Brain metastases as the only manifestation of an undetected primary tumor

BACKGROUND: The prognosis of patients with brain metastasis as the only manifestation of an undetected primary tumor generally is considered to be poor. Therefore, most treatment is palliative. The authors reviewed the clinical outcomes and treatment results of patients presenting with brain metastasis from an undetected primary tumor at The University of Texas M. D. Anderson Cancer Center. METHODS: Between 1977-1996, 220 patients were referred to the study department for the treatment of brain metastasis from an undetected primary tumor. The patients' records were reviewed to identify those for whom brain metastasis was the only manifestation of the primary tumor. The majority of patients were excluded from the current analysis because extracranial metastasis also were present. Thirty-nine patients qualified for this retrospective review. The level of neurosurgical excision varied, but all patients received radiotherapy. Tumor control in the brain and survival were analyzed by various tumor-related and treatment-related factors. RESULTS: In 31 patients, the brain metastasis were adenocarcinomas, whereas the remaining patients had tumors of various other histologies. In 12 patients, the primary tumor eventually was found, most commonly in the lung. The median survival time for all patients was 13.4 months. Overall survival rates (OS) at 1, 3, and 5 years were 56%, 19%, and 15%, respectively. Intracranial disease control was 72% at 5 years. Patients who received gross total resection (GTR) and radiotherapy had significantly better OS than patients who received radiotherapy alone. The OS of patients whose primary tumor was identified was similar to that of patients in whom the primary tumor remained occult. CONCLUSIONS: Brain metastasis as the only manifestation of an unknown primary tumor is a distinct clinical entity. The prognosis for patients with this presentation is better than that of patients with brain metastasis in general. Although the majority of patients die of extracranial disease, a few will achieve long term survival. Treatment to the brain is effective in controlling local disease; aggressive treatment with GTR and radiotherapy is recommended.     

Alpha and omega: studying resuscitation at the beginning and end stages of life

BACKGROUND: To clarify whether or not multiple pulmonary metastases from colorectal cancer are contraindicated for a surgical resection, we retrospectively evaluated the influence of the number of pulmonary metastases on both the postthoracotomy survival and the pattern of the first failure. METHODS: From 1981 to 1993, 36 patients underwent a complete resection for pulmonary metastases from colorectal cancer. RESULTS: Of the various factors investigated including gender, primary site, disease-free interval, tumor size, the number of metastases, type of resection, and the history of hepatic metastases, only the number of pulmonary metastases was found to be significantly related to postthoracotomy survival. The rate of disease-free survival at 5 years was 62% for solitary metastasis (n = 17), 35% for two metastases (n = 8), and 0% for four or more metastases (n = 11). The pattern of failure also differed according to the number of pulmonary metastases. In particular, the incidence of local recurrence at the primary site increased with the number of pulmonary metastases (ie, 1 of 17 patients with a solitary metastasis, 3 of 8 with two metastases, and 6 of 11 with four or more metastases). CONCLUSIONS: These results suggest that multiple metastases might indicate the presence of local recurrence at the primary site; therefore, in cases of multiple pulmonary metastases, the primary site should be thoroughly explored.     

Central nervous system metastasis in breast cancer

BACKGROUND AND PURPOSE: Central nervous system (CNS) metastasis occurs in at least 30% of patients with breast cancer. Standard treatment is the same as in other solid tumors, though clinical behavior, and sensitivity to radiation therapy (RT) and to chemotherapy may differ considerably. Most of these patients die within a few months, but a substantial subgroup may survive a year or more. The last decade has given rise to new diagnostic methods, new surgical and radiotherapeutic techniques, and the clinical evidence of a chemotherapy permissive blood-brain barrier in CNS metastases. The literature was reviewed to assess the clinical impact of early diagnosis, recognition of prognostic factors, and of the recently developed therapeutic approaches. MATERIAL AND METHODS: Review of the literature on CNS involvement in breast cancer focusing on clinical studies on early diagnosis, new modes of treatment, and factors influencing outcome. RESULTS: Although randomized studies are still awaited, systemic chemotherapy seems a valuable alternative for RT of brain metastases in selected cases. In meningeal carcinomatosis, long survival may be independent of intraventricular chemotherapy. Neurotoxicity of intensive intraventricular treatment is considerable. In epidural metastasis, early diagnosis with prompt start of treatment remains the crucial factor for outcome. Radiation therapy is the mainstay of treatment of epidural metastasis, but new surgical techniques and even systemic chemotherapy should be considered in selected cases. CONCLUSIONS: Recognition of prognostic factors combined with appropriate use of various recently developed therapeutic possibilities will improve the clinical outcome including better local tumor control and less treatment-induced neurotoxicity in a considerable number of patients with CNS metastasis from breast cancer.     

Malignant ethmoid-sphenoidal tumors. 130 cases. Retrospective study]

We report on 130 ethmoidal cancers. 96 (74%) were adenocarcinomas (ADKE). 110 were operated upon between 1984 and 1996: 9.1% T1 + T2, 27.7% T3, 36.2% T4a, 27% T4b. Neoadjuvant chemotherapy was administered in 93 patients (76 ADKE). Combined surgical route was performed 103 times, sub-fronto-orbito-nasal (SFON) route 7 times. Post-operative radiotherapy was performed in 36 patients. Complete clinical and radiological response to chemotherapy was noted in 21.5% of cases (23% of ADKE). Post-operative mortality concerned one patient who died from a pulmonary embolism during the third post-operative week. Morbidity included: 3 transient clinical rhinorrheas, 5 meningitis (one of which was responsible for heavy psycho-intellectual disability), 4 deep suppurations associated with osteitis of the bone flap and two superficial suppurations. 44 patients had a local recurrence (10 ADKE). No recurrence appeared in complete chemoresponders. Systematic preservation of intra-orbital contents did not increase the risk of local failure. Eleven patients (4 ADKE) developed cervical nodes and/or systemic metastasis. Death occurred after a mean of three months following the diagnosis of metastasis. Survival rate was: 60% at 3 years, 51.5% at 5 years, 32.5% at 10 years. ADKE survival rate was: 55% at 3 years, 51.5% at 5 years, 23% at 10 years. Survival ws related to tumoral extension: 75% at 5 and 10 years for T3, 45% at 5 years and 38% at 10 years for T4a, 40% at 3 years and null at 5 years for T4b, 5 and 10 years survival rate of complete chemoresponders are 100% whatever the tumour. Prognosis remained poor for epidermoid carcinomas (survival rate: 36% at 3 years, 0% at 5 years) and for melanomas (mean survival: 19.6 months). Post-operative radiotherapy should be indicated for large tumors T3, T4a and T4b).     

Malignant mucosal melanoma of the head and neck: review of the literature and report of 14 patients

BACKGROUND: Fortunately, primary malignant mucosal melanoma of the head and neck is a rare entity. A paucity of data elucidating the predictive factors as well as the unpredictable and aggressive biologic behavior of mucosal melanoma compound the vexing clinical situation. This review summarizes what the literature reveals about the epidemiology, patient survival, patterns of local recurrence, and local and distant metastasis of the disease. Over 1000 patients with this disease have been reported. Survivals at 5 and 10 years is 17% and 5%, respectively. Approximately 19% of patients present with lymph node metastasis and another 16% develop lymph node metastases after treatment, whereas 10% present with distant metastasis. Local metastasis does not affect survival; this is in sharp contrast with skin melanoma. Over 50% of patients experience local treatment failure, and salvage treatment is effective in only 25% of these cases. Local failure is the harbinger of distant metastases. Patients with nasal mucosal melanoma have a 31% 5-year survival rate, whereas sinus melanoma patients fare poorly, with a 0% rate of 5-year survival. METHODS: The authors conducted a retrospective review of 14 patients with characteristics similar to those in the literature in terms of outcome. RESULTS: The 5-year survival rate for these patients was 14%. Whole-body positron emission tomography was performed on 3 patients to detect metastatic disease. The patterns of local recurrence, distant metastasis, and survival for these patients were compared with the same data for patients described in the literature. CONCLUSIONS: Surgery appears to have the greatest efficacy in the management of mucosal melanoma, although radiation therapy may play an increasingly important role in the future.     

High-dose epirubicin in platinum-pretreated patients with ovarian carcinoma: the EORTC-GCCG experience

A follow up study of 20 cases of renal cell carcinoma with regional lymph node metastasis at the department of urology in Niigata Cancer Center Hospital from 1979 to 1993 is presented. During this period, we treated 249 patients with renal cell carcinoma with or without lymph node metastasis. Lymph node metastasis could be estimated in 188 out of 249 patients. Histologically, lymph node metastasis was classified as pN1 in 8 cases, pN2 in 7 cases, and pN3 in 5 cases. The 3- and 5-year survival rates of 20 patients with lymph node metastasis were 45.0% and 16.4%, respectively. Nine of the 20 cases had no distant metastasis and 11 cases had distant metastasis. Three of the 9 patients with distant metastasis had no recurrence. Two of these 3 patients are still alive after 10 years and 3 years and 1 patient died because of acute heart failure. These 3 patients had pN1 metastasis smaller than 1 cm lymph node. Four of the 11 patients with distant metastasis had more than a two-year survival. However, 3 patients died due to renal cell carcinoma although primary and metastatic regions were resected and IFN with chemotherapy were given. Only one patient is still alive without recurrence after 3 years. This case detected as right renal cell carcinoma with pN2 metastasis and bilateral pulmonary metastasis was treated with radical nephrectomy with regional lymph node dissection and administered Methotrexate, VP16 and CisPlatinum chemotherapy and IFN.(ABSTRACT TRUNCATED AT 250 WORDS)     

Predictors of survival for prostate carcinoma patients treated with salvage radical prostatectomy after radiation therapy

BACKGROUND: Salvage radical prostatectomy is a treatment option for patients with recurrent cancer following radiation therapy. This study was conducted to identify predictors of survival for patients treated with salvage radical prostatectomy. METHODS: The authors studied 86 prostate carcinoma patients who underwent salvage radical prostatectomy for locally persistent or recurrent prostate carcinoma at Mayo Clinic between 1967 and 1996. The mean interval from radiation therapy to biopsy-proven recurrence was 3.7 years (range, 6 months to 17 years). Patient age at surgery ranged from 51 to 78 years (median, 66 years). The mean follow-up after surgery was 5.8 years (range, 1.0-15.2 years). Cox proportional hazards models were used to identify clinical and pathologic factors associated with distant metastasis free survival and cancer specific survival. RESULTS: Actuarial distant metastasis free survival, cancer specific survival, and overall survival were 83%, 91%, and 85% at 5 years and 69%, 64%, and 54% at 10 years, respectively. In multivariate analysis, radical prostatectomy Gleason score and DNA ploidy were independent predictors of distant metastasis free survival and cancer specific survival. CONCLUSIONS: Postirradiation Gleason score and DNA ploidy were highly predictive of the clinical outcomes of patients treated by salvage radical prostatectomy after radiation therapy.     

Metastasis of chondrosarcoma

This study was undertaken to analyse metastases of patients with intermediate- or high-grade chondrosarcomas. Out of 24 intermediate-grade tumours, 5 (21%) developed metastases, as did 6 of 10 high-grade tumors (60%) (P = 0.04). Four patients developed pulmonary metastasis only, 5 developed both pulmonary metastasis and metastases of the other sites. Two patients showed a rare metastatic pattern: bone metastases only. The metastasis rate in the primary chondrosarcoma (42%) was higher than that in the secondary chondrosarcomas (0%) (P = 0.03). The metastasis rate was higher in patients with local recurrence (86%) than in those without local recurrence (19%) (P = 0.01). In 5 of 6 patients who had a local relapse and metastasis, the interval between the two relapses was a few months.     

Development of neurosurgery in southern California and the Los Angeles county/University of Southern California Medical Center

We reported a case of successful treatment of bilateral pulmonary metastasis from rectal cancer with high-dose 5'-DFUR plus MMC combination chemotherapy. A woman born in 1948 showed a recurrence in the bilateral lung about 29 months after low anterior resection. High-dose 5'-DFUR plus MMC combination chemotherapy was started in March, 1991. The chest X-ray examination 8 weeks after beginning this therapy showed a remarkable decrease in the size of the pulmonary metastatic foci and CEA decreased in the same way. The dose of 5'-DFUR was reduced after 5 courses, and then CEA increased. No remarkable side effect was encountered and the patient could be safely treated at an outpatient clinic. During this therapy no recurrence has been detected, and we performed a resection of the bilateral pulmonary metastasis by median sternotomy in October, 1991. The above findings suggested that this was an effective and safe therapy for pulmonary metastasis from colon cancers and could be a neo-adjuvant chemotherapy for surgical resection of pulmonary metastasis.     

Carcinoma of the nasopharynx in young patients

PURPOSE: To provide an analysis of eighteen cases of adolescent nasopharyngeal carcinoma treated between 1971 and 1989. METHODS AND MATERIALS: Between 1971 and 1989, 48 cases of nasopharyngeal carcinoma were evaluated at the Medical College of Georgia Hospital and Clinics. Eighteen patients between the ages of 9 and 29 years were treated at the Georgia Radiation Therapy Center. All patients presented for treatment with (AJCC) Stage IV disease. Fifteen patients with lymphoepithelioma and three with squamous cell carcinoma histologies received definitive radiation therapy to a median dose of 64.8 Gy. Males outnumbered females by more than 2:1 and the majority of patients (67%) were black. Nine patients received multiagent adjuvant chemotherapy. RESULTS: Thirteen patients are alive from 7 to 166 months (median 32 months) including three with disease at 17, 24, and 132 months. Overall and disease-free survival at 5 and 10 years were 63% and 54%, respectively. Five patients died from disease; four patients had pulmonary metastases while one had CNS metastasis. Eighty percent of relapses occurred within the first 2 years following treatment. Acute and chronic toxicities were limited, consisting primarily of mucositis and xerostomia. Radiation doses of 65 Gy or more (p = 0.049) and age greater than 20 years (p = 0.005) were positive prognosticators for survival. Adjuvant chemotherapy, race, and sex were not found to be of prognostic value. Disparities in the distribution of patients with lymphoepithelioma and squamous cell histologies and the presentation of advanced regional disease precluded analysis for prognostic significance of histology and nodal status in this series. CONCLUSION: The results of the present series compare favorably with those published from other institutions. High doses of radiation and a high systemic failure rate continue to be the fundamental obstacles to effective management and enhanced survival for patients with nasopharyngeal carcinoma.     

Primary vaginal melanoma: thirteen-year disease-free survival after wide local excision and review of recent literature

OBJECTIVES: We present a case report of a woman who has survived 13 years after conservative treatment with wide excision for vaginal melanoma and review and evaluate the literature on this disease since the last metaanalysis in 1989. STUDY DESIGN: A database literature search along with cross referencing from related articles uncovered 66 patients who were reported to have vaginal melanoma since 1989 with adequate information for our analysis. We add to this one original case reported by us. Where information was available, we analyzed outcomes on these cases on the basis of patient age, tumor thickness, tumor size, and treatment. RESULTS: The patient we describe is only the eighteenth reported patient to survive vaginal melanoma 5 years and only the third to survive for 10 years. Of the 67 patients in our overall review, mean age at the time of diagnosis was 62 years. Patients with tumor size < 3 cm had a mean survival of 41 months compared with 12 months for those with tumor size > or = 3 cm (p < 0.0024). Tumor thickness did not significantly affect patient survival at any of the depths analyzed, although there was a tendency toward significance at depths > 8 mm (p < 0.0778). There also was no significant difference in patient outcome among five treatment groups: (1) wide excision, (2) radical surgery, (3) radiation therapy, (4) wide excision plus radiation therapy, and (5) other. CONCLUSION: Tumor size appears to affect survival in patients with vaginal melanoma. Tumor thickness, at least at the levels at which vaginal melanomas are currently being diagnosed, does not seem to affect survival. Because no single treatment is clearly preferable, we suggest conservative resection where possible. We find it difficult to support radical surgery as primary treatment for vaginal melanoma unless necessary to achieve clear tumor margins. Radiation therapy appears to offer results comparable to those of surgery.     

Radiotherapy and local control in rectal cancer

Recurrence is a stage in the natural history of rectal cancer. Preoperative radiotherapy or postoperative radiochemotherapy lower the rate of recurrence, improving local control. From 1980 to 1997, at the "Divisione di Radioterapia" of the "Università Cattolica del S. Cuore" of Rome 380 patients with rectal cancer of early clinical stage T2-3, candidates for surgery for cure, underwent radiation therapy. 119 patients underwent postoperative radiotherapy (45-50 Gy); 45 patients underwent "sandwich" radiotherapy (45 Gy:27 Gy before and 28 Gy after surgery), of whom 7 were treated with preoperative radiotherapy alone; 145 patients underwent preoperative concomitant radiochemotherapy according to 3 different protocols, radiotherapy (38 Gy) combined with mitomycin C and 5-FU; radiotherapy (50.4 Gy) combined with cisplatin and 5-FU; radiotherapy (45 Gy) combined with 5-FU and folinic acid. 71 patients were treated with preoperative radiotherapy (38 Gy) combined with IORT (10 Gy). Median follow-up was 6 years. Overall local control was 85% at 3 years, 83% at 5 years, 81% at 10 years. The rate of local control at 5 years was: 76% for postoperative radiotherapy, 83% for "sandwich" radiotherapy, 84% for preoperative radiochemotherapy and 93% for preoperative radiotherapy combined with IORT. Local control was shown to be significantly better with preoperative treatment as compared to postoperative treatment (p = 0.02). The incidence of metastases was 35% in the patients with local recurrence and 16% in those with local control. The difference in survival was highly significant in patients with local control as compared to those with local recurrence: at 5 years 87% and 32% respectively. Patients with local control showed a lower incidence of metastasis and a better survival.     

Surgical treatment of pulmonary metastasis from renal cancer: analysis of 9 cases]

Nine patients with pulmonary metastasis from renal cancer were subjected to surgical treatment which included wedge resection (2 cases) and lobectomy (9). One case of multiple lesions in bilateral lungs was treated in the same time by cryosurgery and fulguration. The survival time after operation ranged from 5 to 90 months. In this series, four cases are still alive, others survived for 13 months, 20 months, 34 months, and 90 months, respectively. We suggest that the more active attitude should be taken for the surgical treatment of pulmonary metastasis.     

Hyperfractionation in the reirradiation of head and neck cancers. Result of a pilot study

Surgical resection of primary lesions and single metastasis can be curative, but surgery, used as the only therapeutic option, is not unanimously accepted in patients with multiple metastasis and, apart from other considerations, there are no established clinical criteria to allow us to predict which patients will benefit from a metastectomy. This study evaluates four patients with advanced RCC. Three had multiple pulmonary metastasis at the time of diagnosis and one presented retroperitoneal mass at 36 months of follow-up. All patients were nephrectomized and received adjuvant immunotherapy with an association of IL-2 and 2b alpha-IFN subcutaneously, obtaining partial response of the disease after two treatment courses. Later, the patients underwent debulking surgery. Two patients are still alive and have no evidence of disease progression at 28 months and 8 months of follow-up. This data and that contrasted with other authors, suggests that surgical management would be a reasonable option in patients who have partially responded to immunotherapy, even though the selection of both candidates and surgical strategy should be considered on an individual basis.     

Primary chondrosarcoma of long bones and limb girdles

BACKGROUND: Chondrosarcomas are common solid malignant tumors of bone, second in incidence only to osteosarcomas. The biologic evolution of chondrosarcomas is slow, requiring long follow-up intervals for meaningful survival analysis. METHODS: This study describes the clinicopathologic profiles of 344 patients, 194 male and 150 female (M:F, 1.3:1.0), with primary chondrosarcoma of long bones and limb girdles seen at 1 institution over a period of 80 years. RESULTS: The average age at presentation was 46 years (range, 5-82 years). The pelvis was the most common location (1.7% of all patients). Local pain was the most frequently reported initial symptom (81.4%). Survival analysis was limited to 233 patients whose primary treatment was given at the Mayo Clinic. All 233 patients had potential follow-up of at least 5 years. The overall 5-year survival rate was 77% (the expected rate was 96%). Local recurrence developed in 19.7% of patients and metastatic lesions in 13.7%. The recurrence rate was higher for tumors of the shoulder and pelvis than for tumors of long bones. Radiographically, chondrosarcomas had a characteristic appearance, including a combination of bone expansion and cortical thickening. Entering the tumor at surgery increased the risk of local recurrence. Histologic tumor grade was an important predictor of local recurrence and metastasis. CONCLUSIONS: With adequate initial surgical intervention, chondrosarcoma is primarily a local disease with a low metastatic rate.     

Surgical analysis for metastatic lung tumor from renal cell carcinoma

Metastatic lung tumor from renal cell carcinoma were studied in 29 cases. Eighteen patients were treated surgically, 11 were treated non-surgically. The overall 5-year survival rate with the patients of pulmonary resection was 53.5%, and that with those of conservative therapy was 0%, and this difference is statistically significant (p < 0.05). There was no significant difference in any characteristics such as sex, age, stage, grade, disease free interval, metastatic pattern and combination with or without interferon therapy. There was no significant difference in surgically treated patients with pulmonary metastasis in terms of any factors such as age, sex, stage, grade, disease free interval, pulmonary metastasis pattern, metastatic number, surgical procedure, combination with or without interferon therapy statistically. Analysis for the surgically treated patients with pulmonary metastasis from renal cell carcinoma shows no significant difference in prognosis with any characteristics. This result shows efficacy of surgery even if for the patients with synchronous bilateral multiple pulmonary metastasis from renal cell carcinoma.     

The parotid gland as a filtering station of metastatic head-neck melanoma. Retrospective study of 884 patients

Formation of metastases was observed in 246 cases (27.8%) out of a group of 884 patients with melanoma of the head and neck region treated in the years 1967-1991. In the group of patients with metastases, regional metastases were found in the cervical lymph nodes in 136 cases (55.3%). In 74 patients (30.1%) the first metastasis was a distant metastasis, i.e., the tumor had spread by hematogenic dissemination. In 53 patients (21.5%) the first metastasis was located in the parotid gland. Evaluation of the clinical data of the patients led to interesting results regarding prognosis following the different types of surgical treatment. The 5-year survival rates were established by means of multivariant analysis using the Cox model, taking into account sex and tumor thickness: Following radical tumor removal, including neck dissection and parotidectomy, the 5-year survival rate amounted to 61.8%. If the parotid gland was not removed and only tumor and cervical lymph nodes were resected, 66.2% of the patients were still alive 5 years following surgery. The difference between these two groups was statistically not significant (P = 0.07). In those cases where only the primary tumor was removed, the 5-year survival rate was 85.8% and thus significantly better than in the two other groups (P < or = 0.0001). Two conclusions can be drawn: In metastasizing melanoma of the head and neck the parotid glands are affected in 20% of the cases and thus more frequently than expected. The retrospective analysis of groups of patients differing with regard to the prognosis of their disease cannot be used to provide information on which therapy is the best. This is particularly true for the question whether or not the parotid gland should be removed in addition to a neck dissection. It will be necessary to perform a prospective randomized study in order to find answers to these questions. Such a study could be performed within DOSAK (Deutsch-Osterreich-Schweizerischer Arbeitskreis für Tumoren im Mund-Kiefer-Gesichtsbereich = German, Austrian, Swiss Working Group on Tumors in the Maxillo-Facial Region) in cooperation with different hospitals.     

Immunotherapy in metastatic cancer of the kidney

Evidence accumulated over the last 15 years has clearly demonstrated that metastatic renal cell cancer is an excellent model of the effect of immunotherapy for the treatment of cancer. To date, at least 2 cytokines, interleukin-2 and alpha-interferon have been found to be effective. Objective response is obtained in 15 to 30% of the patients treated with interleukin-2 and 10 to 30% with interferon. Complete response can be achieved in 5% of the cases. Clinically, the best results are seen in patients in good general health and lung metastasis. Complete response for more than 5 years is often observed. Combination protocols with both cytokines and other combinations with infusion of activated lymphocytes have not shown to be more effective than one cytokine alone. It may be possible to obtain higher response rates by combining cytokines with chemotherapy protocols. Surgery still has a role to play however, particularly in patients with an isolate accessible metastasis. Among the perspectives for new immunotherapies, interleukin-12, a strong stimulator of the natural killer population is in phase II trials. Other possibilities include the use of selective populations of lymphocytes as adoptive immunotherapy or combinations using immunotherapy and surgery. Despite the enthusiasm generated by these new techniques, it is imperative to continue rigorous clinical trials in order to develop immunotherapy as a reliable routine treatment.     

Accuracy of recording of deaths from asthma in the UK: the false negative rate

BACKGROUND: A study was carried out to determine the extent to which asthma deaths are wrongly attributed to another cause on UK death certificates. METHODS: Deaths from all causes occurring anywhere in the UK were identified amongst 2382 subjects aged 16-64 years within three years of discharge following hospital treatment for asthma (ICD9 493) in hospitals in the South East Thames region. The deaths were reviewed by an expert panel to assess the proportion of asthma deaths identified by the panel which were attributed to another cause of death on the death certificate (false negatives). RESULTS: Eighty five deaths from all causes were identified in a mean follow up period of two years and three months. In 61 cases (72%) there was sufficient information for the expert panel to be confident about the cause of death. The panel identified 22 deaths from asthma, four of which were certified as non-asthma deaths (two as deaths from chronic obstructive pulmonary disease (COPD) and two as deaths from cardiovascular disease). The proportion of false negative death certificates was four of 22 (18%, 95% confidence interval (CI) 5 to 40). CONCLUSIONS: There is evidence that asthma deaths in the UK are wrongly certified as deaths from both chronic obstructive pulmonary disease and diseases of the cardiovascular system.     

Surgical and medical management of patients with pulmonary metastasis from parathyroid carcinoma

BACKGROUND: The aim of this study was to characterize patients with pulmonary metastasis of parathyroid carcinoma and to evaluate the long-term effect of surgical and medical therapy. METHODS: Seven patients with pulmonary metastasis of parathyroid carcinoma were treated between 1980 and 1992. Six patients underwent resection of pulmonary metastases, and one patient has had long-term bisphosphonate therapy alone. Bisphosphonate was also given before or after operation to three patients. RESULTS: Two patients underwent a unilateral thoracotomy for a single pulmonary lesion, and four other patients with multiple lesions underwent staged bilateral thoracotomies. The postoperative serum calcium level returned to normal after each thoracotomy in three patients who were alive and well 3, 8, and 12 years after the first thoracotomy. Hypercalcemia persisted in the other three patients. In two of the patients, bisphosphonate therapy was also unable to control hypercalcemia. In one patient the serum calcium level has been maintained in the 13 mg/dl range by bimonthly bisphosphonate therapy alone for 3 years. CONCLUSIONS: The aggressive surgical approach to pulmonary metastasis of parathyroid carcinoma was shown to be effective for palliation in selected patients. Bisphosphonate therapy is an alternative to resection but has only a temporary calcium-lowering effect.