Intracavitary afterloading therapy as a new technique of boost irradiation in anal canal carcinoma

PURPOSE: There are different techniques of boost irradiation in the treatment of patients with anal carcinoma. A new system of applicators is presented, which can be used for an intracavitary afterloading therapy. MATERIAL AND METHODS: Three different applicators are available, the first with a central catheter (K1), a second with 5 semicircular fixed catheters (K2) and an eccentric shield, a third with 8 circular fixed catheters and a central shield (K3). RESULTS: The adequate choice of applicator and catheters takes into consideration the individual localisation and extension of anal carcinoma in planning therapy. Thus, in circular growing tumors, an irradiation of the whole circumference of the anal canal is possible. In non-circular growing tumors, the dose applied in the non-affected part of the anal canal can be reduced to a quarter of the dose applied at the tumor. CONCLUSION: The new system of intracavitary afterloading therapy is a good alternative to previous techniques of boost irradiation in the treatment of anal carcinoma. By means of this technique, irradiation can be highly individualized, the tumor better included and non-affected sections of the anal canal saved.     

Palliative irradiation in the treatment of breast carcinoma

It is considered that in 30% of female patients with breast cancer a certain form of evolutive disease occurs within 5 years from documented diagnosis. In these female patients, 58% develop distal metastases. Thus, a great number of these female patients enter the phase when hope for recovery is small. Then supportive therapy is used. It's main task is to alleviate the life of these patients. Palliative radiotherapy is one of the main elements of this therapy. It is directed to decrease the pain, and bleeding, to prevent fractures and decompression of the spinal cord, as well as many other evolution consequences of local or distal disease. The correct and timely definition of indications for radiotherapy, the optimal planning and conduction of the therapy should take into account the patient's characteristics as well as the main postulates on which radiotherapy is based. In this way the satisfying effects on patients with disseminated breast cancer, may be expected.     

Serum ribonuclease in patients with lung carcinoma

Fifty-one previously untreated cases of lung carcinoma and 7 normal healthy controls were evaluated with respect to serum ribonuclease (S-RNase) levels. Cellular immunity was tested in 22 of these 51 cases by leukocyte migration inhibition test (MIT) using extract of culture cell line of lung carcinoma. S-RNase levels in lung carcinomas were significantly elevated. There appeared to be no difference in S-RNase levels by histological classification. More striking was high S-RNase level in disseminated versus localized cases. MIT results indicated impairment of cellular immunity in those cases of more elevated S-RNase. S-RNase may be implicated in blocking phenomenon associated with neoplastic disease.     

Radical hysterectomy with pelvic lymphadenectomy in patients with carcinoma of the uterine cervix--3 years' experience

INTRODUCTION: Almost all patients with invasive cervical carcinoma can be treated with either primary irradiation therapy or primary surgery. Some patients are appropriately treated with the combination of irradiation and surgery. Chemotherapy is not effective as primary treatment of invasive cervical cancer but may be used as additional therapy and when the disease is recurrent or persistent. There are some important advantages of primary extensive surgery over irradiation. The findings at operation and that from the careful pathologic examination of surgical specimens can be very helpful in selection of patients for supplementary postoperation irradiation therapy or chemotherapy, or both [1-6]. AIM OF THE STUDY: The aim of the study was to compare pretreatment clinical evaluations with surgical and postsurgical pathohistological findings. METHODS: Extensive hysterectomy and bilateral pelvic lymphadenectomy were used in the treatment of 251 patients with early invasive cervical cancer. The patients were treated at the Department of Obstetrics and Gynaecology of the Clinical Centre of Serbia in Belgrade, between 1993 and 1995. Cervical cancer was detected by clinical examination, colposcopic and cytologic (Pap smear) findings, colposcopically directed biopsy or conisation and pathological findings, sonography, chest radiography, blood and urine analyses. In some cases we had to make other examinations (cystography, cystoscopy, intravenous pyelography, sygmoidoscopy, rectoscopy, CT scanning and magnetic resonance). The surgical treatment of invasive carcinoma of the cervix was limited to those patients in whom the disease was confined to the cervix or vaginal fornix (stage Ia, stage Ib or stage IIa), and who were in high surgical risk. RESULTS: Over a three year period (1993-1995) there were 251 patients with invasive cervical cancer, treated by primary surgery (radical hysterectomy and bilateral pelvic lymphadenectomy sec. Werthein-Meigs), average age 42 years. Most of the patients demonstrated invasive cervical cancer, clinically classified in Ib st. (81.67%). Some characteristics of pathologic findings, such as parametric width, number of removed lymph nodes, percentage of lymph nodes metastases and correlation with clinical stage of invasive cervical cancer, histologic grade of cervical cancer with lymph node metastasis, pathologic findings after surgical treatment, correlation between clinical and surgical staging, were already presented in tables. DISCUSSION: In the last decades the incidence of invasive cervical cancer and death rate have been decreased. Progress in reducing mortality is primarily attributed to the introduction of cervical cancer screening as part of regular gynaecologic examinations. Regular testing with Papanicolaou (Pap) smear and colposcopy have an important role in this problem [1]. Extensive hysterectomy and bilateral pelvic lymphadenectomy were used in the treatment of 251 patients with early invasive cervical cancer. We found that the clinical diagnosis of disease extent was correct in 67.7% of patients who underwent extensive surgery for early invasive cervical cancer. Sensitivity of clinical findings was 75.8% and positive predictive value was 86.2%. Lymph node metastasis was detected in 17% patients. Brodman at al. [14] found that clinical examinations, including CT scanning and magnetic resonance, were correct in only 62.5% of cases. It is very difficult to detect parametric involvement and lymph node metastasis by clinical examinations. Irradiation therapy was used in the postoperative period as additional treatment of extensive hysterectomy and bilateral pelvic lymphadenectomy in 89.7% of patients. CONCLUSION: The findings at operation and that from the careful pathologic examination of surgical specimens are absolutely irreplaceable and important in grading invasive cervical cancer and selection of patients for supplementary postoperate irradiation therapy.     

Myasthenia gravis associated with small-cell carcinoma of the lung

A 49-year-old man complained of a 3-month history of progressive generalized muscle weakness. He was diagnosed as having small-cell lung carcinoma at the same time. He received an intravenous injection of edrophonium chloride with remarkable improvement of muscle strength. Electromyographic studies revealed a compound muscle action potential that decreased after repetitive stimulation. These findings were considered representative of myasthenia gravis (MG), and inconsistent with Eaton-Lambert syndrome. The appearance of MG with small-cell lung carcinoma seems to be very rare, but possible.     

Muscle metastasis in a patient with epidermoid carcinoma of the lung

Diagnosis of vertically acquired human immunodeficiency virus (HIV) infection is often difficult because of transplacentally acquired maternal antibodies. The polymerase chain reaction (PCR) test is commercially available and has high sensitivity and specificity. To evaluate the usefulness of PCR testing in the early diagnosis of perinatally acquired HIV infection, we reviewed records of 122 children having follow-up in the Northeast Florida Pediatric AIDS Program. Seventy-two children were excluded for various reasons. Of the remaining 50 children, 37 had PCR testing. In 5 children, the initial PCR test was done at > 18 months of age. Results of PCR testing were positive in 8 of 13 (62%) at birth, 12 of 18 (67%) by 1 month of age, 18 of 23 (78%) by 2 months of age, and 20 of 24 (83%) by 3 months of age. In 24 of 27 (85%), results were positive by the time the children reached 4 months of age. Our data suggest that the PCR test is a useful tool for early diagnosis of vertically transmitted HIV infection.     

Bronchioloalveolar carcinoma of the lung

Iodine-123-iodobenzamide (IBZM) is a specific antagonist of dopamine D2 receptors and usually is used to study neuropsychiatric disorders. It also has a substantial affinity for malignant melanomas. This has been attributed to specific dopamine D2 receptor binding on melanoma cells because melanocytes and dopaminergic neurons share the same ectodermal origin and are both able to produce melanin. However, IBZM binding to melanoma metastases occurs predominantly 24 hr after injection, which is much later than maximal specific D2 receptor binding is expected. Furthermore, IBZM binding is not consistent in melanoma patients. This points to another mechanism of IBZM binding to melanoma cells. The aim of this study was to characterize IBZM-binding metastatic melanoma patients clinically and histologically to shed light on the nature of this mechanism. METHODS: Twenty-one patients with proven or suspected metastases of a malignant melanoma entered this prospective study after surgical removal of the primary tumor. Whole-body scans, planar scintigrams and SPECT scans were performed 2-5 hr and 1 day after intravenous injection of 185 MBq IBZM. RESULTS: The suspected diagnosis of metastatic cancer was later confirmed in 17 patients by histology, clinical follow-up, x-ray, CT or other radiologic methods. Four patients were free of tumor tissue at the time of investigation and remained stable for 2 yr thereafter. Twelve of the 17 patients had a melanotic and 5 had an amelanotic subtype of the tumor. Iodine-123-IBZM accumulation occurred in the metastases of 10 of the 12 patients with melanotic melanoma and in 0 of the 5 patients with the amelanotic tumor type (p < 0.01; chi-square test). Furthermore, IBZM accumulation occurred in 0 of the 11 amelanotic metastases but in 20 of the 25 melanotic metastases (p < 0.001). The sensitivity is, thus, 83% for the detection of melanotic melanoma metastases on a patient basis and 80% on a lesion basis. Iodine-123-IBZM scintigraphy demonstrated one previously unknown metastasis. Six initially suspected lesions were not due to melanoma metastases and were IBZM-negative. No false-positive IBZM accumulations occurred in our patients. CONCLUSION: Iodine-123-IBZM binds to melanotic malignant melanomas with high specificity and moderate sensitivity but not to amelanotic melanomas. Our data suggest that the tracer does not bind to membrane dopamine receptors of the tumor but is built in or closely bound to intracellular melanin.     

A safe high-yield technique for cutting needle biopsy of the lung in patients with diffuse lung disease

The approach to the diagnosis and management of patients with diffuse infiltrative lung disease (DILD) is controversial. The results of transbronchial biopsy are often unsatisfactory. The role of open lung biopsy is highly variable. Percutaneous cutting needle biopsy (CNB) is not recommended because of its reported high morbidity/mortality relative to its low diagnostic yield. We report a technique for CNB with a high diagnostic yield and a low morbidity and no mortality in 228 patients with DILD over the past 23 years. METHODS: The salient features of the technique for CNB are as follows: the anesthetic needle does not enter the pleural space; a Franklin Silverman needle is inserted into the intercostal space posteriorly at outer one-third of chest wall; the biopsy is performed with the breath held at normal end expiration; the plane of pleural space is broken with sudden insertion of needle 8 to 15 cm into lung; and the pathway of the needle is maintained parallel to the lateral chest wall. RESULTS: A diagnosis was established in 129 of 145 biopsies (89%) performed by a trained operator (A.H.N.). There were 36 pneumothoraces (25%), four minimal hemoptyses (3%), and two chest tube placements (1%). There were no deaths (0%). CONCLUSION: With meticulous attention to technique and careful selection of patients, the procedure offers a relatively safe alternative to open lung or thoracoscopic lung biopsy in patients with DILD.     

Radical vulvectomy with postoperative irradiation for vulvar cancer: therapeutic implications of a central block

PURPOSE/OBJECTIVE: To report the long-term results of vulvectomy, node dissection, and postoperative nodal irradiation using a midline vulvar block in patients with node positive vulvar cancer. METHODS AND MATERIALS: From 1971 through 1992, 27 patients with carcinoma of the vulva and histologically involved inguinal lymph nodes were treated postoperatively with radiation therapy after radical vulvectomy and bilateral lymphadenectomy (n = 25), radical vulvectomy and unilateral lymphadenectomy (n = 1), or hemivulvectomy and bilateral lymphadenectomy (n = 1). Federation Internationale de Gynecologic et d'Obstetrique stages were III (n = 14), IVA (n = 8), and IVB (n = 5) squamous cell carcinoma. Inguinal lymph nodes were involved with tumor in all patients (average number positive = 4, range 1-15). Postoperative irradiation was directed at the bilateral groin and pelvic nodes (n = 19), unilateral groin and pelvic nodes (n = 6), or unilateral groin only (n = 1). These 26 patients had the midline blocked. In addition, one patient received irradiation to the entire pelvis and perineum. Doses ranged from 10.8 to 50.7 Gy (median 45.5) with all patients except 1 receiving > or = 42.0 Gy. RESULTS: Actuarial 5-year overall survival and disease-free survival estimates were 40% and 35%, respectively. Recurrences developed in 63% (17/27) of the patients at a median of 9 months from surgery (range 3 months to 6 years) and 15 of these have died; two patients with recurrences are surviving at 24 and 96 months after further surgery and radiation therapy. Central recurrences (under the midline block) were present in 13 of these 17 patients (76%), either as central only (n = 8), central and regional (n = 4), or central and distant (n = 1). Additionally, three patients developed regional recurrences and one patient developed a concurrent regional and distant relapse. One patient developed a squamous cell cancer of the anus under the midline block 54 months after the initial vulvar cancer and an additional patient developed transitional cell carcinoma of the ureter (outside the radiation field) 12 months after diagnosis. Factors associated with a decreased relapse-free survival included increasing Federation Internationale de Gynecologic et d'Obstetrique stage (p = 0.01) and invasion of the tumor into the subcutaneous (SC) fat or deep soft tissue (p = 0.05). Chronic lower extremity edema developed in four patients, but there have been no other complications. CONCLUSIONS: Radical vulvectomy has often been considered sufficient central treatment for vulvar carcinoma, with postoperative irradiation directed only to the nodes. Although designed to protect the radiosensitive vulva, use of a midline block in this series resulted in a 48% (13/27) central recurrence rate, much higher than the 8.5% rate previously reported with this technique. Routine use of the midline block should be abandoned and, instead, postoperative irradiation volumes should be tailored to the individual patient.     

Outcome of obstructive uropathy after pelvic irradiation in patients with carcinoma of the uterine cervix

A prospective, randomized study was performed to assess the effectiveness of postoperative closed suction drainage. One hundred and twelve consecutive procedures involving autologous iliac-crest bone graft were performed, from December 29, 1992, to July 1, 1993, following a traumatic injury of the spine in 108 patients. Sixty of the sites from which the bone graft had been obtained were drained with a single large Hemovac device. The drains were maintained for two to five days postoperatively. The remaining fifty-two incisions were closed without a drainage device. All patients were evaluated clinically for problems with wound-healing. The incisions were considered to be healed when they had been asymptomatic for one year. Of eleven patients who had problems with wound-healing, six had been managed with a drain and five had not. The findings of this study do not support the routine use of drainage at the donor sites of iliac-crest bone grafts.     

Efficacy and safety of prophylactic cranial irradiation in patients with small cell lung cancer

In this review we examine the complex interactions between lipoprotein metabolism, immunosuppressive drug therapy, and inflammation and the potential benefits of lipid-lowering drug therapy after heart transplantation. The newer formulations of cyclosporine, Neoral (Novartis Pharmaceuticals; Basle, Switzerland), and other newer agents such as tacrolimus may have advantages in regard to lipid metabolism as compared with traditional triple-drug immunosuppression. Lipoprotein levels may influence both the toxicity and efficacy of cyclosporine. Dyslipidemia may adversely influence inflammation and rejection in the allograft. Two recent clinical trials have shown that lipid-lowering therapy with a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor alone or in combination with low-density lipoprotein apheresis may confer significant benefits toward preventing transplant coronary artery disease.     

Effects of single doses of irradiation on the expression of resistance-related proteins in murine NIH 3T3 and human lung carcinoma cells

In this report the effects of single doses of ionizing radiation on the mRNA expression of several proteins involved in multiple drug resistance were analyzed. Murine NIH 3T3 cells treated with single doses of 5, 10 and 20 Gy during the time interval from 1.5 to 72 h after irradiation were compared with their corresponding controls at the same points of time. The glutathione S-transferase-pi (GST pi) level was elevated in cells treated with 10 or 20 Gy from 24 to 72 h after irradiation compared with the control. Topoisomerase II alpha and thymidylate synthase were decreased in irradiated cells 24-72 h after exposure. These down-regulations were associated with cellular proliferation, determined by mRNA expression of the proliferation marker histone 3. Irradiated cells exhibited no alteration in the P-glycoprotein or glutathione peroxidase mRNA content. The finding that GST pi mRNA was overexpressed after irradiation was validated by investigations on a human lung carcinoma cell line (LXF 289) on the mRNA and protein level. Thus, our results indicate that irradiation alters the expression of proteins involved in multidrug resistance and may, therefore, play a role in clinical drug response.