A.P. Mahesh Kumar

Thoracotomy for pulmonary metastatic osteosarcoma. An analysis of prognostic indicators of survival

Removal of pulmonary metastases of osteosarcoma by thoracotomy is an accepted treatment; however, few investigators have analyzed the value of various prognostic factors in estimating survival. A review of all patients undergoing thoracotomy for recurrent osteosarcoma with pulmonary metastases treated at St. Jude Childrens Research Hospital is reported. Since 1968, two thirds (39/59) of all patients who developed pulmonary metastases have had a total of 66 thoracotomies. Nine patients are alive with no evidence of disease, and six additional patients are alive with disease. Analyzed in 39 evaluable patients, the prognostic factors that correlate with survival by univariate analysis are: sex, number of nodules detected radiographically and resected, completeness of resection, and tumor location (bilateral versus unilateral). By Cox regression analysis, only sex and the number of nodules detected either radiographically or during surgery, and resected, had statistically significant correlation with survival. Thoracotomy is curative for some patients with pulmonary metastatic osteosarcoma and Prognostic factors predictive for survival are defined. Cancer 59:374–379, 1987.

Silver Nitrate Irrigation to Control Bladder Hemorrhage in Children Receiving Cancer Therapy

Silver nitrate irrigations after cystoscopic evacuation of clots stopped intractable hemorrhage from the bladder in 8 of 9 children who had received cyclophosphamide and/or pelvic irradiation for various malignant diseases. This method of management produces fewer adverse side effects yet appears to be as effective as the more drastic measures of control, such as cystectomy or colocystoplasty.

Colorectal carcinoma in adolescents implications regarding etiology

Between October, 1974 and December, 1976, 13 adolescent patients with faradvanced, poorly differentiated colorectal carcinoma had been referred to a pediatric cancer center. All patients received chemotherapy with vincristine, methyl‐CCNU and 5‐fluorouracil. Five of 13 patients are living, one of whom remains disease‐free after 12 months of chemotherapy. Four of the patients were from urban areas and nine from rural areas. One of four from urban areas had intimate exposure to chemicals used in the production of cotton and soy beans. Eight of nine patients from rural areas also had exposure to farm or agricultural chemicals, and three of these patients were intimately involved with the spraying operations. Suggestions regarding etiology and causative factors for the development of carcinoma of the colon in adults have previously been advanced. Results of these studies suggest that alternate etiologies must be suggested for adolescent colorectal carcinoma.

Adjuvant chemotherapy for osteosarcoma of the extremity long‐term results of two consecutive prospective protocol studies

Seventy‐six patients with classic high‐grade osteosarcoma of an extremity received adjuvant chemotherapy by two protocols, initiated in 1972 and 1977, respectively, after appropriate amputations. Chemotherapy consisted of high‐dose methotrexate, doxorubicin, and cyclophosphamide. Dose intensity of high‐dose methotrexate and doxorubicin was greater for the patients treated with the protocol initiated in 1977. The proportion of long‐term disease‐free survivors on the two protocols are 46% and 56%. A better outcome (P = 0.042) was seen for the latter group, which received more intensive chemotherapy. Overall, metastases developed in 35 patients; in 19 who were receiving chemotherapy and in 16 after chemotherapy. The outcome for these two protocols, compared with two control groups that were given no chemotherapy or ineffective chemotherapy (biweekly vincristine and cyclophosphamide), confirms the results of controlled studies that showed an advantage of adjuvant chemotherapy after amputation for osteosarcoma.

Combined therapy to prevent complete pelvic exenteration for rhabdomyosarcoma of the vagina or uterus.

Three children with rhabdomyosarcoma (sarcoma botryoides) of the vagina or uterus were managed by modified radical resection combined with pre‐ and/or postoperative chemotherapy and high‐dose irradiation. This plan of therapy contrasts sharply with the conventional approach: i.e., pelvic exenteration consisting of cystectomy, hystovaginectomy, and oophorectomy, with urinary diversion by ureteroileostomy or ureterosigmoidostomy. Two patients had complete regressions of tumor following preoperative chemotherapy and irradiation. The third patient received no preoperative therapy, but was given postoperative radium implantation, irradiation, and chemotherapy. The surgical approach consisted of hystovaginectomy and oophorectomy without urinary diversion. These patients are free of tumor for 32, 44, and 54 months, respectively. There were no serious toxic reactions to the drugs, nor any significant postoperative urinary tract problems. The results reported here suggest that hystovaginectomy and oophorectomy coordinated with chemotherapy and irradiation is an acceptable alternative to pelvic exenteration in patients with sarcoma botryoides of the vagina or uterus.

Adjuvant multiple drug chemotherapy for osteosarcoma of the extremity

Results of treatment for osteosarcoma of the extremity have been poor with metastases usually causing death within 2 years following diagnosis. Because of the great risk of development of metastases, 20 patients have received adjuvant chemotherapy with Adriamycin, cyclophosphamide and high‐dose meth‐otrexate‐leucovorin rescue for up to 12 months following amputation for osteosarcoma. Sixteen of these patients are surviving; 11 are free of evident tumor from 6 to 34 months following amputation. Five patients were found to have pulmonary metastases while receiving chemotherapy and three patients developed metastases following completion of chemotherapy. One patient died following her third treatment with high‐dose methotrexate‐leucorovin rescue. Other toxicity included nausea, vomiting, mucosal ulcerations, infections, hematologic abnormalities, changes in kidney and liver functions tests, and minor coagulation abnormalities. The natural history of osteosarcoma may have been modified by the use of these agents for periods exceeding the median time to predicted detection of pulmonary metastases. Microscopic metastases of some patients were eradicated by this adjuvant chemotherapy. For patients who developed metastases, these metastases were delayed in their time of detection and in their number at the time of detection.

Acute appendicitis in children with leukemia and other malignancies: Still a diagnostic dilemma

Of 6,099 children treated for malignancy, 16 (ages 3.5 to 18 years) developed acute appendicitis between 1962 and 1989. Fourteen had leukemia (ALL 10, AML 4). One each had rhabdomyosarcoma and Ewings sarcoma. Active malignancy at diagnosis was noted in 10, 4 of whom had severe neutropenia (absolute neutrophil count less than 500/mm3). Of all the leukemics (2,794/6,099), abdominal pain during induction was a frequent complaint. The incidence of appendicitis, however, was low (0.5%). Nine of the 16 patients presented classically, facilitating prompt diagnosis and treatment. Six diagnoses were delayed. Three of these patients presented atypically with vague, nonlocalized pain, abdominal distention, lack of abdominal guarding, fever, dehydration, diarrhea, and unusual symptoms such as upper gastrointestinal bleeding. In each of these 6 patients the appendix was ruptured. Delays led to complications and deaths. Three patients required perioperative transfusions to treat excessive bleeding and two patients with ruptured appendicitis developed wound abscesses. Two patients died; in one, ruptured appendix was diagnosed only at autopsy. The other patient died of uncontrolled sepsis. Typhlitis occurring during induction chemotherapy may present similarly and is the main differential diagnosis. Typhlitis will usually improve with medical treatment alone. Nausea and vomiting (13/16), right lower quadrant pain (13/16), guarding (14/16), tachycardia (12/16), fever (10/16), and rebound tenderness (10/16) were the most frequent signs and symptoms of appendicitis. Persistent localized abdominal pain and guarding, lack of improvement with medical treatment, clinical deterioration, and the development of a mass were our indications for laparotomy. Despite major improvements in therapy, there is still a 37.5% error rate in our ability to accurately diagnose appendicitis in pediatric cancer patients.

Chest wall resection for ewing's sarcoma of the rib: an unnecessary procedure

Approximately 10% of all cases of Ewings sarcoma arise from a rib. Conventional management has included chest wall resection (3 or more ribs) and radiation therapy. These forms of therapy have led to complications such as scoliosis and local deformity. The addition of radiation therapy can result in damage to the lung and adjacent viscera and also potentiate pulmonary restrictive disease. Between 1971 and 1978, 9 patients were treated with surgery, radiation therapy, and combination chemotherapy (three- or four-drug regimen). Only 2 patients (22%) survive. Since 1979, 14 patients were entered into a new protocol consisting of sequential induction chemotherapy, followed by delayed surgical resection whenever feasible. Three patients had complete resection of their primary lesion at onset. Initially, 7 patients had either biopsy (N = 4) or incomplete chest wall resection N = 3). All 4 patients with biopsy only at diagnosis had excellent responses to induction chemotherapy, allowing delayed resection of the involved rib without chest wall resection. Overall, 12 of 14 patients (86%) treated since 1979 survive, with only 2 receiving radiation therapy for residual disease in the primary rib site.

Combined therapy for malignant tumors of the chest W all in children

Abstract Of 1168 children with malignant solid tumors who were admitted to St. Jude Hospital between 1962 and 1976, 22 (1.8%) had primary malignancies of the chest wall, excluding the mediastinum. The treatment plan for these patients varied with the resectability of the tumor, but always included chemotherapy with or without irradiation. Six children had totally resectable tumors and another two had initially unresectable tumors converted to a resectable state with preoperative therapy. All 8 patients have been disease-free for 3–90 mo (median 18.5). Of 11 children with unresectable disease, 4 remain disease-free for 7–175 mo following chemotherapy and irradiation only (3 of 9) or both modalities plus partial resection (1 of 2). The 3 remaining children received en bloc resections for recurrent rhabdomyosarcoma following chemotherapy and irradiation: 2 died at 15 and 18 mo after diagnosis and 1 remains disease-free for 13 mo. The availability of effective combined therapy methods for local control of primary tumors and prevention of metastases made possible a more conservative surgical approach for 4 of 8 patients with resectable disease and permitted conversion of initially unresectable tumors to a resectable state in 2 patients. Moreover, these measures resulted in decreased morbidity without apparent compromise of tumor-free survival. Overall, 13 of 22 patients survive without evidence of disease: 3 of 3 patients with neuroblastoma, 4 of 6 with rhabdomyosarcoma, 4 of 10 with Ewings sarcoma, 1 of 2 with osteosarcoma, and 1 patient with malignant histiocytoma.

Ultrastructure of malignant histiocytoma arising in the acromion

The ultrastructural features of a malignant histiocytoma of the acromial process of the scapula were studied. Material was obtained from two surgical biopsy specimens and an amputation specimen from the tumor. Cells possessing characteristics of histiocytes, fibroblasts, xanthoma cells, and multinucleated giant cells were present throughout the tumor. Smaller numbers of undifferentiated cells and lymphocytes were also observed. Intimate cytoplasmic interdigitations between adjacent tumor cells were found, and instances of degenerating intracytoplasmic cells, possibly representing phagocytosis, were observed. Specimens stained with periodic acid-Schiff reagent with and without exposure to diastase, examined by light microscopy, showed that numerous cells contained phagocytized material consisting of degenerating cells rather than cytoplasmic glycogen. Intraumor lymphocytes apparently represented an inflammatory reaction to the tumor. The tumor giant cells and xanthoma cells were probably modified histiocytes. Results of the study were compared with previous reports of ultrastructural studies of malignant histiocytoma of soft tissues. Fundamental similarities between such studies and this one suggested that the progenitor cell is a histiocyte, whether arising in bone or in soft tissues, and that the progenitor cell is capable of differentiation in both histiocytic and fibroblastic directions.