Effects of dietary fish meal and soybean meal on the ovine innate and acquired immune response during pregnancy and lactation.

In recent years, livestock producers have been supplementing animal diets with fish meal (FM) to produce value-added products for health conscious consumers. As components of FM have unique neuroendocrine-immunomodulatory properties, we hypothesize that livestock producers may be influencing the overall health of their animals by supplementing diets with FM. In this study, 40 pregnant ewes were supplemented with rumen protected (RP) soybean meal (SBM: control diet) or RP FM, commencing gestation day 100 (gd100), in order to evaluate the impact of FM supplementation on the innate and acquired immune response and neuroendocrine response of sheep during pregnancy and lactation. On gd135, half the ewes from each diet (n = 10 FM, n = 10 SBM) were challenged iv with lipopolysaccharide (LPS) to simulate a systemic bacterial infection and the febrile, respiratory and neuroendocrine responses were monitored over time; the other half (n = 10 FM, n = 10 SBM) of the ewes received a saline injection as control. On lactation day 20 (ld20), all ewes (n = 20 FM, n = 20 SBM) were sensitized with hen egg white lysozyme (HEWL) and the serum haptoglobin (Hp) response was measured over time. The cutaneous hypersensitivity response (CHR) to HEWL challenge was measured on ld30 (n = 20 FM, n = 20 SBM), and blood samples were collected over time to measure the primary and secondary immunoglobulin G (IgG) response to HEWL. There was an attenuated trend in the LPS-induced febrile response by the FM treatment when compared with the SBM treatment (P = 0.06), as was also true for the respiratory response (P = 0.07), but significant differences in neuroendocrine function (serum cortisol and plasma ACTH) were not observed between treatments. Basal Hp levels were significantly lower in the FM supplemented ewes when compared with the SBM supplemented ewes (P < 0.01), and the Hp response to HEWL sensitization differed significantly over time between treatments (P < 0.01). The CHR to HEWL was also significantly attenuated in the FM treatment compared with the SBM (P < 0.01); however, treatment differences in the primary and secondary IgG responses to HEWL were not observed. These results indicate that FM supplementation differentially affects the innate and acquired immune responses in pregnant and lactating sheep compared with a typical SBM diet of commercial flocks. The long-term implications of this immunomodulation warrant further investigation.

Survival following extended field irradiation in carcinoma of cervix metastatic to para-aortic lymph nodes.

OBJECTIVE: Our goal was to determine survival after extended-field treatment of para-aortic lymph node (PALN) metastasis. METHODS: Thirty-five patients were treated from 1975-1989 for PALN metastasis. The FIGO stages were IB 10, 2A 3, IIB 9, IIIA 1, IIIB 10, 4A 1, and unstaged 1. The diagnosis in 34 patients was by operative staging and in 1 by CT scan and fine-needle aspiration biopsy. Twelve patients had microscopic PALN metastasis (PALN1) and 23 had grossly enlarged lymph nodes (PALN2). Thirty-four patients had extended-field radiotherapy (RT) plus brachytherapy or pelvic boost. Kaplan-Meier estimates were computer calculated for the entire population. Late radiation morbidity was classified by RTOG/EORTC criteria. RESULTS: The 5-year overall survival rate was approximately 29%. Four patients (3 stage IB, 1 stage IIIA) survived without recurrence. All four had extended field RT. The 5-year survival rate was 41.7% for PALN1 cases and 26.1% for PALN2 cases. Three patients (8.6%) had Grade 4 morbidity. CONCLUSIONS: PALN metastasis in stage IB is curable in approximately 30% of cases. The management approach in this series in stage IB was as follows: If PALN metastasis was identified at exploration for radical hysterectomy, the procedure was aborted and extended-field RT administered. In stages IIB through IVA, operative staging or CT scanning with FNA biopsy of suspicious PALN was performed. If PALN metastasis was confirmed, extended-field RT was administered. A 35% 5-year survival rate was observed in the advanced group. The value of chemotherapy for PALN metastasis remains to be defined but results from clinical trials suggest that cisplatin-based chemotherapy may be beneficial.

Radiotherapy for vaginal carcinoma: a 23-year review.

The purpose of the study was to evaluate prognostic variables and morbidity in patients with vaginal carcinoma. 34 patients, mean age 67 years (+/- 8 SD), were treated between 1976 and 1994. 14 patients had a history of prior hysterectomy. In 13 of the 34 patients the tumour site was the upper vagina, in 9 it was the middle third, in 8 the lower third and in 4 the entire length of the vagina. Disease stage was I in 9 patients, II in 16, III in 7 and IV in 2. There were four treatment groups: external beam therapy + intracavitary brachytherapy (Group WPIC, n = 15); external beam therapy + interstitial brachytherapy (Group WPIS, n = 10); external beam therapy alone (Group WP, n = 7); and brachytherapy alone (Group BA, n = 2). Kaplan-Meier estimates and log-rank tests were used to evaluate survival. Disease-specific 5-year survival was 68% for 28 patients with squamous cell carcinoma and 50% for 6 patients with adenocarcinoma (p-value 0.3). 5-year survival was 78% for stage I disease, 63% for stage II, 33% for stage III and 50% for stage IV (p-value 0.2). Vaginal site of carcinoma, history of hysterectomy and treatment type are not significant prognostic factors. Local failure occurred in 2 patients (13%) in the WPIC group, 2 (20%) in WPIS, 3 (43%) in WP and 1 (50%) in BA. 9 patients (26%) had late small/large intestine and/or bladder morbidity. Vaginal morbidity occurred in 15 patients (44%); 9/15 (60%) in the WPIC group and 3/10 (30%) in the WPIS group having vaginal morbidity. This means that, when combining external beam therapy with brachytherapy, interstitial techniques are preferred over intracavitary techniques.

Assessment of accuracy of daily set-ups in prostate radiotherapy using electronic imaging.

The purpose of the study was to assess the accuracy, using electronic portal imaging, of daily set-ups, in patients undergoing radiotherapy for prostate carcinoma. We used a scanning liquid ion chamber to assess the accuracy of set-ups in 25 consecutive patients undergoing a 6 1/2 week course of radiotherapy to the prostate. Electronic images (EPIs) were collected during 33 treatments to each of four ports. The positions of anatomical structures on the EPIs were compared with the same structures seen on digitally reconstructed radiographs (DRRs) made after CT simulation before beginning radiotherapy. Displacements of the EPIs compared with the DRRs were computer-calculated in millimetres in lateral, longitudinal and rotational directions for each port. 11 patients had ports moved because of discrepancies between the EPIs and the DRRs; eight required moves in the first five treatments to correct systematic (simulator) errors. In the right-left and anterior-posterior directions, nearly 95% of the EPIs were within 5 mm of the simulated port position. In the superior-inferior direction, 98% of the ports were within 5 mm of the simulated port position. Two patients had in-plane rotational errors on the lateral ports (8 degrees and 10 degrees respectively). It was concluded that daily electronic imaging is an effective technique for assessing the accuracy of set-ups in prostate radiotherapy.

Epidermal growth factor enhances intestinal mitotic activity and DNA content after acute abdominal radiation.

BACKGROUND: Mediators of radiation-induced enteritis and colitis remain undefined. Epidermal growth factor (EGF) is an endogenous peptide that is trophic to the gastrointestinal tract. We tested the hypothesis that EGF enhances DNA synthesis and mitotic activity and prevents acute radiation enteritis after total abdominal radiation. METHODS: Four equal groups (n = 6) of Sprague-Dawley rats were studied: I (control), II (radiation), III (EGF), and IV (radiation + EGF). Animals in groups III and IV received EGF (10 micrograms/kg) every 8 hours for 48 hours before radiation exposure and for 72 hours after radiation, and the remaining animals were given an equal volume of vehicle. Animals in groups II and IV were administered a single dose of abdominal radiation (1000 cGy) 48 hours after the start of either vehicle or EGF. Distal ileum and colon were harvested 72 hours after radiation, examined histologically, and assayed for total DNA content. RESULTS: Group II or radiated animals had diarrhea, significant weight loss (p < 0.05), and decreased food consumption consistent with acute clinical radiation enteritis. Mitotic activity and total DNA content were significantly reduced (p < 0.05) when compared with group I (nonradiated controls). Group IV animals treated with EGF and exposed to radiation did not suffer the acute clinical manifestations of radiation enteritis. In addition, total DNA content and mitotic activity of the terminal ileum increased significantly (p < 0.05), and a significant increase in mitotic activity occurred in the distal colon when compared with radiated controls. CONCLUSIONS: The results of this study suggest that (1) a decrease in mitotic activity and total DNA content occurs early and persists for at least 72 hours after acute radiation, (2) EGF treatment significantly increases small and large bowel mitogenicity in acutely radiated animals, and (3) EGF significantly decrease the acute clinical manifestations of radiation enteritis.

Postoperative hip irradiation in prevention of heterotopic ossification: causes of treatment failure.

Over 4 years, 33 patients (mean age, 52 years) underwent hip surgery followed by single-fraction 700-cGy radiation therapy (RT). Records, port films, and plain radiographs were reviewed to assign Brooker classification levels for severity of heterotopic ossification (HO) and assess the amount of new HO developing after surgery. Nineteen patients (58%) developed radiographic evidence of new HO after surgery. All five patients with three or more risk factors and none of 12 with postoperative Brooker level 0 (no radiographic HO) developed new HO. Ten of 16 treated on postoperative day 1, six of 10 on postoperative day 2, none of three on day 3, two of three on day 4, and one of one on day 5 developed new HO. New HO developed outside the irradiated volume in 11 patients. Surgeons should remove all heterotopic bone whenever possible; RT should be administered within 3 days after surgery; portals should cover all potentially involved soft tissue; and future studies should evaluate larger single fractions (900-1,000 cGy) for prevention of HO in patients with three or more risk factors and/or radiographic evidence of residual HO.

Detection and patterns of treatment failure in 300 consecutive cases of "early" endometrial cancer after primary surgery.

From November 1977 to July 1987, 300 consecutive patients with endometrial carcinoma clinically confined to the uterine corpus underwent primary surgery consisting of at least abdominal hysterectomy and adnexectomy. Patients with aggressive disease characteristics received postoperative radiotherapy. Forty-seven patients (16%) demonstrated recurrent disease from 2 to 125 (median of 12.8) months after surgery. Forty-seven percent of the recurrences were detected within the first year following surgery and 70% by 2 years after hysterectomy. Of the 47 recurrences, 29 were at distant sites, 16 were within the pelvis, and 2 consisted of both local and distant recurrences. Patients treated with pelvic radiotherapy after hysterectomy were more likely to experience distant, rather than local recurrences. Only 7 of the 148 patients (5%) treated with postoperative radiotherapy recurred in the pelvis. Approximately half of the recurrences were detected in asymptomatic individuals; physical examination and chest X-ray were the most useful means to detect disease in patients without symptoms. The combination of history, physical examination, pap smear, and chest X ray detected all of the recurrences. Actuarial survivals at 12, 24, and 36 months after recurrence were 42, 24, and 17%, respectively. The site of recurrence, time interval of surgery to recurrence, and use of postoperative pelvic radiotherapy were statistically related to patient prognosis. The identification of patients at risk of recurrence and more effective adjuvant therapy need to be developed in order to decrease the frequency of recurrence. In order to substantially improve the survival of patients with recurrent disease, more sensitive methods of detection, as well as more effective salvage therapy, will be required.

Adjuvant external beam therapy for pathologic stage I and occult stage II endometrial carcinoma.

Eighty-six patients with pathologic Stage I or occult Stage II carcinoma of the endometrium and myometrial invasion and/or Grade 2 or Grade 3 histologic condition received whole-pelvis external radiation therapy (RT) after extrafascial total abdominal hysterectomy and bilateral salpingo-oophorectomy. Twenty-one patients received 4250 cGy in 25 daily fractions for 5 weeks (Group 1), 28 received 4500 cGy in 25 daily fractions for 5 weeks (Group 2), and 37 received 5100 cGy in 30 daily fractions for 6 weeks (Group 3). Seventeen patients had intravaginal brachytherapy after whole-pelvis RT. Local recurrence developed in two patients (2.3%) (one in Group 1 and one in Group 2). Statistical analysis showed that the depth of myometrial invasion significantly influenced survival (P = 0.016). Tumor grade, pathologic stage, whole-pelvis radiation dose, and the use of brachytherapy did not influence survival. Complications occurred in 9.5% of patients in Group 1, 24.7% in Group 2, and 40.5% in Group 3. Three patients who received brachytherapy had rectal injuries. The authors conclude that 4250 cGy in 25 fractions for 5 weeks of whole-pelvis RT appears to induce fewer complications than higher doses, and may be sufficient to prevent local recurrence in most patients who require adjuvant RT. A clinical trial is needed to determine the optimum dose-time-fractionation regimen.

The efficacy of transrectal ultrasound and prostate cancer.

An increased interest in the diagnosis and treatment of prostate cancer, particularly in the last few years, is reflected in the literature. Numerous articles have been published since 1980 on the subject of imaging of the prostate gland. This article is a review of transrectal ultrasound and its efficacy in the diagnosis and treatment of prostate cancer. Included is a review of the normal prostate anatomy, typical and atypical sonographic features, clinical and radiographic staging of prostate cancer, efficacy of the digital rectal examination, role of ultrasound in prostate cancer screening, surgical treatment, and radiotherapy of prostate cancer.

Sacral plexus injury after radiotherapy for carcinoma of cervix.

A 42-year-old woman developed lower extremity weakness and sensory loss 1 year after external and intracavitary radiotherapy for Stage IB carcinoma of cervix. She has been followed for 5 years posttreatment, and the neurologic abnormalities have persisted, but no evidence of recurrent carcinoma has been found. We believe this to be a rare case of sacral plexus radiculopathy developing as a late complication after radiotherapy. Suggestions are made for improving the radiotherapy technique to prevent this complication in future cases.

Advanced head and neck cancer: low-dose, split-course radiation therapy and simultaneous infusion of 5-fluorouracil and cisplatin.

Twenty-three patients with advanced untreated head and neck cancer, nine patients with recurrent cancer, and six patients with recurrent cancer who underwent surgery and had postoperative persistence of tumor were treated with three 2-week courses of irradiation (1,500 cGy in 10 fractions each) concurrently with cisplatin and a 5-day infusion of 5-fluorouracil. A fourth 2-week course of irradiation (2,000 cGy in 10 fractions) brought the final tumor dose to 6,500 cGy. Twenty patients in the untreated group and three patients in the recurrent group (33%) had a complete response. There were 10 local recurrences in the untreated group (43%), seven in the recurrent group (78%), and three in the persistent group (50%). At 17 months after the start of treatment, the survival rate for the untreated patients was 51%, for the patients in the recurrent group it was 11%, and for the patients in the persistent group it was 20% (P = .03). Most patients experienced toxicity, including nausea, vomiting, weight loss, and mucositis. Clinical trials are necessary to determine whether simultaneous chemotherapy and radiation therapy is an improved method of treatment for advanced head and neck cancer.

Extended-field radiation therapy for carcinoma of the cervix.

The survival of cervical carcinoma patients with paraaortic/high common iliac nodal metastases was evaluated by retrospective chart review during a 13-year interval. Thirty-three patients with cervical carcinoma and surgically documented nodal metastases received primary, extended-field radiation therapy. Overall 2-year and 5-year actuarial survival rates after diagnosis were 37% and 31%, respectively. Survival was analyzed in terms of the variables patient age, clinical stage, tumor histologic type, the presence of enlarged paraaortic/high common iliac lymph nodes, the extent of nodal involvement (microscopic versus macroscopic), the presence of intraperitoneal disease, and whether intracavitary brachytherapy was administered. The use of intracavitary radiation therapy was associated with improved local control and survival (P = 0.017). None of the other variables were statistically related to patient survival. Twenty-two of the patients died of cervical cancer and five are surviving without evidence of cancer. Four patients died of intercurrent disease. Two patients developed bowel-related radiation complications; both patients received chemotherapy concurrent with the radiation therapy. One of the two patients died of radiation enteritis. The use of extended-field radiation therapy does benefit a small group of patients and may result in extended patient survival.

FAM chemotherapy +/- aminoglutethimide in the treatment of pancreatic carcinoma.

Human pancreas contains receptors for estrogens and androgens as well as aromatase activity. FAM chemotherapy was administered to 14 patients with pancreatic cancer (seven at Stage IV). The median survival of these patients was 24.4 +/- 4.8 weeks. FAM chemotherapy plus aminoglutethimide/hydrocortisone (AG/HC) (250 mg bid AG + 20 mg bid HC) was administered to 14 patients (seven at stage IV). The median survival of this group was 17.3 +/- 2.9 weeks (P = 0.74 vs FAM alone). We conclude that addition of AG/HC does not add to the survival of patients with carcinoma of the pancreas treated with chemotherapy.

Lonidamine-induced, pH dependent inhibition of cellular oxygen utilization.

The inhibitory effect of lonidamine 1-(2,4-dichlorobenzyl)-1H-indazole-3-carboxylic acid on oxygen utilization by Chinese hamster ovary (CHO) and murine fibrosarcoma (FSa-II) cells was evaluated with a Clark oxygen electrode. The drug produced a small but statistically significant inhibition of oxygen uptake at normal pH (7.4) in CHO and FSa-II cells of 16 and 11%, respectively. However, at low pH (6.65) the inhibitory effect of lonidamine increased dramatically to 60% in both CHO and FSa-II cells. Because of the potential difference between tumor and normal tissue pH, lonidamine and similar drugs may be effective for selectively modifying oxygen utilization and concentration in tumor tissue which might lead to increased radiation and hyperthermic sensitization in tumors compared to normal tissue, resulting in an improvement in the therapeutic ratio.

Bladder and rectal complications following radiotherapy for cervix cancer.

One-hundred and thirty-two patients with cervix carcinoma who were treated with whole pelvis irradiation and two intracavitary applications had bladder and rectal dosimetry during brachytherapy with contrast agents placed into the bladder and rectum prior to orthogonal simulator radiographs. Doses were computer calculated at points A and B, F (bladder), R1 (rectum), and R2 (rectosigmoid). Late occurring bladder and rectal complications were graded on a severity scale of 1 to 3, and 14% had grade 2 or 3 injuries (9% developed fistulas). Statistical evaluation of the data showed that severe bladder and rectal injuries occur more commonly in stage IIIA and IIIB disease and in those receiving high external beam doses (5000 rad +). Analysis of variance tests revealed a significant correlation of brachytherapy dose to points R1 and R2 with severe rectal injuries but there was not a correlation of dose to F with bladder injuries. Nor was there correlation of injuries with dose to point A or the milligram-hour dose. We conclude that our technique for rectal dosimetry is adequate but that an improved technique of bladder dosimetry is needed. Also, when combining whole pelvis irradiation with two intracavitary applications (4000 rad to point A), the whole pelvis dose should probably not exceed 4000-4500 rad.

Addition of etoposide to cyclophosphamide, doxorubicin, and vincristine for remission induction and survival in patients with small cell lung cancer.

A total of 116 patients with small cell lung cancer were randomized to receive either: cyclophosphamide, 750 mg/m2, doxorubicin, 50 mg/m2, and vincristine, 2 mg iv (Regimen A), or the same drugs plus etoposide, 100 mg/m2 iv daily for 2 days (Regimen B) every 3 weeks. Complete responders received whole-brain radiation therapy. The overall response rates were 50% for Regimen A and 65% for Regimen B (P less than 0.05). The complete response rates were 18% for Regimen A and 44% for Regimen B (P less than 0.01). For patients with limited disease, the complete responders were 35% on Regimen A and 52% on Regimen B (P = 0.26); for those with extensive disease, the complete responders were 0% on Regimen A and 35% on Regimen B (P = 0.002). The median survival for complete responders was 17 months on Regimen A and 20 months on Regimen B. The difference is not statistically significant. Toxicity was tolerable for both groups; however, it was greater for the etoposide arm. We conclude that although etoposide improves the overall response rates in patients with small cell lung cancer, especially those with extensive disease, the addition of this drug does not lead to improved survival.

Radiotherapy for prostate carcinoma.

The charts of 96 patients who received radiotherapy at The M. S. Hershey Medical Center for their prostatic carcinoma were reviewed. The 4-year NED (no evidence of disease) survival rates for patients receiving between 6,500 and 7,000 rad of external beam radiation (EBR) were 92, 78, 56, and 50% for stages A, B, C, and D1, respectively. The 4-year NED survival rate for stage B patients was 90% for those receiving approximately 6,500 rad of EBR, 75% for those receiving approximately 7,000 rad of EBR, and 71% for those receiving interstitial implants. Bowel or urinary complications occurred in 27% (21% grade I, 3% grade II, and 3% grade III) of those receiving approximately 6,500 rad of EBR, 40% (25% grade I, 10% grade II, and 5% grade III) of those receiving 7,000 rad of EBR, and 0% of those receiving interstitial implants. The effects of stage, grade, and treatment type on NED survival and complications are discussed.

Absence of bile acid malabsorption as a late effect of pelvic irradiation.

The pathophysiology of chronic radiation-induced diarrhea was evaluated in 28 patients who had undergone pelvic irradiation for gynecologic neoplasms 2 to 7 years previously. Twenty-seven patients undergoing radiotherapy with techniques that did not require abdominal or pelvic irradiation served as controls. The glycine conjugates of cholic acid (GC) were measured in serum by radioimmunoassay. Fasting and 2 hr. pp GC levels for the pelvic irradiated patients were 11.0 +/- 11.1 (mean +/- SD) and 24.8 +/- 17.3 micrograms/dl. Fasting and 2 hr. pp GC levels for controls were 12.6 +/- 7.4 and 28.0 +/- 14.7. There were no significant differences in the post-prandial increases in serum GC between pelvic irradiated patients and controls (p = .23, Type II error probability = .13). There was also no significant difference in the 2 hr. pp and fasting GC ratio (p = .39). There was significant difference between the stool frequency (p less than .01) and the prevalence of diarrhea (p less than .02) between pelvic irradiated patients and controls. The data suggest that bile acid malabsorption due to ileal dysfunction is not an inevitable late complication of pelvic irradiation and is not the major determinant in the pathophysiology of chronic radiation-induced diarrhea.

Failure of lactose-restricted diets to prevent radiation-induced diarrhea in patients undergoing whole pelvis irradiation.

Sixty-four patients were randomized prior to pelvic radiotherapy into one of three dietary groups: the control group maintained a regular diet except that they drank at least 480 cc of milk daily; the lactose-restricted group was placed on a lactose-restricted diet; and the lactase group drank at least 480 cc of milk with lactase enzyme added to hydrolyze 90% of the lactose. The patients kept records of their stool frequency and the number of diphenoxylate tablets required to control their diarrhea during a 5 week course of standard whole pelvis irradiation. The data does not support the concept that one of the mechanisms of radiation-induced diarrhea associated with pelvic irradiation is a reduction the ability of the intestine to hydrolyze ingested lactose due to the effect of the radiation on the small intestine. There was not a significant difference in stool frequency or diphenoxylate usage among the dietary groups.

Treatment outcome of recurrent cervical cancer.

A total of 85 patients with recurrent cervical cancer were reviewed: 17 patients with recurrences were treated by radical surgery, 18 by radiotherapy, 29 by chemotherapy, and 21 cases received no further treatment. Survival was presented according to the site of recurrence and the mode of therapy. All patients were followed for a minimum of 24 months after recurrence. Of the total group, 14% are living without evidence of disease, 29% died of metastatic disease with no involvement in the pelvis, and 45% died of pelvic cancer. Overall, 22% were living more than 2 years, and only 2% lived over 5 years after recurrence. The NED (no evidence of disease) rate for radical surgery group was 47 and 44% for the radiotherapy group. There were no significant differences in median survival between the chemotherapy group and the no-treatment group (6.8 versus 4.8 months). New chemotherapy agents and adjuvant systemic therapy are discussed.