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BACKGROUND This study was conducted to evaluate predictive factors of urinary continence recovery after radical prostatectomy (RP) for high-grade prostate cancer (PCa). METHODS A total of 241 patients with high-grade (Gleason Score 8 or 9) PCa who underwent RP in a single Korean center between January 2011 and May 2018 were retrospectively reviewed. Urinary continence was defined as no pads use. Urinary continence was evaluated at 1, 3, 6, and 12 months after RP. Univariate and multivariate analyses were performed to determine the predictive factors of urinary continence recovery after RP. RESULTS The mean age was 67.6±6.4 years, and the mean PSA was 18.7±21.1 ng/dL. A total of 197 (81.7%) patients underwent nerve-sparing RP, and 198 patients (82.2%) were continent 1 year after RP. Multivariate analysis showed that the age (odds ratio [OR]=1.091 [1.015-1.172], P=0.018), Body Mass Index (BMI) (OR=1.227 [1.057-1.424], P=0.007), and modified surgical technique (OR=0.109 [0.044-0.267], P

Background/Aims: The double-guidewire technique (DGT) and transpancreatic precut sphincterotomy (TPS) are introduced as alternative biliary cannulation techniques for difficult biliary cannulation. This study aimed to evaluate the sequential use of DGT and TPS compared with a needle-knife precut papillotomy (NK). Patients and Methods: Six hundred and thirty-five consecutive patients with naοve papilla and who underwent endoscopic retrograde cholangiopancreatography (ERCP) for biliary cannulation from March 2010 to April 2014 in a single institute were analyzed. When standard techniques were unsuccessful, DGT or NK was performed. TPS was sequentially performed if DGT failed. Results: DGT and NK were attempted in 65 and 58 patients, respectively. A sequential DGT-TPS was performed in 38 patients after a failed DGT. Biliary cannulations were successful in 42%, 74%, and 66% of the DGT, sequential DGT-TPS, and NK patients, respectively (P = 0.002). The cannulation rate was higher in the DGT ± TPS patients (85%) than in the NK patients (P = 0.014). Post-ERCP pancreatitis (PEP) developed in 26% of the successful DGT patients, 37% of the sequential DGT-TPS patients, and 10% of the NK patients (P = 0.008). Of the sequential DGT-TPS patients, the incidence of PEP was significantly reduced in patients with a pancreatic duct (PD) stent compared with patients without a PD stent (24% vs. 62%, P = 0.023). Conclusions: Sequential DGT-TPS is a useful alternative method compared with NK for patients in whom biliary cannulation is difficult. In the sequential DGT-TPS patients, the incidence of PEP was significantly reduced with the use of a PD stent.

The objective of our study was to introduce a safe and effective method for the treatment of cervical pregnancy. This was a case series and took place at the minimal invasive surgery clinic at Soonchunhyang University Bucheon Hospital, Bucheon, Korea. From April 2005 through October 2007, a total of 10 patients with cervical pregnancy underwent hysteroscopic surgery. An 18 F foley catheter was inserted through the cervical canal after dilation, and the uterine cavity was irrigated with 3.5% H 2 O 2 300 mL for prevention of unrelenting bleeding. Hysteroscopic removal of cervical gestation under ultrasonographic guidance was performed uneventfully. All patients had an unremarkable postoperative course. Serum β–human chorionic gonadotropin levels were monitored after surgery and exhibited optimal decrease. All cases had histologic confirmation of products of conception removed from the cervix. The estimated blood loss was less than 50 mL. All patients were discharged after the first or second postoperative day. Hysteroscopic removal of cervical pregnancy with H 2 O 2 is very useful and safe and preserves fertility.

Objectives: We wished to determine the feasibility and early safety of external beam radiation therapy (EBRT) used following balloon aortic valvuloplasty (BAV) to prevent restenosis. Background: BAV for calcific aortic stenosis (AS) has been largely abandoned because of high restenosis rates, i.e., > 80% at 1 year. Radiation therapy is useful in preventing restenosis following vascular interventions and treating other benign noncardiovascular disorders. Methods: We conducted a 20-patient, pilot study evaluating EBRT to prevent restenosis following BAV in elderly patients with calcific AS. Total doses ranging from 12–18 Gy were delivered in fractions over a 3–5 day post-op period to the aortic valve. Echocardiography was performed pre and 2 days post-op, 1, 6, and 12 months following BAV. Results: One-year follow-up is completed (age 89 ± 4). There were no complications related to EBRT. Eight patients died prior to 1 year; 5 of 10 (50%) in the low-dose (12 Gy) group and 3 of 10 (30%) in the high-dose (15–18 Gy) group. None of these 8 patients had restenosis, i.e., > 50% loss of the initial AVA gain, and only three deaths were cardiac in origin. One patient underwent aortic valve replacement and none repeated BAV. By 1 year, 3 of the initial 10 (30%) in the low-dose group and 1 of 9 (11%) in the high-dose group demonstrated restenosis (21% overall). Conclusions: EBRT following BAV in elderly patients with AS is feasible, free of early complications, and holds promise in reducing the 1 year restenosis rate in a dose-dependent fashion. © 2006 Wiley-Liss, Inc.

Background. Lamivudine has been reported to be able to stabilize liver enzyme and hepatitis B virus (HBV) replication with recurrent hepatitis that has been regarded as a frequent and major risk factor for hepatic dysfunction and chronic liver disease in renal transplant recipients. Because large number of hepatitis antigenemia patients among renal transplant patients experience recurrent hepatic dysfunction with HBV recurrence and permanent histological deterioration, preemptive or primary prophylactic use of lamivudine before transplantation may be more beneficial than a trial for the treatment of advanced hepatic dysfunction. Methods. We conducted a double arm study to compare the efficacy of lamivudine between the preemptive (HBV DNA positive) or prophylactic (HBV DNA negative) trial for the maintenance of stable liver function (n=10) and the trial for the salvage of advanced hepatic dysfunction developed after renal transplantation (n=6) in hepatitis B viremia carrier renal transplant recipients. Results. Hepatic dysfunction with recurrent HBV antigenemia developed in 11 of 36 (30.6%) hepatitis antigenemia patients with a mean duration of 8.4 months (range 5-19.4 months). In six patients treated with lamivudine after hepatic dysfunction from recurrent hepatitis B viremia, serum AST and ALT level normalized within 1 month and HBV-DNA disappeared in all cases. HBV-DNA, however, reappeared in three (50%) without any discontinuation of lamivudine. Liver biopsy revealed recurrent chronic active hepatitis with severe activity of fibrosis in four cases, cholestatic fibrosing hepatitis in one, and permanent cirrhotic change in one. In seven patients who had preemptive lamivudine treatment at 9, 6, 2, 2, 1, 0, 0 month before the transplantation, HBV-DNA had converted to negative with a mean follow up of 1.2 months (range 1-2 month) in all case. Three patients who had prophylactic trials with lamivudine have all remained HBV-DNA negative. The recurrence rate of HBV viremia in the preemptive or prophylactic lamivudine treated group is 10.0% (1/10), which is significantly lower than that (42.3%, 11/25) in the nonlamivudinetreated group. The re-recurrence rate of HBV viremia was significantly higher (3/6, 50.0%) in the reactive lamivudine treated group than in prophylactic or preemptive group (1/10, 10%). Conclusion. Although lamivudine treatment after hepatic dysfunction can be a sound conventional treatment modality, this preliminary study may suggest that preemptive or prophylactic trial of lamivudine before hepatic dysfunction might be a more effective strategy for prevention of permanent histological deterioration and recurrence of hepatitis B viremia.

A 3-year-old girl received conventional-dose external beam posterior fossa irradiation (5400 cGy in 30 fractions over 40 days) for good-risk medulloblastoma. Soon thereafter, she experienced an extraneural (occipital scar, cervical lymph nodes) and central nervous system (CNS) recurrence. Intensive cisplatin and cyclophosphamide chemotherapy led to rapid disappearance of the extraneural disease. Methotrexate was administered via a ventricular reservoir. After 2 months of chemotherapy, CNS toxicity progressed rapidly from ataxia to paraplegia to quadriplegia to central respiratory failure. Radiographic scans and autopsy material revealed brain stem necrosis. This unusual toxicity raises concern about the safety of aggressive systemic chemotherapy and intrathecal therapy, when given after conventional radiotherapy.

Patients undergoing bone marrow transplantation often receive total body or total lymphoid irradiation as part of the conditioning regimen prior to marrow infusion. The cytogenetic effects of this therapy on skin fibroblasts were studied. Fibroblast cultures from eight skin biopsies were harvested in early passages for G-banded chromosome analysis. Four biopsies were from three patients who had high-dose cyclophosphamide and total body radiotherapy; one was from within and one was from outside the radiation field of a patient who had high-dose cyclophosphamide and lymphoid radiotherapy, one was from a patient who had combination chemotherapy alone, and one was from a normal control. No abnormal mitoses were found in the control or the patient who had chemotherapy alone, and only two of 30 mitoses from skin outside the lymphoid radiotherapy field were abnormal. However, most cells (49-88%) from five biopsies within radiotherapy fields were abnormal. Typically, abnormal karyotypes were pseudodiploid and contained multiple balanced rearrangements, of which reciprocal translocations were most common. The data indicate that the radiotherapy used for bone marrow transplantation induces extensive, sustained chromosome abnormalities in vivo in skin fibroblasts.

Between November 1976 and December 1987, 84 patients with newly diagnosed acute non-lymphoblastic leukemia who had achieved complete remission underwent non T-cell depleted allogeneic bone marrow transplantation from Human Leukocyte Antigen-Mixed Lymphocyte Culture (HLA-MLC) matched sibling donors. The first 36 patients (November 1976–June 1983) were prepared with cyclophosphamide sibling donors. The first 36 patients fraction total body irradiation with 750 cGy at a dose rate of 26 cGy/minute (Group I). The next 48 patients (July 1983–December 1987) were prepared with similar chemotherapy, but received hyperfractionated total body irradiation with total 1320 cGy, 165 cGy twice a day at a dose rate of 10 cGy/minute (Group II). Patient characteristics between these two groups are similar except for the significantly older age distribution in Group II. Median follow-up of Groups I and II are 8 years and 11 months and 2 years and 3 months, respectively. The Kaplan-Meier relapse-free survival, survival, and relapse rates at 3 years are 56, 58, and 19% in Group I and 69 ( p = 0.22), 77 ( p = 0.07), and 10% ( p = 0.37) in Group II. There is no difference in the incidence of interstitial pneumonitis, viral or idiopathic, engraftment rate, or incidence of graft versus host disease (GVHD) between these two groups. The fractionated total body irradiation treated group had significantly less nausea and vomiting. Multivariate analysis shows that total body irradiation regimen is not a significant factor in regard to relapse rate, relapse-free survival, and survival.

The Children's Cancer Study Group instituted a pilot study to investigate the use of high doses of cytosine arabinoside (AraC) in the intensification phase of treatment for acute nonlymphocytic leukemia (ANLL). Patients achieving remission and not eligible for allogeneic bone marrow transplantation were treated with four doses of high-dose AraC and L-asparaginase. These drugs were repeated either on or after 28 days (q28 days), after recovery of hematologic parameters (for the first 49 patients entered onto this trial); or after 7 days (q7 days), despite dropping blood counts (for the last 53 patients enrolled). After completing an additional 3 months of intensification therapy, patients were then allocated by physician choice to either discontinue therapy or receive 18 28-day cycles of maintenance therapy, including the daily administration of 6-thioguanine. Despite three deaths associated with the toxicity of the aggressive (q7 days) AraC timing, patients receiving this approach demonstrated equal or better disease-free survival from the end of induction (55% versus 42% actuarially at 3 years [P = 0.52]). Maintenance therapy appeared to play no role in improving outcome for people who received the aggressive timing of AraC cycles. Fifty-nine percent were alive disease free actuarially at 3 years from the decision to not give maintenance therapy (n = 27) compared with 62% for those receiving maintenance therapy (n = 16; P = 0.49). On the other hand, patients who received the less aggressive AraC intensification timing (q28 days) had an improved survival rate if maintenance therapy was administered (n = 17) (65% versus 39% for patients not receiving maintenance therapy [n = 24] at 3 years [P = 0.07]). Maintenance therapy therefore may not improve outcome in patients receiving aggressive timing of high-dose AraC but may be important in less intensive postremission regimens in childhood ANLL.

This report is a 20-year follow-up of 14 patients treated with external beam craniospinal irradiation and intrathecal gold (10-45 mCi) for medulloblastoma. Six of the patients died within 2 years of treatment from persistent disease. No patients are alive without complications. Six of eight surviving patients developed arachnoiditis and cauda equina syndrome within 5 to 10 years of treatment. Seven of eight survivors developed aneurysms and/or cerebrovascular accidents 9 to 20 years after treatment. Four of the cerebrovascular events were fatal. Intrathecal gold pools in the basal cisterns and cauda equina delivering an extremely inhomogeneous dose throughout the neuroaxis. Its use is discouraged.

Effective forms of treatment for acute lymphoblastic leukemia (ALL) in childhood now result in survival rates above 70 percent at five years, but the treatments are potentially carcinogenic. To determine the magnitude of this risk and identify possible risk factors for the development of second neoplasms, we studied a large cohort of children treated for ALL. METHODS AND RESULTS. We undertook a retrospective cohort study of 9720 children who had been given a diagnosis of ALL between June 1972 and August 1988 and had been treated according to the therapeutic protocols of the Children's Cancer Study Group. The median follow-up was 4.7 years (range, 2 months to 16 years). We found that 43 second neoplasms occurred among the children in the cohort, including 24 neoplasms of the central nervous system, 10 new leukemias and lymphomas, and 9 other neoplasms. This represented a 7-fold excess of all cancers and a 22-fold excess of neoplasms of the central nervous system. The estimated cumulative proportion of children in whom a second neoplasm developed was 2.53 percent 15 years after diagnosis (95 percent confidence limits, 1.74 percent and 3.38 percent). An even higher risk, particularly of central nervous system tumors, was evident in children five years of age or less at the time of the diagnosis of ALL (P = 0.012). All central nervous system neoplasms developed in children who had previously undergone irradiation. There was no association with exposure to cyclophosphamide or anthracyclines.There is a substantial excess of second neoplasms, especially of the central nervous system, among children treated for ALL. Children five years old or younger and those receiving radiation are at higher risk, especially for second tumors arising in the central nervous system.

✓ In a randomized postoperative trial, adjuvant post-irradiation chemotherapy, consisting of nitrogen mustard, vincristine, procarbazine, and prednisone (MOPP), was tested versus radiation therapy alone for newly diagnosed medulloblastoma in patients between 1 and 21 years of age. Patients treated with irradiation plus MOPP had a statistically significant increase in overall survival rate at 5 years posttreatment compared to patients treated with radiation therapy alone (74% vs. 56%; p = 0.06, adjusted for race and gender). Although the overall study failed to show a statistically significant advantage for irradiation plus MOPP in event-free survival (p = 0.18), statistical significance was attained in children 5 years of age or older (p = 0.05). More severe hematological toxicities occurred in the group with irradiation plus MOPP; however, this hematotoxicity appeared to be tolerable and acceptable. These results suggest that patients may benefit from combined irradiation and chemotherapy following surgery for medulloblastoma.

Five cases of relapsing acute lymphocytic leukemia (ALL) presenting as an ovarian tumor have been treated at this institution, representing the largest reported series. In a review of the literature we identified 18 additional cases of ovarian leukemic relapse. Together, these 23 patients form the basis for this report. Abdominal pain is the most common presenting symptom of ovarian leukemia. An abdominal mass is usually palpable, and at least four patients had hydronephrosis. Nine patients had documented bilateral ovarian involvement; however, bilateral disease was not a poor prognostic sign. Most ovarian relapses occurred more than 36 months after the original diagnosis of ALL, with these "late" relapsers responding more favorably to treatment than "early" relapsers. Definitive statements can not be made from a retrospective review of 23 case reports; however, salpingooophorectomy had no obvious advantage over simple biopsy, and there was no obvious advantage to the routine use of radiation therapy. Most fallures in treating ovarian leukemia occurred within 2 years. Most failures were systemic rather than local, illustrating the need for aggressive multiagent systemic chemotherapy. Survival after ovarian leukemic relapse is possible, with eight of the 23 patients alive and in complete continuous remission following the ovarian relapse (median follow-up since relapse, 42 months; range, 2 to 135+ months). With the use of more intensive chemotherapy in recent protocols, the frequency of ovarian leukemic relapses appears to be decreasing. At this institution, no child with ALL diagnosed in the 1980s has subsequently developed an ovarian relapse.

Tumors originating in horseshoe kidneys are rare; only 21 cases of Wilms tumor reported in horseshoe kidneys. A seven-month-old girl with Wilms tumor arising from the isthmus of a horseshoe kidney is reported. The literature is reviewed, and surgical considerations are discussed.

Ovarian function was followed serially in a group of six postmenarcheal females after successful bone marrow transplantation (BMT). The patients were between 13 9/12 and 22 6/12 (median 16 5/12) years of age at the time of BMT and were followed a median of 20 months (range 17-45 months) posttransplantation. Two subjects received short-term high-dose cyclophosphamide combined with single-dose total lymphoid irradiation (Group I), whereas the remaining four were treated with short-term, high-dose chemotherapy plus single-dose total body irradiation (Group II). Group II subjects also received combination chemotherapy prior to BMT. One subject from Group I continues to have regular menses and normal gonadotropin levels, 36 months post-BMT. The remaining five patients have demonstrated persistently elevated plasma concentrations of LH and FSH over a 17- to 45-month period of time. None of the four patients in Group II has menstruated since undergoing BMT. We conclude that single-dose radiation combined with short-term, high-dose chemotherapy results in profound ovarian damage in the majority of young women undergoing BMT.

An infant with acute monoblastic leukemia who presented with an extramedullary mass and involvement of the bone marrow, cerebrospinal fluid, and skin is described. After achieving remission, she later developed a relapse that was isolated in the skin. Superficial electron beam irradiation to the total skin surface was administered as therapy for the relapse. She remains in remission 12 months following this treatment. The isolated nature of the skin relapse, in addition to the fact that the relapse did not involve a previously irradiated field, suggests that the skin may have harbored the leukemic cells since the time of diagnosis. Cytogenetic data is presented that lends further support to this hypothesis.

Five patients with familial erythrophagocytic lymphohistiocytosis (FEL), aged 6 weeks to 3 years, were treated with VP-16-213. The drug dosage ranged from 100 to 200 mg/m2 administered biweekly until remission was achieved, and then at 1- to 3-week intervals as maintenance therapy. Intrathecal methotrexate was given to two patients with central nervous system involvement. All patients attained remission. Systemic relapses often ensued in all patients when VP-16-213 was delayed because of myelosuppression, or after attempts to lengthen the treatment interval, but they initially responded again to a more intensive chemotherapy schedule. To date, four of the patients died from disseminated disease and terminal infections 15 to 20 months from the time of diagnosis. One child is alive and well 20 months from diagnosis. Three of the dead children had become refractory to the drug. Our observations show that VP-16-213 induces remissions and prolongs survival in FEL. However, since the patients eventually become refractory to the drug and die of the disease, additional forms of therapy are required to improve the outlook of affected children.

A nine-year-old black girl with essential thrombocythemia developed hemoptysis. Only two other cases in the English literature have been described. Ultrastructure and functional characteristics of this patient's platelets were studied. Twenty-six percent of the patient's platelets were very large (megathrombocytes). Spontaneous aggregated from the patient's platelets were not compact, and the pseudopods did not interdigitate. Both qualitative and quantitative defects in platelet organelles were detected. The microtubular system was faulty in organization. Furthermore, the number of granules (especially alpha granules) was reduced. Platelet aggregation studies demonstrated subnormal aggregation in response to ADP, epinephrine, and collagen, but aggregation with ristocetin was normal. It is postulated that a platelet membrane abnormality may be the cause of their defective platelet aggregation.

Testicular function was assessed in eight males who had undergone bone marrow transplantation (BMT) during or shortly after puberty. Their ages ranged between 10 years, 10 months and 17 years, 3 months (median, 13 years, 7 months) at the time of BMT, and they were followed 13 to 77 months (median, 36 months) posttransplantation. Therapy for BMT consisted of high-dose, short-term chemotherapy either alone (Group I) or in combination with single-dose irradiation, total lymphoid (Group II) or total body (Group III). Subjects in Group III had all received combination chemotherapy prior to BMT. Hormonal and clinical evidence of germ-cell dysfunction was common in that 6 patients manifested elevated plasma levels of follicle-stimulating hormone (FSH), and four subjects were found to have a subnormal testicular volume. Of the six patients with abnormal FSH values, four were followed serially, and all showed normalization over time. Leydig cell function was less impaired in that seven of the eight patients produced normal adult male levels of testosterone, including three subjects with elevated luteinizing hormone (LH) levels. All eight developed normal adult male secondary sexual characteristics. It is concluded that the therapy utilized for BMT causes damage primarily to germinal epithelium which appears amenable to recovery. This may be due, in part, to the use of single dose rather than fractionated radiation.

A preparative regimen, consisting of total lymphoid irradiation and cyclophosphamide, was utilized in 40 patients with severe aplastic anemia undergoing allogeneic marrow transplantation. This regimen was successful in decreasing rejection in these previously transfused patients, as only one patient rejected the marrow graft. Twenty-nine of the 40 transplanted patients are surviving from 1.5 to 59 mo, with a median follow-up of 24 mo. The actuarial survival rate for these heavily transfused patients with aplastic anemia is 72% at 2 yr. This preparative regimen is extremely effective in decreasing rejection following transplantation for severe aplastic anemia. Future efforts in this area must be aimed at the elimination of graft-versus-host disease and control of fatal infections.

Advances in both allogeneic marrow transplantation and conventional therapy for acute leukaemia have complicated the choice between bone marrow transplantation (BMT) and other remission treatment options. Because older patients may be more susceptible to BMT-related complications, this study analysed the effect of age on clinical outcome for 149 patients with acute leukaemia in remission receiving allogeneic BMT. Overall projected relapse-free survival at 3 years post-transplant is equivalent for 48 adults (18 years or older) and 101 children (less than 18) at 45.4% (31.1-59.6; 95% confidence interval) and 39.9% (30.1-49.7; 95% C.I.), respectively. Among 73 patients with acute lymphocytic leukaemia (ALL) 35.3% of adults and 30.1% of children survive relapse-free at 3 years. Cox multiple regression analysis demonstrated that higher diagnostic white count, but not pre-transplant extramedullary leukaemia, remission number, or age, was important as an independent adverse clinical prognostic factor for patients with ALL. Overall outcome was better for 76 patients with acute myeloid leukaemia (AML) with 51.6% of adults and 52.9% of children surviving relapse-free at 3 years post-transplant. Cox multivariate regression analysis identified first remission status and lower white cell count, but not patient age, as independent predictors of improved relapse-free survival for AML patients. Adults had greater transplant morbidity, predominantly related to a higher incidence of acute graft-versus-host disease (GVHD), resulting in longer hospital stay. Survival at 100 d, long-term survival and clinical performance status were similar in both age groups. These data suggest that results of allogeneic BMT for adults with acute leukaemia compare favourably with those found in children and are superior to most reports of conventional chemotherapy. Allogeneic BMT remains a reasonable option for remission acute leukaemia patients up to the age of 45.

Thyroid function was measured serially in 28 children with Hodgkin disease diagnosed from 1971 to 1978. The patients' ages ranged from 4 to 16 years at diagnosis, and treatment consisted of chemotherapy only (four patients), radiation alone (15), or radiation plus chemotherapy (nine). None of the four children given chemotherapy only developed thyroid hypofunction, in contrast to 21 (88%) of the 24 children given high doses of radiation (P less than 0.001). Thyroid function in three patients with compensated hypothyroidism and in one child with primary hypothyroidism reverted to normal without thyroid replacement. One child given chemotherapy only and one child given radiation only became transiently hyperthyroid. These results indicate that patients given combined modality therapy for Hodgkin disease are at high risk for thyroid abnormalities. The results of long-term follow-up of thyroid function demonstrate, however, that all such thyroid abnormalities may not necessarily be permanent.

Seven children with advanced nasopharyngeal carcinoma younger than 20 years of age diagnosed between 1975 and 1986 (inclusive) were treated with a uniform adjuvant chemotherapy regimen, which consisted of vincristine (1.5 mg/m2; day 1), doxorubicin (45 mg/m2; day 1), 5-fluorouracil (8 mg/kg; days 1 through 5), and cyclophosphamide (7 mg/kg; days 1 through 5). This combination chemotherapy was given for 12 to 24 months after completion of radiation therapy. The radiation doses to the primary sites ranged from 6000 cGy to a maximum of 6800 cGy. The radiation doses for neck prophylaxis ranged from 4500 cGy to a total of 5000 cGy. Involved sites were irradiated to at least an additional boost of 1000 cGy. One patient had an external dose 6000 cGy to the primary site boosted with brachytherapy of 3000 cGy at the surface of an ovoid. After chemotherapy myelosuppression occurred in all patients and was tolerable. All seven patients are surviving, six disease-free, for 22 months to 12 years (median, 4 years). This study suggests that the combination of radiation therapy and chemotherapy as used here has acceptable toxicity and is effective and further suggests that children with nasopharyngeal carcinoma, even in its advanced stage at diagnosis, may be curable.

The clinical and histopathologic findings in eight cases of malignant lymphoma of the skin in children are presented. All patients had skin lesions as a primary manifestation of the disorder. Three patients had simultaneous regional lymph node involvement documented by the findings of subsequent biopsies. The majority (five patients) had solitary nodules involving the skin of the head and neck region. Three of the skin biopsy specimens were classified as lymphoblastic lymphoma, two large cell lymphoma, two mixed small and large cell lymphoma, and one small cleaved cell lymphoma. Disseminated disease subsequently developed in four patients in an interval that ranged from 4 to 30 months after diagnosis. The follow-up period ranged from 8 to 56 months, and median survival was 56 months. A literature review of 33 previously reported patients and our eight patients indicate that: (1) skin of the head and the neck region is the most common site of involvement (56%); (2) the majority of lymphomas are diffuse (93%); (3) lymphoblastic lymphoma is the predominant type (53%), with a high proportion showing a non-T-cell phenotype; (4) Burkitt's lymphoma and Hodgkin's disease of the skin are extremely rare; and (5) most patients presented in an early clinical stage (Stage IE 56%, Stage IIE 21%), and prolonged disease-free survival was seen mostly in Stage I patients. The cumulative probability of survival for Stage I patients at 24 months was 0.71; while for Stages II to IV patients combined, it was 0.33 at 26 months. Cancer 59:1040-1045, 1987.

Fifteen patients with acute lymphocytic leukemia (ALL) in second or subsequent remission received intensive therapy with cyclophosphamide and single dose, rapid rate (26 cGy/min) total body irradiation (TBI) followed by bone marrow transplantation (BMT) from a histocompatible sibling match. Outcome was compared to that of 23 conventionally treated control patients in second ALL remission who presented to the same institution during the same time period but had no available transplant donor. The 15 BMT patients and 23 control patients had similar characteristics, with the exception that the BMT patients were significantly older at the time of ALL diagnosis (12.6 yr versus 5.7 yr, p = 0.01). BMT patients had a significantly increased chance of remaining disease-free for 36 mo from time on study (43% actuarial versus 5%, p = 0.004) and a greater overall survival rate at 48 mo (47% actuarial versus 9%, p = 0.27) than the conventionally treated patients. In all, 5 of the bone marrow transplant patients (33%) remain alive and free of disease 24–48 + mo from transplantation. Several pre- and posttransplant characteristics were analyzed to determine predictive factors for a successful BMT outcome for patients with ALL in second or subsequent remission. Significant risk factors for predicting leukemic relapse included initial white blood count (WBC) greater than 50,000/microliters at ALL diagnosis (100% relapse rate versus 37% for patients with lower WBCs, p = 0.001) and presence of any extramedullary disease pre-BMT (100% relapse rate versus 37% for patients without extramedullary disease, p = 0.03). All 5 disease-free BMT survivors had initial WBCs less than 50,000/microliters and no evidence of extramedullary disease pretransplantation. Maintenance chemotherapy with 6-mercaptopurine (6MP) and methotrexate was given to four patients starting 100 days after bone marrow transplantation. Use of maintenance chemotherapy was associated with a significantly increased chance of remaining disease free (100% of patients surviving leukemia-free versus 17% for patients not receiving maintenance chemotherapy, p = 0.02). Presence of graft-versus-host disease (GVHD) did not influence leukemia-free survival. These results confirm that intensive therapy followed by bone marrow transplantation is the treatment of choice for patients with ALL in second or subsequent remission who have a histocompatible sibling match. Furthermore, the data suggest that a controlled trial to evaluate the efficacy of maintenance chemotherapy post-BMT for ALL patients is warranted.

An apparently normal 13-year-old girl developed multiple severe complications over several years after radiation therapy for Stage IIB Hodgkin's disease, including hypothyroidism, esophageal stenosis, restrictive lung and pericardial disease, extrahepatic biliary fibrosis, and sudden death presumed secondary to a myocardial infarction. Cultured skin fibroblast cells from the patient exhibited marked sensitivity to gamma radiation in vitro. The D0 of the radiation survival curve (the inverse of the straight line portion of the curve and that dose of radiation which theoretically leads to one lethal hit per cell) was 89 cGy, compared to a mean D0 for nine normal individuals of 155 cGy, and 85 cGy for two patients with the radiation sensitive disease ataxia-telangiectasia (AT). Profound clinical heterogeneity in response to cancer therapeutic agents may exist, with some individuals who show no signs or symptoms of DNA repair deficiency (for example, as is manifested by individuals with AT) exhibiting marked in vivo and in vitro sensitivity to certain DNA-damaging agents.

In two patients fatal veno-occlusive disease of the liver developed after bone marrow transplantation for underlying malignancies. Both had received significant pretransplant chemotherapy, including cystosine arabinoside, and total body irradiation. The diagnosis of veno-occlusive disease should be considered in patients in whom hepatomegaly, ascites and deteriorating liver function tests develop after they have received cancer chemotherapy.

Neutrophil engulfment by megakaryocytes was observed within 20 to 30% of megakaryocytes from two children: one with metastatic rhabdomyosarcoma, the other with fever of unknown origin. Other cell types and neutrophil precursors were not observed within megakaryocytes. Only late megakaryocytes were involved in the process, and often these cells appeared vacuolated or degenerating at the light and electron microscope level. Ultrastructurally the engulfed neutrophils were intact and were within the open canalicular system of the megakaryocyte cytoplasm. No evidence of neutrophil granule exocytosis could be demonstrated in ultrastructural morphologic and peroxidase preparations; however, many neutrophils appeared to be endocytosing portions of the megakaryocyte cytoplasm. The phenomenon could not be transferred to normal marrow incubated with patient serum or plasma. Thus, our patients differ from previous observations of emperipolesis in: 1) the extreme frequency of the observation; 2) the selective involvement of neutrophils; and 3) the association of the anomaly with dysmorphic and/or disrupted megakaryocytes. These observations are consistent with a neutrophil response to altered and/or injured megakaryocytes.

Two girls, each less than 2 yr of age, developed acute megakaryoblastic leukemia (malignant myelosclerosis). Both presented with anemia, severe thrombocytopenia, and a low percentage of blasts in their peripheral blood. Their marrow showed marked reticulin fibrosis with an increase in blasts and immature megakaryocytes. The blasts stained negatively for myeloperoxidase and Sudan Black B, but showed acid phosphatase (ACP) and alpha-naphthyl acetate esterase (ANAE) activity inhibitable by sodium fluoride. They were identified as megakaryoblasts by the platelet peroxidase reaction. Cytogenetic studies showed multiple chromosomal abnormalities in both cases. Chemotherapy with vincristine, prednisone, and L-asparaginase was without effect, while daunorubicin and cytosine arabinoside induced a complete remission in one case. The second case responded to a combination of cytosine arabinoside, daunorubicin, and 6-thioguanine. This article documents that acute megakaryoblastic leukemia occurs in early childhood and describes its clinical, pathologic, and cytogenetic features. Previous reports of childhood “myelofibrosis” are reviewed, and their possible relationship with acute megakaryoblastic leukemia is discussed.

Acute graft-versus-host disease is a major problem in allogeneic bone-marrow transplantation. We performed a randomized study to compare the effectiveness of two regimens in the prevention of acute graft-versus-host disease. Thirty-five patients received methotrexate alone, and 32 received methotrexate, antithymocyte globulin, and prednisone. Of the patients who received methotrexate alone, 48 per cent had acute graft-versus-host disease, as compared with 21 per cent of those who received methotrexate, antithymocyte globulin, and prednisone (P = 0.01). The age of the recipient was a significant factor in the development of acute graft-versus-host disease: Older patients had a higher incidence of the disease (P = 0.001). We conclude that the combination of methotrexate, antithymocyte globulin, and prednisone significantly decreased the incidence of acute graft-versus-host disease and should be used to prevent this disorder in patients receiving allogeneic marrow transplants.

Thyroid function studies were followed serially in 27 long-term survivors (median 33 months) of bone marrow transplantation. There were 15 men and 12 women (median age 13 1/12 years, range 11/12 to 22 6/12 years). Aplastic anemia (14 patients) and acute nonlymphocytic leukemia (eight patients) were the major reasons for bone marrow transplantation. Pretransplant conditioning consisted of single-dose irradiation combined with high-dose, short-term chemotherapy in 23 patients, while four patients received a bone marrow transplantation without any radiation therapy. Thyroid dysfunction occurred in 10 of 23 (43 percent) irradiated patients; compensated hypothyroidism (elevated thyroid-stimulating hormone levels only) developed in eight subjects, and two patients had primary thyroid failure (elevated thyroid-stimulating hormone levels and low T4 index). The abnormal thyroid studies were detected a median of 13 months after bone marrow transplantation. The four subjects who underwent transplantation without radiation therapy have remained euthyroid (median follow-up two years). The only variable that appeared to correlate with the subsequent development of impaired thyroid function was the type of graft-versus-host disease prophylaxis employed; the irradiated subjects treated with methotrexate alone had a higher incidence of thyroid dysfunction compared to those treated with methotrexate combined with antithymocyte globulin and prednisone (eight of 12 versus two of 11, p less than 0.05). The high incidence and subtle nature of impaired thyroid function following single-dose irradiation for bone marrow transplantation are discussed.

Allogeneic bone marrow transplantation was performed in 10 patients with disseminated Burkitt's lymphoma or poor-prognosis T-cell lymphoblastic lymphoma. All patients received a cytoreduction regimen consisting of cyclophosphamide, cytosine arabinoside, bis-chloro-nitroso-urea, and total-body irradiation. Eight patients received marrow from HLA-matched sibling donors. One patient received marrow from a parent donor and one patient died during initial cytoreduction and did not undergo total-body irradiation or marrow infusion. Six patients had Burkitt's lymphoma stages III and IV at diagnosis, and three of the six are alive at 18, 28, and 73 months. Four patients had T-cell lymphoblastic lymphoma, stages III and IV at diagnosis, and two of the four are alive at 29 and 49 months. Overall survival in the nine patients who underwent transplantation is 56 percent by life-table analysis. Follow up for the surviving patients ranges from 18 to 73 months (median 29 months). All five survivors are at home with unmaintained remissions.

An afterloading brachytherapy device for treatment of residual cancer in an enucleated orbit with two cesium-137 sources was designed using a thermoplastic material, Aquaplast. The device consists of a face-mask support held in place with elastic bands around the head and an acrylic afterloading applicator. The device is very easy to make, holds the sources firmly in place, allows full mobility of the patient, and gives excellent dose distribution to the target area. It was easily tolerated by a 7-year-old child during the 50 h of treatment.

Between August 1978 and November 1981, 33 boys with acute lymphocytic leukemia (ALL) (26 non-T, 7 T-cell) younger than 16 years underwent bilateral wedge testicular biopsies at the time of initial diagnosis. Seven (4 non-T, 3 T-cell) demonstrated focal leukemic infiltrates. Rebiopsy after successful induction therapy without testicular irradiation showed eradication of leukemic infiltrates in five, persistent focal infiltrates in one, and a diffuse infiltrate in one. The two patients who had persistent leukemic involvement had a T-cell phenotype, and in one of them overt testicular disease developed 2 years later. All 33 patients were followed prospectively for a minimum of 3 years. Fifteen (14 non-T, 1 T-cell) remained in remission for 3 years and underwent another testicular biopsy before the cessation of therapy. Two patients, both non-T and both of whom were free of testicular involvement at diagnosis, showed testicular infiltrates at that time. Of the seven boys with positive specimens at diagnosis, only two remained disease-free for 3 years and showed no testicular involvement upon the completion of chemotherapy. In this study, microscopic testicular involvement by lymphoblasts occurred in 21% of newly diagnosed boys with ALL; this occurred only if the leukocyte count exceeded 25,000/microliter. These patients in general had a poor prognosis, probably reflecting the overall heavy tumor burden. However, it was not possible to predict accurately those patients who would have leukemic testicular infiltrates at the cessation of chemotherapy by performing biopsy of the testes at the time of initial diagnosis or after induction therapy.

Total lymphoid irradiation (TLI) is immunosuppressive and, in rodent, can induce a state where transplantation of allogeneic bone marrow results in chimerism and permanent acceptance of organ allografts from the donor strain. We attempted to apply this treatment to a large animal model. Twelve splenectomized dogs were treated with TLI (150 rads per fraction, total dose 1950-3000 rads) before bilateral nephrectomy and renal allotransplantation. Eight dogs received bone marrow from the kidney donor. In 13 untreated control dogs renal allografts functioned (serum creatinine level less than 2.0 mg/dl) for a mean +/- (SE) of 4.7 +/- 0.3 days. In the four TLI treated dogs who did not receive bone marrow the renal allografts functioned for 15-76 days (two dogs died with functioning grafts). In the eight TLI treated dogs who received donor bone marrow, two died immediately after transplantation, two rejected at 3 and 13 days, one died at 13 days with a functioning graft, and two have had the grafts function for longer than 500 days. Chimerism was not detected in the one dog tested. The response of peripheral blood lymphocytes to stimulation with phytohemagglutinin and in mixed lymphocyte culture was suppressed for at least on month after TLI. The results confirm the immunosuppressive effect of TLI. The absence of kidney rejection in two recipients of donor bone marrow show the potential of this approach to induce long-term immunologic unresponsiveness as to an organ allograft, but the outcome is unpredictable and further experiments are needed to define the optimal conditions for administration of TLI and bone marrow to the recipients.

Naproxen was used as an antipyretic agent in febrile pediatric cancer patients with evidence of active malignant disease. Sixteen children with leukemia and lymphoma who had fever for more than 72 hours were given naproxen to control fever. Their ages ranged from 16 months to 17 years. There were ten female and six male patients. Their temperature was greater than 38.3 degrees C and the leukocyte count ranged from 400/microliters to 33.3 X 10(3)/microliters, with an absolute neutrophil count (ANC) from 0 to 4514/microliters. The children had no evidence of infection by clinical or laboratory evaluations. All patients were receiving triple antibiotics when naproxen was started. Fourteen patients responded to naproxen with complete lysis of fever within 6 hours of initiation of treatment. Two patients did not respond to naproxen, but proved to have culture-positive infections. There were no side effects from the drug. Naproxen is an effective antipyretic in patients with cancer. It may be useful as a means of differentiating fever secondary to active malignant disease from that due to infection.

As CrlILDRBN with acute lYmphocytic leukem!a survive longer, leukemic involvement of the testes is being recognized more frequently 1-3 and testicular biopsy, even in asymptomatic patients, is being performed on a routine basis. '-5 However, leukemic involvement of the ovaries has received little attention, and the significance of ovarian-associated relapse in relation to the eventual outcome of the patient has not been investigated. We describe two female patients with ALL who completed three years of chemotherapy. Both developed ovarian-related relapses after cessation of therapy.

Purpose Patients with non-Hodgkin's lymphoma who fail to achieve a complete remission or who relapse are rarely cured with conventional therapies. For this group of patients, intensive therapy and bone marrow rescue may be curative. Our goal was to assess the effects of autologous transplantation in patients with B-cell lymphomas and a poor prognosis. To avoid occult or overt contamination with lymphoma, monoclonal antibodies BA-1, BA-2, and BA-3 were used for ex vivo marrow treatment. Patients and methods Seventeen patients underwent intensive therapy and autologous bone marrow transplant using the forementioned marrow. Ten of the 17 patients (Group I) had disease that was in complete or partial remission. The other seven patients either had disease that was not responsive to treatment or had bone marrow transplant as their initial therapy at relapse. Results The ex vivo treatment did not adversely affect engraftment. For those patients who could be evaluated, the median time to white cell engraftment was 24 days; the median durations of red cell and platelet support were 24 and 29 days, respectively. Eleven of the 17 patients had complete remissions at the evaluation 28 days after transplant. Three patients subsequently experienced a relapse, three died while their disease was in complete remission, and five are alive and disease-free 405 to 1,674 days after transplant. Group I patients had an estimated 40 percent disease-free survival rate at three years compared with 0 percent for Group II patients (p Conclusion Our data support autologous bone marrow transplantation as an important treatment modality for the non-Hodgkin's lymphomas. With the current preparative regimens available, however, its use should be limited to patients with disease that is still responding to conventional therapies.

Nine children with various hematologic disorders underwent bone-marrow transplantation following total-body irradiation with 750 rads at a rate of 26 rads/min. from a 13-MeV linear accelerator in conjunction with cytotoxic drugs. This treatment was tolerated reasonably well, with acceptable side effects. Three patients were alive and well at 18, 11, and 7 months post-transplantation at the time this paper was written.

• A baby born after a cesarean section experienced transient respiratory depression. The mother had a postsuccinylcholine apnea caused by homozygosity for the atypical allele for serum pseudocholinesterase; the baby was heterozygous for this allele and the usual allele for serum pseudocholinesterase. The possible relationship between the genotype of the baby and the respiratory difficulty at birth is raised. ( Am J Dis Child 133:825-826, 1979)

Between 1979 and 1985, nine children with recurrent CNS leukemia who had previous radiation of more than 1800 cGy to the brain were treated with intermittent central nervous system irradiation and intrathecal chemotherapy (IIIC). There was no isolated CNS recurrence. Three patients died; one from generalized recurrent disease, two from complications associated with bone marrow transplantation. Six patients are alive without evidence of disease between 9 years and 2sol412 years from the diagnosis of recurrent CNS leukemia. This experience suggests that 111C may be an effective treatment for preventing the recurrence of CNS leukemia with minimal side effects.

The intratissue pH of SCK tumor and leg muscle of unanesthetized mice were determined byfore, during and after hyperthermia with the use of bulb type pH microelectrodes having pH-sensitive hemisphere 20–40 μm in outer radius. Intratumor pH was heterogeneous throughout tumor (range, 6.60–7.38; average, 6.96), and was more acidic than the intramuscle pH of mouse leg (average, 7.46). Hyperthermia at 43.5°C for 30 min induced a further increase in acidity (decrease in pH of about 0.2 units) in tumor hut not in muscle. The heat-induced acidity in tumor lasted for 12 hr following hyperthermis and then recovered to almost control pH value 24 hr after heating. The cause of the increase in acidity in the bested tumors is not clear, hut it appears to result from an increase in the contents of acidic metabolities and a sluggish drainage of them due to induced vascular damage. The increased acidity in the heated tumors may inhibit the repair of thermal damage and sensitizes the tumor cells to subsequent heating.

Six patients with aplastic anemia underwent bone marrow transplantation following conditioning with high dose cyclophosphamide and single dose total lymphoid irradiation with 750 rad, 26 rad/min at the midplane of the patient. They all received bone marrow from human leukocyte antigens/mixed lymphocyte culture (HLA/MLC) matched siblings. Five of 6 patients were alive without complications at 12, 11, 7, 4 and 4 months respectively. The remaining patient died from sepsis which he had prior to transplantation. There were no graft rejection, graft-vs-Host Disease (GVHD) or interstitial pneumonitis among these patients. The procedure was well tolerated with minimal side effects. The results will be compared with those of groups whose bone marrow was previously transplanted with different immunosuppressive methods.

recurrent pulmonary infections. The facial features included coarse eyebrows, upturned nose, and micrognathia. At first, we assumed that the child had the MarshallSmith syndrome, but the patient had no phalangeal abnormalities at 19 months. In addition to these features, the patient had mild camptodactyly, limited motion of the knees, and wide distal ends of the long bones. The facial features also included a large bifrontal diameter, fiat occiput, ocular hypertelorism, and a small fish-like mouth, features found in the Weaver-Smith syndrome. Furthermore, the patient had behavioral characteristics similar to those of patients reported by Weaver and his associates, z The child was shy toward strangers, and tilted her head downward in viewing her environment. The serum amino acid studies showed a moderate decrease in the levels of glycine, alanine, and lysine. She did not have excessive postnatal growth. Since this patient has features thought to discriminate between the Marshall-Smith syndrome and the Weaver-Smith syndrome, we assume that these syndrome are morphologic variants of a single entity.

Ovarian function was followed serially in a group of six postmenarcheal females after successful bone marrow transplantation (BMT). The patients were between 13 9/12 and 22 6/12 (median 16 5/12) years of age at the time of BMT and were followed a median of 20 months (range 17-45 months) posttransplantation. Two subjects received short-term high-dose cyclophosphamide combined with single-dose total lymphoid irradiation (Group I), whereas the remaining four were treated with short-term, high-dose chemotherapy plus single-dose total body irradiation (Group II). Group II subjects also received combination chemotherapy prior to BMT. One subject from Group I continues to have regular menses and normal gonadotropin levels, 36 months post-BMT. The remaining five patients have demonstrated persistently elevated plasma concentrations of LH and FSH over a 17- to 45-month period of time. None of the four patients in Group II has menstruated since undergoing BMT. We conclude that single-dose radiation combined with short-term, high-dose chemotherapy results in profound ovarian damage in the majority of young women undergoing BMT.

• Malignant histiocytosis developed in a 19-year-old boy 3½ years after the initial diagnosis of lymphoblastic lymphoma of T-cell origin. The experience with this young adult suggests that a close surveillance of the survivors of lymphoma is mandatory, and a prompt biopsy of enlarged lymph nodes in patients treated for lymphoma should be a routine procedure. (Am J Dis Child1983;137:474-476)

Between November 1976 and December 1980, a total of 18 patients with acute nonlymphocytic leukemia (ANLL) underwent bone marrow transplantation during initial remission. There were ten males and eight females, age ranged between 6 years and 28 years with median age of 14.5 years. These patients were conditioned with high dose cyclophosphamide (60 mg X Kg. I.V.) for two consecutive days followed by total body irradiation with 750 rads, 26 radsl min. to the midplane of the patient by 10 Mv linear accelerator. Individual tissue compensators to head and neck, lung and lower extremity were used for all oatients to imorove dose homoaeneitv. Follow UD time ranqes between 53 months and 3 months with a median-of 13"months. Four patients developed acute graft versus host disease (GVHD) and one patient developed chronic GVHD. Two patients developed interstitial pneumonitis. Two oatients relapsed at 24 months and 6.5 months resoectivelv. There was no rejection. Time to engraftment was between I7 days and 43-days with a median of 23 days. Four patients died, one from relapse, two from sepsis and interstitial pneumonitis and one from GVHD and sepsis. Thirteen patients (72%) are surviving free of disease with median follow up time of 13 months. Preliminary results indicate that conditioning with total dose of 750 rads in combination with cyclophosphamide is an acceptable method for bone marrow transplantation in ANLL and provides less discomfort to the patients.