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L Stitt

Publications and source records attributed to L Stitt.

At least 37 records · Page 2Linked to original sources
PubMed1998

Low-grade gliomas in children: tumor volume response to radiation.

Object. The authors conducted a retrospective review to examine and document the frequency, degree, and timing of the radiologically confirmed response to radiotherapy of low-grade gliomas in children. Methods. Between 1963 and 1995, 80 patients 17 years of age or younger were referred to the London Regional Cancer Centre in London, Ontario, after diagnosis of a low-grade glioma. All patients underwent surgical resection or biopsy procedures and 47 underwent radiotherapy (40 postoperatively and seven at the time of tumor progression). Nineteen patients with residual measurable lesions who received radiation therapy were selected for volumetric analysis of tumor response to this treatment. The extent and timing of response to radiation were determined by the process of comparing postoperative, preirradiation computerized tomography (CT) scans with postirradiation, follow-up CT scans. For one patient the comparison was made by using serial magnetic resonance images. Residual tumor was found on postoperative CT scans in all cases. The mean preradiotherapy tumor volume was 17.1 cm(3), and the postradiotherapy volume was reduced to a mean of 11.5 cm(3). A reduction in tumor was demonstrated in eight patients by the time of their first postirradiation follow-up CT scan and in two patients a slower reduction in volume over time was shown, bringing the total number of "responders" to 10. In five of these 10 patients the tumor had shown a maximum response by the time of the first postirradiation CT scan; the median time to response was 3.3 months. A 25% or greater reduction in tumor volume was seen in eight (42%) of the 19 patients. A 50% or greater reduction was noted in five (26%) of the patients. A complete response was demonstrated at 7, 12, and 15 months, and 5 years, respectively, in four patients (21%). One responder's tumor eventually increased in size after radiotherapy and he died of his disease. The magnitude of the radiographically demonstrated response to radiation did not correlate significantly with clinical outcome (that is, survival or symptom improvement). Conclusions. On the basis of this CT scan analysis of the response of low-grade gliomas in children to radiotherapy, the authors suggest that these lesions respond to radiation, as demonstrated by tumor shrinkage on serial imaging. Major or complete responses occur occasionally. However, low-grade gliomas in children mimic other benign brain tumors such as pituitary adenomas and meningiomas in that, although growth is frequently arrested after radiotherapy, residual tumor can persist for many years, illustrating that tumor shrinkage may not be a good measure of treatment efficacy. Nevertheless, radiation therapy can result in improvement of clinical symptomatology in association with or independent of visible tumor reduction. As radiation treatment techniques become increasingly conformal and because studies indicate that lower doses of radiation may be equally effective, improvement of symptoms may be an important consideration when weighing treatment options, particularly in patients with residual or unresectable disease.

Journal Article↗
PubMed1998

Does delay in breast irradiation following conservative breast surgery in node-negative breast cancer patients have an impact on risk of recurrence?

PURPOSE: This retrospective review was conducted to determine if delay in the start of radiotherapy after definitive breast surgery had any detrimental effect on local recurrence or disease-free survival in node-negative breast cancer patients. METHODS AND MATERIALS: A total of 568 patients with T1-T2, N0 breast cancer were treated with breast-conserving surgery and breast irradiation, without adjuvant systemic therapy between January 1, 1985 and December 31, 1992, at the London Regional Cancer Centre. Adjuvant breast irradiation consisted either of 50 Gy in 25 fractions or 40 Gy in 15 or 16 fractions, followed by a boost of 10 Gy or 12.5 Gy to the lumpectomy site. The time intervals from definitive breast surgery to breast irradiation used for analysis were 0-8 weeks (201 patients), > 8-12 weeks (235 patients), > 1216 weeks (91 patients), and > 16 weeks (41 patients). The time intervals of 0-12 weeks (436 patients) and > 12 weeks (132 patients) were also analyzed. Kaplan-Meier estimates of time to local recurrence and disease-free survival rates were calculated. The association between surgery-radiotherapy interval, age (< or = 40, > 40 years), tumor size (< or = 2, > 2cm), Scharf-Bloom-Richardson (SBR) grade, resection margins, lymphatic vessel invasion, extensive intraductal component, and local recurrence and disease-free survival were investigated using Cox regression techniques. RESULTS: Median follow-up was 63.5 months. Patients in all 4 time intervals were similar in terms of age and pathologic features. There was no statistically significant difference between the 4 groups in local recurrence or disease-free survival with surgery-radiotherapy interval (p = 0.189 and p = 0.413, respectively). The 5-year freedom from local relapse was 95.4%. The crude local recurrence rate was 6.9% (7.8% for 436 patients treated within 12 weeks (median follow-up 67 months) and 3.8% for 132 patients treated > 12 weeks from surgery (median follow-up 52 months). In a stepwise multivariable Cox regression model for disease-free survival, allowing for entry of known risk factors, tumour size (p < 0.001), grade (p < 0.001), and age (p = 0.048) entered the model, but the surgery-radiotherapy interval did not enter the model. CONCLUSION: This retrospective study suggests that delay in start of breast irradiation beyond 12 and up to 16 weeks does not increase the risk of recurrence in node-negative breast cancer patients. The certainty of these results are limited by the retrospective nature of this analysis and the lack of information concerning the late local failure rate.

Adult↗
PubMed1998

Pulmonary retransplantation.

BACKGROUND AND METHODS: Despite improving results in lung transplantation, a significant number of grafts fail early or late postoperatively. The Pulmonary Retransplant Registry was founded in 1991 to determine the predictors of outcome after retransplantation, so as to facilitate decisions concerning the appropriateness of lung retransplantation in individual patients. In this study, 230 patients underwent retransplantation in 47 centers from 1985 to 1996. Logistic regression methods were used to determine variables associated with, and predictive of, survival and lung function after retransplantation. RESULTS: Actuarial survival was 47%+/-3%, 40%+/-3% and 33%+/-4% at 1, 2, and 3 years, respectively. On multivariable analysis, the predictors of survival included ambulatory status or lack of ventilator support preoperatively (P=.005, odds ratio 1.62, 95% confidence interval 1.15-2.27), followed by retransplantation after 1991 (P=.048, odds ratio 1.41, 95% confidence interval 1.003-1.99). Ambulatory, nonventilated patients undergoing retransplantation after 1991 had a 1-year survival rate of 64%+/-5% versus 33%+/-4% for nonambulatory, ventilated recipients. Eighty-one percent, 70%, 62%, and 56% of survivors were free of bronchiolitis obliterans syndrome at 1, 2, 3, and 4 years after retransplantation, respectively. Factors associated with freedom from stage 3 (severe) bronchiolitis obliterans syndrome at 2 years after retransplantation included an interval between transplants greater than 2 years (P=.01), the lack of ventilatory support before retransplantation (P=.03), increasing retransplant experience within each center (5th and higher retransplant patient, P=.04) and total center volume of 5 or more retransplant operations (P=.05). CONCLUSIONS: Nonambulatory, ventilated patients should not be considered for retransplantation with the same priority as other candidates. The best intermediate-term functional results occurred in more experienced centers, in nonventilated patients and in patients undergoing retransplantation more than 2 years after their first transplantation. In view of the scarcity of lung donors, patient selection for retransplantation should remain strict.

Actuarial Analysis↗
PubMed1998

Low-grade gliomas in children: tumor volume response to radiation.

OBJECT: The authors conducted a retrospective review to examine and document the frequency, degree, and timing of the radiologically confirmed response to radiotherapy of low-grade gliomas in children. METHODS: Between 1963 and 1995, 80 patients 17 years of age or younger were referred to the London Regional Cancer Centre in London, Ontario after diagnosis of a low-grade glioma. All patients underwent surgical resection or biopsy procedures and 47 underwent radiotherapy (40 postoperatively and seven at the time of tumor progression). Nineteen patients with residual measurable lesions who received radiation therapy were selected for volumetric analysis of tumor response to this treatment. The extent and timing of response to radiation were determined by the process of comparing postoperative, preirradiation computerized tomography (CT) scans with postirradiation, follow-up CT scans. For one patient the comparison was made by using serial magnetic resonance images. Residual tumor was found on postoperative CT scans in all cases. The mean preradiotherapy tumor volume was 17.1 cm3, and the postradiotherapy volume was reduced to a mean of 11.5 cm3. A reduction in tumor volume was demonstrated in eight patients by the time of their first postirradiation follow-up CT scan and in two patients a slower reduction in volume over time was shown, bringing the total number of "responders" to 10. In five of these 10 patients the tumor had shown a maximum response by the time of the first postirradiation CT scan; the median time to response was 3.3 months. A 25% or greater reduction in tumor volume was seen in eight (42%) of the 19 patients. A 50% or greater reduction was noted in five (26%) of the patients. A complete response was demonstrated at 7, 12, and 15 months, and 5 years, respectively, in four patients (21%). One responder's tumor eventually increased in size after radiotherapy and he died of his disease. The magnitude of the radiographically demonstrated response to radiation did not correlate significantly with clinical outcome (that is, survival or symptom improvement). CONCLUSIONS: On the basis of this CT scan analysis of the response of low-grade gliomas in children to radiotherapy, the authors suggest that these lesions respond to radiation, as demonstrated by tumor shrinkage on serial imaging. Major or complete responses occur occasionally. However, low-grade gliomas in children mimic other benign brain tumors such as pituitary adenomas and meningiomas in that, although growth is frequently arrested after radiotherapy, residual tumor can persist for many years, illustrating that tumor shrinkage may not be a good measure of treatment efficacy. Nevertheless, radiation therapy can result in improvement of clinical symptomatology in association with or independent of visible tumor reduction. As radiation treatment techniques become increasingly conformal and because studies indicate that lower doses of radiation may be equally effective, improvement of symptoms may be an important consideration when weighing treatment options, particularly in patients with residual or unresectable disease.

Adolescent↗
PubMed1998

Genetic background influences timing, morphology and dissemination of lymphomas in p53-deficient mice.

To examine the influence of genetic background on tumorigenesis in p53-deficient mice, we used selective breeding to produce congenic mice with a null p53 gene mutation introduced into the VM inbred strain. Cohorts of homozygous p53 null (-/-) mice from the original C57B6/129Sv mixed strain and the VM congenic strain were monitored for spontaneous tumor development, as were control cohorts of wild-type (+/+) and heterozygous (+/-) animals. Twenty-six of 28 C57B6/129Sv (-/-) mice died by the study end date (median survival =184.5 days). Twenty-three of 26 VM (-/-) mice died and their survival was significantly shorter (111 days, P<0.0001). Of 26 C57B6/129Sv (-/-) mice that died, 21 were autopsied: all 21 had lymphomas. Of 26 VM mice that died (23 -/-, 3 +/-), 21 were autopsied: 19 developed lymphoma and two had sarcomas. Several mice had additional neoplasms. Lymphomas in VM mice were distinct from those in C57B6/129Sv mice in that they i) arose on average more than two months earlier, ii) involved thymus more often than spleen or lymph nodes and iii) were more often poorly differentiated, high grade tumors. These results demonstrate that genetic background alone influences the onset, morphology and dissemination of lymphomas in p53-deficient mice and suggest the presence of genes which modify the timing and biological nature of lymphomas in these mice.

Animals↗
PubMed1997

Long-term follow-up of axillary node-positive breast cancer patients receiving adjuvant systemic therapy alone: patterns of recurrence.

PURPOSE: Prognostic factors for locoregional failure have been poorly documented. The purpose of this retrospective review is to examine the patterns of failure of 320 patients with Stage II or III axillary node-positive breast cancer who received adjuvant chemotherapy without locoregional radiation. METHODS AND MATERIALS: The records of 735 patients who were referred to the London Regional Cancer Centre between 1980 and 1989 with a diagnosis of Stage II or III breast cancer were reviewed. Three hundred and twenty patients were identified who underwent segmental mastectomy with axillary dissection or modified radical mastectomy and adjuvant chemotherapy without adjuvant locoregional radiation. Seventy-one percent of these patients had undergone a modified radical mastectomy, 40% had T1 tumors, 49% T2, and 11% T3. Resection margins were positive in 13 patients. The median number of axillary nodes removed was 11. Fifty-four percent had one to three positive axillary nodes, 27% had four to seven positive nodes, and 19% had in excess of seven positive nodes. RESULTS: Median follow-up for the 320 patients was 77 months. One hundred and fourteen patients developed a locoregional recurrence as the site of first relapse (31 in the intact breast, 29 on the chest wall, 21 in the axilla, 22 in the supraclavicular fossa, 1 in the internal mammary chain, and 10 in multiple sites). Thirty-three percent of segmental mastectomy patients and 13% of modified radical mastectomy patients developed local recurrence. Seven percent of patients recurred in axillary or supraclavicular nodes each. Factors with regard to locoregional recurrence which on univariate analysis were significant included type of mastectomy (i.e., segmental vs. modified radical), size of primary tumor, positive resection margins, and percentage of ideal chemotherapy dose intensity (< 66% vs. > or = 66%). After multivariate analysis, only type of mastectomy, size of primary tumor, and percentage of ideal chemotherapy dose intensity retained significance. The number of positive axillary nodes was not a significant factor. Number of positive axillary nodes plus the above four clinical factors were analyzed in terms of regional recurrence specifically. By univariate and multivariate analysis, only size of primary tumor retained significance. Again, the number of positive axillary nodes was not a relevant factor. CONCLUSION: Patients receiving adjuvant chemotherapy who are at high risk of locoregional recurrence include those who undergo segmental mastectomy and those with larger tumors (> 5 cm in diameter). Breast or chest wall radiation is recommended for these groups. Supraclavicular radiation is recommended for patients with tumors larger than 5 cm in diameter. Axillary recurrences were relatively infrequent in patients who had undergone an adequate Level I and II axillary dissection, and therefore, axillary radiation was not recommended.

Adult↗
PubMed1997

Extracapsular axillary node extension in patients receiving adjuvant systemic therapy: an indication for radiotherapy?

PURPOSE: This is a retrospective review into the patterns of failure of 82 patients with Stage II or III breast cancer who had extracapsular extension (ECE) of axillary nodal metastases and who received systemic chemotherapy or hormonal therapy without loco-regional radiation. METHODS AND MATERIALS: The clinical records of patients with axillary node positive (T1-T3, N1, 2) Stage II or III breast cancer seen at the London Regional Cancer Centre between 1980-1989 were reviewed. Patients were identified who underwent segmental mastectomy with axillary node dissection or modified radical mastectomy and received adjuvant chemotherapy or tamoxifen but did not undergo loco-regional radiation. Eighty-two patients within this group had pathologic evidence of extracapsular axillary node extension (ECE). For 45 of these patients the extension was extensive, and for the remaining 37 it was microscopic. This ECE-positive group was compared to a subgroup of 172 patients who did not have pathologic evidence of extracapsular axillary node extension but had metastatic carcinoma confined within the nodal capsule. RESULTS: Median age of the 82 ECE-positive patients was 56 years. Twenty-five patients had had a segmental mastectomy, the remainder a modified radical mastectomy. Median actuarial survival was 60 months, with a median disease-free and loco-regional failure-free survival of 38 months. Seventy-eight percent of these patients developed a recurrence, which was loco-regional in 60% (21% local, 21% regional, 2% local and regional, and 16% loco-regional and metastatic). There was a 36% recurrence rate in intact breast, 14% the chest wall following modified radical mastectomy, 7% relapsed in the axilla, 12% in supraclavicular nodes, and 1% in the internal mammary nodes. A comparison of the 82 ECE-positive patients with a group of 172 ECE-negative patients determined that there was a statistically significant difference between the two groups in terms of survival (overall and disease-free) and loco-regional recurrence. Univariate analysis of the entire 254 node-positive patient group revealed extracapsular nodal extension (ECE) to be a prognostically significant factor for actuarial and disease-free survival as well as for loco-regional failure, but ECE did not remain an independently prognostic factor after multivariate analysis. Segmental mastectomy, positive resection margins, and ER negative status increased the risk of loco-regional recurrence within the ECE-positive group. CONCLUSIONS: Extracapsular axillary node extension is a prognostically significant factor for actuarial survival, disease-free survival, and loco-regional failure but not independent of other adverse prognostic factors. It is a marker for increased loco-regional recurrence associated with doubling of breast, chest wall, and supraclavicular recurrence rates. The risk of axillary relapse in patients who have had an adequate level I and II axillary dissection but demonstrate extracapsular extension is low (7%). We recommend breast/chest wall and supraclavicular radiation for all patients with pathologic evidence of such extranodal extension who have had a level I and II axillary dissection regardless of the number of positive axillary nodes. Axillary irradiation should be considered for patients who have had only an axillary sampling or level I axillary dissection.

Analysis of Variance↗
PubMed1997

Supratentorial low-grade glioma in adults: an analysis of prognostic factors and timing of radiation.

PURPOSE: To review the outcomes of patients with low-grade glioma diagnosed by modern imaging and treated at a center where postponing radiotherapy was common practice. METHODS: We reviewed the records of patients (age > or = 18 years) with pathologically confirmed supratentorial low-grade fibrillary astrocytoma, oligodendroglioma, and mixed glioma treated at a regional cancer center in Canada between 1979 and 1995. RESULTS: Median survival for the entire group (N = 167; mean age 40.6 years) was 10.5 years with 5- and 10-year survival rates of 72% and 50%, respectively. Median progression-free survival was 4.9 years with 5- and 10-year progression-free rates of 50% and 12%, respectively. Overall and progression-free survivals were longer for patients with an oligodendroglioma or mixed glioma than with astrocytoma (median 13 v 7.5 years, P = .003; progression-free 5.6 v 4.4 years, p = .054). Age at diagnosis < or = 40 years, seizures at presentation, minimal residual tumor after surgery, Karnofsky performance status > or = 70, and oligodendroglioma or mixed glioma pathology were associated with significantly longer median survival on univariate and multivariate analyses. Radiotherapy deferred until tumor progression (v immediate radiotherapy) was associated with longer survival on univariate analysis, but an imbalance in other variables accounted for this advantage such that timing of radiotherapy was not an independent (favorable or adverse) prognostic factor on multivariate analysis. CONCLUSION: Patients with low-grade glioma diagnosed by modern imaging can be expected to live a long time; timing of radiotherapy may be a less important determinant of survival than nontreatment variables and residual tumor bulk.

Actuarial Analysis↗
PubMed1997

Axillary node dissection in patients with breast cancer diagnosed through the Ontario Breast Screening Program: a need for minimally invasive techniques.

OBJECTIVE: To determine the role of axillary node dissection by studying patient and tumour characteristics of invasive breast cancer through the Ontario Breast Screening Program (OBSP). DESIGN: A retrospective evaluation. SETTING: The London, Ont., branch of the OBSP. PATIENTS: Three groups of women seen were studied: 50 women with screen-detected breast cancers, which were palpable and detected by the nurse-examiner, 62 women with occult screen-detected breast cancers and 353 age matched women with invasive breast cancer from the LRCC prospective database, who served as controls. MAIN OUTCOME MEASURE: The proportion of involved axillary nodes within the 3 groups based on patient and tumour characteristics. RESULTS: Twenty-five (22.3%) of the 112 women had screen-detected tumours less than 1 cm in dimension, but only 1 had an involved axillary node. Twelve (19%) of the 62 women with occult screen-detected tumours had involved lymph nodes compared with 17 (34%) of the 50 women with palpable screen-detected cancers (NS). In the control group tumour dimension less than 1 cm versus 1 cm or larger had a marked effect on the probability of axillary node involvement (12.5% v. 40.7%, p = 0.001). In the palpable screen-detected group 3 times as many women with outer quadrant or central lesions had involved nodes as those with inner quadrant lesions (38% v. 12%) and for those with a family history of breast cancer almost twice as many had involved axillary nodes. In occult screen-detected patients there was more nodal involvement in patients aged 60 years or less than in those older than 60 years (35% v. 10%, p = 0.042); only 4 of 41 patients older than 60 years had involved nodes at surgery. A significant difference in nodal involvement was found with respect to high or intermediate grade versus low grade lesions in the occult group (44% v. 12%, p = 0.033). In the control group, tumour grade (intermediate and high [45.3%] v. low [20.0%]) and hormone replacement therapy (HRT) (current or recent use [56.5%] v. no use [34.5%]) were significant findings (p < 0.001 and p = 0.005 respectively). CONCLUSIONS: Women older than 60 years with tumours smaller than 1 cm had a low probability of nodal positivity (0% to 8.7%), but there is insufficient information in this group to give a 95% or better prediction of nodal status at the time of surgery. Studies of minimally invasive techniques such as sentinel node biopsy are needed in this group to minimize surgical morbidity in these women who, as a result of early diagnosis, have an excellent long-term outlook.

Age Distribution↗
PubMed1996

Pulmonary retransplantation: does the indication for operation influence postoperative lung function?

OBJECTIVE: An international series of pulmonary retransplantation was updated to determine the factors associated with pulmonary function, bronchiolitis obliterans syndrome stage, and survival after operation. METHODS: One hundred sixty patients underwent retransplantation in 35 centers from 1985 to 1995. Logistic regression methods were used to determine variables associated with 3-month and 2-year survival after retransplantation. Values of forced expiratory volume in 1 second were contrasted between groups by unpaired, two-tailed t tests. RESULTS: The median follow-up in surviving recipients was 780 days. Actuarial survival was 45% +/- 4%, 41% +/- 4%, and 33% +/- 4% at 1, 2, and 3 years, respectively. On multivariable analysis, the only predictor of 3-month survival was preoperative ambulatory status (p = 0.005), whereas center experience with at least five pulmonary retransplantations was the sole predictor of 2-year survival (p = 0.04). The prevalence of stage 3 (severe) bronchiolitis obliterans syndrome was 12% at 1 year, 15% at 2 years, and 33% at 3 years after retransplantation. Retransplant recipients with stage 3 bronchiolitis obliterans syndrome at 1 year had a significantly worse actuarial survival than those with stages 0 to 2 (p < 0.01). By 3 years after retransplantation, the forced expiratory volume in 1 second was significantly lower in patients who underwent reoperation because of obliterative bronchiolitis than in patients who underwent retransplantation because of acute graft failure or an airway complication (p = 0.02). Only 31% of patients who underwent retransplantation because of obliterative bronchiolitis were free of bronchiolitis obliterans syndrome at 3 years versus 83% of patients who underwent retransplantation because of other indications (p = 0.02). CONCLUSIONS: Preoperative ambulatory status predicts early survival and center volume predicts intermediate-term outcome after retransplantation. Improved management strategies are necessary to prevent the development of progressive graft dysfunction after retransplantation for obliterative bronchiolitis.

Actuarial Analysis↗
PubMed1996

The predictive power of semiquantitative immunohistochemical assessment of p53 and c-erb B-2 in lymph node-negative breast cancer.

A series of 107 lymph node-negative (LNN) breast cancers was stained immunohistochemically with a combination of p53 and c-erb B-2. The immunohistochemical results were semiquantitated using a previously described system by Allred et al. p53 immunopositive cases were further screened for DNA mutations by the polymerase chain reaction-single-strand conformation polymorphism method (PCR-SSCP). Three representative cases showing mobility shifts were directly sequenced. One hundred of 103 invasive carcinomas were of no special type (infiltrating ductal carcinomas not otherwise specified). The three special type carcinomas included a tubular carcinoma, a classic infiltrating lobular carcinoma, and a mucinous carcinoma. Twenty-six patients (25.2%) had grade I carcinomas, and 77 patients (75%) had grade 2 or 3 carcinomas. There were four cases composed predominantly of ductal carcinoma in situ (DCIS) with foci of microinvasion. Twenty-seven of 107 patients (25%) died of disease. All those who died had grade 2 or 3 tumors. Univariate analysis showed that p53 and c-erb B-2 positivity (score > 6) were associated with a decreased overall survival (OS) (P = .0012 and P = .010, respectively), and a decreased disease-free survival (DFS) (P = .0009 and P = .027, respectively). The multivariate model selected these two variables as the best predictors of both OS and DFS (all P = or < .01). These results suggest that semiquantitative immunohistochemical analysis of p53 and c-erb B-2 provides prognostic information in LNN disease.

Adult↗
PubMed1996

Schwann cell differentiation of modified myoepithelial cells within adenoid cystic carcinomas and polymorphous low-grade adenocarcinomas: clinicopathologic assessment of immunohistochemical staining.

Adenoid cystic carcinomas and polymorphous low-grade adenocarcinomas have a known propensity for perineural invasion. Although modified myoepithelial cells have been shown to possess characteristics of a variety of cell types, they have not yet been found to mimic nerve tissue. Histologic evidence of Schwann cell differentiation would suggest the pathophysiologic mechanism by which these tumours exhibit neurotropism. An archival study of 41 specimens was performed to evaluate the Schwann cell staining properties of adenoid cystic and polymorphous low-grade adenocarcinomas using antibodies to S-100 protein, GFAP, neuron-specific enolase, and using a solochrome stain. Charts were reviewed to assess correlations between immunohistochemical and histochemical staining properties and various clinical parameters. The findings strongly suggest that neuronal differentiation does occur within these tumours. Furthermore, it was determined that solochrome positivity confers a significantly less favourable disease-free interval in these neoplasms. This new finding was highly statistically significant and has potential implications in the determination of prognosis for patients with these tumours.

Adenocarcinoma↗
PubMed1995

High-dose continuous venous infusion of interleukin-2: influence of dose and infusion rate on tumoricidal function and lymphocyte subsets.

Previous clinical studies have demonstrated a dose-response relationship between enhancement of certain immune parameters and interleukin-2 (IL-2) dose in trials with low dosages of the cytokine. This has not been demonstrated for high-dose (greater than 18 x 10(6) IU/m2 per day) IL-2. We completed phase II trials of sustained administration of indomethacin and ranitidine with IL-2 given as a continuous infusion over 5 days for three courses. Peripheral blood mononuclear cells, both fresh and cultured in vitro with IL-2 or IL-2 and indomethacin, were tested for tumoricidal function against K562 and Daudi targets; these results were then correlated with actual delivered dose and mean infusion rate per course. Similar correlations were calculated between delivered dose or infusion rate and absolute and proportional counts of lymphocyte subsets as determined by flow cytometry. No enhancement of in vitro tumoricidal function with either increasing delivered dose or increasing infusion rate was seen. No consistent pattern of correlation was found between the absolute counts of lymphocyte subsets after each course of IL-2 with delivered dose or infusion rate. The percent rise in absolute counts of selected T- and NK-cell subsets at the end of course 1 compared with baseline values correlated positively with infusion rate; however, a similar correlated between the infusion rate and an increase in lymphocyte tumoricidal function was lacking. Little evidence was found for improved tumoricidal function of mononuclear cells or consistent enhancement of lymphocyte subset counts in patients able to tolerate doses of IL-2 beyond 18 x 10(6) IU/m2 per day in a 5-day continuous infusion schedule.

Carcinoma, Renal Cell↗
PubMed1995

Recurrence of obliterative bronchiolitis and determinants of outcome in 139 pulmonary retransplant recipients.

An international series of pulmonary retransplantation was updated to identify the predictors of outcome and the prevalence and recurrence rate of obliterative bronchiolitis after operation. The study cohort included 139 patients who underwent retransplantation in 34 institutions in North America and Europe between 1985 and 1994. Eighty patients underwent retransplantation because of obliterative bronchiolitis, 34 because of acute graft failure, 13 because of intractable airway complications, 8 because of acute rejection, and 4 because of other indications. Survivors were followed up for a median of 630 days, with 48 patients alive at 1 year, 30 at 2 years, and 16 at 3 years after retransplantation. Actuarial survival was 65% +/- 4% at 1 month, 54% +/- 4% at 3 months, 45% +/- 4% at 1 year, 38% +/- 5% at 2 years, and 36% +/- 5% at 3 years; nonetheless, of 90-day postoperative survivors, 65% +/- 6% were alive 3 years after retransplantation. Life-table and univariate Cox analysis revealed that more recent year of retransplantation (p = 0.009), identical match of ABO blood group (p = 0.01), absence of a donor-recipient cytomegalovirus mismatch (p = 0.04), and being ambulatory immediately before retransplantation (p = 0.04) were associated with survival. By multivariate Cox analysis, being ambulatory before retransplantation was the most significant predictor of survival (p = 0.008), followed by reoperation in Europe (p = 0.044). Complete pulmonary function tests were done yearly in every survivor of retransplantation and bronchiolitis obliterans syndrome stages were assigned. Eleven percent of patients were in stage 3 at 1 year, 20% at 2 years, and 25% at 3 years after retransplantation. Values of forced expiratory volume in 1 second decreased from 1.89 +/- 0.13 L early after retransplantation to 1.80 +/- 0.15 L at 1 year and 1.54 +/- 0.16 L at 2 years (p = 0.006, year 2 versus baseline postoperative value). Most of this decrease occurred in patients who underwent retransplantation because of obliterative bronchiolitis, whereas the pulmonary function of patients who underwent retransplantation because of other conditions did not significantly change. We conclude that survival after pulmonary retransplantation is improving. Optimal results can be obtained in patients who are ambulatory before retransplantation. Compared with recent data after primary lung transplantation, bronchiolitis obliterans syndrome does not appear to recur in an accelerated manner after retransplantation. As long as early mortality as a result of infection can be minimized, pulmonary retransplantation appears to offer a reasonable option in highly selected patients.

ABO Blood-Group System↗
PubMed1995

Seventy-two pulmonary retransplantations for obliterative bronchiolitis: predictors of survival.

BACKGROUND: Obliterative bronchiolitis (OB) occurs in up to 40% of patients in the intermediate term after lung transplantation. In recent years an increasing number of recipients with end-stage OB have been treated with retransplantation. METHODS: Seventy-two patients with OB underwent retransplantation at 26 North American and European centers a median of 590 days after their first transplant operation. The predictors of survival were determined using life table and Cox proportional hazards methods, and the recurrence rate of OB was determined in survivors. RESULTS: The actuarial survival rate was 71% +/- 5% at 1 month, 43% +/- 6% at 1 year, and 35% +/- 6% at 2 years; nonetheless, of the 90-day postoperative survivors, 63% +/- 7% were alive 2 years after retransplantation. Institutional experience with more than three pulmonary retransplantations (p = 0.008), reoperation in Europe (p = 0.013), donor-recipient ABO blood group identity (p = 0.018), and more recent year of retransplantation (p = 0.03) were associated with survival. On multivariate analysis, reoperation after 1989 (p < 0.001), retransplantation performed in Europe (p = 0.017), and being ambulatory immediately before reoperation (p = 0.022) were found to be predictive of a positive outcome. Pulmonary function test analyses confirmed that the forced expiratory volume in 1 second decreased from postoperative baseline values by 11% +/- 9% at 1 year and 27% +/- 10% at 2 years (p = 0.02; year 2 versus baseline). Fourteen percent of patients were in stage 3 of the bronchiolitis obliterans syndrome at 1 year postoperatively, with 33% affected at 2 years. CONCLUSIONS: The results of pulmonary retransplantation for OB are improving. Current evidence indicates that OB does not recur in an accelerated manner after retransplantation, although pulmonary function does worsen again by 2 years. Pulmonary retransplantation is appropriate only in selected patients with OB who are ambulatory and are operated on at experienced centers.

Adolescent↗
PubMed1994

Timing of surgery in relation to the menstrual cycle in premenopausal women with operable breast cancer.

Recent studies have suggested that the timing of surgery in relation to the menstrual cycle might influence survival of premenopausal women with operable breast cancer. The data of 96 premenopausal patients who underwent primary surgery for operable breast carcinoma between 1975 and 1988 were analysed. At 10 years, disease-free and overall survival rates of patients whose initial surgery was 1-12 days after the starting date of the last menstrual period (follicular phase) were significantly poorer compared with survival of those who underwent operation more than 12 days after the last menstruation (luteal phase) (disease-free survival rate 40 versus 72 per cent, P = 0.002; overall survival rate 40 versus 79 per cent, P = 0.001). These differences in survival remained significant in a second analysis based on the menstrual phase at the time of both initial and definitive operation. Menstrual phase had the greatest impact on the survival of patients with positive axillary nodes (P = 0.009). Prospective studies are required to elucidate the relationship between the timing of all surgical procedures during the menstrual cycle and survival.

Adult↗
PubMed1994

Timing of surgery influences survival in receptor-negative as well as receptor-positive breast cancer.

Analysis of oestrogen and progesterone receptor (ER, PR) status was interpreted in relation to menstrual phase at the time of surgery and survival in 84 women diagnosed with breast cancer between 1975 and 1988. We showed previously (Br J Surgery 1994, 81, 217-220) that long-term survival was significantly poorer when surgery was performed during the follicular phase of the menstrual cycle compared to luteal phase; we now demonstrate that this effect on survival is at least as important in receptor-negative as receptor-positive patients. At 10 years, overall survival (OS) of ER-positive patients who had their biopsy during the follicular phase was significantly poorer than for those whose biopsy was performed during the luteal phase of their menstrual cycle (52 versus 88%, P = 0.02). OS for the ER-negative follicular phase group was also significantly poorer than that for the ER-negative luteal phase group (33 versus 76%, P = 0.009). The OS difference between the PR-positive follicular phase group and PR-positive luteal phase group was of borderline significance (60 versus 87%, P = 0.06), while the difference in OS between the PR-negative follicular phase group and that of the PR-negative luteal phase group was highly significant (13 versus 76%, P = 0.001). Disease-free survival for these groups followed a similar trend. The survival differences in receptor-negative women suggest that hormonal fluctuations at the time of surgery may have complex indirect effects on tumour growth and metastasis. The mechanism, if indeed independent of the tumour steroid receptors, could also apply in other cancers.

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