Advantage of rapamycin over mycophenolate mofetil when used with tacrolimus for simultaneous pancreas kidney transplants: randomized, single-center trial at 10 years.

Simultaneous pancreas kidney transplantation (SPKT) is the treatment of choice for patients with type 1 diabetes and end-stage renal disease. Rapamycin and mycophenolate mofetil (MMF) have been used for maintenance immunosuppression with tacrolimus in SPKT; however, long-term outcomes are lacking. From September 2000 through December 2009, 170 SPKT recipients were enrolled in a randomized, prospective trial receiving Rapamycin (n = 84) or MMF (n = 86). All patients received dual induction therapy with thymoglobulin and daclizumab, and low-dose maintenance tacrolimus and corticosteroids. Compared to MMF, rates of freedom from first biopsy-proven acute kidney or pancreas rejection were superior for Rapamycin at year 1 (kidney: 100% vs. 88%; P = 0.001; pancreas: 99% vs. 92%; P = 0.04) and at year 10 (kidney: 88% vs. 71%, P = 0.01; pancreas: 99% vs. 89%, P = 0.01). The higher rates of rejection were associated with withholding MMF (vs. Rapamycin, p = 0.009), generally for gastrointestinal or bone marrow toxicity. There was no significant difference in creatinine, proteinuria, c-peptide, viral infections, lymphoproliferative disorders or posttransplant diabetes. HbA1C and lipid levels were normal in both groups, although higher in the Rapamycin arm. There were no significant differences in patient or allograft survival. In this 10-year SPKT study, Rapamycin in combination with tacrolimus was better tolerated and more effective than MMF. Overall, the patient and allograft survival were equivalent.

Zoom endoscopic monitoring of small bowel allograft rejection.

BACKGROUND: The small bowel has been successfully transplanted in patients with irreversible intestinal failure. This report aims to describe endoscopic monitoring of small bowel rejection. METHODS: A magnification endoscope (zoom endoscope) was used in this study. In the first part of the study (October 1998 to March 2000, 271 endoscopy sessions), the specific endoscopic findings that correlated with rejection were determined. An analysis then was performed on data from the second period (March 2001 to November 2002, 499 sessions) to evaluate the zoom endoscope's accuracy in monitoring rejection. RESULTS: Specific endoscopic findings of rejection found in the first period included background erythema, villous congestion, blunted villous tip, and shortened villous height. When the rejection was successfully treated, endoscopic appearance returned to normal. On the basis of these findings, five endoscopic criteria (villous shortening, villous blunting, background erythema, villous congestion, and mucosal friability) were used to score endoscopic sessions in the second period. Endoscopic diagnosis of rejection was compared with histology. Adult patients showed a sensitivity of 45%, a specificity of 98%, a positive predictive value of 82%, and a negative predictive value of 88%. In pediatric patients, these values were, respectively, 61%, 84%, 57%, and 86%. On 59 distinct occasions (30 in period 1 and 29 in period 2) in which the results were endoscopy negative yet biopsy positive (mild) for rejection, we elected not to treat these rejections on the basis of clinical evaluation, and 58 (98%) resolved without further therapy. CONCLUSIONS: With the use of magnification, endoscopy is a useful tool for monitoring acute rejection in the small bowel allograft.

Analysis of rejection episodes in over 100 pediatric intestinal transplant recipients.

Rejection after intestinal transplant is a significant source of morbidity and mortality. We analyzed number of rejections, severity, and duration of episodes in pediatric recipients of intestinal transplants. One hundred eighteen intestinal transplants were performed: intestine (n = 27), liver-intestine (n = 27), modified multivisceral (n = 7), and multivisceral (n = 57). A total of 186 rejections were classified: mild (n = 89), moderate (n = 70), severe (n = 27). Duration of episodes doubled for each increasing step in severity. Treatment of mild rejection was with steroids, moderate rejection was treated with OKT3, severe rejection required OKT3 and organ removal. Most rejections occurred during the first month posttransplant, with the incidence of all rejections declining after 6 months posttransplant. Intestine and liver-intestine recipients had significantly higher probability of developing severe rejections, as compared to MVT. In summary, recipients of MVT seemed to be protected from rejection as compared to intestine or liver-intestine recipients.

Analysis of risk factors for the development of posttransplant lymphoprolipherative disorder among 119 children who received primary intestinal transplants at a single center.

UNLABELLED: Posttransplant lymphoproliferative disorder (PTLD) is a well-known complication after pediatric transplantation. We analyzed all potential risk factors to assess patient and graft outcomes of 119 children who received intestinal transplantations. MATERIALS AND METHODS: Between August 1994 and March 2005, 119 patients underwent cadaveric intestinal transplantation. Their median age at transplant was 1.4 years (range: 0.6-17), median weight was 9.5 kg (range: 4.7-67), and 57% were boys. The median follow-up among 49 ongoing survivors was 41 months (range: 4-121). All PTLD cases were biopsy proven. In the past 5 years, treatment included antiviral therapy, immunosuppression withdrawal, and use of rituximab. RESULTS: The incidence of PTLD was 11.8% (14/119). No patient experienced graft failure secondary to PTLD, while two patients died from PTLD (14.2%). The PTLD group was divided into an early onset group (<4 months, 6 of 14; 42.8%) and a late onset group (>2 years, 8 of 14; 57.2%). No patient experienced PTLD between 4 months and 2 years after transplantation. The use of OKT3 was the only significant risk factor for the development of PTLD. No factor was specifically associated with the early versus late development of PTLD. CONCLUSIONS: The only factor associated with a significantly higher risk of PTLD was the use of OKT3 to treat a rejection episode. Finally, since the the introduction of anti-CD20 antibodies as part of the treatment protocol for PTLD, the risk of death due to PTLD appears to have become manageably low.

The Miami experience with almost 100 multivisceral transplants.

We report our experience with 98 patients who received primary multivisceral transplantations. Three eras can be distinguished based on the evolution of technique, immunosuppression, and monitoring: August 1994 to December 1997 (first era); January 1998 to December 2000 (second era); and January 2001 to present (third era). Sixteen patients were transplanted during the first era, 18 during the second era, and 64 during the third era. Fifty-three patients are alive with a median follow-up of 37.5 months (range: 1 to 116 months). The leading cause of mortality was infection (n = 17), followed by rejection (n = 6). Seven patients required retransplantation and five of them subsequently died. The estimated 3-year survival was 25% +/- 11% for era 1; 44% +/- 12% for era 2; and 58% +/- 7% for era 3. Additionally, 45.3% (29/64) of patients in the third era never developed rejection versus 23.5% (8/34) of patients in the first two eras combined. The percentage of patients who developed a moderate or severe rejection was significantly less in the third era compared with the first two eras combined, 31.6% (20/64) versus 67.6% (23/34). A comparison of the hazard rate of developing severe rejection showed a protective effect of the multivisceral graft (P = .0001). In conclusion, multivisceral transplantation is indicated for patients with short bowel syndrome and extended abdominal catastrophies. Evolution in surgical techniques, immunosuppression, and monitoring have improved patient survival, which is now similar to that of other complex solid organ transplants.

An association of lower serum citrulline levels within 30 days of acute rejection in patients following small intestine transplantation.

INTRODUCTION: In a prospective protocol we studied whether serum citrulline level within 30 days of an acute rejection was predictive of the episode. METHODS: An acute rejection episode was defined as the date of occurrence of any biopsy-proven rejection in which treatment was initiated until two successive biopsies showed no further rejection. We compared the mean citrulline level based on values determined within 30 days of the start of an acute rejection episode with the mean citrulline level measured on the same patient during a rejection-free period. Serum citrulline measurements were available immediately prior to the occurrence of rejection for 22 patients who experienced 37 episodes. RESULTS: For the 12 episodes of mild rejection, the mean serum citrulline level +/- SE (standard error) was 15.0 + 2.3 micromol/L prior to rejection and 18.8 +/- 2.4 micromol/L during the rejection-free periods. A paired t test of the mean differences was not significant (P = 17). For the 25 episodes of moderate or severe rejection, the mean serum citrulline level was 12.4 +/- 1.1 micromol/L before rejection and 18.8 +/- 2.0 micromol/L during the rejection-free periods. A paired t test of the mean difference was statistically significant (P = .002). CONCLUSIONS: Although further study of citrulline as a marker for the early detection of acute rejection episodes is needed, our hope is that its use will help to prevent some of these early episodes from evolving into full-blown moderate or severe grades of rejection.

Pilot Randomized Trial of Tacrolimus/Everolimus vs Tacrolimus/Enteric-Coated Mycophenolate Sodium in Adult, Primary Kidney Transplant Recipients at a Single Center.

BACKGROUND: Recent studies suggest that the combination of tacrolimus (TAC) and everolimus (EVL) could become a viable option for use as standard maintenance immunosuppression in non-highly sensitized kidney transplant recipients. METHODS: We conducted a single-center, open-label, randomized pilot trial comparing two maintenance immunosuppression regimens in non-highly sensitized, adult, primary kidney transplant recipients: (TAC/EVL, Group A) vs our standard maintenance regimen of TAC plus enteric-coated mycophenolate mofetil (TAC/EC-MPS, Group B). In both treatment arms, dual induction therapy consisting of anti-thymocyte globulin (Thymoglobulin) and basiliximab was given. Early corticosteroid withdrawal (by 7-10 days posttransplantation) was also planned in both arms. There were 30 study participants, 15 per treatment arm. Results during the first 12 months posttransplantation are reported here. RESULTS: Between 1 month and 12 months posttransplantation, mean TAC trough levels ranged between 5 and 8 ng/mL in both arms. Mean trough EVL level in Group A ranged between 4 and 6 ng/mL, and mean EC-MPS dose in Group B ranged from 1440 mg at 1 month to 945 mg at 12 months. One patient in Group A vs three patients in Group B experienced a first biopsy-proven acute rejection during the first 12 months posttransplantation (P = .32). Four patients in each group experienced biopsy-proven chronic allograft injury (interstitial fibrosis/tubular atrophy) (P = .99). There was a slight trend toward more favorable renal function in Group A at months 1-3 posttransplantation (P = .06, .10, and .18 for estimated glomerular filtration rate, respectively). No graft failures or deaths were observed in either group during the first 12 months posttransplantation. Four patients in each group developed an infection during the first 12 months posttransplantation. Two patients in Group A developed new-onset diabetes after transplant during the 12-month follow-up period, vs no patients in Group B (P = .13). CONCLUSION: TAC/EVL may be a viable alternative to TAC/EC-MPS for use as standard maintenance immunosuppression in non-highly sensitized kidney transplant recipients and should be given further consideration.

Patterns of failure following surgical resection of renal cell carcinoma: implications for adjuvant local and systemic therapy.

PURPOSE: This report is a patterns-of-failure analysis of resected renal cell carcinoma (RCC) performed to determine the relative incidences of local failure (LF) and distant failure, to identify the pathologic features predicting for each using a multivariate analysis, and to assess the relative impact of each form of failure on overall survival (OS). In this way, the potential value of and selection of patients for adjuvant local and/or systemic therapy can be better evaluated. MATERIALS AND METHODS: The records of 172 patients with unilateral, nonmetastatic RCC who were treated with definitive surgery between 1978 and 1988, and who had a minimum follow-up duration of 1 year, were identified through the Memorial Sloan-Kettering tumor registry. Distribution by stage included T1, 10 patients; T2, 102; T3a, 32; T3b, 27; and T4, one. The incidences of positive lymph nodes (LNs) and positive margins were 5.8% and 6.4%, respectively. RESULTS: LF developed in only six patients, yielding a 7-year actuarial incidence of 5%. In this subset, four patients developed distant metastases (DM), three occurring concurrently with or before LF. DM developed in 30 patients, yielding a 7-year actuarial incidence of 26%. Among the variables that had an impact on the development of DM according to univariate log-rank tests, only positive LNs (P = .026) and renal vein extension (P = .001) remained as significant independent prognosticators. The overall 7-year actuarial survival rate was 80%. Eleven patients died of RCC during follow-up, nine of whom (82%) died of metastatic disease. CONCLUSION: LF is rare following surgical management of RCC, and shows no clear causal relationship with the development of DM. Patients die of DM, and not LF. These data do not support the role of adjuvant radiation therapy in this disease. Patients with LN involvement or renal vein extension have a significantly increased risk for developing DM, and are therefore appropriate candidates for trials investigating systemic therapy.

A prospective randomized trial of adjuvant brachytherapy in the management of low-grade soft tissue sarcomas of the extremity and superficial trunk.

PURPOSE: This study was designed to evaluate the impact of adjuvant brachytherapy (BRT) on local and systemic recurrence rates in patients with low-grade sarcoma. PATIENTS AND METHODS: Forty-five patients with histologic low-grade, completely resected soft tissue sarcomas of the extremity or superficial trunk were entered onto this trial. Following resection of all gross disease, patients were randomized to the BRT arm (n = 22) or to the no-BRT arm (n = 23). On the fifth or sixth postoperative day, catheters were loaded with iridium 192 to deliver a dose of 45 Gy to the tumor bed over 4 to 6 days. RESULTS: The two groups were evenly distributed with respect to the distribution of presentation status (primary v recurrent), tumor site (trunk v extremity, proximal v distal extremity), tumor size (< 5 cm v > or = 5 cm), tumor depth (superficial v deep), and microscopic tumor margins (positive v negative). The predominant histopathologic diagnosis in each group was liposarcoma (BRT, 13 of 22 [59%]; no BRT, 14 of 23 [61%]) with other histopathologic subtypes evenly distributed between the two groups. The median follow-up duration among the ongoing survivors is 67 months. One patient in the BRT group developed systemic disease and died of progressive disease. Local recurrence occurred in five of 23 patients (22%) in the no-BRT group and six of 22 patients (27%) in the BRT group (P = .60). CONCLUSION: Adjuvant radiation in the form of BRT does not appear to decrease local recurrence rates following complete resection of low-grade extremity and superficial trunk soft tissue sarcomas. Other adjuvant approaches, such as external-beam radiotherapy, are required to have a significant impact on local recurrence rates in this group of patients.

Impact of adjuvant radiation on the patterns and rate of relapse in advanced-stage Hodgkin's disease treated with alternating chemotherapy combinations.

The role of adjuvant radiation therapy (RT) in the management of advanced-stage Hodgkin's disease (HD) was analyzed in 222 patients who attained a complete remission (CR) with alternating chemotherapy combinations. Mechlorethamine, vincristine, procarbazine, and prednisone/doxorubicin, bleomycin, vinblastine, and dacarbazine (MOPP/ABVD) or MOPP/ABV alternating with the lomustine, melphalan, and vindesine combination (MOPP/ABV/CAD) were similarly effective in inducing a CR in 222 of 270 (83%) patients. These patients were scheduled to receive consolidative RT to bulky disease or other critical sites of initial nodal involvement to a total dose of 2,000 cGy, with an optional additional boost of 1,000 cGy. However, only 125 (56%) patients received radiation to all initial nodal sites of disease. In 69 (31%) patients, only selected nodal sites were included in the radiation fields, and 28 (13%) did not receive any RT. Of the 222 CR patients, 42 (19%) relapsed during a median follow-up period of 6.5 years (range, 2 to 15 years). Of these, 26 (62%) patients relapsed exclusively in unirradiated nodal sites, six (14%) within irradiated sites, and 10 (24%) both within and outside irradiated fields. The actuarial 10-year relapse-free survival (RFS) and overall survival (OS) for patients receiving radiation to all initially involved nodal sites were 89% and 94%, respectively, compared with 68% and 71% (P less than .0001) for patients who had only partial or no RT. Cox proportional hazards regression analysis showed that RT to all sites of initial disease was the most significant independent covariate (P less than .005) affecting RFS and OS. These data demonstrate that residual microscopic disease is relatively frequent in patients with apparent CR after alternating combination chemotherapy, and that irradiation of all sites of initial nodal involvement decreases relapse and improves survival in advanced-stage HD.

Prognostic factors among 185 adults with newly diagnosed advanced Hodgkin's disease treated with alternating potentially noncross-resistant chemotherapy and intermediate-dose radiation therapy.

The initial promising results with alternating chemotherapy regimens (mechlorethamine, vincristine, procarbazine, and prednisone/doxorubicin, bleomycin, vinblastine, and dacarbazine [MOPP/ABVD]; lomustine, melphalan, and vindesine [CAD] plus MOPP plus ABV) combined with intermediate-dose radiation therapy (RT) have been sustained with further follow-up; 82.2% of patients (152 of 185) achieved a complete remission (CR), and overall survival is 71.7% +/- 4.4% at 8 years (median follow-up is 55 months among the survivors). No statistically significant differences were found in CR percentage, CR duration, or survival between stages IIB, IIIB, and IV patients. For that reason, stepwise Cox regression analyses to identify the important prognostic factors were performed on overall survival, tumor mortality, freedom from disease progression, and survival following disease progression. Pretreatment characteristics were also tested for association with the probability of achieving CR, CR duration, and death due to other causes. Characteristics that were consistently associated with an independently unfavorable prognosis were low hematocrit, high serum lactic acid dehydrogenase (LDH), age more than 45 years, inguinal node involvement, mediastinal mass greater than .45 of the thoracic diameter, and bone marrow involvement. Patients with two or more unfavorable characteristics were much more likely to fail treatment (median survival, 62.4 months) than those with none or only one unfavorable factor (greater than 95% survival). This striking difference between the low- and high-risk groups remained even if the comparison was restricted to patients less than or equal to 45 years of age. These results provide a basis for selecting the young patients at high risk of failure for more intensive initial treatment with either autologous bone marrow rescue or hematopoietic growth factors.

Refinement of clinicopathologic staging for localized soft tissue sarcoma of the extremity: a study of 423 adults.

PURPOSE: The prognostic value of factors used in clinicopathologic staging of localized soft tissue sarcoma (STS) of the extremity were analyzed comprehensively. PATIENTS AND METHODS: Four hundred twenty-three patients with STS that was confined to the extremity were admitted to Memorial Sloan-Kettering Cancer Center from 1968 to 1978. Cox models for the hazards rates of tumor mortality, development of a distant metastasis, strictly local recurrence, and postmetastasis survival were developed. Tests of changes in the prognostic value of the important variables over time were performed, as well as an analysis of the effect of a local recurrence on the hazard rate of distant metastasis. RESULTS: Three unfavorable characteristics contained independent prognostic value for the rates of distant metastasis and tumor mortality: high grade (P less than .00001), deep location (P less than .0002), and size greater than or equal to 5 cm (P less than .007). Their Cox model coefficients did not differ significantly (P greater than or equal to .65); thus, a staging scheme based on the risk of ever developing a distant metastasis would assign equal prognostic weights to grade, depth, and size. The tumor grade effect during the initial 18 months was much larger in magnitude than those for depth and size, and its effect disappeared beyond that time (P = .0003). Thus, a staging scheme based on the risk of early metastatic spread would assign a distinctly larger prognostic weight to grade and lesser but equal weights to depth and size. There was no local recurrence effect on the rate of distant metastasis in the high-risk group (high grade, deep, and greater than or equal to 5 cm; P = .75), but there was a significant association among the remaining groups combined (P = .0039). The magnitude of this association actually increased according to the number of favorable characteristics presented (P = .0024). CONCLUSIONS: The refinement of clinicopathologic staging may depend on the choice of outcome variable: ultimate prognosis versus early metastatic spread. Additionally, the observed local recurrence effect may be explained by a tendency for some patients to acquire one or more unfavorable risk factors at the time of local recurrence.

Differential vulnerability of mixed and cutaneous nerves in lead neuropathy.

The prevalence of demyelinated fibers in mixed nerve (sciatic) and cutaneous nerve (sural) and the change in lead levels in various tissues over time were assessed in a model of lead neuropathy in the rat. Long-Evans rats were given drinking water containing 4% lead acetate and killed between one and 213 days of exposure. Lead levels in blood, brain, kidney, and femur increased over the 213-day period. Lead levels in sciatic nerve appeared to increase rapidly during the first few weeks of exposure and then decline to a lower plateau. The neuropathy was characterized by segmental demyelination and remyelination; neither axonal degeneration nor a microangiopathy was found. Sciatic nerve had a significantly greater prevalence of demyelinated fibers than sural nerve; the prevalence of demyelinated fibers was similar in proximal and distal sciatic nerve. The variable, brain-lead concentration times days on lead, which is an indicator of cumulative brain exposure, was the best predictor of the prevalence of demyelination. The differential involvement of sciatic and sural nerves in lead neuropathy may either indicate that Schwann cells myelinating different nerve-fiber populations have different susceptibilities to lead toxicity, or that lead preferentially enters sciatic nerve.

Non-Hodgkin's lymphomas: characteristics of long-term survivors following conservative treatment.

A most important set of prognostic factors for survival among 467 patients with non-Hodgkin's lymphoma receiving conservative treatment was determined statistically by the Cox proportional hazards model. Non-Hodgkin's lymphoma was diagnosed in these patients between 1958 and 1969. Initial biopsy material was classified according to the Working Formulation, and the Rappaport, Kiel, and Lukes-Collins systems. The Cox analysis identified a group of 37 patients with a median survival of 150 months. These patients had the following characteristics: small lymphocyte, plasmacytoid lymphocyte, small cleaved, large cleaved or non-cleaved follicular center cell histologic subtype (Lukes-Collins); no bulky involvement of mesenteric nodes or critical organs--kidney, urinary tract, or pleura; stages I to III disease (78 percent stage I or IE); no B symptoms; age below 60 years; initial resection as a reflection of localized disease. Patients with advanced-stage non-Hodgkin's lymphoma receiving conservative treatment have a relatively short survival (median, less than five years) regardless of histologic subtype.

Long-term results of a prospective randomized trial of adjuvant brachytherapy in the management of completely resected soft tissue sarcomas of the extremity and superficial trunk.

PURPOSE: A prospective randomized trial evaluating adjuvant brachytherapy for soft tissue sarcomas was conducted between July 1982 and July 1987. METHODS AND MATERIALS: One hundred twenty-six patients with soft tissue sarcoma of the extremity or superficial trunk (STS) underwent grossly complete resection with limb-sparing surgery. Intra-operatively, patients were randomized to receive either adjuvant brachytherapy (BRT) or no further therapy (no BRT). BRT consisted of an Iridium-192 implant which delivered 4200-4500 cGy over 4-6 days. Total hospital stay for combined surgery and BRT was 10-14 days. Patients in each group were well matched with respect to age, sex, site, tumor size, depth, histologic type, and grade. Median follow-up is 66.5 months for all living patients. RESULTS: At 5 years, local control was 82% in the BRT group vs. 67% in the no BRT group (p = .049). When analyzed by histologic grade, high grade tumors had local control of 90% with BRT vs. 65% with no BRT (p = .013). There was no difference in local control in the low grade patients in either arm. At 5 years, the proportion free of distant metastases was approximately 76% in both arms, with no difference between BRT and no BRT. When analyzed by grade, high grade patients had a similar proportion free of distant metastasis in the BRT vs. no BRT arms despite improved local control in those receiving BRT. Similarly, the disease-specific survival for all patients at 5 years was 81% for BRT vs. 80% for no BRT (p = NS). When analyzed by grade, and treatment (BRT vs. no BRT), 5-year disease-specific survival for high grade was the same in both groups. CONCLUSIONS: Adjuvant BRT significantly improves local control in completely resected STS. This improvement is confined to patients with high grade histology. BRT provides excellent local control in this group, and significantly shortens the treatment time when compared to adjuvant external beam radiation. However, the improved local control does not translate into either decreased distant metastasis or increased disease-specific survival.

Performance status after treatment for squamous cell cancer of the base of tongue--a comparison of primary radiation therapy versus primary surgery.

PURPOSE: To compare the quality of life and functional outcome in patients with squamous cell cancer of the base of tongue treated with primary radiation vs. primary surgery. METHODS AND MATERIALS: At our institution, patients with base of tongue cancer are primarily treated either by radiation or surgery depending upon the philosophy of their primary physician. Primary radiation consists of 45-54 Gy external beam radiation followed by an 192Ir implant delivering an additional 20-30 Gy over 2-3 days. A neck dissection is done at the same time as the implant for those with involved nodes. Primary surgery consists of resection of the base of tongue lesion, neck dissection and postoperative radiation therapy. Because both groups have similar local control in our experience (80-90%), we used a subjective performance status scale for head and neck cancer patients to assess the quality of life in these patients (0-100, 0 = worst function, 100 = normal function). This scale measures ability to eat in public, understandability of speech, and normalcy of diet. There were 30 radiation patients (21: T1-T2; nine: T3-T4) and ten surgery patients (five: T1-T2; five: T3-T4) available for long-term quality of life assessment. RESULTS: Patients treated with radiation had consistently better performance status scores and quality of life according to our study. This was true for those with early (T1-2) as well as more advanced (T3-4) disease. For eating in public, T1-2 patients had scores of 85 vs. 75 (p = .31) and T3-4 patients had scores of 82 vs. 35 (p < .0001) for radiation vs. surgery, respectively. For understandability of speech, T1-2 patients had scores of 92 vs. 65 (p = .0021), and T3-4 patients had scores of 95 vs. 35 (p < .0001) for radiation vs. surgery, respectively. For normalcy of diet, T1-2 patients had scores of 74 vs. 50 (p = .047), and T3-4 patients had scores of 78 vs. 32 (p = .0012) for radiation vs. surgery, respectively. In addition, we compared scores for early vs. advanced disease treated by the same modality. For radiation, there was no difference in all three functional categories for T1-2 vs. T3-4 (p = .84), showing that quality of life scores remain high for all stages. For surgery, functional status deteriorated significantly when comparing T1-2 vs. T3-4 (p = .0014), consistent with the fact that larger tumors require more extensive operations. CONCLUSION: Radiation therapy provides a better performance status than surgery for base of tongue cancer. This is true for both early and advanced disease. Because radiation also provides similar local control and survival, our data suggests that radiation may be the preferred strategy. Functional scores remain high for all T stages treated with radiation, but deteriorate with more advanced T stages for patients treated with surgery. Similar studies using objective criteria are needed to further compare these treatments.

Identification of a Drosophila 60S ribosomal protein.

We have previously reported the cloning and sequencing of a cDNA from Drosophila (DL43; GenBank Accession # U40226) which predicts a small protein homologous to a ribosomal protein in yeast and rat. In this study we show that a 330 nucleotide transcript encoding the putative ribosomal protein is expressed in Drosophila Kc cells under normal growth conditions (25 degrees C). This RNA is associated with the translational machinery and is present on polysomes. The DL43 cDNA was transcribed using T7 RNA polymerase and the resulting transcripts translated in a wheat germ extract. SDS/PAGE analysis of the in vitro transcribed and translated DL43 cDNA yields a small protein of approximately 9 kDa. Using two-dimensional gelelectrophoresis we have established that the radiolabeled DL43 protein comigrates with a small basic protein in the 60S ribosomal subunit. The electrophoretic mobilities of the in vitro and in vivo synthesized DL43 proteins are indistinguishable providing support for the identity of this protein.

A lyophilized human reference plasma for coagulation factors. Evidence for stability of factors I, II, V, and VII through XII.

Results are reported of a one-year study on the stability of a lyophilized normal human reference plasma, originally standardized for eight clotting factor activities against a freshly prepared pool of citrated, platelet-poor normal human plasma. The stability of any particular coagulant activity in this reagent was represented mathematically as a function of the observed clotting times obtained under specific assay conditions, where any observed change in the clotting times over the trial period was taken to reflect a change in the stability of the reference plasma. Taking into consideration estimates of variability contributed by different donors of factor-deficient substrata-plasma, different lots of substrate from the same donor, different technologists, and certain age-of-substrate lot trends, there was no statistically significant change in functional activity for Factors V and VII through XII in the reagent when it was stored unreconstituted below -25C. By less rigorous criteria, both clottable fibrinogen (Factor I) and the thrombin-forming potential of prothrombin (Factor II) also were stable during this same period. Based on these results, it was concluded that when suitably prepared, lyophilized human plasma can be used as a stable, secondary standard reference for the assay of coagulation factors.

Radiation-associated sarcoma of bone and soft tissue.

Radiation-associated sarcomas are uncommon, constituting less than 5% of all sarcomas, and generally associated with a poor prognosis. We reviewed the medical records of 565 patients with sarcoma and a second malignancy seen at our institution between 1943 and 1989; 160 of these patients (28%) were considered to have a radiation-associated sarcoma. The most common diagnosis for which radiation had been given was breast cancer (26%), followed by lymphoma (25%) and carcinoma of the cervix (14%). The most common histologic types of radiation-associated sarcoma were osteogenic (21%), malignant fibrous histiocytoma (16%), and angiosarcoma/lymphangiosarcoma (15%). Most of the tumors were high grade (87%). Three variables had prognostic significance in multivariate analysis: the presence of metastatic disease, the completeness of operative resection in patients with localized disease, and the size of the primary tumor in patients who underwent complete resection of the sarcoma. Survival was independent of histologic subtype or site of disease.

Vascular soft-tissue sarcomas. An analysis of tumor-related mortality.

Between 1982 and 1990, 69 adult patients were admitted to Memorial Sloan-Kettering Cancer Center with a diagnosis of angiosarcoma, lymphangiosarcoma, or malignant hemangiopericytoma. The existing literature regarding sarcomas focuses on individual histologic conditions or site-specific activity and includes pediatric patients, which makes estimates of survival difficult. We describe the clinical course of all vascular sarcomas, the survival without distant recurrence of patients with vascular sarcomas, and the overall survival of patients with vascular sarcomas. Using Cox's stepwise regression model, histologic characteristics of the tumors, tumor grade, tumor size, and other factors were assessed to determine their prognostic significance. Noncurative treatment and the presence of metastases were the only two factors influencing survival. Tumor grade approached significance. Disease recurrence was common among curatively treated patients (37% of such patients), and more than half of these recurrences involved distant sites. The survival of these patients depends on complete surgical resection and is independent of individual histologic characteristics of the tumor.