Non-Hodgkin's lymphomas of stage III extent. Is total lymphoid irradiation appropriate treatment?

Many investigators have regarded Stage III lymphomas as a generalized form of disease and have accordingly recommended systemic treatment programs. Between 1961 and 1973, 68 patients with clinical or pathologic Stage III non-Hodgkin's lymphomas were seen in the Division of Radiation Therapy at Stanford University Medical Center and were treated by high dose (3500 rads or more) total lymphoid radiation therapy only. Of the 17 patients who had a diffuse histologic pattern, the actuarial survival at 5 years was 39%, but only three patients have remained free of disease. In contrast, for the 51 patients who had a nodular histologic pattern, the actuarial survivals at 5 and 10 years were 75% and 65%, respectively. Corresponding relapse-free survivals for patients with nodular lymphomas were 43% and 33%, respectively. Of 28 patients who relapsed with nodular lymphomas, 18 (64%) had relapses confined to lymph nodes; six of these were extensions to previously unirradiated epitrochlear-brachial nodes. Seven of the 18 patients were treated only with further conventional external radiation therapy at the time of their relapses and remain free of disease for additional periods of 2 to 5 years. Hence, 30 of 51 (59%) patients with nodular lymphomas have thus far been controlled by high dose total lymphoid irradiation only. Over 90% of relapses among patients with nodular lymphomas were seen within the first 5 years. The data suggest that high dose conventional radiation therapy to incorporate not only the routine total lymphoid fields but also the epitrochlear, mesenteric, and Waldeyer's ring region has curative potential even in Stage III non-Hodgkin's lymphomas, especially in the nodular group.     

Generation of superoxide anion and induction of superoxide dismutase and peroxidase in bean leaves infected with pathogenic fungi

PURPOSE: The purpose of this study was to review management strategies with respect to systemic therapy, radiation therapy treatment techniques, and patient outcome (local regional control, distant metastases, and overall survival) in patients undergoing conservative surgery and radiation therapy (CS + RT) who had four or more lymph nodes involved at the time of original diagnosis. METHODS AND MATERIALS: Of 1040 patients undergoing CS + RT at our institution prior to December 1989, 579 patients underwent axillary lymph node dissection. Of those patients undergoing axillary lymph node dissection, 167 had positive nodes and 51 of these patients had four or more positive lymph nodes involved and serve as the patient population base for this study. All patients received radiation therapy to the intact breast using tangential fields with subsequent electron beam boost to the tumor bed to a total median dose of 64 Gy. The majority of patients received regional nodal irradiation as follows: 40 patients received RT to the supraclavicular region without axilla to a median dose of 46 Gy, 10 patients received radiation to the supraclavicular region and axilla to a median dose of 46 Gy. Thirty of the 51 patients received a separate internal mammary port with a mixed beam of photons and electrons. One patient received radiation to the tangents alone without regional nodal irradiation. Adjuvant systemic therapy was used in 49 of the 51 patients (96%) with 27 patients receiving chemotherapy alone, 14 patients receiving cytotoxic chemotherapy and tamoxifen, and 8 patients receiving tamoxifen alone. RESULTS: As of December 1994, with a minimum evaluable follow-up of 5 years and a median follow-up of 9.29 years, there have been 18 distant relapses, 2 nodal relapses, and 5 breast relapses. Actuarial statistics reveal a 10-year distant metastases-free rate of 65%, 10-year nodal recurrence-free rate of 96%, and a 10-year breast recurrence-free rate of 82%. All five patients who sustained a breast relapse were successfully salvaged with mastectomy. Both patients with nodal relapses (one supraclavicular and one axillary/supraclavicular) failed within the irradiated volume. Of the 40 patients treated to the supraclavicular fossa (omitting complete axillary radiation), none failed in the dissected axilla. With a median follow-up of nearly 10 years, 29 of the 51 patients (57%) remain alive without evidence of disease, 15 (29%) have died with disease, 2 (4%) remain alive with disease, and 5 (10%) have died without evidence of disease. Overall actuarial 10-year survival for these 51 patients is 58%. CONCLUSIONS: We conclude that in patients found to have four or more positive lymph nodes at the time of axillary lymph node dissection, conservative surgery followed by radiation therapy to the intact breast with appropriate adjuvant systemic therapy results in a reasonable long-term survival with a high rate of local regional control. Omission of axillary radiation in this subset of patients appears appropriate because there were no axillary failures among the 41 dissected but unirradiated axillae.     

Radiotherapy of choroidal metastases: breast cancer as primary site

Forty-two cases of metastatic breast cancer to the choroid treated by radiation therapy were reviewed. Fifteen patients (36%) had bilateral and 27 patients (64%) had unilateral choroidal involvement. In 12 patients (29%) the choroid was the first site of dissemination. The median survival period after choroidal metastases was 10 months. Most patients were treated with Co60 in doses of 2500 rads tumor dose (TD) in ten fractions, 2500 rads, (TD) in five fractions and 3000 rads (TD) in ten fractions. An early group of patients had orthovoltage therapy. Good visual responses were obtained with each of the above treatment programs. Radiation treatment in the range of 2500-3000 rads TD in a short course is recommended for palliation of metastatic breast cancer to the choroid.     

Locally recurrent carcinoma of the breast. Results of radiation therapy

Local and regional recurrences are frequent problems in breast cancer management. Radiation therapy is effective in producing long term remission. This study evaluates the results of radiation therapy of 215 patients with recurrent disease limited to the chest wall and/or regional lymph node areas. The local results showed complete control in 67% of cases (mean and median durations 32 months and 22 months, respectively), partial control in 24% of cases (mean and median 11 and 8 months, respectively) and no control in the remaining 9%. The radiation dose recommended for the treatment of recurrent mammary carcinoma is 5000 rads in 5 weeks for relatively small lesions. Supplementary local doses of 500-1000 rads in 1 week may be given to bulky lesions as necessary for residual disease. Although local relapse indicates a poor prognosis, it is by no means totally hopeless. Of 215 patients treated 44 (21%) survived 5 years and 10 (5%) survived 10 years following radiation therapy of recurrent disease. There were seven patients, or 3%, who were free of cancer at 5 to 15 years. Radiation therapy was valuable in controlling local lesions, and thus, in improving quality of survival, even in those patients who eventually died of metastatic disease.     

Pelvic radiation therapy as a risk factor for ischemic colitis complicating abdominal aortic reconstruction

Ischemic colitis is an infrequent but potentially devastating complication of abdominal aortic reconstruction. Identification of patients with predisposing risk factors for the development of ischemic colitis can guide intraoperative measures to preserve or restore colonic blood flow during aortic surgery. Previous radiation therapy for pelvic malignancy may be one such predisposing risk factor. Two cases are presented in which ischemic colitis complicated abdominal aortic reconstruction in the setting of previous pelvic irradiation. In the months after radiation therapy for prostate cancer, one patient underwent infrarenal abdominal aortic aneurysm repair. Ischemic infarction of the sigmoid colon developed acutely after surgery and required emergent sigmoid colectomy. The second patient underwent reconstruction of an infrarenal abdominal aortic aneurysm after having had radiation therapy for a bladder tumor. Despite an initial satisfactory result, the patient's abdominal pain and diarrhea progressively worsened and he eventually required sigmoid colectomy for severe ischemic colitis. In both of these patients, the inferior mesenteric arteries were patent and had not been reimplanted. The association of pelvic radiation therapy with ischemic colitis after aortic reconstruction should focus attention to the operative details for maintaining the colonic circulation in these patients. Reimplantation of the inferior mesenteric artery in particular may prevent both the acute and the insidious variants of this complication in patients who undergo aortic surgery and decrease the incidence of this complication in patients with a history of radiation therapy to the pelvis.     

Irradiation of spontaneous carotid-cavernous fistulas

Two patients with spontaneous carotid-cavernous fistulas were successfully treated with cobalt 60 irradiation to the sellar region. Angiographically, one patient showed combined-type shunts comprising a dural internal carotid-cavernous fistula and a direct internal carotid-cavernous fistula; the other patient had a mixed dural external and internal carotid-cavernous fistula. The respective total radiation dose was 3,200 rads and 3,024 rads. The patients responded satisfactorily to the treatment, with disappearance of the fistulas on angiograms and patency of the internal and external carotid arteries.     

How to manage locally advanced primary and recurrent cancer of the uterine cervix: The surgeon's view

Locally advanced cancer of the uterine cervix covers a broad disease spectrum comprising primary tumours of >4 cm in size or FIGO stage >IIA and all local tumour relapses except the rare cases of small recurrences in a retained cervix. Treatment designs have to consider the probability of pelvic and periaortic lymph node metastases and – albeit less frequent in primary disease – distant metastases.Established treatment standards aiming to achieve pelvic and eventually periaortic tumour control are chemoradiation for locally advanced primary disease as well as post-surgical pelvic recurrences, and pelvic exenteration for post-radiation central relapses. A subset of patients with pelvic side wall relapses can now be successfully treated by laterally extended endopelvic resection as well. Based on the current results it is not evident whether neoadjuvant chemotherapy, radical hysterectomy and eventually adjuvant radiation are comparable or superior treatment alternatives for locally advanced intermediate stage cases. Likewise, the benefit of (laparoscopic) surgical staging including the exstirpation of bulky pelvic and periaortic lymph nodes has not been convincingly demonstrated to date. Both surgical treatment concepts need further well-designed prospective randomized trials for their evaluation. From the surgeon's perspective total mesometrial resection, therapeutic lymph node dissection, laterally extended endopelvic resection and new developments in restoration/substitution of pelvic functions have the potential to improve the therapeutic index for defined cohorts of patients suffering from locally advanced cancer of the uterine cervix.     

Irradiation of clinically uninvolved cervical lymph nodes

Of 402 patients with cancers of the oral cavity, oropharynx, and supraglottic larynx treated at Stanford between 1957 and 1972, 164 had clinically uninvolved cervical lymph nodes prior to the initiation of radiation therapy. Lymph node metastases developed later in 38 per cent of patients with primary oral cavity carcinomas who were treated with interstitial radium implants alone. No late cervical lymph node involvement was found in those patients who received high dose external irradiation to at least the primary site and first echelon lymph nodes. Lymph node failures were ultimately noted in 20 of the 140 patients (14 per cent), who received partial or complete neck irradiation, but 18 of these occurred in patients with uncontrolled primary lesions, suggesting that re-seeding of cervical lymph nodes had taken place rather than failure of the initial irradiation to control subclinical metastases. Our present policy is to treat the primary lesion and adjacent lymph nodes with high dose megavoltage techniques, combined with interstitial irradiation if possible. Bilateral supplemental inferior neck radiation ports are added for patients with advanced primary neoplasms and for those with clinically involved cervical lymph nodes. All other patients undergoing radiation therapy for stage T1 primary lesions and clinically negative necks also receive ipsilateral low neck irradiation. In addition, cervical lymph nodes are electively irradiated when the primary lesion has been resected. When these policies are adopted, the incidence of cervical lymph node failures is extremely low in patients whose primary sites remain controlled, and morbidity from the cervical radiation fields is negligible.     

Neuro-Beh?et: a follow-up of 4 cases treated with chlorambucil

Four patients diagnosed with Beh?et's disease developing neurologic manifestation are described. Central nervous system findings were observed in three of them and peripheral neuropathy in ther other patient. All the patients were treated with chlorambucil, 0.1-0.2 mg/kg/day as initial dose. Three of them ended the immunosuppressive therapy after a period of treatment between 12-18 months. None of the four patients suffered neurologic relapses once that the therapy with chlorambucil was started. In a similar way to other authors, we think that treatment with chlorambucil in neuro-Beh?et's disease may be useful to reduce morbility related to neurologic relapses.     

-Inguinal irradiation versus no lymph node therapy in small vulvar carcinoma with clinically negative lymph nodes (T1, NO-1)-

OBJECTIVE: The objective of this retrospective study was to determine if groin radiation was superior to no therapy in patients with small vulvar cancer with not palpable or not suspicious inguinal lymph nodes (T1, N0-N1). METHODS: From 1974 to 1990, 135 patients with invasive T1, NO-1 vulvar cancer underwent radical vulvectomy with hot knife, groin nodes were left in situ. In 65 patients vulvectomy was followed by inguinofemoral irradiation: 70 patients had none. There were more cases with clitoris carcinoma (p < 0.04) in the group with groin irradiation but no other significant difference in prognostic factors was found. RESULTS: The actuarial 5-year survival was 93.7% with groin irradiation versus 92.4% without lymph node therapy. Inguinal relapses occurred in only 4.6% of cases with groin irradiation versus 10% without lymph node treatment (n.s.). CONCLUSIONS: Radiation therapy to the groin seems to reduce groin relapses in early vulvar cancer.     

Improved freedom from PSA failure with whole pelvic irradiation for high-risk prostate cancer

PURPOSE: To determine the impact of whole pelvic irradiation on the risk of PSA failure in prostate cancer patients, at high predicted risk for lymph node involvement, receiving definitive radiotherapy. MATERIALS AND METHODS: Between October 1987 and December 1995, 506 patients with clinically localized prostate cancer were treated with definitive radiotherapy at UCSF and affiliated institutions. Treatment consisted of 4-field whole pelvic irradiation followed by a prostate-only boost, or prostate-only treatment (median follow-up was 35 months and 30 months, respectively). PSA failure was defined as: 1. a PSA value > or = 1 ng/ml; or 2. a PSA value that rose > or = 0.5 ng/ml in < or = 1 year posttreatment on two consecutive measurements, with the first rise defined as the time of failure. The calculated risk of lymph node positivity (%rLN+) was defined as 2/3(iPSA) + 10(GS-6), and high risk was defined as %rLN+ > or = 15%. Univariate and multivariate analyses were performed. RESULTS: A total of 201 high-risk patients were identified. High-risk patients who received whole pelvic irradiation had significantly improved freedom from PSA failure compared to those who received prostate-only treatment (median PFS = 34.3 months vs. 21.0 months; p = 0.0001). Potential confounding variables, including initial PSA, Gleason score, T stage, radiation dose, year of treatment, use of three-dimensional (3D) conformal techniques, and use of hormone therapy, did not account for the observed difference in time to PSA failure. Multivariate analysis revealed type of radiation treatment to be the most significant independent predictor of outcome. CONCLUSION: Whole pelvic radiotherapy significantly improves the PSA failure-free survival in patients with a high calculated risk of lymph node positivity.     

Immunoepidemiology of Dracunculus medinensis infections I. Antibody responses in relation to infection status

OBJECTIVES: The sites of recurrent carcinoma of the prostate were localized with radiolabeled monoclonal antibody, and these sites were correlated with the response of patients treated with pelvic radiation after prostatectomy. METHODS: Radionuclide scans were performed with indium 111-labeled CYT-356, a monoclonal antibody that binds to prostate epithelial cells, in 48 men diagnosed with recurrent carcinoma detected by prostate-specific antigen (PSA) screening after radical retropubic prostatectomy. RESULTS: In 48 patients with recurrent carcinoma detected by PSA screening following radical retropubic prostatectomy, 73% had monoclonal antibody activity beyond the prostatic fossa, and only 3 patients (6%) had activity in the prostatic fossa alone; 65% had monoclonal antibody activity in pelvic lymph nodes despite the fact that lymph node dissections were pathologically negative at the time of prostatectomy in 90% of the patients; and 23% of patients had monoclonal antibody activity in abdominal and extrapelvic retroperitoneal nodes. Of 48 patients, 13 underwent external beam radiation therapy after monoclonal antibody scans. Six patients had scans showing activity beyond the field of radiation, and radiation therapy failed in 4 of these patients. Seven patients had scans with no activity beyond the field of radiation therapy, and radiation therapy failed in only 2 of these patients. CONCLUSIONS: The scans frequently show monoclonal antibody uptake in pelvic, abdominal, and extrapelvic retroperitoneal sites beyond the region of limited obturator node dissections and may account for the understaging and subsequent failure of radical prostatectomy in some patients. The monoclonal antibody scan seems to be a good predictor of which patients will respond to radiation therapy after radical prostatectomy, but because these patients often have nodal activity beyond the radiated field, this initial response may not be curative.     

Assessment of abdominal lymph nodes in a normal paediatric population: an ultrasound study

During a 9 month period, 50 consecutive children were evaluated by ultrasound to determine the size, location (mesenteric vs para-aortic), number, shape and texture of abdominal lymph nodes in a normal paediatric population. High resolution linear array transducers were used with graded compression. Nodes ranging from 10 to 20 mm were recorded in the majority of subjects. In all cases mesenteric lymph nodes were larger and more numerous than para-aortic nodes. Para-aortic lymph nodes were not seen in isolation.     

Initial relapses in previously treated Hodgkin's disease. I. Results of second treatment

Two hundred forty-three consecutive patients with Hodgkin's disease who relapsed after an initial course of treatment at the Stanford University Division of Radiation Therapy underwent subsequent systematic evaluation and retreatment. An analysis of the influence of numerous parameters, including sex, histopathology, original stage, relapse site, and original and second therapy, on actuarial survival and on relapse-free survival was undertaken. Most relapses (87%) occurred within 3 years of the initial treatment course. The 5-year relapse-free survival measured from the time of second treatment increased from 14% before to 39% after the introduction of multiple agent chemotherapy (MOPP) for relapsing disease. Patients treated with MOPP chemotherapy for nodal relapses showed increased subsequent relapse-free survival (61%) when compared with patients treated only with radiotherapy for nodal relapses. Based on the combined findings of this analysis, recommendations are made regarding the management of patients with Hodgkin's disease who have suffered a relapse.     

Primary mediastinal seminoma. Efficacy of chemo-radiotherapy alone

A treatment policy must be established for primary mediastinal seminoma. We have treated five patients with this entity during 18 years. All our patients presented with a bulky mass as is usual for this disease. Our first patient was treated surgically and then with radiation, but developed recurrences and died 11 years after the initial diagnosis. Three subsequent patients, one with multiple lymph node metastases, were treated with radiation followed by cisplatin. Our most recent patient received two courses of adriamycin-reinforced PVB, and then radiation for consolidation, followed by another course of chemotherapy. For these five patients, the 5- and 10-year survival rates were both 100%. A review of the literature emphasized the fact that either radiation or surgery has recently been replaced by chemotherapy as the front-line treatment of this rare tumor in light of a better response to the latter form of treatment. We fully agree with this policy. Based on the favorable long-term results of our patients we conclude that chemo-radiotherapy can cure primary mediastinal seminoma, even in its extended form, without surgery. An initial three courses of cisplatin-based chemotherapy like adriamycin-reinforced PVB or BEP should be followed by radiation of up to 4,000 cGy for consolidation. Surgery may play a limited role for tumors that are small at presentation, or for any possible viable residue seen on roentgenograms following chemo-radiotherapy.     

NLM Medical Library Resource Improvement Grant Program: an evaluation

Since 1967 we have been using preoperative radiation therapy for hypernephroma as proposed by RICHES. Radiation therapy, to include the para-aortic lymph nodes, is given in 250 rad increments 4 times weekly to a total dose of 3000 rads. After an interval of 3 weeks following the radiation therapy, we are performing the radical nephrectomy. 100 patients were treated by this method in the years 1967-1975: 32 patients were in stage I, 7 in stage II, 50 in stage III and 11 patients in stage IV. In 26 patients more than 5 years have passed since the beginning of the treatment: 46% od these survived. The survival for 3 years is 63, for 1 year after the surgery 80%. The surgical mortality rate is 2%. The object od the preoperative treatment is: 1. Devitalization of growing cells in the periphery of the tumor, thus preventing metastases and local recurrence. 2. Decreasing the size of the tumor and thereby facilitating surgery. In one-third of the cases there is radiologically demonstrable decrease in the size of the tumor mass, probably secondary to obliteration of the dilated veins in the capsule. The delay of six weeks has had no adverse effect on the outcome of the disease.     

The Nicolas Andry Award-1995. Fracture healing. Radiation induced alterations

This study investigated the effects of radiation on fractures in a rat femur model. Two different radiation dosage fractionation schemes (1100 rads given in one dose and 2500 rads given in 10 divided doses over 12 days) and three different times of initiation of radiation (1 day before fracture, 3 or 10 days after fracture) were studied. Fractures exposed to these levels of radiation all appeared to heal during the course of this experiment, although with varying degrees of delay, with the exception of those exposed to a single dose of 1100 rads 3 days after fracture. These animals remained at a more immature level of repair histologically compared with the control group, throughout the entire time evaluated. The strength of the final repair remained less than the control for all the groups receiving treatment. These results may offer some explanation for the clinical observations of an increased incidence of delayed union and nonunion of fractures, an increased incidence of fracture and refracture in irradiated bone, and an increased incidence of fracture and nonunion in constructs using radiation in conjunction with allogeneic bone. Furthermore, the observed effects were generally no different in the animals treated with the two clinically relevant dose fractionation schemes chosen for this study.     

Antistaphylococcal and antistreptococcal killing kinetics of ciprofloxacin, ofloxacin, sparfloxacin, and trovafloxacin

BACKGROUND: Use of blood culture studies for early diagnosis of Mycobacterium avium complex (MAC) infection has become important due to the recent development of effective antibiotic therapy for this condition. This study assessed the abdominal computed tomography (CT) findings in patients with AIDS who presented with bacteraemic MAC infection. METHODS: A retrospective analysis of abdominal CT scans was performed in 24 patients who presented with MAC-positive blood culture. CT images were reviewed specifically to evaluate for lymph node enlargement and attenuation, hepatomegaly, splenomegaly, bowel wall abnormality and for any other pathological changes. Comparison was made to prior reports of the CT findings in this disease process. RESULT: Enlarged intra-abdominal mesenteric and/or retroperitoneal lymph nodes were found in 10 patients (42%). These nodes were characterized by homogeneous, soft-tissue attenuation in eight of the 10 patients. Hepatomegaly, splenomegaly and small bowel wall thickening were noted in 12 (50%), 11 (46%) and four (14%) patients, respectively. CT findings were evaluated as normal in six (25%) patients. CONCLUSIONS: Enlarged mesenteric and/or retroperitoneal lymph nodes in AIDS patients with bacteraemic MAC were observed much less frequently on CT than previously reported in AIDS patient populations. Normal abdominal CT findings do not exclude this diagnosis and may reflect a trend towards earlier detection of MAC disease.     

Superior mesenteric artery syndrome presenting with acute massive gastric dilatation

A 14-year-old girl presenting with acute massive gastric dilatation secondary to duodenal obstruction by the superior mesenteric artery is described. The diagnosis was facilitated by contrast-enhanced abdominal computerized tomography. She was successfully treated by gastrostomy and subsequent duodenal derotation. This unique presentation of the superior mesenteric artery syndrome is discussed.     

Laparoscopic splenectomy. Technique and results in a series of 27 cases

Between early 1992 and December 1994, laparoscopic splenectomy was performed in 27 patients with idiopathic thrombocytopenia (ITP), hairy-cell leucemia, HIV, or Hodgkin's disease. In all cases medical treatment, especially cortisone therapy, failed. In Hodgkin's disease the splenectomy was combined with liver biopsies and dissection of parailiacal, paraaortic, and mesenteric lymph nodes for abdominal staging. The operation was performed using four trocars; the splenic vessels were divided by a linear stapler. In general the spleen was removed in a bag through a slightly enlarged trocar incision or after morcellation. Three patients needed a small laparotomy for the removal (laparoscopic assisted). In a recent case of Hodgkin's disease the intact spleen was removed via posterior colpotomy. In 22 of 27 cases (81%) the operation was finished laparoscopically. Five times a conversion to conventional laparotomy was necessary because of bleeding of enlarged lymph nodes at the hilum. Wound infections occurred in two cases. In one patient with ITP the platelet count did not improve and continuous blood loss led to relaparotomy at the 1st postoperative day. No surgical bleeding was found. All patients tolerated a fluid diet at the 1st postoperative day and hospitalization time was 4.4 days (range 3-14). Regarding the low complication rate and the advantages of a smaller abdominal trauma in the postoperative period, the laparoscopic approach for elective splenectomy and laparoscopic abdominal staging has a substantial benefit for the patients.