A cost comparison of two strategies for treating stage IB2 cervical cancer.

Patients with stage IB2 cervical cancer at our institution are treated primarily with definitive chemoradiation, or chemoradiation followed by adjuvant hysterectomy. We sought to compare the cost differences associated with these two strategies. We identified all patients with stage IB2 cervical cancer who received their entire treatment regimen at our institution between 1995 and 2004. All patients received a combination of chemotherapy, external beam radiation, and one brachytherapy procedure, followed by either a second brachytherapy procedure or a simple hysterectomy. We retrieved cost data associated with hospitalization for the completion of respective treatment, including pharmacy, laboratory and pathology, radiation, and operating room services, as well as the costs of supplies and room and board. We identified 46 patients with stage IB2 cervical cancer, 23 who received a second brachytherapy procedure and 23 who underwent simple hysterectomy. Patients displayed similar demographics and similar disease characteristics including initial tumor diameter and histology. The cost of care for adjuvant hysterectomy group was greater ($8,316.70 vs 5,508.70, P < 0.0001). Specific differences included higher operating room costs ($1520 vs 414, P < 0.0001), pharmacy costs ($675 vs 342, P < 0.0001), and laboratory/pathology costs ($597 vs 89, P < 0.0001). We conclude that definitive chemoradiation appears to be associated with lower costs for management of stage IB2 cervical cancer when compared to simple adjuvant hysterectomy.

Characterization of lymphocytotoxic antibodies in renal transplantation.

Anti-B cell, anti-T cell, and antiperipheral blood lymphocyte antibodies were investigated in the sera from 115 cadaveric kidney graft recipients pre- and post-transplantation. These antibodies were characterized: optimal temperature for cytotoxicity (4 C or 22 C), immunoglobulin class (IgG or IgM), and reactivity after platelet absorption, and thereafter defined according to their influence on the graft survival. Patients with IgM anti-B cell antibodies, reacting mostly at 4 C, the activity of which could not be removed by platelet absorption, have a prognosis of the graft as good as those with no antibody, i.e., the graft function (serum creatinine and severity of rejection) at 3 years was comparable between those two groups. However, when the anti-B cell antibodies unabsorbable on platelets are of IgG class and detected at 4 C and 22 C, the graft outcome is poorer (P less than 0.025 at 3 months). A similar prognosis is observed in patients with antiperipheral blood lymphocyte antibodies of IgG or IgM class, absorbable or not on platelets (P less than 0.05). Lymphocytotoxic antibodies of the IgG class are always associated with a poor graft outcome. On another hand, the cold anti-B cell antibodies of the IgM class are not associated with graft failure but no enhancing effect could be seen.

Improved renal allograft function and survival following nonspecific blood transfusions. I. Induction of soluble suppressor factors inhibiting the mitogenic response.

A small number of blood transfusions (1-3) seems sufficient to improve the cadaveric renal allograft outcome, probably via induction of some nonspecific suppressive activity. This activity was assessed by the concanavalin A (Con A) enhancement method; when present, the response of freshly isolated patients' cells to a submitogenic dose of Con A was lowered, leading to a Con A ratio greater than 5, significantly (P less than 0.0001) higher than the one observed in normal controls or untransfused uremic patients. The correlation between this suppressive activity and graft outcome was determined. Thirty-five patients were studied over a 12-month period for graft function (creatinine level) and survival. Both parameters were significantly improved in the group of patients whose Con A ratio was greater than 5 after transfusions. A soluble suppressor factor, or factors, released into the supernatant of patients' lymphocytes cultured for 48 hr, seems responsible for this suppressive activity. Moreover this process is nonspecific, since it suppresses mitogenic response of cells isolated from normal untransfused volunteers, and could be observed when peripheral blood mononuclear cells were used, but not with purified adherent or nonadherent cells. Addition of indomethacin to the cells during the elaboration of the supernatant abolished this activity. However, amounts of PGE2 secreted into the supernatant during the 48 hr of culture could not be correlated with this suppressive activity. These findings suggest that induction of nonspecific immunosuppression by a few blood transfusions could predict a better kidney graft outcome.

Monitoring of cytomegalovirus infections by the CD8+CD38+ T-cell subset in kidney transplant recipients.

BACKGROUND: The CD8+CD38+ T-cell subset can predict progression to acquired immune deficiency syndrome among human immunodeficiency virus-positive subjects. This T-cell subset usually increases during other active viral infections (cytomegalovirus [CMV], Epstein Barr virus). We report on its usefulness in the early detection of CMV infection in kidney transplant recipients. METHODS: Quantitation of CD8+CD38+ T cells was monitored by dual-color flow cytometry analysis on 77 patients during the posttransplantation period. Seventeen of the 52 patients at risk for CMV disease (33%) had primary infection or reactivation and three patients had herpes simplex virus infection only. RESULTS: In every patient with CMV disease, high values for the CD8+CD38+ subset were detected with a 90% positive predictive value for the primary infections. Elevated values were observed at the very first clinical signs of the viral disease or within the few preceeding days. Acute rejection episodes did not provoke false-positive results. CONCLUSION: This immunologic marker is sensitive and easily obtainable on a daily basis. It may help to direct therapy during rejection or serve as a tool for early detection of clinical viral diseases.

Prospective evaluation of pretransplant blood transfusions in cadaver kidney recipients.

BACKGROUND: A beneficial effect of pretransplant transfusions on graft survival was demonstrated in the early 1970s. In the mid-1980s, however, retrospective studies showed that transfusions had lost their graft-protective effect in the cyclosporine era. During the last 10 years, deliberate transfusion pretreatment of transplant patients has been discontinued. METHODS: Within a collaborative project of 14 transplant centers, prospective recipients of cadaver kidney grafts were randomized to receive either three pretransplant transfusions or transplants without transfusions. RESULTS; The graft survival rate was significantly higher in the 205 transfusion recipients than in the 218 patients who did not receive transfusions (at 1 year: 90+/-2% vs. 82+/-3%, P=0.020; at 5 years: 79+/-3% vs. 70+/-4%, P=0.025). Cox regression analysis showed that this effect was independent of age, gender, underlying disease, prophylaxis with antilymphocyte antibodies, and preformed lymphocytotoxins. CONCLUSIONS; Transfusion pretreatment improves the outcome of cadaver kidney transplants even with the use of modern immunosuppressive regimens.

Inhibitory effect of isoniazid on antipyrine clearance in man.

The effect of both concomitant administration and pretreatment with isoniazid on the activity of the hepatic drug-metabolizing enzymes of healthy young volunteers, as indicated by the antipyrine clearance test, is reported. Concomitant administration of isoniazid with antipyrine results in a significant decrease in the hepatic clearance of the latter compound. In contrast, pretreatment for 14 days with isoniazid had no effect on antipyrine elimination kinetics. It is concluded that isoniazid depresses hepatic drug metabolism only when present in significant amounts at the hepatic site of drug oxidation.

Kidney graft survival: role of blood transfusions and lymphocytotoxic antibodies.

In 121 primary cadaver kidney grafts, a significant increase in graft survival has been observed in recipients transfused prior to transplantation, whatever the number of units received or the time of administration. This beneficial effect of blood transfusion was shown to be independent of the recipient's sex, blood group, HLA-A, B match grade and dialysis time. In longitudinal screenings, the incidence of post-transplant antibodies did not differ according to transfusion status of recipient. However, the graft survival was significantly improved in transfused patients without antibody or with an IgM anti-B (cold) antibody (95% survival at 4 years) as compared to nontransfused with the same characteristics. Patients with IgG anti-B (warm), anti-T or anti-PBL antibodies IgG/IgM shared a uniformly poor graft prognosis whether or not they had been transfused.

Computerized transcutaneous control of a multichannel implantable urinary prosthesis.

In the present paper we describe a personal computer interface of a multichannel implantable urinary prosthesis. This system is composed of two main parts: the first one is internal and consists of an implant using a 4-microns CMOS gate array chip controlling a wide variety of waveforms via eight monopolar channels. The second, an external controller featuring a versatile software, a PCB card plugged in a portable microcomputer, and a radiofrequency-coupled technique. This device is used to transmit the power, the data and the synchronization clock to the implant by a simple binary signal modulating a 20 MHz carrier. We also report the features of implant encapsulation and electrode design and fabrication. In the experimental phase, we studied the effect of early electric stimulation of the bladder during the spinal shock phase in the dog. We present the operative techniques that enabled us to perform chronic electrostimulation of the sacral roots and discuss the results.

[Development of organ transplantation in Quebec from 1985 to January 1990]. / Evolution de la transplantation d'organes au Québec de 1985 à janvier 1990.

In Québec, the first organ transplantations have been realized in 1958. Several kidney transplant programs started at that time. Cardiac, liver, pancreas and lungs programs followed and reached a full development in the eighties when Cyclosporin became available. Today, there are 4 university transplant programs in Québec (McGill, Montréal, Laval and Sherbrooke) with a total of 7 kidney, 4 liver, 4 heart, 2 pancreas and 2 lungs centers. More than 2,900 transplantations have been realized. Since 1970, organ procurement and distribution is organized by a central agency called Québec-Transplant (previously Métro-transplantation). Organ donation is done on a voluntary basis as every where in North America. More than 90% of the organs comes from cadaveric donors and more than 90% of the relatives accept organ donation. 50% of the donors have deceased from head trauma and 50% from cerebral hemorrhage. In 1989, multi-organ harvesting has been realized in 64% of the donors. Despite efforts and progresses, the number of patients awaiting an organ transplant is steadily growing and outlast the number of available organs. It is hoped that maximal utilisation of the donors and growing exchanges at a national and international level will help to solve this crucial problem.

The utility of PEG3350 without electrolytes for 2-day colonoscopy preparation in children.

OBJECTIVES: Successful colonoscopy preparation requires a method which is easy to administer. Simplifying this technique would be useful for adult and pediatric gastroenterologists. Most cleanout agents are not well tolerated by children. Polyethylene glycol without electrolytes (PEG3350 without electrolytes) has been used for constipation and bowel cleanout, but has not been studied as 2-day preparation for colonoscopy in children. This study evaluates the dosing, effectiveness and satisfaction with PEG3350 without electrolytes as a 2-day cleanout for colonoscopy preparation in children. METHODS: Parents of patients aged 5 years or older undergoing colonoscopies were approached for participation. All caretakers received standard instructions with a suggested food handout and a diary to track the doses of PEG3350 administered and to document other adjunct measures (suppository, enema). On the procedure day, parents and children completed appropriate satisfaction questionnaires. Post procedure, the physician rated the visualization of the mucosa. A pediatric gastroenterologist investigator and a second blinded pediatric gastroenterologist assessed the effectiveness using standard procedure photos. RESULTS: 30 patients aged 5-16 years were recruited (15 males, 15 females). The majority of parents and children reported being "very satisfied" or "satisfied" with the preparation. The preparation was rated by the principal investigator and independent pediatric gastroenterologist as effective in all cases. The mean number of doses was 4.7 on Day 1 and 4.9 on Day 2. The average dose given was 1.90 g/kg/day. CONCLUSION: PEG3350 without electrolytes appears to be safe, effective, and well tolerated as a 2-day clean out for colonoscopy preparation in children with an average dose of 1.90 g/kg/day.

Lack of benefit of early protocol biopsies in renal transplant patients receiving TAC and MMF: a randomized study.

We conducted a randomized, multicenter study to determine whether treatment of subclinical rejection with increased corticosteroids resulted in beneficial outcomes in renal transplant patients receiving tacrolimus (TAC), mycophenolate mofetil (MMF) and prednisone. One hundred and twenty-one patients were randomized to biopsies at 0,1,2,3 and 6 months (Biopsy arm), and 119 to biopsies at 0 and 6 months only (Control arm). The primary endpoint of the study was the prevalence of the sum of the interstitial and tubular scores (ci + ct)> 2 (Banff) at 6 months. Secondary endpoints included clinical and subclinical rejection and renal function. At 6 months, 34.8% of the Biopsy and 20.5% of the Control arm patients had a ci + ct score >or= 2 (p = 0.07). Between months 0 and 6, clinical rejection episodes were 12 in 10 Biopsy arm patients and 8 in 8 Control arm patients (p = 0.44). Overall prevalence of subclinical rejection in the Biopsy arm was 4.6%. Creatinine clearance at 6 months was 72.9 +/- 21.7 in the Biopsy and 68.90 mL/min +/- 18.35 mL/min in the Control arm patients (p = 0.18). In conclusion, we found no benefit to the procurement of early protocol biopsies in renal transplant patients receiving TAC, MMF and prednisone, at least in the short term. This is likely due to their low prevalence of subclinical rejection.

The effect of age on clinical/pathologic features, surgical morbidity, and outcome in patients with endometrial cancer.

OBJECTIVE: To evaluate the effect of age on clinical/pathologic features, surgical morbidity, and outcome in patients with endometrial cancer. METHODS: All women with surgically treated endometrial cancer at the University of Washington in Seattle, Washington between January 1990 and January 2000 were eligible; 396 patients underwent retrospective chart review. Statistical analysis was performed by SPSS. Median follow-up time was 33 months (range, 1 to 120 months). RESULTS: Age was < 45 years in 15% of patients, between 46 and 64 years in 47% of patients, and > 65 years in 38% of patients. Younger patients were statistically more obese than older patients (Body Mass Index of 40.3 kg/m2 vs. 35.3 kg/m2 vs. 31.0 kg/m2, P < 0.001). Intraoperatively, there were no differences between the three groups in the percentage of patients with lymph node sampling, operative time, blood loss, or complications. Postoperatively, older patients had more wound infections (P = 0.002), more cardiac events (P = 0.001), and more episodes of ileus (P = 0.025). Evaluation of pathology revealed that patients < 45 years old were statistically more likely to have endometrioid histology, grade I tumors, and stage IA disease. Women over age 65 were significantly more likely to have papillary serous histology, grade 3 tumors, and stage IC as compared to the younger patients. A subset analysis of patients > 75 years of age showed an increase in the percentage of patients with papillary serous histology (22% vs. 3%, P = 0.055), grade 3 disease (42% vs. 16%, P < 0.001), and stage IC disease (21% vs. 3%, P = 0.001) when compared to patients < 45 years old. Evaluation of endometrioid tumors only revealed a similar pattern of deeper myometrial invasion and higher tumor grade as age increased. CONCLUSIONS: Younger patients with endometrial cancer are generally more obese, with lower grade, lower stage disease, and with more favorable histologic cell types. Despite this, approximately a quarter have stage II-IV disease and 9% have positive lymph nodes. The older patients represent a dramatically different subset of patients. They are more likely to have aggressive papillary serous histology, higher grade tumors, and advanced stage disease. Age should be a consideration in appropriate referrals to gynecologic oncologists.

Restrictive antibiotherapy after renal transplantation.

Forty-two patients were followed up after 44 renal transplantations in an effort to evaluate possible benefits from the following protocol: systematic microbiologic and clinical surveillance, early and aggressive research for the cause of suspected infections, refusal to use prophylactic antibiotherapy, and selection of treatment according to the established cause of the infection. During 18,030 days of follow-up 124 infections were recorded, of which 110 were bacterial, 11 viral and 3 protozoal. Eighty originated in the urinary tract, 17 in skin wounds and 10 in the lower respiratory tract. Septicemia occurred three times, and one death due to infection was recorded. In the treatment of bacterial infections patients received antibiotics for 2486 days. Ampicillin (given for 816 days) and "minor" drugs such as sulfonamides and urinary antiseptics (given for 1036 days) were used 74.5% of the time, whereas gentamicin was used only 2.6% of the time (64 days). Combined antibacterial therapy was needed 1.2% of the time (29 days). A restrictive policy regarding anti-biotherapy seems to be beneficial to renal transplant recipients.

E1Cold cytotoxic antibodies in kidney graft recipients. / Les lymphocytotoxines froides chez les receveurs de greffe rénale

Serial serum samples from 39 renal allograft recipients were screened for cold and warm cytotoxic antibodies before and after grafting. In the group of patients who developed antibodies only after grafting, 6 had cytotoxins reactive at 37 degree C and 5 had cytotoxins reactive at 15 degree. At one year, all the patients with cold alloantibodies has functioning grafts, but none of the patients with warm antibodies had kept their graft. In three patients with cold antibodies, the cytotoxins reacted with a subpopulation of cells enriched in B lymphocytes but not with T cells eluted from nylon wool columns. This suggests that certain kinds of antibodies which appear in the blood after grafting may have enhancing properties.

Influence of HLA-A and HLA-B cross-reactive antigen matching on kidney graft survival.

The presence of cross-reactive (CR) antigens of the HLA-A and B specificities between donor and recipient carries a better graft outcome than an HLA match not taking it into account. This influence of CR antigens has been observed in the case of cadaver kidneys matched only for none or one HLA antigen. If two or more antigens are matched this effect is not seen anymore. This improved graft survival could not be explained on the basis of the number of transfusion nor the incidence of cytotoxic antibodies.