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Species with fragmented populations and low population size often display low within-population genetic diversity and strong among-population differentiation. Laurus nobilis L. (Lauraceae), common laurel, has a scattered distribution throughout the Mediterranean, with only few autochthonous populations. Our goal was to elucidate if this species has range-wide genetic structure and if planted material can be traced back to its origin. Genetic diversity was investigated using 4 polymorphic nuclear microsatellites (nSSR) transferred from two species of Lauraceae. Sixty-six laurel trees were selected from 7 widely separated populations within the Mediterranean distribution area of the species. A total of 34 alleles (9 alleles per locus on average) were found. Mean genetic diversity within-population (Hs), was 0.558. Genetic differentiation among populations (GST = 0.243) was high compared to that of other angiosperms. Laurus nobilis can be separated into two main gene pools, one from western (Tunisia, Algeria and France) and the other from eastern Mediterranean (Turkey). The Algerian, Tunisian and French populations presented a strong genetic similarity, compatible with the fact that North African laurel populations could be recently introduced from north-western Mediterranean stock.

Duodenal mucosa–associated lymphoid tissue (MALT) lymphoma is very rare, and little is known about its clinical characteristics, endoscopic and endosonographic features, and treatment. We hereby report a case of duodenal MALT lymphoma successfully treated by radiation therapy (RT). The patient was referred to us with epigastric pain and positive fecal occult blood testing. His symptoms failed to resolve with eradication therapy for a Helicobacter pyloriinfection that was diagnosed by a gastric biopsy performed elsewhere. Endoscopy at our institution revealed hypertophy of the duodenal folds with erosions involving a third of the circumference few centimeters beyond the ampulla of Vater. Histopathologic and immunophenotypic features were consistent with a MALT lymphoma. There was no evidence of a H. pyloriinfection by gastric biopsy and urea breath test. Computed tomography scan of the abdomen and pelvis was normal. Endoscopic ultrasound showed thickening of the duodenal wall and hypoechoic infiltration into the submucosal layer. The patient was treated with RT with a complete response. Two and a half years later, he remains in complete clinical, endoscopic, and histopathologic remission. This case illustrates the importance of RT in patients with duodenal MALT lymphoma whose disease did not respond to H. pylorieradication.

The unambiguous identification of closely related species is useful for many practical purposes in forest tree species. For example, international laws require timber identification and the control of the origin of forest reproductive material. In this paper, we present a mitochondrial DNA marker which can be used to differentiate among groups of fir species (Abies spp.). Eight Mediterranean and one North American fir species (used as reference) were analysed at the fourth intron of the NAD subunit 5 gene. A total of six different haplotypes was identified, one in the American Abies concolor, the other five in Mediterranean species. Two different haplotypes were found each in the widespread A. alba and in A. cephalonica, one haplotype being shared among the two species. A single species specific haplotype was found in the near-eastern A. cilicica. The two southwestern species A. pinsapo and A. numidica shared one haplotype. The fifth haplotype was shared by all remaining eastern Mediterranean firs, A. cephalonica, A. bornmuelleriana, A. equi-troiani, and A. nordmanniana. Differences in haplotype sequences were mainly due to large insertions/deletions. Agarose gel electrophoresis thus provides a fast, cheap and reliable diagnosis method for species or species group identification.

The BRCA1 and BRCA2 gene products are thought to play important roles in the processing of DNA damage. To assess whether heterozygous mutations in these genes are associated with cellular radiosensitivity, we performed an in vitro radiation clonogenic survival assay on dermal fibroblasts obtained from 8 sequence-proven BRCA heterozygotes (6 BRCA1, 2 BRCA2). These data were compared to results obtained from a previous set of 17 prospectively studied cancer patients who had a negligible risk for a BRCA mutation. In addition, results from radiation-induced chromatid break assay performed on lymphocytes obtained from 9 BRCA heterozygotes (8 BRCA1, 1 BRCA2) were compared to results from a control group of 18 women with no cancer history. Results from both assays suggested that cells containing a heterozygous mutation in BRCA1 or BRCA2 were more radiosensitive than controls. For the fibroblast studies, the mean surviving fraction at 2 Gy (SF2) for carriers was 0.279 vs. 0.348 for the control set (p = 0.007). For the lymphocyte studies, the mean number of chromatid breaks after 125 cGy of radiation was 0.79 breaks per cell for the carriers vs. 0.45 for the controls (p = 0.0005). There was no apparent difference in the radiosensitivity between cells with BRCA1 vs. BRCA2 mutations (p = 0.769), although the small sample size minimizes the certainty of this observation. These preliminary results are consistent with a relationship between a germline mutation in BRCA1 or BRCA2 and a hypersensitivity to radiation. This phenotype could possibly predispose to an increased risk of radiation-induced mutagenesis and carcinogenesis. © 2001 Wiley-Liss, Inc.

Purpose:A multi-institutional, prospective, randomized trial was undertaken in patients with advanced head-and-neck squamous cell carcinoma to address (1) the validity of using pathologic risk features, established from a previous study, to determine the need for, and dose of, postoperative radiotherapy (PORT); (2) the impact of accelerating PORT using a concomitant boost schedule; and (3) the importance of the overall combined treatment duration on the treatment outcome.

Despite its subjectivity and inaccuracy, digital rectal examination (DRE) has a long history of well-documented prognostic significance in patients with prostate carcinoma. To the authors' knowledge, very few studies have evaluated the relative prognostic merits of transrectal ultrasound (TRUS) versus DRE. This question is addressed in this study. The outcome for 558 men with T1–T3, N0, M0 adenocarcinoma of the prostate who underwent both DRE and TRUS and received external beam radiation without androgen ablation was evaluated relative to the prognostic information from DRE, TRUS, or both. The outcome endpoints were no evidence of disease (NED) (no relapse or rising prostate specific antigen level) and freedom from metastases. Prognostic factors were evaluated with univariate and multivariate techniques. The median follow-up was 55 months. Both purely DRE-based and purely TRUS-based T categories correlated significantly with NED status. For DRE T categories, 6-year NED rates for T1/T2 and T3 disease were 64% and 36%, respectively (P < 0.001). For TRUS T categories, the rates for T1/T2 and T3 were 63% and 39%, respectively (P < 0.001). There were significant differences in patient composition between DRE and TRUS T categories. Only 40% of patients were in the same DRE and TRUS category, but the majority of the reclassification based on TRUS was within rather than between major T categories (T1/T2 vs. T3). Changes between the prognostically significant T1/T2 versus T3 categories occurred in ≤25%. This accounted for the similarity in NED outcome for DRE and TRUS T categories. However, TRUS categories did not discriminate significantly for metastatic recurrence between T1/T2 and T3 categories, whereas DRE categories did. Upstaging or downstaging by TRUS relative to DRE did not alter the DRE prognostic groupings substantially. There was no clinically meaningful superiority of TRUS over DRE in the definition of prognostically useful T categories. Moreover, the addition of TRUS to DRE did not enhance the prognostic value of DRE findings in any meaningful way. Despite its subjectivity and inaccuracy, DRE provides prognostic information at least equivalent to TRUS and is preferable because of its low cost. Cancer 1999;85:1577–85. © 1999 American Cancer Society.

Prospective randomized and retrospective studies on adjunctive chemotherapy in patients with advanced locoregional nasopharyngeal carcinoma have yielded conflicting results and the role of chemotherapy in this disease had not been clearly defined. The authors report the results of a single institution, matched cohort study comparing a group of 61 patients with advanced stage nasopharyngeal carcinoma treated with induction chemotherapy followed by radiation therapy with a matched group treated with radiotherapy alone. Between 1985 and 1992, 61 patients with advanced locoregional nasopharyngeal carcinoma received induction chemotherapy (cisplatin, 100 mg/m² on Day 1 and 5-fluorouracil [5-FU], 1000 mg/m², on Days 1-5) for 3 cycles followed by definitive radiation therapy (CT/RT group). This group was matched with a group of 61 patients from a population of 378 patients who received radiation therapy alone (RT group). Matching characteristics were T classification, N classification, histology, and level of cervical lymph node metastases. These characteristics were found to be significant determinants of distant metastasis (DM) and/or survival in a multivariate analysis that was performed in the entire radiotherapy group. Radiation therapy consisted of 66-72 gray in 6.5 to 7 weeks in both groups. Fifty-nine patients (97%) in both groups had Stage IV disease. Fifteen patients (25%) in both groups had lower cervical lymph node metastases. The tumor histologic types also had similar distribution in both groups. Median follow-up time among surviving patients of the CT/RT group was 4.9 years (range, 1.3-9.8 years). The 5-year cumulative incidence of DM was 19 ± 5% for the CT/RT group and 34 ± 6% for the RT alone group (P = 0.019; log rank test). This reduction in distant failure was more prominent in patients with intermediate (N2-N3 disease; upper or midcervical lymph nodes), or high risk (N2-N3 disease; lower cervical lymph nodes) of DM. This reduction in DM translated into improvement in disease free survival (DFS) and overall survival (OS). The 5-year actuarial DFS rates were 64 ± 6% for the CT/RT group compared with 42 ± 7% for the RT group (P = 0.015). The 5-year actuarial OS rates were 69 ± 6% (CT/RT group) and 48 ± 7% (RT group), respectively (P = 0.012). The incidence of locoregional failure was slightly lower in the CT/RT group, but this difference did not reach statistical significance. There was no significant difference in the incidence and severity of acute mucositis between the two groups during radiotherapy. The 5-year cumulative incidence of Grade 3 or higher late complications was also similar in both groups (5 ± 3% in the CT/RT group and 8 ± 3% in the RT group; P = 0.721). This matched cohort study provides additional evidence that induction cisplatin-5-FU chemotherapy prior to definitive radiation improves freedom from distant metastasis, DFS, and OS for patients with locoregional Stage IV nasopharyngeal carcinoma without increasing treatment-related morbidity. Cancer 1997; 79:1279-86. © 1997 American Cancer Society.

Purpose: This study was conducted to test for the relationship between tumor and normal tissue radiosensitivity, by comparing local tumor control to the severity of acute and late normal tissue reactions in head and neck cancer patients treated by definitive radiotherapy.Methods and Materials: Two hundred eighty-six patients with head and neck cancer who were treated at the University of Texas M. D. Anderson Cancer Center between 1983 and 1993 were selected for the study. Of these, 124 (43%) were treated by a concomitant boost regimen and 162 (57%) by hyperfractionation. All patients had at least 1 year of follow-up. The tumor stage distribution according to the 1992 American Joint Committee on Cancer (AJCC) staging system was as follows: T1, 3%; T2, 53%; T3, 40%; T4, 4%. The average doses delivered were 71.2 Gy and 76.2 Gy for the concomitant boost and hyperfractionation regimens, respectively, with no significant variation between patients. Acute and late reactions were recorded using the Radiation Therapy Oncology Group (RTOG)/European Organization for Reasearch on Treatment of Cancer (EORTC) grading system (0 to 4). The median follow-up period was 38 months (range: 12–107 months). The time to local tumor recurrence was analyzed in relation to the severity of acute and late reactions expressed as the maximum recorded grades, and to the time intensity of acute mucositis, expressed as the area under the curve of mucositis grade vs. time. Univariate and multivariate analyses also included T stage, N stage, and site of origin as other prognostic variables, and were carried out using a proportional hazards model.Results: Fifty-four patients (19%) suffered local failure. T stage was found to significantly influence local control (p = 0.009). There was a nonsignificant trend for higher failure rates in patients with maximum Grade 1 or 2 vs. those with Grade 3 or 4 acute mucositis (28 and 18%, respectively; p = 0.17). No correlation was found between the severity of late reactions and local tumor control after radiotherapy. Analysis by time intensity of mucositis revealed a wide variation between individuals with a nonsignificant trend for higher local failure rates in patients with low mucositis time intensity scores.Conclusions: These clinical results suggest a possible relationship between normal tissue and tumor radiosensitivity. However, additional studies with a larger numbers of patients, and using refined normal tissue endpoints that incorporate a time function are needed to fully elucidate this question.