Etoposide, ifosfamide and cisplatin (VIP) plus concurrent radiation therapy for previously untreated limited small cell lung cancer (SCLC): a Hoosier Oncology Group (HOG) phase II study

Results of a previous Hoosier Oncology Group (HOG) study revealed a small survival advantage for VIP versus etoposide and cisplatin (EP) for patients with extensive stage small cell lung cancer (SCLC). This phase II study evaluated VIP with concurrent thoracic radiotherapy in patients with limited stage SCLC. Eligible patients had a Karnofsky Performance Score > or = 50, no prior chemotherapy or radiotherapy, and adequate end organ function. Fifty-three patients were entered. Radiotherapy was given as a daily fraction of 1.8 Gy, five fractions per week for 5 weeks for a total dose of 45 Gy, beginning on day 1 of VIP. The first 13 patients received etoposide 75 mg/m(2), cisplatin 20 mg/m(2), and ifosfamide 1.2 g/m(2) on days 1-4 with Mesna every 3 weeks for four cycles unless the patient demonstrated disease progression or undue toxicity. Excessive toxicity was seen in the first 13 patients; therefore, VIP was modified by deleting the 4th day for all subsequent patients. The major toxicity in this trial was myelosuppression. Grade 3/4 anemia, granulocytopenia, and thrombocytopenia occurred in 38, 75, and 34% of patients, respectively. There were four treatment-related deaths [three patients (23%) on the 4-day regimen and one patient (2.5%) on the 3-day regimen]. Twenty-five patients (47.2%) achieved a CR and 11 patients (20.8%) had a PR for an overall response rate of 68%. Minimum follow up for all patients is 5 years. Overall, 46 of 53 patients have died. Median, 1, 2 and 5 year overall survival for the entire group is 15.1 months, 69.8, 35.9, and 13.2, respectively. The results of this phase II trial of VIP with concurrent early thoracic radiotherapy failed to demonstrate a superior response rate over other series utilizing EP. In addition, treatment-related morbidity and mortality appears to be unacceptably high with the VIP regimen.     

Polymorphism of the DNA repair gene XRCC1 and risk of primary lung cancer.

DNA repair plays a critical role in protecting the genome of the cell from insults of cancer-causing agents, such as those found in tobacco smoke. Reduced DNA repair capacity, therefore, can increase the susceptibility to smoking-related cancers. Recently, three coding polymorphisms in X-ray cross-complementing group 1 (XRCC1) DNA repair gene have been identified, and it is possible that these polymorphisms may affect DNA repair capacity and thus modulate cancer susceptibility. We investigated the relationship between the codon 399 polymorphism in XRCC1 gene and lung cancer risk in male smokers. The study population consisted of 192 lung cancer patients and 135 healthy controls. The distribution of XRCC1 genotypes was not significantly different between cases and controls. When the cases were categorized by histological type, however, the presence of at least one Gln allele was associated with a significant increased risk for squamous cell carcinoma [crude odds ratio (OR) = 1.77, 95% confidence interval (CI) = 1.06-2.93 and adjusted OR = 1.66, 95% CI = 0.99-2.79]. The risk for the disease increased as the number of Gln alleles increased (Arg/Gln genotype: adjusted OR = 1.45, 95% CI = 0.84-2.5; Gln/Gln genotype: adjusted OR = 3.26, 95% CI = 1.17-9.15). When the subjects dichotomized by cigarette consumption into two pack-year groups (< or =40 pack-years, >40 pack-years), the Gln allele was associated with an increased risk for squamous cell carcinoma only in the group of individuals having < or =40 pack-years of smoking (Arg/Gln genotype: adjusted OR = 1.48, 95% CI = 0.78-2.8; Gln/Gln genotype: adjusted OR = 5.75, 95% CI = 1.46-22.69). These results suggest that XRCC1 codon 399 polymorphism may be an important genetic determinant of squamous cell carcinoma of the lung in persons with lower degrees of cigarette use.     

Operable squamous esophageal cancer: Current results from the East

From 1958 through 1992 a total of 3603 patients underwent surgery for esophageal squamous cell carcinoma in our department. Among these patients 3099 resections were performed, for an overall resectability of 86.0%. Of the resections, 2341 (75.5%) were classified as curative and 758 (24.5%) palliative. The overall morbidity and 30-day mortality rates were 23.4% and 3.8%, respectively. For resected cases the mortality was 4.0%. The more than 5-year follow-up rate of patients with resection was 97%. The actual 5-, 10-, and 15-year survival rates were 30.4%, 23.6%, and 17.9%, respectively. Recurrence or metastasis remained the cause of death in 60.9% and 25.5% of patients who lived longer than 5 years and 15 years, respectively, after operation. The TNM staging, lymph node metastasis, extraesophageal invasion, tumor differentiation, tumor length, and category of operation were major determinants influencing long-term prognosis. The left thoracotomy approach was used exclusively in 2613 cases (84.3% of all resected cases) in which intrathoracic resections and anastomoses were performed. The stomach was used as a substitute for the esophagus in 98.8% of the resected cases compared with 1.2% colon transplants. The former procedure was far safer than the latter. Above-average results presented in this paper support the surgical policy we have pursued thus far: to resect the primary tumor by partial or subtotal esophagectomy and to remove all lymph nodes wherever they were found in all patients with disease earlier than stage III. Early detection and early treatment no doubt are the only ways to materially improve the long-term surgical results.

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Resumen Entre 1958 y 1992, 3.603 pacientes fueron sometidos a cirugía por carcinoma escamocelular del esófago en nuestro departamento; se efectuaron 3.099 resecciones, para una tasa global de resectabilidad de 86%. De las resecciones, 2.341 (75.5%) fueron clasificadas como curativas y 758 (24.5%) como paliatives. Las tasas globales de morbilidad y de mortalidad a 30 días fueron 23.4% y 3.8%, respectivamente.La mortalidad para los casos resecados fue 4.0%. La rata de seguimiento para los pacientes operados más de 5 años atrás fue 97%. Las tasas actuariales de sobrevida a 5, 10 y 15 años fueron 30.4%, 23.6% y 17.9% respectivamente.La recidiva y las metástasis se mantuvieron como causas de muerte en 60.9% y 25.5% respectivamente de los pacientes que sobrevivieron más de 5 años y 15 años luego de la operación.La estadificación TNM, las metástasis ganglionares, la invasión extraesofagiana, el grado de diferenciacíon tumoral, la longitud del tumor y la categoría de la operación fueron los principales factores determinantes de pronóstico a largo plazo.Se utilizó el abordaje por toracotomía izquierda exclusiva en 2.613 casos (84.3% de la totalidad de casos resecados) en los cuales se efectuó resección intratorácica con anastomosis. El estómago fue utilizado como sustituto del esófago en 98.8% de los casos resecados, en contraste con el trasplante de colon que se hizo en 1.2% de los casos. El uso del estómago como sustituto es, por mucho, un procedimiento bastante más seguro.

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Résumé Entre 1958 et 1992, 3603 patients ont été opérés d'un cancer épidermoïde de l'oesophage. Parmi eux, 3099 résections ont pu être effectuées avec un taux de résecabilité de 86%. Parmi ces résections, 2341 (75.5%) ont été considérées comme curatives, et 758 (24.5%) ont été considérées comme palliatives. La morbidité et la mortalité à 30 jours ont été respectivement de 23.4% et de 3.8%. En cas de résection, la mortalité a été de 4%. Quatre-vingt dix-sept pourcent des patients ont été suivis pendant plus de 5 ans. Les taux de survie actuarielle à 5, 10 et 15 ans ont été respectivement de 30.4%, 23.6%, et 17.9%. La récidive ou les métastases ont été la cause principale de décès chez 60.9% et 25.5% des patients ayant vécu plus de 5 et 15 ans après l'opération. Le stade TMN, l'existence de métastases ganglionnaires, l'extension extraoesophagienne, la différentiation tumorale, la longueur de la tumeur et le type de l'intervention ont été des déterminants majeurs du pronostic. Une thoracotomie gauche a été utilisée exclusivement chez 2613 patients (84.3% de toutes les résections en cas de résection et anastomoses intrathoraciques). Une gastroplastie a été utilisée chez 98.8% des cas de résection et un transplant colique seulement dans 1.2% des cas. II n'y avait aucune différence entre les deux en ce qui concerne les complications. Les résultats nettement au-dessus de la moyenne dans cette série sont en faveur de la chirurgie: réséquant la tumeur primitive par une oesophagectomie totale ou subtotale, accompagnée d'un curage lymphatique aussi complet que possible chez les patients stade III ou moins. La détection et le traitement précoces sont sans doute les seules façons d'améliorer les résultats à long terme.

     

Early-onset primary torsional dystonia in a 4-generation Chinese family with a mutation in the DYT1 gene

Primary torsion dystonia (PTD) is a clinically and genetically heterogeneous movement disorder. At least thirteen different types of dystonia can be distinguished on a genetic basis. The DYT1 gene was first mapped by Ozelius et al in 1989. Kramer et al linked the same locus to PTD in 12 Ashkenazi Jewish families in 1990.     

Clinical features of pathologic childhood aerophagia: early recognition and essential diagnostic criteria

OBJECTIVE: This study investigated the early recognition and diagnosis of pathologic childhood aerophagia to avoid unnecessary diagnostic approaches and serious complications. METHODS: Between 1995 and 2003, data from 42 consecutive patients with pathologic childhood aerophagia, aged 2 to 16 years, were reviewed. An esophageal air sign was defined as an abnormal air shadow on the proximal esophagus adjacent to the trachea on a full-inflated chest radiograph. RESULTS: Of the 42 patients, the chief complaints were abdominal distention (52.4%), recurrent abdominal pain syndrome (21.4%), chronic diarrhea (11.9%), acute abdominal pain (7.1%) and others (7.2%). Mean symptom duration before diagnosis was 10.6 months (range, 1 to 60 months), and it exceeded 12 months for 16 (38.1%) patients. The clinical features common to all patients were abdominal distention that increased progressively during the day, increased flatus on sleep, increased bowel sound on auscultation and an air-distended stomach with increased gas in the small and large bowel by radiography. Visible or audible air swallowing (26.2%) and repetitive belching (9.5%) were also noted. Esophageal air sign was observed in 76.2% of the patients and in 9.7% of the controls (P=0.0001). The subgroups of pathologic childhood aerophagia divided by underlying associations were pathologic childhood aerophagia without severe mental retardation (76.2%), which consisted of psychological stresses and uncertain condition, and pathologic childhood aerophagia with severe mental retardation (23.8%). CONCLUSIONS: The common manifestations of pathologic childhood aerophagia may be its essential diagnostic criteria, and esophageal air sign may be useful for the early recognition of pathologic childhood aerophagia. Our observations show that the diagnostic clinical profiles suggested by Rome II criteria should be detailed and made clearer if they are to serve as diagnostic criteria for pathologic childhood aerophagia.     

The relationship between birth weight and childhood asthma: a population-based cohort study

BACKGROUND: Because obesity promotes inflammation and imposes mechanical constraints to the airways, a high birth weight may be a risk factor for asthma in childhood. However, to our knowledge, few studies have examined this potential relationship. OBJECTIVE: To determine the relationship between high birth weight and risk of emergency visits for asthma during childhood. DESIGN: Population-based cohort study. SETTING: Alberta, Canada. PARTICIPANTS: All neonates born at term (> or =37 weeks) between April 1, 1985, and March 31, 1988, in Alberta (N = 83,595). We divided the cohort into birth-weight categories: low (<2.5 kg), normal (2.5-4.5 kg), or high (>4.5 kg). The cohort was observed prospectively for 10 years.Main Outcome Measure Comparison of risk of emergency visits for asthma over 10 years across the birth-weight categories. RESULTS: Neonates born with a high birth weight had a significantly increased risk of emergency visits for asthma during childhood compared with neonates born with a normal birth weight (relative risk [RR], 1.16; 95% confidence interval [CI], 1.04-1.29). The relationship between birth weight and emergency visits for asthma beyond a birth weight of 4.5 kg was linear, such that every increment of 0.10 kg in birth weight was associated with an additional 10% (95% CI, 2%-19%) increase in the risk of emergency visits for asthma. Other factors associated with an elevated risk for emergency asthma visits during childhood included male sex (RR, 1.26; 95% CI, 1.22-1.30), aboriginal status (RR, 1.20; 95% CI, 1.11-1.29), and low-income status (RR, 1.11; 95% CI, 1.06-1.16). CONCLUSIONS: A high, but not low, birth weight is a risk factor for increased emergency visits during childhood. The risk increases linearly beyond a birth weight of 4.5 kg.