Ureteroarterial fistulas after radical pelvic surgery: pathogenesis, diagnosis, and therapeutic modalities.

Ureteroarterial fistulas (UAF) are a rare but potentially life-threatening complication of intra-abdominal malignancy, typically occurring after vascular or pelvic surgery. Patients with a history of radical pelvic surgery, chronic indwelling ureteral stents, and prior pelvic radiation appear to be at increased risk. The predisposing risk factors suggest that gynecological oncologists are the likely specialty to face this problem and should be familiar with the clinical presentation and etiology of UAF. We present two such cases to illustrate these salient points of clinical diagnosis and management.

Residual, unresectable, or recurrent colorectal cancer: external beam irradiation and intraoperative electron beam boost +/- resection.

While combinations of external beam radiation (XRT) and surgery decrease pelvic recurrence and improve survival in the subgroups with residual disease (postop XRT) or initially unresectable disease (preop XRT), local recurrence is still unacceptably high, and survival could be improved. In view of this, pilot studies were instituted at Massachusetts General Hospital in which 32 patients received the standard previous treatment of external beam irradiation and surgery but in addition had an intraoperative electron beam boost of 1000-1500 rad to the remaining tumor or tumor bed. For the 16 patients who presented with unresectable primary lesions, the addition of intraoperative radiotherapy has resulted in a total absence of local recurrence with a minimum 20 month follow-up, and survival rates are statistically better than for the previous group treated with only external beam irradiation and surgical resection. In the group with residual disease, again there have not been any local recurrences in the 7 patients who received all treatment modalities versus 54% and 26% for the group with gross and microscopic residual treated with only external beam techniques. The remaining 9 patients presented with recurrent unresectable lesions--3 are alive (2 NED) at greater than or equal to 3 years.

Local control in medically inoperable lung cancer: an analysis of its importance in outcome and factors determining the probability of tumor eradication.

PURPOSE: For patients who are medically unable to tolerate a surgical resection for technically resectable non-small-cell lung carcinoma, radiation therapy is an acceptable alternative. We report on the effect of achieving local control of the primary tumor on survival end-points, and analyze factors that may influence local control. METHODS AND MATERIALS: We reviewed the records of 152 patients with medically inoperable non-small-cell lung carcinoma treated at our institutions. All patients had technically resectable lesions and no evidence of metastatic disease. Treatment was delivered using megavoltage irradiation to doses ranging from 45 to 75 Gy. RESULTS: For patients with tumors 3 cm or less, locally controlling the tumor significantly improved survival (p = .0371). Patients with T1 tumors had a higher probability of survival and disease-free-survival than patients with larger tumors if the primary tumor was locally controlled, but this survival advantage disappeared if the tumor was not controlled. Overall, patients with smaller tumors had a lower incidence of distant spread, but this association was maintained only when the primary tumor was controlled (36 month risk of 10%, 23%, and 57% for tumors < 3 cm, 3-4.9 cm, 5 cm or greater, respectively, p = .0027). For patients whose tumors were not controlled, there was no significant difference in the risk of distant dissemination by tumor size. Higher radiation doses influenced local control and metastatic spread. We observed no influence of the initial field size in the risk of local control and in the probability of survival. CONCLUSION: Radical radiation therapy is an effective treatment for small (T1 or < 3 cm) tumors when treated to doses of 65 Gy or more, and should be offered as an alternative to surgery in elderly or infirm patients. New therapeutic strategies to improve the local control rate should be considered for larger tumors, through the use of hyperfractionated treatment, endobronchial "boost" irradiation, and sensitizing chemotherapy agents.

Low doses of prophylactic cranial irradiation effective in limited stage small cell carcinoma of the lung.

PURPOSE: Prophylactic cranial irradiation (PCI) for the prevention of brain metastasis in small cell lung cancer remains controversial, both in terms of efficacy and the optimal dose-fractionation scheme. We performed this study to evaluate the efficacy of PCI at low doses. METHODS AND MATERIALS: One hundred and ninety-seven patients were referred to our institution for treatment of limited stage small cell carcinoma of the lung between June 1986 and December 1992. Follow-up ranged from 1.1 to 89.8 months, with a mean of 19 months. Eighty-five patients received PCI. RESULTS: Patients receiving PCI exhibited brain failure in 15%, while 38% of untreated patients developed metastases. This degree of prophylaxis was achieved with a median total dose of 25.20 Gy and a median fraction size of 1.80 Gy. At these doses, acute and late complications were minimal. Patients receiving PCI had significantly better 1-year and 2-year overall survivals (68% and 46% vs. 33% and 13%). However, patients with a complete response (CR) to chemotherapy and better Karnofsky performance status (KPS) were overrepresented in the PCI group. In an attempt to compare similar patients in both groups (PCI vs. no PCI), only patients with KPS > or = 80, CR or near-CR to chemotherapy, and treatment with attempt to cure, were compared. In this good prognostic group, survival was still better in the PCI group (p = 0.0018). CONCLUSION: In this patient population, relatively low doses of PCI have accomplished a significant reduction in the incidence of brain metastasis with little toxicity. Whether such treatment truly improves survival awaits the results of additional prospective randomized trials.

Radiation therapy in the management of medically inoperable carcinoma of the lung: results and implications for future treatment strategies.

Surgery is the treatment of choice for resectable non-small cell lung carcinoma. For patients who are medically unable to tolerate a surgical resection or who refuse surgery, radiation therapy is an acceptable alternative. We reviewed the records of 152 patients with medically inoperable non-small cell lung carcinoma treated at our institution between 1982 and 1990. Patients with metastatic disease, mediastinal lymph node involvement or unresectable tumors were excluded. The actuarial overall survival at 2 and 5 years was 40% and 10%, respectively. The disease-free survival at 2 and 5 years was 31% and 15%. The disease-free survival for patients with T1 tumors was 55% at 2 years, versus 20 and 25% for T2 and T3 lesions, respectively (p = .0006). Increasing tumor dose was also associated with increasing disease-free survival (p = .0143). Overall, 66% percent of the patients were considered to have failed. Of these, 70% showed a component of local failure and 45% failed distantly. Patients with T1 tumors experienced a lower probability of failing locally or distantly than did patients with T2 or T3 tumors. A reduced risk of local and distant failure was seen for patients treated to doses of greater than 65 Gray, especially for T1 tumors. We conclude that radical radiation therapy is an effective treatment for small tumors when treated to doses of 65 Gray or more. Since local failure is the prominent pattern of relapse in patients with large tumors, new therapeutic strategies should be considered for this patient group.

Effective palliative radiation therapy in advanced and recurrent ovarian carcinoma.

PURPOSE: To retrospectively review our experience using radiation therapy as a palliative treatment in ovarian carcinoma. METHODS AND MATERIALS: Eighty patients who received radiation therapy for ovarian carcinoma between 1983 and 1998 were reviewed. The indications for radiation therapy, radiation therapy techniques, details, tolerance, and response were recorded. A complete response required complete resolution of the patient's symptoms, radiographic findings, palpable mass, or CA-125 level. A partial response required at least 50% resolution of these parameters. The actuarial survival rates from initial diagnosis and from the completion of radiation therapy were calculated. RESULTS: The median age of the patients was 67 years (range 26 to 90 years). A median of one laparotomy was performed before irradiation. Zero to 20 cycles of a platinum-based chemotherapy regimen were delivered before irradiation (median = 6 cycles). The reasons for palliative treatment were: pain (n = 22), mass (n = 23), obstruction of ureter, rectum, esophagus, or stomach (n = 12), a positive second-look laparotomy (n = 9), ascites (n = 8), vaginal bleeding (n = 6), rectal bleeding (n = 1), lymphedema (n = 3), skin involvement (n = 1), or brain metastases with symptoms (n = 11). Some patients received treatment for more than one indication. Treatment was directed to the abdomen or pelvis in 64 patients, to the brain in 11, and to other sites in 5. The overall response rate was 73%. Twenty-eight percent of the patients experienced a complete response of their symptoms, palpable mass, and/or CA-125 level. Forty-five percent had a partial response. Only 11% suffered progressive disease during therapy that required discontinuation of the treatment. Sixteen percent had stable disease. The duration of the responses and stable disease lasted until death except in 10 patients who experienced recurrence of their symptoms between 1 and 21 months (median = 9 months). The 1-, 2-, 3-, and 5-year actuarial survival rates from diagnosis were 89%, 73%, 42%, and 33%, respectively. The survival rates calculated from the completion of radiotherapy were 39%, 27%, 13%, and 10%, respectively. Five percent of patients experienced Grade 3 diarrhea, vomiting, myelosuppression, or fatigue. Fourteen percent of patients experienced Grade 1 or 2 diarrhea, 19% experienced Grade 1 or 2 nausea and vomiting, and 11% had Grade 1 or 2 myelosuppression. CONCLUSIONS: In this series of radiation therapy for advanced ovarian carcinoma, the response, survival, and tolerance rates compare favorably to those reported for current second- and third-line chemotherapy regimens. Cooperative groups should consider evaluating prospectively the use of radiation therapy before nonplatinum and/or nonpaclitaxel chemotherapy in these patients.

Effects of castration, and testosterone in vitro, on the hypothalamic synthesis of different peptide fractions.

The incorporation of [3H]tyrosine ([3H]tyr) into different hypothalamic peptide fractions isolated from normal and castrated rats on a Sephadex G-25 column has been studied in vitro. Luteinizing hormone releasing factor (LH-RF) activity was determined in the different fractions by measuring their ability to elicit release of radioimmunoassayable luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in ovariectomized rats treated with oestrogen and progesterone. For a further purification, the fraction with LH-RF activity was applied to a CM-Sephadex G-25 column eluted with a gradient of ammonium acetate. The large radioactive peptides emerged from the Sephadex G-25 column in fraction S-1, while the small peptides with LH-RF activity were eluted in fraction S-2. Gonadectomy significantly increased the incorporation of [3H]tyr into the peptides of fractions S-2. Only in the purified fraction with LH-RF activity was the radioactivity incorporated higher in gonadectomized than in normal rats. The enhanced incorporation in fraction CM-3 observed after castration implies an increase in the hypothalamic synthesis of peptides with LH-RF activity. The addition of testosterone (2 mug/ml) to the incubation medium of hypothalamus from gonadectomized rats, corrected these modifications. Gonadectomy decreased the incorporation of tyrosine into the large peptides, and incubation with testosterone corrected this change. The modifications in the incorporation of [3H]tyr into the large and small peptides produced by castration appear to indicate that gonadectomy, as well as stimulating the production of LH-RF, enhances the synthesis of other hypothalamic peptides while inhibiting the synthesis of proteins. On the other hand an increase in the breakdown of large peptides into small peptides cannot be excluded.

Pentobarbital anesthesia and the response of tumor and normal tissue in the C3Hf/sed mouse to radiation.

Studies of the effect of pentobarbital anesthesia on the radiation response have been performed using early generation isotransplants of three spontaneous tumors of the C3H mouse: a mammary carcinoma (MCaIV), a fibrosarcoma (FSaII), and a squamous cell carcinoma (SCCVII). The enhancement ratio of pentobarbital [ER(PB)] for TCD50 as the end point was greater than or equal to 1 for all conditions tested. The ER(PB) for O2 3 ATA conditions and two equal doses was 1.46, 1.72, and 2.21 for MCaIV, FSaII, and SCCVII, respectively. The ER(PB) using MCaIV was the same for O2 and carbogen at 1 or 3 ATA. Also, tumor size of MCaIV did not significantly affect the ER(PB) for O2 3 ATA conditions. Further, with the two-dose protocol the anesthesia and the hyperbaric oxygen needed to be used at the second dose; condition at the first dose was not critical. For fractionated irradiation of MCaIV (10 and 15 equal doses) the ER(PB) was smaller than for two-dose treatment; also the effect was less for intratumor temperature of 35 degrees C than 26-27 degrees C. There was no effect of the anesthesia on the acute response of normal skin of the leg. Lung damage by hyperbaric oxygen was not an important factor in these results. Additionally, ERs were computed for O2 at 3 ATA. This ER(O2 3 ATA) was larger for anesthesized than conscious mice. The ER(O2 3 ATA) for MCaIV was high (greater than 1.5) even for radiation given in 10 or 15 equal doses.

Meningioma: analysis of recurrence and progression following neurosurgical resection.

The rates of survival, tumor recurrence, and tumor progression were analyzed in 225 patients with meningioma who underwent surgery as the only treatment modality between 1962 and 1980. Patients were considered to have a recurrence if their studies verified a mass effect in spite of a complete surgical removal, whereas they were defined as having progression if, after a subtotal excision, there was clear radiological documentation of an increase in the size of their tumor. There were 168 females and 57 males (a ratio of 2.9:1), with a peak incidence of tumor occurrence in the fifth (23%), sixth (29%), and seventh (23%) decades of life. Anatomical locations were the convexity (21%), parasagittal area (17%), sphenoid ridge (16%), posterior fossa (14%), parasellar region (12%), olfactory groove (10%), spine (8%), and orbit (2%). The absolute 5-, 10-, and 15-year survival rates were 83%, 77%, and 69%, respectively. Following a total resection, the recurrence-free rate at 5, 10, and 15 years was 93%, 80%, and 68%, respectively, at all sites. In contrast, after a subtotal resection, the progression-free rate was only 63%, 45%, and 9% during the same period (p less than 0.0001). The probability of having a second operation following a total excision after 5, 10, and 15 years was 6%, 15%, and 20%, whereas after a subtotal excision the probability was 25%, 44%, and 84%, respectively (p less than 0.0001). Tumor sites associated with a high percentage of total excisions had a low recurrence/progression rate. For example, 96% of convexity meningiomas were removed in toto, and the recurrence/progression rate at 5 years was only 3%. Parasellar meningiomas, with a 57% total excision rate, had a 5-year probability of recurrence/progression of 19%. Only 28% of sphenoid ridge meningiomas a second resection, the probability of a third operation at 5 and 10 years was 42% and 56%, respectively. There was no difference in the recurrence/progression rates according to the patients' age or sex, or the duration of symptoms. Implications for the potential role of adjunctive medical therapy or radiation therapy for meningiomas are discussed.

Small cell anaplastic carcinoma of the prostate: seven new cases, review of the literature, and discussion of a therapeutic strategy.

Small cell anaplastic carcinoma of the prostate (SCCP) is a rare entity; a literature review disclosed fewer than 150 cases. SCCP has an aggressive course, and both local and distant failure is common. The optimal treatment method has not been clearly established. We review our experience with 7 patients, with attention paid to clinical and pathological details based on a review of the histological specimens. Three patients had mixed tumors of both SCCP and adenocarcinoma, 3 had pure adenocarcinomas that recurred as small cell, and 1 had pure small cell. Our series confirms the aggressive nature of the disease, with all patients dying of their disease < or = 42 months after diagnosis. All patients progressed locally, and at least 5 later developed distant metastases. Treatment with combination chemotherapy and/or hormones resulted in short-lived responses in most patients. We recommend use of hormonal manipulation and combination chemotherapy as well as surgery and/or radiation therapy to the prostate for local control and emphasize that histologic recognition of the entity is important for proper treatment.

Small-cell lung carcinoma: an analysis of 194 consecutive patients.

The treatment of small-cell lung carcinoma (SCLC) requires the careful combination of chemotherapy and radiation therapy. To understand the factors involved in the outcome of these patients, the authors undertook a study of patients treated for limited stage SCLC. The charts of 194 consecutive patients treated at our facilities between 1986 and 1994 were reviewed. All patients underwent thoracic radiation therapy (TRT), 50% received prophylactic cranial irradiation (PCI), and all but one received chemotherapy. The probability of survival at 5 years was 14%, and the disease-free survival (DFS) was 17%. Patients receiving a combination of platinum and etoposide (PE) and Cytoxan (Bristol-Myers, Evansville, IN, U.S.A.), Adriamycin (Adria Laboratories, Dublin, OH, U.S.A.), and Vincristine (Eli Lilly, Indianapolis, IN, U.S.A.) (CAV) experienced a DFS at 3 years of 31%, versus 14% for CAV only and 18% for PE only (p = 0.004). In a multivariate survival analysis, only PCI (p = 0.001), having received PE and CAV (p = 0.01), and response to treatment (p = 0.001) were significant. Radiation dose and field size did not influence outcome. The combination of PE and CAV chemotherapy produced the best results in our series. Unanswered questions regarding the optimal TRT dose, field size, and timing of TRT await the results of ongoing randomized trials.

Radiotherapy of polymorphic reticulosis.

The term "lethal mid-line granuloma" does not properly reflect current knowledge that several different diseases can produce non-infectious mid-facial destruction. The disorders producing erosion of the upper aerodigestive passages are more accurately classified by clinical and histological criteria as either Wegener's or non-Wegener's causes. The non-Wegener's causes of mid-facial erosion include extranodal lymphoma, idiopathic mid-line granuloma and polymorphic reticulosis. Polymorphic reticulosis (PR) is a rare disease which is histologically identical to lymphomatoid granulomatosis (LG). The term PR has been used to describe LG localized to the upper airways. PR-LG is characterized by a remarkably polymorphic angiocentric mixed cellular infiltrate. The disease is locally invasive, has the potential for distant spread, and can cause fever, sweats and weight loss. When it is localized to the upper airways, PR-LG is potentially controllable by radiation therapy. Local symptoms at other body sites can be successfully palliated by radiation. The clinical presentation of two recent patients with PR-LG is summarized, as well as the radiotherapy employed. The pertinent literature is reviewed.

On the mechanism for enhancement of tumor radiation to hyperbaric oxygen in sodium pentobarbital anesthetized rodents.

Pentobarbital anesthesia has been observed to increase markedly the effectiveness of respiration of oxygen at 3 atmospheres of pressure absolute to increase the response of early generation isotransplants of C3H mouse tumors to two-dose irradiation. A possible mechanism of this phenomenon is suppression of oxygen utilization by the pentobarbital and hence increasing mean pO2 and oxygen diffusion lengths. Measurements of QO2 of suspension of MCaIV and FSaII cells from freshly excised tumor tissue have been measured for cells suspended in PBS, Hank's buffered with HEPES +/- glutamate. The oxygen utilization by these tumor cells in vitro (when measured at congruent to 10 minutes after excision) is low, viz. 1 nmole/min/mg protein as compared with 6-9 nmoles/min/mg protein for established cell lines cultured in vitro. The suppression of QO2 by 2mM pentobarbital is less than 10%. This is a concentration of pentobarbital that is judged to be close to that which obtains in the tissues of the animals in the radiation response assays. Pentobarbital at .2mM did not change the cell survival characteristics of Chinese V79 cell spheroids irradiated in vitro. The results of these experiments do not indicate the suppression of oxygen utilization is an important contributor to the observed phenomenon of the increased response of tumors irradiated in mice respiring oxygen at high pressure. The role of hypothermia produced by the anesthesia is under further study.

Serum luteinizing hormone follicle-stimulating hormone and prolactin in neonatal-androgenized rats.

Serum levels of LH, FSH, Prolactin and Testosterone of 90 days old male rats androgenized soon after birth were determined by specific radioimmunoassay and were compared to untreated rats. LH and FSH levels were also determined in 90 days old female rats neo-natally treated with testosterone and compared with normal diestrus rats. Androgenization of male rats significantly increased serum FSH and Prolactin levels without producing changes in plasma LH and testosterone concentrations. Similar increase in the FSH levels were found in androgenized female rats although plasma FSH concentrations were lower than in the male groups. These results obtained in male rats give an additional evidence that androgens acting in the first days of life are responsible of the higher levels of FSH and Prolactin that characterize the male or tonic pattern of gonadotrophin secretion.

Validation of the tumor, nodes and metastasis classification of renal cell carcinoma.

A retrospective analysis of 252 patients with renal cell carcinoma was performed with the tumor, nodes and metastasis system of cancer staging. Each patient received a clinical and a pathological classification. Patient survival was calculated for each pT stage. All patients with stage pT1 disease (100 per cent) were alive at 5 years, as were 91 per cent of those with stage pT2 tumors. Higher T stages showed poorer survival; 58 per cent of the patients with stage pT3 and only 25 per cent with stage pT4 tumors were alive at 5 years. Invasion into the inferior vena cava (pT3c) had an adverse effect on survival, which was statistically significant compared to patients in the pT3a and pT3b subgroups. The type of surgical procedure performed had no influence on ultimate survival, nor did the use of adjuvant radiation therapy. The tumor, nodes and metastasis system clearly documents that the survival of patients with renal cell carcinoma depends on the local extent of the primary tumor, determined at the time of surgical exploration.

CT evaluation of locally advanced carcinoma of the distal colon and rectum.

Computed tomography (CT) correctly identified extraluminal extension in carcinoma of the rectum and distal sigmoid in 20 patients who were deemed clinically inoperable because of tumor fixation. All patients received preoperative radiation therapy and subsequent surgical resection of the tumor. The findings at surgery corroborated the presence and location of tumor extension deep to the wall of the colon. Based on this preliminary data, further investigation into the place of CT in treatment planning of colon carcinomas is indicated.