Milton H. Donaldson

Paratesticular rhabdomyosarcoma in childhood.

The paratesticular region was the primary site in 20 of 289 children (7%) entered on the Intergroup Rhabdomyosarcoma Study. The 20 patients were 1.7‐ to 19‐years‐old at diagnosis. Fifteen underwent retroperitoneal node dissection (12) or biopsy (3), and 6/15 (40%) had nodal involvement by tumor. Nineteen of the 20 patients had no gross local or metastatic disease after surgery. All 20 received chemotherapy, and 13 also received radiotherapy. Treatment was effective: 16 of 18 evaluable patients (89%) were free of disease at a median of 23 months from diagnosis (range, 8–43 months). Since the incidence of tumor‐involved retroperitoneal nodes is high, a dissection should be performed. If the nodes are free of tumor, retroperitoneal radiotherapy may not be necessary. Reduction of morbidity in patients with paratesticular rhabdomyosarcoma is desirable, because the disease has a good prognosis.

Extremity lesions in the intergroup rhabdomyosarcoma study (IRS-I): A preliminary report

The sites in which rhabdomyosarcoma occurs most frequently in children and young adults are the head and neck, genitourinary tract, and the extremities. Among these three sites, tumors of the extremities have been associated with the highest relapse rate and lowest survival rate in patients treated by protocols of the Intergroup Rhabdomyosarcoma study (IRS). In five of six patients treated by primary extremity amputation, tumor recurred. Seven of 21 patients in Clinical Group I (completely resected tumors), and 9 of 27 patients in Clinical Group II (patients with gross tumor excision but positive lymph nodes, “microscopic residual” disease, or extension beyond the muscle of origin) had relapses. Thirteen of 18 patients (72%) in Clinical Group III (gross residual disease) responded to a chemotherapy‐radiotherapy regimen, but ten have subsequently had relapses; and 13 of 18 are dead. Of 30 patients in Clinical Group IV (disseminated disease on entry), 15 initially responded to chemotherapy, but 25 of 30 are dead. The period of surveillance is 21/2 years, with a mean of 46.3 months at last examination. Increased rates of relapse were seen in patients with extremity tumors, as opposed to tumors in other sites, irrespective of the specific IRS chemotherapy‐radiotherapy regimen employed. In Clinical Group I (nonamputation), relapse rates by histologic subtype of rhabdomyosarcoma were alveolar subtype, 5/8; embryonal, 1/7; and all other subtypes, 1/6. In Clinical Group II, relapse rates were alveolar, 6/12; embryonal, 5/11; all other subtypes, 3/10.

Platelet function in recipients of platelets from donors ingesting aspirin.

Abstract The effect of fresh platelet transfusions from donors ingesting aspirin was evaluated in a group of thrombocytopenic recipients. Prolonged bleeding times were corrected to normal in recipients of platelets from donors who had taken aspirin 36 hours before donation, but not in those receiving platelets from donors who had taken aspirin within 12 hours of donation. In healthy volunteers, the abnormalities induced by aspirin ingestion on the bleeding time and epinephrine-induced platelet aggregation disappeared by 72 hours after ingestion. Analysis of the data indicates that when approximately 20 per cent of the circulating platelets have not been exposed to aspirin, the hemostatic function of the platelet pool is maintained. Thus, widespread use of aspirin should not present a serious problem in the selection of platelet donors.

Severe cyclophosphamide hemorrhagic cystitis controlled with phenol

Abstract Cyclophosphamide (cytoxan) is an alkylating agent used extensively in the chemotherapy of leukemia, lymphomas, and selected solid tumors. Experimentally, cyclophosphamide is currently used for the treatment of steroid-resistant nephrosis in children. The drug is inert as administered orally or systemically but is metabolized to form a potent cytotoxic agent that is excreted in the urine. Adverse reactions include leukopenia, anorexia, nausea, vomiting, alopecia, vesical fibrosis, and sterile hemorrhagic cystitis. It is this last complication that may reach such severe proportions that hemorrhage cannot be controlled by conventional means. The usual cyclophosphamide cystitis is characterized by dysuria, urgency, and gross or microscopic hematuria. Approximately 7% of patients undergoing cyclophosphamide therapy develop this complication. 1,2 Cystoscopically, the bladder appears edematous and hyperemic, with multiple punctate hemorrhagic areas. Histologically, telangiectasia of subepithelial blood vessels can be found. In the great majority of cases a spontaneous remission of the hemorrhage will result with cessation of the drug and forced hydration, 3–8 but occasionally more aggressive measures must be taken to control the bleeding. Local fulgeration with the resectoscope or ball-tip electrode is usually unsuccessful, probably due to the further local mucosal breakdown with the fulgerating current. Suprapubic placement of a cystostomy tube will make irrigations more effective. Bilateral ureteral catheterizations or nephrostomies may be used to divert the cytotoxic urine. Division of the hypogastric vessels is ineffective. Unfortunately, urinary diversion into an ileal conduit may be the only means of control for this severe complication. 9–11

Bone Marrow Necrosis in Children Three Instances

Divisions of Hematology and Oncology, The Children’s Hospital of Philadelphia and Department of Pediatrics, Thomas Jefferson University, Philadelphia, Pa. Correspondence to: Thomas R. Kinney, M.D., Division of Hematology, Children’s Hospital of Philadelphia, Civic Center Boulevard, Philadelphia, Pa. 19104. NE OF THE MOST stressful complaints for both physician and parents is that of bone pain which the child can only vaguely describe and poorly localize. This complaint is often attributed to &dquo;growing pains&dquo; and the child is dismissed with no more investigations than the physical examination. Obviously, there may be many causes of such a complaint, from psychosomatic to organic. When encountered, the symptom requires a thoughtful exploration of the patient’s entire circumstances, including the family situation, the school environment and, certainly, the various organic possibilities. One of the organic causes of bone pain is bone marrow necrosis, an uncommon complication of a variety of disorders including infections, hematologic disorders and malig-

Perianal rhabdomyosarcoma in childhood

The case of a child with a stage I perianal embryonal botryoid rhabdomyosarcoma is presented, with description of coordinated management utilizing local excision, irradiation, and cyclic chemotherapy resulting in a 3‐year tumor‐free survival. Previously reported pediatric cases are summarized.

The value of maintenance therapy following treatment of central nervous system leukemia

The efficacy of intrathecal (IT) maintenance chemotherapy following central nervous system (CNS) leukemia was demonstrated in a retrospective study of 77 such episodes. The median durations of CNS and bone marrow (BM) remissions were significantly longer for the 41 maintained episodes (10+ and 9.5 months, respectively) compared with the 36 unmaintained episodes (4 and 2 months, respectively). Patients were comparable in each of these two groups. For those patients receiving maintenance therapy, there appeared to be an advantage in using four or more doses of IT medications for treatment of CNS leukemia, regardless of the number of doses necessary to clear the cerebrospinal fluid (CSF).

Endodermal Sinus Tumors in Childhood: A Review and Report of Two Good Responses to Combined Radiation and Chemotherapy

From: the Departments of Oncology and Surgery Children’s Hospital of Philadelphia. WO GIRLS with endodermal 1 sinus tumors were seen at the Children’s Hospital of Philadelphia within the same year. Little information could be found on treatment, and there were many names for what seemed to be a single entity. This paper has been written in an attempt to clarify some of this confusion, and to describe the two girls, both of whom responded to therapy much better than expected.

576 EPIDEMIOLOGY OF SIDS: TWO POPULATIONS AT RISK?

Descriptive epidemiologic studies of Sudden Infant Death Syndrome (SIDS) have not helped elucidate possible causes but have defined population characteristics that must be addressed by prospective theories. Many such studies have had poorly defined populations. Careful pathologic and statistical studies are still needed to characterize this population. In New Jersey, 826 infants died of SIDS from 1/1/76 to 12/31/81. A State law mandating autopsies in such cases has led to an autopsy rate in excess of 98%. A match of birth and death certificates was available for 767 such deaths over this six-year period. Significant findings included the peak age at death between 1 and 2 mo. and a mean age at death of less than 2 mo. The incidence of SIDS in the non-white population (NWP) (3.17/1,000 LB) was significantly greater than in the white population (WP) (0.89/1,000 LB). The male predominance was present in the WP (250 males/388) but not in the NWP (189 males/379). The well-described seasonal variation was noted but was entirely explained by a significant increase only in the males. Significantly more children ≥3 mo. of age died in the winter months. This was not true of infants <3 mo. of age at the time of death. This analysis suggests that victims of SIDS may represent two distinct populations: a group of younger infants without male predominance and a second group of older infants containing significantly more males who die in winter months when respiratory infections are more common.

650 TOXICITY IN THE INTERGROUP RHABDOMYOSARCOMA STUDY(IRS): A PRELIMINARY REPORT

To date a total of 640 patients have been registered in the Intergroup Rhabdomyosarcoma Study. Twelve early deaths have been reported. All occurred within 34 days of the start of therapy. Five had pharyngeal primaries and 2 had primaries in the maxillary sinus - all seven had Group III disease (gross residual disease). Most fatalities were associated with granulocytopenia and thrombocytopenia. Four fatalities were associated with membranous colitis at autopsy.Forty-seven of 417 evaluable patients (11%) developed hematuria. The hematuria was moderate or severe in 80% of cases. It occurred with equal frequency throughout treatment and occurred for the first time in some patients after therapy was stopped. Severe neutropenia (<500/mm3) was observed in 67% of patients in Regimen E and 72% of patients in Regimen F (Clinical Groups III and IV). Adriamycin cardiomyopathy has not been observed in this study.Since most early deaths occurred in patients with head and neck primaries, the use of less intensive initial chemotherapeutic regimens may be advisable for these patients.