinoma, to determine the influence of primary surgeon on morbidity. Patient characteristics analyzed (mean/proportion) were age (41 years), quetelet index (25.4), American Society of Anesthesiologists classification of physical status (0.5% > 2), previous laparotomies (23%), previous radiation (0.7%), prophylactic antibiotics (95%), prophylactic heparin (67%), tumor size (1.0 cm), histology (68% SCC), grade (68% grades 2 or 3), vascular space involvement (45%), pelvic lymph node metastases (6%), and depth of invasion (6.6 mm). Morbidity characteristics analyzed (mean/proportion) were blood loss (910 ml), operative time (3.0 hr), intra-op complications (5%), post-op infectious (21%) and non-infectious complications (7%), transfusions (35%), post-op hospital stay (9.9 days), time to normal urine residual (9.0 days), and bladder dysfunction at 3 months post-op (21%). Mean tumor size was the only preoperative characteristic that was significantly different among surgeons (P < 0.001). Of the factors evaluated for morbidity, mean blood loss (P < 0.0001), operative time (P < 0.001), and postoperative hospital stay (P < 0.001) varied among physicians as did the incidence of blood transfusion (P < 0.0001) and bladder dysfunction at 3 months postoperatively (P < 0.0001). On multivariate analysis, surgeon was independently significant for blood loss (P < 0.0001), operative time (P < 0.0001), postoperative hospital stay (P < 0.001), incidence of blood transfusion (P < 0.0001), and bladder dysfunction at 3 months postoperatively (P < 0.0001). Despite differences in tumor size, patients appeared similar among the surgeons. Differences in patient morbidity among surgeons do exist and are of significant magnitude. Since the design of surgical trials to assess the therapeutic ratio should include not only measures of efficacy, but also measures of morbidity to be meaningful, intersurgical morbidity between centers/surgeons must continue to be quantified.

Adult↗

IgG subclass concentrations in absolute, partial and transient IgA deficiency in childhood.

Sixty-seven children with symptomatic IgA deficiency were studied on two separate occasions. Eighteen had aIgAd at presentation, and 49 had pIgAd. IgA concentrations had risen to the normal range for age in 22.2% of children presenting with aIgAd and 77.6% presenting with pIgAd when restudied at a median interval of 3.2 and 3.0 years, respectively. IgG subclass concentrations were measured by enzyme immunoassay in serum samples collected at enrollment from 12 children with aIgAd and 22 children with pIgAd. IgG2 and IgG4 concentrations for these 34 children were below the 5th centile for age and sex more frequently than expected (IgG2: chi square 5.8, P less than 0.025; IgG 4: chi square 18.4, P less than 0.0005). The prevalence of IgG2 deficiency or IgG4 deficiency did not differ significantly between those with aIgAd and those with pIgAd. IgG2 concentrations remained below the 5th centile more frequently than expected when retested in 31 children whose pIgAd had resolved (chi square 4.6, P less than 0.05). Children with aIgAd at presentation had IgG1 and IgG2 concentrations above the 95th centile more frequently than expected (IgG1: chi square 19.7, P less than 0.0005; IgG2: chi square 13.5, P less than 0.001) but this was not seen for IgG3 and IgG4 concentrations. Children with pIgAd did not have elevated IgG1 or IgG2 concentrations at presentation. High IgG1 and IgG2 concentrations in aIgAd may be a compensatory mechanism to afford protection from infection or could be part of a selective secondary response to repeated episodes of infection.

Adolescent↗

Decreased incidence of adverse infusion reactions in hypogammaglobulinemic children receiving low pH intravenous immunoglobulin.

Eighteen patients (ages eight months to 20 years) with disorders of immunoglobulin and antibody production received infusions of two preparations of intravenous immunoglobulin in a blind crossover trial. The incidence and severity of immediate adverse infusion reactions was significantly lower with low pH immunoglobulin; ten patients (56%) experiencing immediate reactions with the standard preparation and only one patient experiencing an immediate reaction with the low pH preparation (p less than 0.01). Infusion times were significantly less with the low pH preparation (p less than 0.02) and patient tolerance, determined by visual analogue scores, was significantly better than with the standard preparation (p less than 0.01). However, the incidence of delayed reactions (44%) was the same for both infusions.

Adolescent↗

Therapy-related leukemia and myelodysplasia in small-cell lung cancer. Report of a case and results of morphologic, cytogenetic, and bone marrow culture studies in long-term survivors.

The bone marrow of 11 patients with small-cell lung cancer, who survived more than two years following combined-modality therapy, was subjected to morphologic, cytogenetic, and bone marrow culture studies. One patient, after a prodrome of anemia and thrombocytopenia, developed acute leukemia 60 months after the start of chemotherapy. Four months before frank leukemia developed, bone marrow culture studies showed a marked inability to form colonies. Cytogenetic studies demonstrated an abnormal clone of cells that included the deletion of the long arm of chromosome 5. No morphologic abnormalities were noted in the bone marrow of any other long-term survivor; however, the mean corpuscular volume of peripheral red blood cells was greater than normal in three of four patients who remain alive and disease free. In one of these patients marrow culture studies also failed to grow colonies. The other patients showed a decreased ability to form multilineage colonies and colonies of the granulocyte-macrophage lineage in vitro compared with a control population. All patients showed some degree of aneuploidy on cytogenetic analysis; in two cases approximately 50% of cells were aneuploid. However, no clonal abnormality was detected in any patient. Follow-up for the development of secondary acute leukemia and other long-term complications continues in these patients.

Aged↗

Monoclonal antibodies to an epithelial ovarian adenocarcinoma: distinctive reactivity with xenografts of the original tumor and a cultured cell line.

Four monoclonal antibodies (mAb) (8C, 10B, M2A, and M2D) were produced against the human epithelial ovarian adenocarcinoma cell line, HEY. The affinity constants of binding of the mAb to cultured HEY cells were 8 X 10(8) M-1 (M2D) and 10(9) M-1 (8C and 10B). mAb 8C reacted with a major glycoprotein of Mr 90,000 on the surface of HEY cells. The four mAb differed from previously reported mAb to epithelial ovarian adenocarcinomas on the basis of their reactivity with cultured ovarian adenocarcinoma cell lines using a cell-binding radioimmunoassay, and their staining of cryostat sections of various human normal and tumor tissues using an immunoperoxidase reaction. All four mAb reacted with s.c. tumors derived by injecting cultured HEY cells into thymectomized CBA/CJ mice. However, only two of the four mAb (8C and 10B) also reacted with s.c. tumors of the original HEY xenograft from which the cultured cell line was derived. In addition, mAb 8C and 10B reacted by immunoperoxidase staining with 2 and 4 different cases, respectively, of 11 epithelial ovarian adenocarcinomas examined. Cultured HEY cells were adapted to grow i.p. in BALB/c-nu/nu mice and the i.p. tumors retained their reactivity with the monoclonal antibodies. These tumor-bearing mice offer a useful model system for studying the potential of mAb, especially 8C and 10B, for the diagnosis and treatment of patients with peritoneal extension of epithelial ovarian adenocarcinomas.

Adenocarcinoma↗

Amiodarone pulmonary toxicity.

Numerous cytoplasmic lamellar bodies were seen in many cell types in an open lung biopsy from a patient on amiodarone therapy. These membrane-bound lamellar bodies were characterized by distinct, concentric parallel membranes and peripheral granular densities. Their morphology and distribution suggest a metabolic disorder of phospholipid degradation induced by this drug. The differential diagnosis of lamellar body accumulation in the lung is discussed. This case emphasizes the desirability for ultrastructural study of lung biopsies in such potentially reversible lung disease.

Amiodarone↗

Campylobacter jejuni enterocolitis. A clinicopathologic study.

Sixteen patients with diarrhea due to Campylobacter jejuni seen within a one-year period at a general hospital were studied to review the clinical and pathological features of this illness. Campylobacter jejuni causes an acute diarrheal illness often associated with fever, delayed-onset hematochezia, and severe abdominal pain. Roentgenographically, one may see colonic and ileal ulceration. Sigmoidoscopically, the rectal appearance is similar to that from acute idiopathic ulcerative colitis, while rectal biopsy specimens show preservation of glandular architecture and a range of focal inflammatory changes. These changes are most severe in patients with a history of frank blood in stool, provided the specimens are taken within the first week of illness. No correlation between stool frequency, abdominal pain, or fever and the severity of proctitis in rectal biopsy specimens can be drawn, which suggests that the pathogenic determinants for thesse clinical manifestations may not be in the rectum, but higher in the colon or in the small intestine.

Campylobacter↗