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Hereditary nonpolyposis colorectal cancer accounts for about 5% of all colorectal malignancies and is most commonly accompanied by endometrial cancer. Two experts on HNPCC outline the appropriate screening, diagnostic, and management strategies. [ABSTRACT FROM AUTHOR]

Abstract Background Recent data in esophageal cancer suggests the variant allele of a single-nucleotide polymorphism (SNP) in XRCC1 may be associated with resistance to radiochemotherapy. However, this SNP has not been assessed in a histologically homogeneous clinical trial cohort that has been treated with a uniform approach. In addition, whether germline DNA may serve as a surrogate for tumor genotype at this locus is unknown in this disease. Our objective was to assess this SNP in relation to the pathologic complete response (pCR) rate in subjects with esophageal adenocarcinoma who received cisplatin-based preoperative radiochemotherapy in a multicenter clinical trial (Eastern Cooperative Oncology Group 1201). As a secondary aim, we investigated the rate of allelic imbalance between germline and tumor DNA. Methods Eighty-one eligible treatment-naïve subjects with newly diagnosed resectable esophageal adenocarcinoma received radiotherapy (45 Gy) concurrent with cisplatin-based chemotherapy, with planned subsequent surgical resection. The primary endpoint was pCR, defined as complete absence of tumor in the surgical specimen after radiochemotherapy. Using germline DNA from 60 subjects, we examined the base-excision repair SNP, XRCC1 Arg399Gln, and 4 other SNPs in nucleotide excision (XPD Lys751Gln and Asp312Asn, ERCC1 3' flank) and double-stranded break (XRCC2 5' flank) repair pathways, and correlated genotype with pCR rate. Paired tumor tissue was used to estimate the frequency of allelic imbalance at the XRCC1 SNP. Results The variant allele of the XRCC1 SNP (399Gln) was detected in 52% of subjects. Only 6% of subjects with the variant allele experienced a pCR, compared to 28% of subjects without the variant allele (odds ratio 5.37 for failing to achieve pCR, p = 0.062). Allelic imbalance at this locus was found in only 10% of informative subjects, suggesting that germline genotype may reflect tumor genotype at this locus. No significant association with pCR was noted for other SNPs. Conclusions Assessed for the first time in a prospective, interventional trial cohort of esophageal adenocarcinoma, XRCC1 399Gln was associated with resistance to radiochemotherapy. Further investigation of this genetic variation is warranted in larger cohorts. In addition, these data indicate that germline genotype may serve as a surrogate for tumor genotype at this locus.

Abstract Background The Northern California county of Marin (MC) has historically had high breast cancer incidence rates. Because of MC's high socioeconomic status (SES) and racial homogeneity (non-Hispanic White), it has been difficult to assess whether these elevated rates result from a combination of established risk factors or other behavioral or environmental factors. This survey was designed to compare potential breast cancer risks and incidence rates for a sample of middle-aged MC women with those of a demographically similar population. Methods A random sample of 1500 middle-aged female members of a large Northern California health plan, half from Marin County (MC) and half from a comparison area in East/Central Contra Costa County (ECCC), were mailed a survey covering family history, reproductive history, use of oral contraceptives (OC) and hormone replacement therapy (HRT), behavioral health risks, recency of breast screening, and demographic characteristics. Weighted data were used to compare prevalence of individual breast cancer risk factors and Gail scores. Age-adjusted cumulative breast cancer incidence rates (2000–2004) were also calculated for female health plan members aged 40–64 residing in the two geographic areas. Results Survey response was 57.1% (n = 427) and 47.9% (n = 359) for MC and ECCC samples, respectively. Women in the two areas were similar in SES, race, obesity, exercise frequency, current smoking, ever use of OCs and HRT, age at onset of menarche, high mammography rates, family history of breast cancer, and Gail scores. However, MC women were significantly more likely than ECCC women to be former smokers (43.6% vs. 31.2%), have Ashkenazi Jewish heritage (12.8% vs. 7.1%), have no live births before age 30 (52.7% vs. 40.8%), and be nulliparous (29.2% vs. 15.4%), and less likely to never or rarely consume alcohol (34.4% vs. 41.9%). MC and ECCC women had comparable 2000–2004 invasive breast cancer incidence rates. Conclusion The effects of reproductive risks factors, Ashkenazi Jewish heritage, smoking history, and alcohol consumption with regard to breast cancer risk in Marin County should be further evaluated. When possible, future comparisons of breast cancer incidence rates between regions should adjust for differences in income and education in addition to age and race/ethnicity, preferably by using a sociodemographically similar comparison group.

Abstract AIDS-associated, CCR5-tropic (R5) HIV-1 clones, isolated from a patient that never developed CXCR4-tropic HIV-1, replicate to a greater extent and cause greater cytopathic effects than R5 HIV-1 clones isolated before the onset of AIDS. Previously, we showed that HIV-1 Env substantially contributed to the enhanced replication of an AIDS clone. In order to determine if Nef makes a similar contribution, we cloned and phenotypically analyzed nef genes from a series of patient ACH142 derived R5 HIV-1 clones. The AIDS-associated Nef contains a series of residues found in Nef proteins from progressors 1. In contrast to other reports 123, this AIDS-associated Nef downmodulated MHC-I to a greater extent and CD4 less than pre-AIDS Nef proteins. Additionally, all Nef proteins enhanced infectivity similarly in a single round of replication. Combined with our previous study, these data show that evolution of the HIV-1 env gene, but not the nef gene, within patient ACH142 significantly contributed to the enhanced replication and cytopathic effects of the AIDS-associated R5 HIV-1 clone.

Abstract Clostridium septicum myonecrosis is associated with diabetes, colorectal and haematological malignancies. We present a case of metastatic myonecrosis in a diabetic patient with a perforated caecal tumour. The literature since 1989 is reviewed and 28 cases of Clostridium septicum myonecrosis are discussed.

In the roundtable that follows, clinicians discuss a study published in this issue of the Journal in light of its methodology, relevance to practice, and implications for future research. Article discussed: Bedient CE, Magrina JF, Noble BN, et al. Comparison of robotic and laparoscopic myomectomy. Am J Obstet Gynecol 2009;201:566.e1-5. [ABSTRACT FROM AUTHOR]

Background Stress and burnout among medical professionals are common and costly, placing professionals, organizations, and patients at risk. Objectives To determine feasibility and acceptability of a longitudinal mind–body skills training initiative to help staff decrease stress and burnout, improve well-being, and empower them to utilize basic mindfulness methods with coworkers, patients, and families. Methods Prospective cohort, mixed methods approach. Nurses, doctors, technicians, social workers, child life specialists were eligible to participate. The 12-month curriculum consisted of 16 hours of intensive education/practice over 2 days, with training in mindfulness skills, self-compassion, nonviolent communication, overcoming barriers to practice, and mindful listening/speaking, followed by monthly 1 hour booster/debriefing sessions. Results A total of 37 staff participated (RN = 18, MD = 5, Technician = 6, Social Worker = 3, Child life = 3, others = 2) in the initial training, and 24 (65%) completed the 3- and 12-month follow-up surveys. Compared with pretraining scores, there were significant improvements 3 to 12 months after the initial training in stress ( P

Purpose: This study aimed to evaluate the toxicity and clinical outcomes for cervical cancer patients treated definitively with intensity-modulated radiation therapy (IMRT) compared with non-IMRT treatment. Methods and Materials: This prospective cohort study included 452 patients with newly diagnosed cervical cancer treated with curative intent (135 IMRT and 317 non-IMRT). Treatment involved external irradiation and brachytherapy, and 85% of patients received concurrent chemotherapy. All IMRT patients underwent an F-18 fluorodeoxyglucose positron emission tomography (FDG-PET/CT) simulation. A 3-month post-therapy PET was obtained to evaluate treatment response. Toxicity was scored by the Common Terminology Criteria for Adverse Events Version 3.0. Results: The IMRT and non-IMRT groups had similar stage distribution and histology. For all patients, the post-therapy FDG-PET response correlated with overall recurrence risk (p < 0.0001) and cause-specific survival (p < 0.0001). Post-treatment FDG-PET findings were not significantly different between the IMRT and non-IMRT patients (p = 0.9774). The mean follow-up for all patients alive at the time of last follow-up was 52 months (72 months non-IMRT, 22 months IMRT). At last follow-up, 178 patients (39 IMRT, 139 non-IMRT) had developed a recurrence. The difference in recurrence-free survival between the two groups did not reach statistical significance (p = 0.0738), although the IMRT group showed better overall and cause-specific survivals (p < 0.0001). Of the patients, 62 patients (8 IMRT and 54 non-IMRT) developed Grade 3 or greater bowel or bladder complications, and by cumulative hazard function analysis the risk was significantly less for patients treated with IMRT (p = 0.0351). Conclusion: Cervical cancer patients treated with FDG-PET/CT-guided IMRT have improved survival and less treatment-related toxicity compared with patients treated with non-IMRT radiotherapy. [ABSTRACT FROM AUTHOR]