Therapeutic concepts of proteinuria and intra-glomerular hypertension

Leukemia has rarely been reported as a late complication of 131I therapy, occurring mostly after cumulative doses of 800 mCi. We observed two cases of acute myeloid leukemia (AML) after 131I therapy for hyperthyroidism and thyroid carcinoma, respectively. The first patient was a 45-year-old woman treated with a single dose of 27 mCi 131I for hyperthyroidism. She developed AML (FAB M2) 14 months after receiving 131I; the second patient was a 44-year-old man affected by refractory thyroid carcinoma who received a total dose of 1 Ci 131I plus radiotherapy and developed AML (FAB M6) 8 years after the first exposure to 131I. Although it is a very rare event, the occurrence of leukemia after 131I treatment should be kept in mind, considering the widespread use of 131I, particularly in the treatment of hyperthyroidism, and the unfavorable outcome of secondary leukemia.     

Radiation-induced malignant mesenchymoma of the chest wall following treatment for breast cancer

21 years after radiotherapy for breast cancer, a 63-year-old woman developed a malignant mesenchymoma of the chest wall. The total irradiation dose was 132 Gy. The first clinical symptom of this second malignancy was a slight irregular calcification around the implanted silicon protheses observed in a conventional chest X-ray. Radiation-induced sarcoma is a very rare complication of radiotherapy. In cases of chest wall calcification after radiation therapy further investigation should be carried out, because some patients with radiation-induced sarcoma could be saved, if an early diagnosis is reached.     

Salvage therapy of advanced squamous cell carcinoma of the mouth cavity and oropharynx. Results of interstitial high-dose-rate brachytherapy combined with ablative tumor surgery

PURPOSE: The clinical effect of high-dose-rate (HDR) interstitial brachytherapy combined with tumor resection was investigated in this retrospective study on patients with recurrent oral and oropharyngeal squamous cell carcinoma. PATIENTS AND METHODS: Oral and oropharyngeal squamous cell carcinoma in 38 patients were treated over a period of 7 years (1988-1994) by HDR interstitial brachytherapy using Gammamed 12i equipment. Pretreatment of patients in terms of irradiation and surgery differed (33 irradiated with a total dose between 60.0 and 75.6 Gy, including 8 patients with additional surgery; 1 patient with surgery alone, and 4 patients without any pretreatment). Indications for interstitial brachytherapy differed according to individual responses to treatment and medical histories. RESULTS: Interstitial brachytherapy was successful in the majority of patients, i.e. complete remission: 12, partial remission: 19, no change: 2, progression: 5. Local control and overall survival including patients with surgical treatment was 59% and 81% at 6 months and 47% and 49% after 12 months, respectively. CONCLUSION: Interstitial HDR brachytherapy with Iridium 192 is recommended in patients with local recurrences or second primary carcinomas after previous external radiotherapy in the head and neck region. Combination of interstitial brachytherapy and surgery is preferable for these patients.     

Ganciclovir-associated hypercalcemia in a renal transplant patient

We report a patient with nasopharyngeal cancer with long-term follow-up of more than 16 years after the first course of radiotherapy in 1981. He developed a lung metastasis in 1996 after having a second course of radiotherapy for neck recurrence in 1989. The patient was a 42-year-old man with a nasopharyngeal tumor and a fixed upper neck metastasis (T1N1M0), which was treated with definitive radiotherapy. He manifested regional recurrence, at the margin of the radiation portal, with an 8 year disease-free interval, which was treated successfully by definitive re-irradiation. He developed a solitary lung metastasis, which was treated by video-assisted thoracoscopic lung resection, 7 years disease-free after the second course of radiotherapy. For 20 months after the removal of the lung metastasis he has been generally well without any signs of recurrence of sequelae. This case indicates the efficacy of definitive re-irradiation for regional recurrence and the necessity for long-term observation after radiation therapy for nasopharyngeal cancer.     

Fibronectin expression in cancer tissues from patients undergoing radiation therapy

Fibronectin expression and distribution were examined in cancer tissues from 19 patients with cancer of the head and neck regions. Samples taken before and after irradiation of approximately 10 Gy, 20 Gy or 30 Gy were analyzed by the avidin-biotin-horseradish peroxidase method using mouse monoclonal antibodies against human fibronectin. The results were correlated with the patient's prognosis after radiation therapy. No remarkable changes in the fibronectin expression or distribution were found between tissue specimens taken before and after each dose of irradiation. The prognosis, however, varied according to the degree of expression and the distribution pattern of fibronectin. Seven patients in which the cancer tissue was encircled by a thick fibronectin network are still alive without recurrence 4.5-6 years after treatment, whereas 6 patients in which fibronectin was only faintly expressed or focally distributed died or developed recurrence soon after treatment. The present findings demonstrate that fibronectin expression and distribution in cancer tissue are intimately related to the patient's prognosis, and that the analysis of these two parameters is applicable as a predictive assay in radiotherapy of cancer of the head and neck regions.     

United States Thrombotic Thrombocytopenic Purpura Apheresis Study Group (US TTP ASG): multicenter survey and retrospective analysis of current efficacy of therapeutic plasma exchange

PURPOSE: Clinical experiences in interstitial 192-iridium HDR brachytherapy for the treatment of unresectable pancreatic carcinoma are presented. Brachytherapy has been used as boost irradiation in a multimodality treatment concept together with external radiotherapy and simultaneous chemotherapy. Practicability during clinical routine, tolerability and toxicity of treatment are investigated. PATIENTS AND METHODS: Nineteen patients (9 female, 10 male, median age 67 years) with unresectable carcinoma of the pancreas have been treated with interstitial brachytherapy. Distribution according to UICC stages showed 4, 10 and 5 patients in stage II to IV respectively. In all cases afterloading technique with 192-iridium in HDR-modus was used. A total dose of 10 to 34 Gy to the reference isodose was delivered (single dose 1.88 to 5 Gy, median 2.5 Gy). Brachytherapy was followed by external radiotherapy, delivering an additional dose of 40 to 58 Gy. Nine patients received simultaneous chemotherapy (5-fluorouracil, leucovorin). Treatment planning was performed based on CT scans, allowing spatial correlation of isodose curves to the patient's anatomy. RESULTS: Median survival time was 6 months. A trend of lower survival rates with advanced stage of disease (median survival stage IV 4 months, stage II and III 6.5 months) was seen. Local control rate was 70%. Brachytherapy treatment was well tolerated, severe acute side effects were not observed. One patient developed pancreatic fistulae 4 months and 1 patient a gastric ulcer 7 months after treatment. Pain release was achieved in all patients. CONCLUSIONS: 192-iridium HDR-brachytherapy is an effective tool in the treatment of unresectable pancreatic carcinoma with a high rate of local control and a low rate of side effects and is comparable IORT or seed implantation.     

Autoimmune endocrine disease induced by recombinant interferon-alpha therapy for chronic active type C hepatitis

To elucidate the role played by interferon-alpha (IFN alpha) in the pathogenesis of autoimmune endocrine disease, we determined the autoantibody status, thyroid function test results, hemoglobin-A1c levels, and clinical symptoms of 58 patients who received IFN alpha for treatment of chronic active type C hepatitis. Each patient was treated for 6 months with a total dose of 391 +/- 140 x 10(6) U (mean +/- SD). Thyroid microsomal and/or thyroglobulin antibodies newly appeared or were increased in titer in 6 patients, 2 of whom developed hypothyroidism during IFN alpha therapy. Neither islet cell antibodies nor insulin-dependent diabetes mellitus developed during IFN alpha therapy, although hemoglobin-A1c levels were increased in 2 patients. One patient became positive for antimitochondrial antibodies, and another patient with preexisting antimitochondrial antibodies also manifested deterioration in liver function test results. Parietal cell antibodies and smooth muscle cell antibodies were the most frequent newly developed antibodies in 7 patients. Adrenal medullary cell antibodies and nuclear antibodies newly developed in 2 and 1 patients, respectively. At least 1 of 8 autoantibodies newly appeared in 19 patients (32.8%) and hypothyroidism developed in 2 patients (3.4%) during IFN alpha therapy. On the other hand, in 19 age- and sex-matched patients who did not receive IFN alpha, no autoantibody appeared, and no autoimmune disease developed during a follow-up period of 3 months. These findings suggest that IFN alpha acts as an immunomodulatory agent, inducing autoantibody production and the development of autoimmune disease in susceptible patients. Special attention should be paid to the development of hypothyroidism during IFN alpha therapy.     

Metastasizing auricular basal cell carcinoma

Basal cell carcinoma represents the most common skin cancer and involves the head and neck area in 80% to 85% of all patients treated. Despite their frequent occurrence, metastatic spread from these tumors is rare. This paper presents a case of a patient who had a metastasizing basal cell carcinoma. Despite control of primary disease by radical surgery and adjunctive irradiation, bony metastasis was found within nine months of therapy. Palliative therapy was given, but the patient died five months later. The pathophysiology of the metastasizing basal cell carcinomas is described, and a rationale for therapy presented.     

Modern methods of wound treatment. 1. One wound is not the same as all the others

Papillary carcinoma, the commonest thyroid malignancy, has a good prognosis and low incidence of distant metastases. Brain metastasis is extremely rare with a frequency of about 1% in reported series. In this paper we present the clinical details of one case of histologically proven brain metastasis from papillary thyroid cancer, first presented with neurological symptoms, initially treated with excisional biopsy and radiotherapy in other hospital, without clinical response. The patient was then referred to our service, where he underwent a total thyroidectomy and modified radical neck dissection, with the aim of posterior radioactive iodine treatment for the brain lesion. Unfortunately, he died of neurological complications, two months after the neck treatment. Also presented is a review of the literature of this unusual clinical presentation.     

An insertion or deletion in the extramembrane loop connecting helices E and F of archaerhodopsin-1 affects in vitro refolding and slows the photocycle

A 34-year-old woman and a 54-year-old woman were treated with interferon-alpha (IFN-alpha) for chronic hepatitis C. Three months after the cessation of the IFN-alpha therapy, each patient developed hypothyroidism with the presence of thyroid-stimulation-blocking antibody (TSBAb) and TSH-binding inhibitor immunoglobulin (TBII). These two patients were treated with thyroxine, and both TSBAb and TBII activities gradually decreased. Although both TSBAb and TBII became negative several months after the start of the replacement therapy, the replacement dosage of L-thyroxine could not be reduced. Thyroid biopsies showed that the follicular epitheliums were flattened in both cases with lymphocytic infiltration. These findings suggest that IFN-alpha may induce hypothyroidism and the transient emergence of TSBAb and TBII.     

Haemolytic uraemic syndrome following bone marrow transplantation. Case report and review of the literature

Thrombotic microangiopathy (TMA) can be a late complication of bone marrow transplantation (BMT). A patient is described in whom the haemolytic uraemic syndrome developed 10 months after BMT and who died of E. coli sepsis while on maintenance haemodialysis. The literature is reviewed, regarding clinical presentation, incidence, pathogenesis and therapy. TMA can be observed, after an interval of 3-12 months, in about 6-26% of patients following BMT. Reported cases vary considerably in clinical severity, from mild presentations to severe TMA with high mortality rates despite intensive therapy. Important pathogenetic roles are ascribed to the conditioning total body irradiation and the use of cyclosporin A, but other factors may be involved as well. Next to supportive therapy, plasma exchange and the use of ACE inhibitors may be of value in treating BMT-associated TMA.     

Pelvic recurrence of cervical cancer: the prognostic relationship to the retreatment modalities

OBJECTIVE: To investigate the prognostic factors in relation to retreatment modalities in patients with recurrent cervical carcinoma. METHODS: According to initial therapy, 194 patients with recurrence were grouped as: (1) surgery, 22 cases; (2) surgery and radiotherapy, 24 cases, and (3) radiotherapy alone, 148 cases. Factors such as clinical stage, sites of recurrence, time of diagnosis of recurrence after initial therapy and modalities of retreatment were analyzed. RESULTS: There were 19 cases alloted to stage I, 51 cases to stage II (IIa 23 and IIb 28) and 124 cases to stage III (IIIa 21 and IIIb 103); histopathologically confirmed squamous cell carcinoma in 181 cases and adenocarcinoma 13 cases. Central recurrences were found in 91 cases and lateral or pelvic recurrences in 103 cases. Time of diagnosis of recurrence within 2 years from initial treatments was shown in 118 patients and above 2 years in 76 patients. In 147 of the 194 patients retreated, those of the group 1 obtained a median survival rate of 24 months, which was significantly longer than that of group 2, and group 3. The sites of recurrence did not significantly affect the survival. CONCLUSION: Radiotherapy remains the treatment of choice for patients with pelvic recurrence after surgery. Previously irradiated patients retreated for recurrence by radiotherapy and (or) chemotherapy had lower response rates. The optimal therapy for these patients should be comprehensive managements including surgery, radiotherapy and chemotherapy.     

Hypothyroidism induced by drugs, radiotherapy, and surgery

Primary hypothyroidism may occur as a consequence of, or concomitant, with numerous therapies such as amiodarone, lithium, cytokines, antithyroid drugs, iodine, etc. On the other hand, hypothyroidism may be diagnosed in patients after radioiodine therapy, external radiotherapy to the neck and partial or subtotal thyroidectomy.     

Concomitant infusion cisplatin and hyperfractionated radiotherapy for locally advanced nasopharyngeal and paranasal sinus tumors

PURPOSE: This is a prospective study to improve the therapeutic ratio in the treatment of patients with locally advanced nasopharyngeal and paranasal sinus tumors by using split-course concomitant infusion cisplatin chemotherapy and hyperfractionated radiotherapy. METHODS AND MATERIALS: From 1983 to 1993, 21 patients with locally advanced nasopharyngeal and paranasal sinus tumors (T3 and T4, or recurrent tumors involving the facial bones and/or the base of the skull) were treated with a regimen of split-course hyperfractioned radiotherapy (1.2 Gy/fraction/bid) and concomitant infusion cisplatin (5-10 mg/m2/24 h). The therapy was given in three separate 2-week sessions with 1 to 2 week breaks between sessions. Seventeen of 21 patients were treated with curative intent with cumulative radiation doses ranging from 64.8 to 70.8 Gy. Four patients were treated with palliative intent to a total dose of less than 60 Gy or to a limited field due to previous irradiation. RESULTS: Sixteen of 17 patients (94%) treated curatively achieved a complete response. Of the 16 patients who achieved complete response, 7 patients (50%) were alive at the time of analysis (36 to 126 months). One patient was alive at 4 years with no evidence of disease, and died in 10 years at the age of 80 of unknown cause. Two patients died of local recurrence at 21 and 45 months and one patient died of a cerebrovascular accident at 12 months with disease status unknown. Five patients died of distant metastases. The one patient who had a partial response died in 25 months with local disease and metastases to the bone and lung. Four patients that were previously irradiated received a reduced total dose or treated to a limited irradiation field. All had near complete responses, but died within a year of treatment, with the exception of one patient who died at 23 months. Acute reactions included intense erythema of the mucosa in all patients. Five of 21 (23%) developed punctate mucositis and 3 of 21 (14%) developed confluent mucositis. Hematologically, one patient developed neutropenia (1800 WBC/mm3) and one developed thrombocytopenia (38,000/mm3). A rising creatinine was observed in three patients (2.0, 1.7, 1.7) all of whom were treated with the higher 10 mg/m2/day dose of infusional cisplatin. In all three of these cases, the creatinine slowly returned to normal over a 6-month period. Hormonal evaluations were performed in three patients and all were within normal ranges. There was no evidence of neck fibrosis or trismus. One patient with gross recurrent disease of the orbit developed blindness of the involved eye due to corneal opacification. The orbital area had been reirradiated in this patient. CONCLUSIONS: Concomitant infusion cisplatinum with hyperfractionated radiation improved tumor control, but did not increase normal tissue injury. Acute reactions were minimized by splitting the treatment with a 1- to 2-week break after each 2 weeks of radiation treatment. Late complications were not increased by using a hyperfractionated radiation regimen. The local failure rate was only 18% (3 of 17 patients), but the distant failure rate was 35% (6 patients). Further investigation is needed to prove if adjuvant chemotherapy after concomitant chemoradiation improves survival by decreasing the distant failure in such advanced cases.     

Salivary duct carcinoma: a clinicopathologic study of three cases with a review of the literature

Three cases of salivary duct carcinoma are presented. They occurred in a 60 year old man, a 66 year old man and a 57 year old woman. All of the lesions were located in the parotid gland. The tumor size ranged from 3 to 5 cm across the largest diameter. Facial paralysis was observed in two cases. Histologically, intraductal and invasive adenocarcinoma showing papillary, cribriform, and solid patterns with comedolike necrosis was observed. Immunohistochemically, the tumor cells were positive for keratin and epithelial membrane antigen. No myoepithelial cells were demonstrated within the tumor by staining for S-100 protein, alpha-smooth muscle actin or muscle specific actin. Ultrastructurally, intracytoplasmic lumina with microvilli, a moderate number of mitochrondria, lysosomes, and tight junctions were found. Regional lymph node metastasis was observed in one case, and distant metastasis developed in two cases. All of the patients were treated with adjuvant postoperative irradiation. One patient died of disease at 11 months after the initial diagnosis, another was alive with disease at 8 months, and the third patient was alive without disease at 2 years and 3 months. Salivary duct carcinoma should be differentiated from low-grade salivary gland carcinomas using morphologic and clinical criteria because of its poor prognosis even with aggressive therapy.     

Transient hypothyroidism after iodine-131 therapy for Grave's disease

We studied 355 patients with Grave's disease to characterize transient hypothyroidism and its prognostic value following 131I therapy. METHODS: The patients received therapeutic 131I treatment as follows: 333 received a dose < 10 mCi (6.6 +/- 1.9 mCi) and 22 received a dose > 10 mCi (12.8 +/- 2.9 mCi). Diagnosis of transient hypothyroidism was based on low T4, regardless of TSH within the first year after 131I followed by recovery of T4 and normal TSH. RESULTS: After administration of < 10 mCi 131I, 40 patients developed transient hypothyroidism during the first year; transient hypothyroidism was symptomatic in 15. There was no transient hypothyroidism after high doses (> 10 mCi) of 131I. Iodine-131 uptake > 70% at 2 hr before treatment was a risk factor for developing transient hypothyroidism (Odds ratio 2.8, 95% confidence interval 0.9-9.4). At diagnosis of transient hypothyroidism, basal TSH levels were high (51%), normal (35%) or low (14%); therefore, the transient hypothyroidism was not centralized. If hypothyroidism developed during the first 6 mo after basal TSH > 45 mU/liter ruled out transient hypothyroidism. CONCLUSION: The development of transient hypothyroidism and its hormonal pattern did not influence long-term thyroid function. Since no prognostic factors reliably predicted transient hypothyroidism before 131I or at the time of diagnosis, if hypothyroidism appears within the first months after 131I, the reevaluation of thyroid function later is warranted to avoid unnecessary chronic replacement therapy.     

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.     

Head and neck cancer: guidelines for chemotherapy

Head and neck cancer is estimated to be one of the most prevalent cancers in the world. This tumour type accounts for 5% of all new cancer cases in the US and Europe each year. Patients with locally recurrent or metastatic squamous cell carcinoma of the head and neck have a poor prognosis, with a median duration of survival between 4 and 6 months. During the past few years, screening for potentially active new compounds, new associations and new modalities of chemotherapy administration have had some degree of success. Clinical investigations have also focused on the addition of chemotherapy to locoregional treatment for patients with locally advanced disease. Induction chemotherapy or concomitant chemo- and radiation therapy can result in high response rates, and reduced incidence of distant metastases. However, there is no clear demonstration of any benefit from the addition of chemotherapy to locoregional therapy on overall survival in patients with resectable disease. In patients with resectable laryngeal or hypopharyngeal cancer, chemotherapy combined with radiotherapy can be considered as a standard treatment option for larynx preservation, keeping total laryngectomy reserved for salvage therapy. In patients with unresectable head and neck cancer, simultaneous chemoradiotherapy has been shown to improve locoregional control and survival, at the cost of greater toxicity. Outside clinical trials, this approach can also be considered as a standard therapy for unresectable disease.