Biomedical subjects
Publications and source records attributed to D S Shimm.
A 31-year-old woman with a leiomyosarcoma of the broad ligament discovered during pregnancy is described. Treatment consisted of resection followed by pelvic irradiation. The patient experienced distant visceral metastases with disease control in the pelvis 30 months after diagnosis.
Sixty-eight patients with FIGO stage I, grade 2 or 3 adenocarcinoma of the endometrium were treated according to a protocol involving 10 Gy external pelvic irradiation, prompt hysterectomy with surgical staging, and postoperative therapy individualized according to surgical-pathologic findings. Five-year survival for the entire group was 78%, 87% for those with grade 2 disease, and 59% for those with grade 3 disease. For patients whose disease was found to be confined to the uterus, surgical stage I, the 5-year survival was 98%. Patients with surgical stage I, grades 2 and 3 disease had 97 and 100% probabilities of surviving 5 years, respectively. Five-year disease-free probability was 96% for all patients with surgical stage I carcinoma, 97% for patients with grade 2 disease, and 94% for patients with grade 3 disease. Myometrial penetration influenced survival; no patient with less than 50% myometrial penetration died or suffered a relapse, while only 40% of patients with deeper penetration survived 5 years. Twenty-three percent of patients with surgically confirmed disease spread beyond the corpus survived 5 years; 29% remained disease-free at this interval. Ten of the 68 patients developed recurrences, none has had a known pelvic recurrence. Two major complications, one requiring surgery, were seen, both in patients receiving postoperative external beam irradiation. The rationale behind low-dose, preoperative external pelvic irradiation is described, and an approach to high-grade, FIGO stage I adenocarcinoma of the endometrium is outlined.
Records of 98 patients undergoing surgery for squamous cell carcinoma of the vulva between 1960 and 1982 were analyzed to evaluate and develop treatment policy. There were 32, 34, 26, and 6 patients in FIGO stages I-IV, respectively. Eighty-six patients underwent radical vulvectomy, 8 patients underwent less extensive procedures, and 4 underwent more extensive procedures. Eighty-seven patients underwent inguinal node dissection, and 40 underwent pelvic node dissection as well. Eight patients received external beam irradiation. Actuarial 5-year survival was 57%. Age, tumor size, FIGO (clinical) stage, surgically determined T and N stages, tumor differentiation, lymph vessel invasion, extent of surgical procedure, and adjuvant irradiation were analyzed to determine their effects on local control, freedom from distant metastases, and survival, using single variable and multivariate analysis. Local control was significantly related to FIGO stage; freedom from distant metastasis was significantly related to surgical N stage, tumor size, and surgical T stage; survival was significantly related to surgical N stage, tumor size, surgical T stage, age, and lymph vessel invasion. Metastatic involvement of inguinal lymph nodes was significantly correlated with tumor size and differentiation. Of 87 evaluable patients, 33 had inguinal node involvement, and of these, 17 developed recurrent disease. All 7 patients with pelvic node metastases had positive inguinal nodes, and all died; the cause of death could be determined in 5, of whom 4 manifested distant metastases. Pelvic lymphadenectomy conferred no survival benefit in this series, even in the presence of positive inguinal nodes. Local vulvar recurrence is a significant problem in patients with positive inguinal nodes, and postoperative irradiation should be directed to this area in these patients. Patients with vulvar recurrences, especially those occurring at least 2 years after surgery, can be successfully salvaged, and should therefore be treated aggressively.
Twenty-two patients with invasive primary carcinoma of the vagina were treated with radiation therapy for cure between 1970 and 1980 at Massachusetts General Hospital. Eighteen demonstrated squamous cell carcinoma and six demonstrated adenocarcinoma. The 5-year actuarial survival was 0.38; no difference was noted between the different histologies. For stages I, II, III and IV disease, 5-year actuarial survivals were 0.71, 0.29, 0.48, and 0.52. A dose-response relationship could be demonstrated for both survival and local control. No serious complications were observed. On the basis of these results, increased reliance on implant techniques to increase the radiation dose to subvaginal tissues, is advocated in stage II disease.
Before patients with apparently localized cancer are offered potentially curative surgery or radiation therapy, physicians often order a battery of imaging studies to exclude metastases. The yield of radionuclide liver and bone scans and computed tomography of the brain in breast, colorectal, and lung carcinomas was examined as follows: the literature was reviewed to obtain the autopsy prevalences of brain, liver and bone metastases in breast, colorectal and all histologies of lung carcinoma, to estimate the sensitivities and specificities of radionuclide liver and bone scans and computed tomography of the brain. Using Bayes' theorem, the predictive accuracies of positive and negative clinical evaluations and imaging studies were computed. For most of the examples analyzed, the imaging studies do not provide information beyond that obtained by the history, physical examination, and inexpensive laboratory tests and radiographs that would alter the physician's decision to offer curative treatment directed towards local disease. This method is presented as a model for clinical decision making where the information gained by an additional study is evaluated for its use in altering therapeutic decisions.
We report a case of primary Wilms' tumor of the endocervix in a 13-year-old girl. The tumor was polypoid, filled the vagina, and was attached to the endocervix by a stalk. Microscopic examination disclosed blastematous, epithelial, and stromal elements characteristic of Wilms' tumor. The patient's kidneys were normal on intravenous pyelographic examination and on palpation at laparotomy, and she has remained free of disease for 9.6 years after hysterectomy.
A pilot study using low-dose preoperative radiation therapy, i.e., 10 Gy in 3 to 4 days as an adjuvant preoperative procedure for grade 2 or 3 (FIGO classification) endometrial carcinoma, was done. The concept of low-dose preoperative radiation therapy is to administer treatment, either surgical or radiotherapeutic, postoperatively according to the surgical and pathologic findings, allowing identification of those patients with previously undiagnosed extensive metastatic disease outside the pelvis found at laparotomy in whom routine pelvic radiation therapy is futile, as well as those patients with relatively low risk of recurrence who may not require further radiotherapy. Forty-four patients with clinical Stage I, grade 2 or 3 with adenocarcinoma of the endometrium were entered into the pilot study. Following surgery, 68% remained Stage I by pathologic examination, and in the remaining patients the stages were changed to II in seven, III in three, and IV in four. Postoperative treatment was administered according to extent of the disease found at surgery. The 4-year actuarial probability of survival rate for the entire group of patients with clinical Stage I disease was 80%; corresponding disease-free rate was 77%. For the Stage I disease confirmed by pathologic examination, the corresponding rate was 96%. The rates for Stages II through IV, as shown by pathologic findings at laparotomy, were 53% and 42%, respectively. In this pilot stud, a treatment policy for clinical Stage I, grade 2 or 3 adenocarcinoma of the endometrium using low-dose preoperative radiation therapy is recommended.
Forty-nine patients with biopsy-proven Waldeyer's ring lymphoma were treated with radiation therapy between 1968 and 1979; 45 to 50 Gy were given to Waldeyer's ring structures with a 5- to 10-Gy boost to the primary site. Uninvolved low cervical nodes received 40 to 50 Gy. Chemotherapy was reserved for treatment failures. Actuarial 5-year survival was 53%, disease-free survival was 48%, and local control was 98%. Patients with Stage I disease fared better than patients with Stage II disease, and unilateral adenopathy conferred a better prognosis than bilateral adenopathy. When classified by the Rappaport system, nodular lymphomas had a better prognosis than diffuse lymphomas, and of the diffuse lymphomas, histiocytic lymphoma was a more lethal disease than lymphocytic lymphoma. Patients with diffuse undifferentiated lymphomas in the Rappaport system, or high-grade lymphomas in the Working Formulation, fared poorly. Most relapses were systemic, and actuarial 5-year survival after salvage was only 20%. A logical approach to the treatment of this disease can be based on these prognostic features.
Twenty-eight patients with sarcomas of the uterine corpus were followed at least 22 months or until death. All underwent laparotomy, eleven had radiation therapy, and six had chemotherapy. Three year actuarial survival was 24%, and three year actuarial local control was 36%. Multivariate analysis demonstrated that, as with sarcomas at other sites, the most important factors influencing survival were grade (P = 0.020) and stage (P = 0.022). For local control, multivariate analysis indicated the most important factors to be stage (P = 0.001) and radiation TDF (P = 0.01). Of 21 failures, 16 involved the pelvis, seven involved the upper abdomen, and 11 involved distant sites. The importance of both local and distant disease control is emphasized.
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The effect of hypoglycemia and hypoxia on cell survival following single and fractionated 44 degrees C heat treatments was investigated. These studies show that short-term glucose deprivation or oxygen deprivation does not increase sensitivity to single or fractionated heat treatments compared to normal nutrient conditions. However, simultaneous hypoglycemia and hypoxia leads to an increased sensitivity to single heat treatments, and to an even greater increase in sensitivity to fractionated heat treatments. Sensitivity to heat treatment under nutrient-deprived conditions correlates with intracellular ATP levels at the time of treatment. These data indicate that it is not nutrient concentration per se, but rather the effect of nutrient level on intracellular ATP concentration that affects thermal sensitivity.
Primary gastric lymphoma, lymphoma originating in the stomach, without involvement of peripheral or mediastinal lymph nodes, viscera, or the bloodstream, is sufficiently uncommon that the indications for radiation therapy, the dose of irradiation necessary for control of lymphoma, optimum field size, and patterns of failure have never been established. The authors identified 26 patients, and reviewed their charts and pathologic material. Their overall 5-year survival was 57%. Factors significantly influencing 5-year survival were serosal penetration (32% versus 91%), regional lymph node involvement (33% versus 81%), and location on the lesser curvature (20% versus 89%). Histologic characteristics, extent of surgery, and, provided the patient was irradiated, involvement of surgical margins did not influence survival. Overall, survival was not affected by irradiation, but in patients with poor prognostic factors there appeared to be a beneficial effect. Analysis of local control in this and other series suggests that patients should receive at least 40 Gy, and that whole abdominal irradiation is not necessary. The majority of failures were distant, indicating a need for effective systemic therapy.
Epithelioid sarcoma is an uncommon tumor characterized by its appearance in the distal extremities (especially the forearm, wrist, and ankle), the tendency to recur locally, and high probability of spread to regional lymph nodes. Most patients have been treated surgically, and the potential role of radiation therapy alone or combined with surgery is not well defined. The authors treated eight patients with epithelioid sarcoma. Four patients were male; patients ranged in age from 7 to 66 years (median, 54.5). Six patients had upper extremity lesions, and two had lower extremity lesions. Median maximum tumor dimension was 3.0 cm. Three patients had Grade 2 lesions, and the others had grade 3 lesions. Regional lymph nodes were involved initially or during the course of the disease in five of our eight patients (62%). Five patients were treated following surgery for primary or recurrent tumor, with a median dose of 68 Gy (TDF 109). Four were NED with follow-up at 18, 24, and 84 months, respectively, and the other patient failed locally and in regional nodes at 6 months (treated successfully by salvage amputation) and is now living at 96 months with distant metastases. One patient treated pre-amputation with 50 Gy (TDF 81) is NED at 12 months. Two patients received radiation therapy alone, with a median dose of 65 Gy (TDF 104). One patient with a 22-cm primary died with persistent local disease as well as metastases, and the other died with distant metastases but with local control at 18 months. Four patients with local control did not undergo amputation, and all have unimpaired function of the affected extremity. Local control and survival for this group of patients is similar to that for other patients with upper extremity or high grade sarcomas. The authors concluded that radiation combined with surgery achieves a low rate of local recurrence, and a high likelihood of maintaining a functional extremity and good cosmesis.
We report the radiation therapy of keratoacanthoma in 13 patients using orthovoltage X rays and electrons. All patients had an excellent cosmetic result, and time to regression was dose dependent up to a dose corresponding to TDF 50; increasing dose beyond this level did not accelerate time to regression past 2.4 months. We also note a heretofore undocumented association between keratoacanthoma and second malignancy.
After staging splenectomy, the risk of overwhelming sepsis in patients with Hodgkin's disease reaches 21% in certain subgroups. Youth, recent splenectomy and vigorous chemoradiotherapy predispose patients to this complication. Because of its explosive course and its known microbiology, post-splenectomy sepsis is better suited to prevention than to treatment. Since immunisation prior to treatment produces good antibody responses, all patients with Hodgkin's disease should probably be vaccinated against encapsulated bacteria at least 10 days prior to the onset of therapy.
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We reviewed the records of 28 patients with superior vena cava syndrome (SVCS) between 1973 and 1978 to establish the risk from invasive diagnostic procedures and the therapeutic value of the information obtained. Of 23 patients, this syndrome was the initial manifestation in 18. Bronchoscopy with endobronchial biopsy, thoracentesis, pleural biopsy, lymph node biopsy, and, in one patient, thoracotomy were performed without major complications. Small cell undifferentiated carcinoma of the lung was found in seven of the 18 patients with SVCS as the initial manifestation of their disease. We believe that carefully performed invasive diagnostic procedures can be carried out safely. Furthermore, accurate histological diagnosis assumes major importance with the development of effective chemotherapy for small cell undifferentiated carcinoma of the lung.
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