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Three-dimensional conformal radiation therapy (3DCRT) is a mode of high precision radiotherapy which has the potential to improve the therapeutic ratio of radiation therapy for locally advanced non-small cell lung cancer. The preliminary clinical experience with 3DCRT has been promising and justifies further endeavour to refine its clinical application and ultimately test its role in randomized trials. There are several steps to be taken before 3DCRT evolves into an effective single modality for the treatment of lung cancer and before it is effectively integrated with chemotherapy. This article addresses core issues in the process of target volume definition for the application of 3DCRT technology to lung cancer. The International Commission on Radiation Units and Measurements Report no. 50 definitions of target volumes are used to identify the factors influencing target volumes in lung cancer. The rationale for applying 3DCRT to lung cancer is based on the frequency of failure to eradicate gross tumour with conventional approaches. It may therefore be appropriate to ignore subclinical or microscopic extensions when designing a clinical target volume, thereby restricting target volume size and allowing dose escalation. When the clinical target volume is expanded to a planning target volume, an optimized margin would result in homogeneous irradiation to the highest dose feasible within normal tissue constraints. To arrive at such optimized margins, multiple factors, including data acquisition, data transfer, patient movement, treatment reproducibility, and internal organ and target volume motion, must be considered. These factors may vary significantly depending on technology and techniques, and published quantitative analyses are no substitute for meticulous attention to detail and audit of performance.

During a systematic search for germ-line APC mutations causative of familial adenomatous polyposis, we discovered what appeared to be an insertion mutation while simply checking exon 14PCR products by agarose gel electrophoresis (AGE). On AGE, exon 14PCR product from the known affected member of this family gave two bands: one of normal length, the other retarded on the gel equivalent to an increase in length of some 20-25 bp. Direct sequencing of DNA purified from the two bands gave identical results, and was consistent with amplification from the same two alleles: one wild-type, and the other having an 1893del4 mutation. This suggested that the normal length band on AGE consisted of DNA homoduplexes (normal:normal and mutant:mutant) and the retarded band consisted of DNA heteroduplexes (normal:mutant and mutant:normal). This hypothesis was tested by subjecting purified material from each of the two bands alone to a single cycle of heat denaturation and annealing, which showed that either band was equally capable of regenerating both bands. Because the anomalous migration of the heteroduplexes is observed in the presence of ethidium bromide, it implies that they have a cruciform of cruciform-like structure. This case illustrates the necessity to be aware of anomalous DNA migration and always sequence all putative mutations.

This study describes the initial reliability and validity data on the Adolescent Dissociative Experiences Scale (A-DES), a screening measure for pathological dissociation during adolescence. The A-DES showed good scale and subscale reliability, and, as hypothesized, increased scores were associated with reported trauma in a patient population. A-DES scores were able to distinguish dissociative disordered adolescents from a normal sample and from a patient sample with a variety of diagnoses.

We have investigated a series of FAP patients in the Northwest of England in order to identify and characterise the specific APC mutations. Using SSCP, we found 27 mutations in a total of 50 families investigated. The mutations were predominantly frameshift or nonsense mutations and there were two splice site changes. We have described two patients with severe Gardner's phenotype from different ethnic backgrounds who share the same mutation at codon 1537. Although the frequency of the most common mutation appears low, it is not dissimilar to that reported by other groups.

Background: Inhaled glucocorticoid therapy has systemic effects including hypothalamic-pituitary-adrenal (HPA) suppression. The optimal test for detecting these effects has not been defined., Methods: Timed urine collections and 09.00 hour plasma cortisol levels were obtained from 12 normal volunteers receiving inhaled placebo, beclomethasone (BDP) 800 or 2000 micrograms/day. The 24 hour urine samples were collected as follows: first hour after waking (hour 1), the next two hours after waking (hours 2 and 3), remainder of day, and overnight, with results expressed as urine cortisol/creatinine (UCC) ratios and as hourly cortisol output in the timed collections. Twenty four hour urinary cortisol excretion was also calculated. Medication was blinded and given in random order with a washout period of at least 11 days between each treatment arm., Results: None of the UCC ratios changed with BDP 800 micrograms/day. UCC ratios at hour 1, hour 2 and 3, and overnight, and 24 hour urinary free cortisol excretion were reduced after BDP 2000 micrograms/day, whilst remainder of day UCC ratio and the plasma cortisol level did not change significantly. Cortisol output showed similar changes. In a follow up study BDP 1400 micrograms/day also reduced UCC ratios for the first two hours after waking., Conclusions: UCC ratios are as sensitive as the more cumbersome 24 hour urinary free cortisol excretion, and more sensitive than single morning plasma cortisol measurements, in detecting the effects of inhaled beclomethasone on the HPA axis.

Twelve patients with irresectable or recurrent hilar cholangiocarcinoma were treated with internal biliary drainage followed by intraluminal (iridium-192) and external-beam radiotherapy. Biliary drainage was accomplished by means of a combined surgical and interventional radiological approach. Initial biliary decompression was performed surgically by tumour resection, intrahepatic biliary enteric bypass or distal biliary-enteric anastomosis with a temporary stent. Maintenance of internal biliary drainage and application of intraluminal radiotherapy were accomplished radiologically with the use of percutaneous dilatation and metallic expandable biliary endoprostheses. Median survival was 14.5 months; all 12 patients survived for at least 6 months. Early complications during radiotherapy were minor and included two patients with cholangitis and one with transient haemobilia. Jaundice was relieved in ten of 12 patients, while episodes of cholangitis were seen during long-term follow-up in 11 (median 1.5 episodes per patient). Internal biliary drainage, in conjunction with radiotherapy, appears to be safe and effective palliation of irresectable or recurrent hilar cholangiocarcinoma. Patients can maintain a reasonable quality of life with an acceptable incidence of cholangitis, without the hindrance of external drainage devices.

Familial adenomatous polyposis (FAP) is associated with a number of extraintestinal manifestations, which include osteomas, epidermoid cysts, and desmoid tumors, often referred to as "Gardner syndrome." Recent studies have suggested that some of the phenotypic features of FAP are dependent on the position of the mutation within the APC gene. In particular, the correlation between congenital hypertrophy of the retinal pigment epithelium (CHRPE) and APC genotype indicates that affected families may be divided into distinct groups. We have investigated the association between the dentoosseous features of GS on dental panoramic radiographs (DPRs) and APC genotype in a regional cohort of FAP families. DPRs were performed on 84 affected individuals from 36 families, and the dento-osseous features of FAP were quantified by a weighted scoring system. Significant DPR abnormalities were present in 69% of affected individuals. The APC gene mutation was identified in 27 of these families, and for statistical analysis these were subdivided into three groups. Group 1 comprised 18 affected individuals from seven families with mutations 5' of exon 9; these families (except one) did not express CHRPE. Groups 2 comprised 38 individuals from 16 families with mutations between exon 9 and codon 1444, all of whom expressed CHRPE. Group 3 comprised 11 individuals from four families with mutations 3' of codon 1444, none of whom expressed CHRPE. Families with mutations 3' of codon 1444 had significantly more lesions on DPRs (P < .001) and appeared to have a higher incidence of desmoid tumors. These results suggest that the severity of some of the features of Gardner syndrome may correlate with genotype in FAP.

Purpose: Local failure is a major obstacle to the cure of locally advanced non-small-cell lung cancer. 3-Dimensional conformal radiation therapy (3-DCRT) selects optimal treatment parameters to increase dose to tumor and reduce normal tissue dose, potentially permitting dose escalation. There are several ongoing trials of dose escalation using 3-Dimensional conformal radiation therapy for non-small-cell lung cancer. We performed this analysis to determine if data derived from dose volume histograms could be used as the basis for designing the method of dose escalation in these trials., Methods and Materials: Between 1990 and 1993, 31 patients were treated with 3-DCRT and had complete normal tissue dose volume histograms created as part of the planning process. The stage distribution was stage I/II 13%, stage IIIa in 45%, and stage IIIb in 42%. The median radiation dose to gross disease was 70.2 Gy (52.2-72 Gy). Elective mediastinal irradiation (50.4 Gy) was administered to 52% (16/31) of patients., Results: The major toxicity encountered in this experience was pulmonary. Dose-volume-histogram data were used to analyze the predictors of toxicity and showed a correlation between risk of pulmonary toxicity and indices of dose to lung parenchyma. Grade 3 or higher pulmonary toxicity occurred in 38% (3/8) of pts with >30%of lung volume receiving > or =25 Gy, versus 4% (1/23) of pts. with < or = 30% lung receiving > or = 25 Gy (p=0.04). Grade 3 or higher pulmonary toxicity occurred in 29% (4/14) of patients with a predicted pulmonary normal tissue complication probability of 12% or higher versus 0% (0/17) in patients with a predicted probability of less than 12% (p=0.03). The single fatality occurred in a patient with a calculated pneumonitis probability of 85% and a high percent (49%) lung volume receiving >= 25 GY., Conclusion: This preliminary experience demonstrates a correlation between lung dose-volume-histogram data and the risk of severe pulmonary toxicity. This provides an opportunity to modify the method of radiation dose escalation. Dose-volume-histogram data can allow escalation according to the risk to the lung parenchyma (which is the major organ of concern) rather than escalation according to tumor dose levels. Because of teh major inter-patient variability of intrathoracic tumor bulk and anatomic distribution, this strategy is intuitively appropriate. This approach may facilitate completion of dose escalation studies and identification of maximum tolerable pulmonary dose levels.

A native North American family with acute intermittent porphyria was investigated by molecular methods to locate the causative mutation and identify carriers of the mutant allele. All 15 exons of the porphobilinogen deaminase gene were screened by single-strand conformation polymorphism analysis, and a unique banding pattern was observed in exon 14. Sequencing revealed a one base-pair insertion in this exon that shifts the reading frame of the mRNA, and generates a premature stop codon. Family members were tested for the mutation by amplification of exon 14 followed by digestion with the restriction enzyme NlaIII. The activity of erythrocyte porphobilinogen deaminase was measured in 36 family members. The results agreed with mutational analysis in 32 cases. However, four individuals who were not gene carriers had low enzyme activity, and in the absence of molecular genetic data would have been incorrectly diagnosed. This is the first study to identify the molecular basis of acute intermittent porphyria in native North Americans.

Purpose: To evaluate the feasibility and efficacy of a strategy using induction chemotherapy followed by radiation therapy (RT) as a means of organ-function preservation in patients with advanced oropharynx cancer., Patients and Methods: From January 1983 to December 1990, 33 patients with advanced squamous cell oropharynx cancer whose appropriate surgical management would have required a tongue procedure and potential total laryngectomy were treated with one to three cycles of cisplatin (CDDP)-based induction chemotherapy. Patients with a complete response (CR) or partial response (PR) at the primary site then received definitive external-beam RT with or without interstitial implant with or without neck dissection with surgery to the primary tumor site reserved for disease persistence or relapse; patients with less than a PR after chemotherapy had appropriate surgery and postoperative RT recommended., Results: With a median follow-up period of 6.2 years, actuarial overall and failure-free survival rates at 5 years are 41% and 42%, respectively. Chemotherapy toxicity contributed to the death of two patients and was possibly a factor in two others. Local control was achieved in 14 patients (42%) without any surgery to the larynx or tongue. Among 13 patients currently alive, all had a preserved larynx and only one required tongue surgery; 12 of 13 have speech subjectively described as always understandable; and nine of 13 have no significant restrictions in their diet., Conclusion: This treatment program is feasible and effective in patients with advanced oropharynx cancer and produces an excellent functional outcome in most long-term survivors. Modifications to optimize patient selection, minimize toxicity, and improve local control are indicated. The relative toxicity, efficacy, and functional outcome provided by this and other chemotherapy and RT programs versus either standard surgery and/or RT options can only be addressed in a randomized comparison of these therapies.

Purpose: To compare the quality of life and functional outcome in patients with squamous cell cancer of the base of tongue treated with primary radiation vs. primary surgery., Methods and Materials: At our institution, patients with base of tongue cancer are primarily treated either by radiation or surgery depending upon the philosophy of their primary physician. Primary radiation consists of 45-54 Gy external beam radiation followed by an 192Ir implant delivering an additional 20-30 Gy over 2-3 days. A neck dissection is done at the same time as the implant for those with involved nodes. Primary surgery consists of resection of the base of tongue lesion, neck dissection and postoperative radiation therapy. Because both groups have similar local control in our experience (80-90%), we used a subjective performance status scale for head and neck cancer patients to assess the quality of life in these patients (0-100, 0 = worst function, 100 = normal function). This scale measures ability to eat in public, understandability of speech, and normalcy of diet. There were 30 radiation patients (21: T1-T2; nine: T3-T4) and ten surgery patients (five: T1-T2; five: T3-T4) available for long-term quality of life assessment., Results: Patients treated with radiation had consistently better performance status scores and quality of life according to our study. This was true for those with early (T1-2) as well as more advanced (T3-4) disease. For eating in public, T1-2 patients had scores of 85 vs. 75 (p = .31) and T3-4 patients had scores of 82 vs. 35 (p < .0001) for radiation vs. surgery, respectively. For understandability of speech, T1-2 patients had scores of 92 vs. 65 (p = .0021), and T3-4 patients had scores of 95 vs. 35 (p < .0001) for radiation vs. surgery, respectively. For normalcy of diet, T1-2 patients had scores of 74 vs. 50 (p = .047), and T3-4 patients had scores of 78 vs. 32 (p = .0012) for radiation vs. surgery, respectively. In addition, we compared scores for early vs. advanced disease treated by the same modality. For radiation, there was no difference in all three functional categories for T1-2 vs. T3-4 (p = .84), showing that quality of life scores remain high for all stages. For surgery, functional status deteriorated significantly when comparing T1-2 vs. T3-4 (p = .0014), consistent with the fact that larger tumors require more extensive operations., Conclusion: Radiation therapy provides a better performance status than surgery for base of tongue cancer. This is true for both early and advanced disease. Because radiation also provides similar local control and survival, our data suggests that radiation may be the preferred strategy. Functional scores remain high for all T stages treated with radiation, but deteriorate with more advanced T stages for patients treated with surgery. Similar studies using objective criteria are needed to further compare these treatments.

Purpose: Although resection of single brain metastases and postoperative whole-brain radiation therapy (WBRT) improves survival, compared with treatment using WBRT alone, the value of postoperative WBRT after resection of brain metastases is controversial. We analyzed the largest reported series of lung cancer patients with resected brain metastases to evaluate the impact of postoperative WBRT., Materials and Methods: Between 1974 and 1989, 185 patients with non-small-cell lung cancer (NSCLC) underwent resection of brain metastases. Patients who had received preoperative WBRT (23%, 42 of 185) were excluded. The remaining patients were divided into group A (no WBRT; n = 32), group B (patients received WBRT and were prognostically matched to group A; n = 32), and group C (all other WBRT patients; n = 79). Most patients received postoperative doses of 30 Gy in 10 fractions. Higher doses were used in 16% of group B and 18% of group C patients., Results: Overall 5-year survival rates were as follows: group A, 12%; B, 8%; C, 16%. Overall brain failures occurred in 38% of patients in group A, 47% in group B, and 42% in group C. The use of WBRT (group A v groups B plus C) had no apparent impact on survival or on overall brain failure rates. In particular, no improvement in either of these parameters could be demonstrated when group B was compared with group A. Focal failure (defined as failure within the brain adjacent to the site of the resected brain metastases) occurred as follows: group A, 34% (11 of 32); groups B plus C, 23% (25 of 111) (P = .07). WBRT significantly reduced focal failure for patients with adenocarcinoma (group A, 33% [eight of 24]; groups B plus C, 14% [11 of 79]; P = .05). Nonfocal failure (anatomically distinct from the resected metastasis) occurred in 9% of patients in group A (three of 32), 21% in groups B plus C (23 of 111) (P = .07)., Conclusion: Long-term survival is possible when NSCLC brain metastases are resected. Postoperative WBRT as used in this series only had an impact on the focal control of brain metastases and this effect was of borderline significance. The lack of conclusive benefit supports the need for ongoing randomized trials to test the value of adjuvant postoperative WBRT. Brain failures were relatively common in all three groups of patients, which suggests that doses greater than 30 Gy need to be studied.

Twenty-five untreated patients with advanced, resectable squamous cell carcinoma of the hypopharynx, for whom standard treatment would have required total laryngectomy, were treated with one to three cycles of cisplatin-based chemotherapy with larynx preservation as the goal. Patients with a major (complete or partial) response to chemotherapy at the primary site were treated with definitive radiation therapy, with total laryngectomy reserved for salvage; patients with less than a partial response to chemotherapy had total laryngectomy and postoperative radiation therapy recommended. Four patients had a poor response to chemotherapy and thus were not candidates for laryngectomy. Total laryngectomy was required for initial induction chemotherapy failure in five patients and for local recurrence in five others. Three additional patients had unresectable recurrence. Successful larynx preservation was achieved in 32% (8 of 25). With a median follow-up period of 41 months, the actuarial overall and failure-free 2-year survival rates were 44% and 32%, respectively. These preliminary data suggest larynx preservation is feasible in patients with advanced lesions of the hypopharynx. Improved local and regional control must be incorporated into the larynx preservation approach for hypopharyngeal lesions. A prospective, randomized study is necessary for a more valid comparison with conventional therapy, including comparative assessments of survival, morbidity, cost and functional results.

We analyzed the results of surgical treatment of all patients presenting with untreated superior sulcus tumors between 1974 to 1991 inclusive at our institution. Most patients received preoperative radiotherapy. We attempted to analyze the influence of surgical resection and intraoperative brachytherapy in obtaining locoregional control and disease-free survival. One hundred twenty-four patients underwent thoracotomy and 100 patients underwent resection. The overall 5-year survival rate was 26% for all patients and 30% for resected patients. Those patients receiving a complete resection achieved a 41% 5-year survival. The best single group were those patients undergoing a lobectomy (versus wedge resection) and en-bloc chest wall resection (60% 5-year survival). We were unable to demonstrate an advantage for the use of intraoperative brachytherapy in those patients with complete resection. For those patients with incomplete resection, the use of brachytherapy combined with preoperative or postoperative external radiation therapy resulted in a 9% 5-year survival. Locoregional failure was significant both in patients with complete resection and in patients with incomplete resection. Adverse prognostic factors included Horner's syndrome, N2 and N3 disease, T4 disease, and incomplete resections. In superior sulcus tumors, every attempt to completely resect the tumor by en-bloc chest wall resection combined with lobectomy and adequate nodal staging remains the surgical treatment of choice together with either preoperative, postoperative, or "sandwich" external radiation therapy.

Background: Long-term survival and possible cure can be achieved in selected patients after resection of liver metastases from a colorectal primary tumor. In this study, the authors used radioactive implants as adjunctive therapy for patients who had incomplete resections of liver metastases., Methods: From 1979 to 1990, 17 implants were performed in 12 patients (median age, 61 years). Brachytherapy was performed for microscopically positive margins in 7 implants and for gross residual disease in 10 implants. Volume implants were performed for gross residual disease using 125I seeds, with a median matched peripheral dose of 160 Gy. Most of the implants for microscopic residual disease were planar implants with 125I suture seeds, with a median treatment dose of 150 Gy., Results: There were no serious postoperative complications. Overall median survival was 18 months, and 42% of patients survived 2 years or more. Extrahepatic metastases occurred in 83% of patients (10 of 12). Intrahepatic failure close to the implanted site occurred in 42% of patients (5 of 12), and intrahepatic failure anatomically remote from the implant site occurred in 25% (3 of 12)., Conclusions: This approach is feasible and achieves reasonable local control of residual disease after resection of hepatic metastases from colorectal cancer. The anatomic pattern of failure supports efforts to intensify local therapy and to address the high rate of distant metastases.

Three-dimensional conformal radiotherapy is a mode of precision radiation treatment that currently is being integrated into the multidisciplinary management of lung cancer. 3-DCRT represents a technical improvement in comparison with conventional treatment. This has been achieved without the use of innovations in accelerator hardware that are currently being developed and tested. When these technical advances are widely available for clinical use, they will be integrated with the current 3-DCRT systems, which are for the most part composed of improvements in software. Thus, 3-DCRT is a modality in a state of flux that should have great clinical potential in the future. The accurate dose volume histogram data available with current 3-DCRT systems will facilitate strategies to predict and prevent radiation pneumonitis.

Recent advances in the understanding of multiple personality disorder provide the groundwork for its creative reconciliation with psychoanalysis. This paper uses psychoanalytic, modern developmental, and psychological assessment perspectives to conceptualize multiple personality disorder as a developmentally protective response to chronic childhood trauma. Implications of this theory for clinical work with these patients are discussed.

Between January 1988 and June 1992, 20 patients with unresectable malignant tumors at the skull base were treated. Eleven had T4 lesions of the paranasal sinus/cavity complex, and 9 had T4 nasopharynx cancer. All patients had stage IV disease by the American Joint Committee on Staging Criteria. The histology was squamous cell cancer in 15 patients and other minor salivary gland histologies in 5. There was brain and/or dural invasion in 11 patients and orbital invasion in 9. All patients received radiation therapy with accelerated fractionation to a total of 70 Gy in 6 weeks. Concomitant cisplatin (100 mg/m(2)) was given on days 1 and 22 of radiation. Seven patients received mitomycin C (7.5 mg/m(2)) on days 1 and 22, plus adjuvant chemotherapy with cisplatin and vinblastine. Median follow-up was 11 (range: 1 to 43) months. At 2 years, local progression-free survival was 94%, distant metastases-free survival was 57%, and overall survival was 80%. Complications occurred in 20% and caused the death of 1 patient. Treatment of this group of patients with aggressive chemotherapy and radiation therapy produced excellent local control in our early experience, but longer follow-up is needed. There is a high rate of distant failure. Future strategies are outlined.

One case of non-penetrance of the familial adenomatous polyposis (FAP) gene at 59 years of age and late onset of polyps on endoscopy and biopsy in this and two other families is described. Screening protocols should include dental screening as well as indirect ophthalmoscopy and endoscopy to detect minimal manifestations of the gene. In the absence of a specific DNA predictive test, bowel screening should continue well beyond 30 years of age.

Over the past 20 years, it has become evident that limb preservation is possible in the management of soft tissue sarcomas of the extremities. Amputation has been generally replaced by more conservative operations that preserve limb function, followed by radiation therapy. Although external beam irradiation has been the most commonly applied adjuvant, there has been increasing interest in using brachytherapy instead of external beam therapy. The reasons for this tren include the apparent equivalence of local control for properly selected patients using brachytherapy, improved patient convenience, shorter treatment time, and lower cost. A recently published report of a prospective randomized trail shows statistically significant improvement in local control when brachytherapy is added to surgery for high grade sarcomas. The treatment concepts used when using brachytherapy challenge many of the orginal teachings for external beam irradiation with regard to field size, volume irradiated, and the tissues that require treatment in the postoperative setting. This article addresses thse controversies, as well as reviews the evolving role of brachytherapy in the management of soft tissue sarcomas. Issues such as patient selection, integration with other local therapies, and complications are highlighted, and special situations are discussed.

High dose rate brachytherapy for lung and esophageal cancer is performed by placing a high activity Iridium 192 source into the lumen of the airway of esophagus. Because of the high activity of the source it remains in place for only a matter of minutes, and fractionated treatments are feasible. Before this development, conventional dose rate brachytherapy required hospitalization with attendant patient discomfort, expense, and complicated radiation safety requirements. The development of high activity remote afterloading machines has removed these practical disadvantages and has led to a great interest in the use of this technology for radical treatment and palliation of obstructing malignancies. There are several unresolved issues concerning this modality for both lung and esophageal cancer. For both diseases, optimal dose and fractionation schemes are not well defined but the palliative benefits for recurrent lung cancer have been clearly shown. The use of a brachytherapy boost following radical external beam radiation therapy of lung cancer is not proven to be advantageous. For esophageal cancer, the value of brachytherapy for palliation is not established. However, there are preliminary data to suggest that it can improve outcome when used routinely after radical treatment with external beam radiation therapy.

Purpose: The specific aim of 3-dimensional conformal radiation therapy is to improve the target dose distribution while concomitantly reducing normal tissue dose. Such an approach should permit dose escalation until the limits of acceptable normal tissue toxicity are reached. To evaluate the feasibility of tumor dose escalation for nine patients with lung cancer, we determined the dose distribution to the target and normal tissues with 3-dimensional conformal radiation therapy and conventional planning., Methods and Materials: Plans were compared to assess adequacy of dose delivery to target volumes, dose-volume histograms for normal tissue, and normal tissue complication probabilities (NTCP) for nine patients with lung tumors., Results: The mean percentage of gross disease which received < or = 70.2 Gy with 3-dimensional conformal radiation therapy (3DCRT) was 40% of the mean percentage of gross disease which received < or = 70.2 Gy with conventional treatment planning (CTP). The mean NTCP for lung parenchyma with 3DCRT was 36% of the mean NTCP with CTP. The mean esophageal NTCP with 3DCRT was 88% of the mean NTCP with CTP., Conclusion: This preliminary analysis suggests that three dimensional conformal radiation therapy may provide superior delivery of high dose radiation with reduced risk to normal tissue, suggesting that this approach may have the potential to improve the therapeutic ratio of high dose radiation therapy for lung cancer.

Purpose: The presence of a positive or close margin after resection of a squamous cancer of the head and neck is associated with a significant risk of local recurrence. To determine the efficacy of postoperative radiation therapy for patients with advanced oral cavity and oropharyngeal cancers with inadequate margins of resection, the present retrospective analysis was undertaken., Methods and Materials: One hundred and two patients were treated with surgery and postoperative radiation therapy for advanced squamous cell carcinomas of the oral cavity and oropharynx. The anatomic subsites treated include oral tongue (n = 29), floor of mouth (n = 22), base of tongue (n = 31) and tonsillar fossa (n = 20). Twenty-five patients (25%) had positive margins, 41 patients (40%) had close margins (< or = 0.5 cm from the surgical margin) and 36 (35%) had negative margins. The median radiation dose was 6000 cGy., Results: With a median follow-up of 7 years, the actuarial control rate for patients with positive, close and negative margins was 79%, 71%, and 79%, respectively. When postoperative doses of > or = 60 Gy were delivered to patients with positive/close margins (excluding patients with oral tongue lesions), the 7-year actuarial control was 92%. In similar patients receiving < 60 Gy, the actuarial control was 44% (p = 0.0007). Compared to other anatomic subsites, inferior control rates were obtained with oral tongue lesions. For this subsite, the control rates for positive, close, and negative margins were 50%, 62% and 69% respectively., Conclusion: We conclude that excellent local control can be achieved with postoperative radiation therapy, despite the presence of inadequate margins of resection, when doses of > or = 60 Gy are used. Future strategies must be directed at further improving these results in patients with oral tongue lesions.

Background: The authors report the long-term treatment results for advanced stage base of tongue (BOT) and tonsillar fossa (TF) carcinomas treated with surgery and postoperative radiation therapy (RT) at Memorial Sloan-Kettering Cancer Center., Methods: Between 1973 and 1986, 51 patients with squamous cell carcinoma of the BOT (n = 31 patients) and TF (n = 20 patients) were treated with surgery plus RT. Indication(s) for RT included: advanced disease (Stage T3/T4, 34 patients [66%]); close or positive margins (33 patients, 64%) and multiple positive neck nodes (43 patients, 84%)., Results: The 7-year actuarial local control rates for BOT and TF lesions were 81% and 83%, respectively. Local control was achieved in 17 of 18 (94%) patients with T3 lesions, and 12 of 16 (75%) patients with T4 lesions. Among patients with positive or close margins who received postoperative doses of 60 Gy or more, the long-term control rate was 93%. The presence of a treatment interruption had a negative effect on the local control rates. The actuarial control among patients who required a treatment break was 64%; for those not requiring interruption of their treatment, the actuarial control was 93% (P = 0.05). At 7 years, the overall survival for all patients was 52%, and the disease-free survival was 64%. The actuarial incidence of neck failure was 21% and 18% for BOT and TF, respectively. The likelihood of having distant metastasis at 7 years for all patients was 30%. The actuarial incidence of having a second malignancy was 35% for patients with BOT disease. Second malignancy was not observed among patients with TF lesions., Conclusions: The authors conclude that surgery and postoperative RT can provide excellent long-term, disease-control rates for patients with advanced BOT and TF tumors. However, current strategies for BOT lesions have been directed at tongue preservation without surgery.

With the decreasing length of psychiatric hospitalizations, identification of test indicators of suicide risk becomes critically important. This Rorschach study was designed to model a clinical decision-making scenario concerning adolescent suicide risk. Using Psychiatric Evaluation Form (PEF) scores, we selected a sample of 25 severely depressed and suicidal adolescents; 26 severely depressed, not suicidal adolescents; and 28 not suicidal, not depressed adolescent inpatients at The Sheppard and Enoch Pratt Hospital. A Rorschach Index using the Exner (1986) Comprehensive System for scoring was developed to predict group membership. Four of six of the features on this index selected 64% of suicidal subjects. This constellation included traditional affective variables (vista responses, color-shading blends, color dominated responses, and morbid content) as well as measures of cognitive distortion (inaccurately perceived human movement responses [M-] and special scores). We discuss the implications of these findings for the diagnosis and treatment of the suicidal adolescent.

Background: Although the need for corticosteroids in acute severe asthma is well established the appropriate dose is not known., Methods: The response to intravenous hydrocortisone 50 mg (low dose), 100 mg (medium dose), and 500 mg (high dose), administered every six hours for 48 hours and followed by oral prednisone, was compared in patients with acute asthma in a double blind randomised study. After initial emergency treatment with bronchodilators subjects received oral theophylline or intravenous aminophylline and nebulised salbutamol four hourly. Patients were given low, medium, or high doses of intravenous hydrocortisone and then 20, 40, or 60 mg/day respectively of oral prednisone with a reducing regimen over the following 12 days. Beclomethasone dipropionate, 400 micrograms twice daily by metered dose inhaler, was also started. Peak expiratory flow (PEF), forced expiratory volume in one second (FEV1), and visual analogue dyspnoea scores (VAS) were recorded daily in hospital and PEF and VAS twice daily after discharge for a total of 12 days., Results: The 66 subjects (40 female) who completed the study had a mean (SD) age of 31(14) years. On presentation mean (SD) FEV1% predicted in the low (n = 22), medium (n = 20), and high dose (n = 24) groups was 17(13), 19(12), and 19(11) and after emergency bronchodilator treatment 32(20), 30(12), and 36(13). After 24 hours of treatment the respective post-bronchodilator FEV1% predicted values were 62(22), 62(23), and 65(28) compared with 71(24), 69(22), and 71(24) after 48 hours. No significant difference between the groups was detected. PEF and VAS improved with treatment over the 12 days but was not influenced by steroid dose., Conclusions: Hydrocortisone 50 mg intravenously four times a day for two days followed by low dose oral prednisone is as effective in resolving acute severe asthma as 200 or 500 mg of hydrocortisone followed by higher doses of prednisone.

We used a posteriorly based transpalatal flap for interstitial nasopharyngeal brachytherapy in five patients with nasopharyngeal carcinoma. All of these implants were done with iodine 125 seeds. The disease in three of five patients has been controlled locally for 27, 30, and 40 months, respectively. Two patients experienced local failure and died. There have been no palatal healing problems despite high doses of previous radiation in all of our patients. No palatal incompetence has been seen. This technique appears safe and should be considered for discrete lesions of the high posterior or superior nasopharynx that cannot be approached by less invasive methods.

Between January 1981 and June 1990, 36 previously untreated patients with squamous cancer of the base of the tongue were treated with radiation therapy. This therapy consisted of a 5,000-5,400-cGy external beam plus a 2,000-3,000-cGy boost to the base of the tongue with an iridium-192 implant. Necks with negative nodes were only irradiated, while necks with positive nodes were treated with irradiation plus neck dissection. Actuarial local control and survival at 2 years were 87.5%. Neck control was achieved in 35 of 36 patients. When implantation was performed with the nonlooping technique, the injury rate was statistically higher than in patients who underwent implantation with the looping technique (P = .02). Thirty patients participated in a function assessment involving a Performance Status Scale for patients with head and neck cancer. The authors concluded that management of base-of-tongue cancer with external beam irradiation plus brachytherapy is both oncologically and functionally successful.

Objective: To compare the clinical effectiveness and patient acceptance of a large spacer device (Nebuhaler) for delivery of metered dose aerosol (MDI) terbutaline with nebulised wet aerosol terbutaline., Design: Randomised open crossover study over two sequential four week treatment periods, following a two week run-in., Setting: Multi-centre including five adult thoracic units and three paediatric centres throughout Australia., Patients: Thirty-eight adults and 23 children with clinical asthma and reversible airflow obstruction (increase in forced expiratory volume in one second [FEV1] of greater than or equal to 15% in response to inhaled bronchodilator) entered the study proper. Six adults and one child withdrew., Interventions: Terbutaline was administered four times daily via Nebuhaler/MDI or nebuliser. Clinical assessment with spirometry and peak flow readings was made after run-in and at the end of each treatment period. Patients recorded on diary cards daily peak expiratory flow rates and symptom scores and comparisons of these results for each treatment period were made. At the completion of the study patients answered a treatment preference questionnaire., Results: No differences were found between the two treatment periods in diary card peak flow recordings and symptom score data, and in clinical assessment of spirometry and peak expiratory flow rates. There were also no differences between spirometry and peak flow values recorded at the clinic at randomisation and at the end of each treatment period, suggesting stable basal airflow obstruction over the period of the study. Thirty-two per cent of adults and 52% of children preferred the Nebuhaler/MDI combination, mainly because of convenience of use. Treatment preference was not related to any measured index of lung function., Conclusions: MDI terbutaline delivered via Nebuhaler provides clinical benefit similar to that of wet aerosol terbutaline in the long-term domiciliary management of patients with stable airflow obstruction.

We have used the polymerase chain reaction to amplify two variable number of tandem repeats (VNTRs) within a region of repetitive DNA located in intron 40 of the von Willebrand factor (vWf) gene. Heterozygosity for VNTR I was observed in 30 out of 39 normal unrelated individuals tested (77%), and for VNTR II in 29 out of 44 (66%) similar individuals. Family studies were carried out on 11 kindreds with von Willebrand disease (vWD). Ten of these families were found to be informative for one or other of the VNTRs or for a combination of data from both VNTRs. This method can be used for antenatal diagnosis and for carrier diagnosis in recessive forms of vWD. It is also useful for tracking the gene associated with vWD in type I families where there may be one or more individuals with a phenotypically uncertain diagnosis.

To assess the place of bronchoscopy in the investigation of pleural effusion, 245 patients presenting during a two year period were reviewed. Of the 46 patients who had bronchoscopy, a positive yield was obtained in 13, though in five of these a second pleural aspiration was also diagnostic. Bronchoscopy was more likely to be diagnostic in patients presenting with a cough (12/24) than in those with no cough (1/22) (p less than 0.001), and in those whose chest X-ray revealed significant radiological abnormalities such as hilar enlargement, lung mass or persisting consolidation (12/29), than in those without such changes (1/17) (p less than 0.01). Bronchoscopy has a limited role in the investigation of pleural effusion. The presence or absence of cough, and the appearance of the chest X-ray, are both important considerations when planning the investigation of an undiagnosed pleural effusion.

To define the indications for elective neck treatment, the cases of 474 previously untreated patients were reviewed who had locally confined major salivary gland cancers treated between 1939 and 1982. Clinically positive nodes were present in 14% (67 of 474). Overall, clinically occult, pathologically positive nodes occurred in 12% (47 of 407). By univariate analysis, several factors appeared to predict the risk of occult metastases; however, multivariate analysis revealed that only size and grade were significant risk factors. Tumors 4 cm or more in size had a 20% (32 of 164) risk of occult metastases compared with a 4% (nine of 220) risk for smaller tumors (P less than 0.00001). High-grade tumors (regardless of histologic type) had a 49% (29 of 59) risk of occult metastases compared with a 7% (15 of 221) risk for intermediate-grade or low-grade tumors (P less than 0.00001). In view of the low frequency of occult metastases in the entire group, routine elective treatment of the neck is not recommended. High-grade tumors and larger tumors have a high rate of occult neck metastases, and treatment should be considered in this group.

This retrospective analysis of 49 cases of primary carcinoma of the vagina treated with radiation therapy alone from 1970-1988 examines the results of treatment with an emphasis on the importance of brachytherapy technique. Thirty-six patients were treated with combined external beam radiation and brachytherapy, 11 patients were treated with external beam alone, and two patients were treated with brachytherapy alone. Brachytherapy techniques used included intracavitary implants, temporary Ir-192 interstitial implants, and permanent I-125 interstitial implants. Intracavitary therapy included the use of a fractionated high dose rate intravaginal cylinder, tandem and ovoids, and a low dose rate intravaginal cylinder. The 5-year actuarial survival was 44% for Stage I (six patients), 48% for Stage II (27 patients), 40% for Stage III (10 patients), and 0% for Stage IVa and IVb (six patients). There was a significant increase in the 5-year actuarial survival for those patients who had brachytherapy as part of their treatment compared to those patients treated with external beam alone (50% vs. 9%) (p < .001). For Stages II and III, there was a trend toward improved actuarial and crude disease free survival with the use of a temporary Ir-192 interstitial implant as part of the treatment compared to the use of intracavitary brachytherapy as part of the treatment (80% vs. 45%) (p = 0.25) and (75% vs. 44%) (p = 0.08), respectively. Brachytherapy plays an important role in the management of primary vaginal cancer. A temporary interstitial implant should be used over an intracavitary form of therapy for more invasive disease.

Survival for clinical Stage IIIa (T1-3, N2) non-small cell lung cancer is very poor because of poor local disease control and systemic spread. To address these shortcomings, we initiated a treatment program with induction chemotherapy, surgery, and postoperative radiation reserved for patients with residual disease at thoracotomy. Between 1984 and 1986, 41 patients with clinically evident N2 disease were treated with induction chemotherapy followed by resection and the selective use of intraoperative brachytherapy. All patients with tumor in the resection specimen received two cycles of chemotherapy and 15 patients received radiation therapy. With a median follow-up of 5.4 years, overall survival is 27% at 3 years, and 12% at 5 years. Despite the adverse selection process median survival is 19 months for patients receiving postoperative radiation therapy, and 22 months for the more favorable patients not requiring radiation therapy, supporting the selective use of postoperative radiation in this setting. In summary, this treatment has yielded good median survival and long-term survival for some of the patients. However, the ultimate value of this approach can only be determined by prospective trials which compare it to standard therapy.

A case of pulmonary actinomycosis presenting with a right calf abscess and complicated by effusive constrictive pericarditis is discussed. Clinical improvement occurred with antibiotic therapy and pericardiectomy. There was no evidence of recurrence after 18 months.

Thoracic failure is a significant obstacle to the cure of limited stage small-cell lung cancer (LSCLC) patients treated with combined modality therapy. In 1985 we initiated a prospective trial to evaluate the impact of twice daily thoracic irradiation without concomitant chemotherapy on control of intrathoracic tumor in LSCLC. Twenty-nine patients treated in this fashion were compared with 36 patients treated from 1979-1982 with once daily thoracic irradiation and concomitant chemotherapy. Both groups received the same induction chemotherapy; cyclophosphamide, Adriamycin, and vincristine (CAV) alternating with cisplatin and etoposide. For consolidation, the twice daily patients received thoracic irradiation, 45 Gy in 1.5 Gy fractions given twice daily, and the once daily patients received thoracic irradiation, 45 Gy in 2.5 Gy fractions given once daily with concomitant cyclophosphamide and vincristine. After completion of radiotherapy both groups received maintenance chemotherapy. The complete response (CR) rate after thoracic irradiation was higher for twice daily patients (86% (25/29) compared to the once daily patients [61% (22/36), p = 0.02]. However, this advantage was offset by the shorter duration of thoracic control among CR patients treated with twice daily thoracic irradiation compared to once daily thoracic irradiation (32% vs 67% at 2 years, p less than 0.05). In view of the enhanced initial response of LSCLC to twice daily thoracic irradiation, this basic radiotherapeutic approach seems appropriate, but new strategies using higher doses of twice daily thoracic irradiation or concomitant chemotherapy appear to be necessary to enhance long-term thoracic control.

Since January 1985, 12 patients with local/regional extrahepatic biliary system cancer (2: gallbladder; 5: Klatskin; and 5: common bile duct) underwent combined modality therapy. An endoscopic retrograde cholangiopancreatography, percutaneous transhepatic cholangiogram, and biliary drainage were performed in 5 patients, and 7 patients underwent laparotomy and biopsy or subtotal resection. All patients initially received 5,000 cGy to the tumor bed and primary nodal area and 10 received an additional 1,500-cGy boost to the tumor bed. Chemotherapy (5-fluorouracil/mitomycin-C) was delivered at the beginning of each radiation treatment course. Four patients received an additional 1-4 cycles of maintenance chemotherapy and 7 received a boost with brachytherapy. The median survival was 17 months and the overall 4-year actuarial survival was 36%. Four patients have no evidence of disease at 16, 30, 48, and 64 months, respectively. The patterns of failure as a component of failure were local/regional progression, 50%; abdominal failure, 58%; and distant failure, 8%. Of the 8 patients who developed failure, 6 developed a component of local/regional progression. Our data continue to show that this approach is feasible and may result in an improvement in survival. Continued follow-up will be needed to determine the ultimate impact of this aggressive approach.

Embryos of eggs from Single Comb White Leghorn hens were analyzed to determine whether nest holding time and method of storage had a significant effect on postoviposition embryonic growth prior to incubation. Eggs were collected from 38- to 42-wk-old hens naturally inseminated and housed in floor pens. The experiment had a 2 x 2 factorial arrangement of treatments with two nest holding times and two storage methods. Eggs were collected within 1 h of oviposition, placed on cardboard egg flats, and stored unpacked (Treatment 1), or put on flats, and packed in 30-dozen egg cases (Treatment 2). Eggs in Treatments 3 and 4 were marked within 1 h of oviposition, but remained in the nest for 6 to 7 h. These eggs were separated into unpacked (Treatment 3), and packed (Treatment 4) groups. All eggs were stored at 13.8 C for 4 days. A total of 250 embryos were staged after storage for development using the Eyal-Giladi and Kochav classification. Least square means (LSM) for stage of development were: Treatment 1, 10.76; Treatment 2, 11.52; Treatment 3, 12.41; and Treatment 4, 12.36. For the main effects, nest holding time significantly affected stage of development (P = .0001), but storage method (P = .1140) and nest holding time by storage method interaction (P = .0730) did not. Comparison of LSM of Treatment 1 versus 3 (P = .0001), 2 versus 4 (P = .0152), and 1 versus 2 (P = .0214) were significant, but Treatment 3 versus 4 (P = .8595) was not.(ABSTRACT TRUNCATED AT 250 WORDS)

In January 1988, we initiated a prospective study evaluating a new treatment approach with chemotherapy and radiotherapy for unresectable head and neck cancer. Weeks 1-4 were the initial debulking phase. Radiotherapy was delivered using 1.8 Gy/day to large portals including gross disease and all areas at risk. Cisplatinum, 100mg/m2, was given concomitant with radiotherapy on days 1 and 22. Weeks 5 and 6 were the boosting phase. This involved twice-a-day irradiation. The AM fraction of 1.8 Gy was given to the entire area at risk, whereas the PM dose of 1.6 Gy was limited to the gross disease alone. Thus a total of 70 Gy/6 weeks was delivered. A total of 24 patients were treated, 22 of whom have completed this protocol and are evaluable. All patients had massive disease, with 15 having gross involvement of brain, orbit, skull base, or carotid artery. Follow-up ranged from 3-22 months (median 12 months). Major responses were achieved in 96%, with 64% complete responses and 32% partial responses. Two patients with PR were able to undergo complete surgical resection, making the overall rate of complete response, including surgery, 73%. At 1 year, actuarial survival was 69%, and local progression-free survival was 56%. Distant metastases developed in 5 (23%). This approach appears both safe and effective in producing excellent regression and local control for far advanced head and neck cancer. More time is needed to see if these results are sustained. Efforts to build upon this experience appear warranted.

Because of their proximity to nerve roots and the spinal cord, it is frequently difficult to achieve complete resection of paraspinal tumors. We have used brachytherapy in an attempt to prevent local recurrence and its associated neurological sequelae. This report analyzes our experience with 35 patients to determine the feasibility, optimal techniques, and efficacy of this approach. The tumor types were non small-cell lung cancer (18), sarcomas (9), and other tumor types (8). Temporary, single plane implants using Ir-192 (median minimum peripheral dose 3000 cGy) were used in 21 patients, and permanent I-125 implants were used in 14 cases (median matched peripheral dose 12,500 cGy). Local control was achieved in 51% (18/35). However, local control was poor when lung cancers were implanted and in cases where the dura was exposed. Radiation myelitis did not occur despite the combined effects of previous external beam radiotherapy (N = 21) and brachytherapy. Our experience demonstrates that combined surgery and paraspinal brachytherapy can be performed with acceptable toxicity and is reasonably effective in preventing local relapse and its neurologic sequelae, particularly for tumors other than lung cancers.

Limited-stage small cell lung cancer is frequently treated with induction combination chemotherapy (ICC), followed by consolidation with thoracic irradiation. It has been suggested that patients who do not have a complete response to ICC are unlikely to have control of occult distant metastasis and consequently have such a poor prognosis that thoracic irradiation is unlikely to be of benefit. To examine this hypothesis, 48 patients treated on prospective protocols who achieved a complete response to ICC or subsequently to thoracic irradiation were analyzed. Twenty-four patients had a complete response to ICC (CR-ICC), and 24 subsequently converted to complete-response status after thoracic irradiation (CR-TI). The two groups had similar prognostic factors and treatment. Comparing CR-ICC and CR-TI patients, survival was 40% versus 26% at 2 years and 35% versus 4% at 5 years, respectively (P less than .05). Freedom from distant metastasis was 41% at 5 years for the CR-ICC patients and 8% for the CR-TI patients (P less than .05). A modest number of CR-TI patients were long-term survivors, suggesting a value for thoracic irradiation as consolidation therapy.

Thirty-eight histologically confirmed desmoid tumors were treated with conservative surgical resection and interstitial iridium 192. Patients included in this series constituted a poor prognostic group. Seventy five percent (75%) had previous recurrences of their disease and 50% had tumors 8 cm or greater in size. In addition, 16% of the patients had gross residual disease after surgical excision and 79% had positive or close margins of resection. With a median follow-up of 5.5 years, the 5-year actuarial in-field local control rate was 75% and the overall local control rate was 66%. Four of the 12 local recurrences developed at the periphery of the implant volume and four patients failed at least 3 cm or more beyond the treated volume. After salvage therapy, the 5-year actuarial local control rate was 95%. Two patients required amputation for recurrent disease. Thirty of 34 patients remain free of disease with an excellent functional result achieved. The authors conclude that surgical resection and postoperative interstitial iridium 192 is effective therapy for patients with desmoid tumors. Despite the fact that most patients in this series had bulky, recurrent tumors, excellent long-term local control and limb function were achieved.